Episodes

Abbreviations

BCT – Breast Conservation Therapy

CHT - Chemotherapy

CT – Computed Tomography

CTV – Clinical Tumor Volume

DCIS - Ductal carcinoma in situ

ENE – Extranodal Extension

ER – Estrogen Receptor

GTV – Gross Tumor Volume

H&P – History and Physical

HER2 - Human Epidermal Growth Factor Receptor 2

HRT – Hormone Replacement Therapy

IDC – Invasive Ductal Carcinoma

IMN – Internal Mammary Nodes

Ki67 - percentage score defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed, commonly used measure of cellular proliferation in breast cancer tissue

LAD - Lymphadenopathy

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

NAC – Neoadjuvant Chemotherapy

NCCN – National Comprehensive Cancer Network

OAR – Organs at Risk

PMRT – Post Mastectomy Radiation Therapy

PR – Progesterone Receptor

PTV – Planning Tumor Volume

RNI – Regional Nodal Irradiation

RT – Radiation Therapy

SLNB – Sentinel Lymph Node Biopsy

T stage – Tumor Staging

TNM – Tumor Node Metastasis

V20 – Volume receiving 20 Gray

Staging

https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging

Breast Screening Guidelines

https://www.komen.org/breast-cancer/screening/when-to-screen/average-risk-women/

Highlights

• When presenting with a new breast mass, start with a detailed history and physical exam, paying specific attention to family history of cancer, gynecologic history and history of any irregular mammograms. On physical exam, consider performing a bilateral breast exam, paying specific attention to size/mobility of breast mass, location in the breast, any suspicious skin changes and evaluate for any palpable lymphadenopathy.

• LN stations can be easier to remember if using the pectoralis minor as a landmark. As we work our way medially, level 1 LNs are inferior/lateral to pec minor, level 2 is deep to pec minor, level 3 is superior/medial to pec minor. Level 4 represents our supraclavicular LNs and then, there are the IMNs.

• T staging represents the index breast lesion– anything measuring 2 cm or less is T1, 2-5 cm T2, >5 cm T3, extension to the CW, adherence to the pec muscle, or skin involvement represents T4. If the patient has mobile level I or II LNs, that is N1; if those LNs are fixed OR there’s an isolated IMN, that’s N2; any level III or IV involvement or a + IMN with multistation LAD, is N3.

• Per the NCCN guidelines, staging imaging should be considered if there is suspicion for metastatic disease. There are many indications to obtain genetic testing which can also be found on the NCCN guidelines but the main highlights are get testing for patients diagnosed with breast cancer any age 45 or younger, TNBC, any close blood relative with breast/ovarian/pancreatic cancer or deNovo high risk prostate cancer, Ashkenazi Jewish decent, or if the patient is a male.

• For our simulation, we would obtain imaging in a head first, supine setup on a breast board with the ipsilateral arm raised, and head turned to the contralateral side. We would wire her left breast, any scars, drain sites, and mark breast borders, placing the superior border at the level of the inferior clavicle head, medial at the patient’s midline, lateral at the mid-axillary line, and inferior 1-2 cm below the inframammary fold. I would also obtain a DIBH scan, if available to me.

• We want to keep the mean heart < 4Gy but other very important metrics to meet focus on the LAD for which we want the Dmax <20 Gy and V15Gy<10% and ipsilateral lung V20 <30%.

Acknowledgements

Thank you to Dr. Alexandra Bennett, who was featured in this episode.

https://college.mayo.edu/academics/residencies-and-fellowships/radiation-oncology-residency-minnesota/meet-our-trainees/

Thank you to Dr. Kim Corbin.

https://www.mayoclinic.org/biographies/corbin-kimberly-s-m-d/bio-20163919

Abbreviations

AI - Aromatase Inhibitor

BCT – Breast Conservation Therapy

BI-RADS - Breast Imaging Reporting and Data System

CT – Computed Tomography

CTV – Clinical Tumor Volume

DCIS - Ductal carcinoma in situ

ER – Estrogen Receptor

GTV – Gross Tumor Volume

H&P – History and Physical

HER2 - Human Epidermal Growth Factor Receptor 2

HRT – Hormone Replacement Therapy

IDC – Invasive Ductal Carcinoma

IMN – Internal Mammary Nodes

Ki67 - percentage score defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed, commonly used measure of cellular proliferation in breast cancer tissue

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

OAR – Organs at Risk

PBI – Partial Breast Irradiation

PR – Progesterone Receptor

PTV – Planning Tumor Volume

RT – Radiation Therapy

SLNB – Sentinel Lymph Node Biopsy

T stage – Tumor Staging

USPSTF - United States Preventive Services Taskforce

V20 – Volume receiving 20 Gray

WBI – Whole Breast Irradiation

Staging

https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging

Breast Screening Guidelines

https://www.komen.org/breast-cancer/screening/when-to-screen/average-risk-women/

USPSTF Breast Cancer Screening

https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening

Choosing Wisely

https://www.choosingwisely.org/societies/society-of-surgical-oncology/

FAST FORWARD

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext

ASTRO Clinical Practice Guideline

https://www.sciencedirect.com/science/article/pii/S1879850023002965?via%3Dihub

Breast-Conserving Surgery with or without Irradiation in Early Breast Cancer

https://www.nejm.org/doi/full/10.1056/nejmoa2207586

Highlights

• The breast overlies the pectoralis major muscle. It extends laterally into the low axilla which is often times called the axillary tail of Spence. Where does most of the glandular tissue lay? Often in the upper outer quadrant which is where the majority of breast cancers arise from.

• Lymphatic drainage from breast cancer is important to understand. There are multiple levels that are at risk for nodal metastasis, The axilla has three levels delineated by the pec minor, which is an important landmark. Level 1 is located inferior and lateral to the pec minor, level 2 is directly posterior to the pec minor, and level 3 (infraclav) is superior and medial to the pec minor. Other regions at risk are the supraclavicular and the IMNs, which are adjacent to the sternum and located in the first three intercostal spaces. Of note, when considering risks in lymphatic spaces, a medial primary tumor is twice as likely to drain to the IMNs. 

• Most breast cancers are ER/PR+ and are more commonly observed in post-menopausal patients. Another important biomarker is HER2 status which stands for human epidermal growth factor receptor 2 and is amplified in about 1/4 to 1/3 of cancers. The most biologically aggressive cancer is termed ‘triple negative breast cancer’ in which ER, PR and HER2 are negative (not expressed), and is observed in about 15% of cases. If you have a patient with TNBC, it’s advised to have a genetic screen for the presence of a deleterious mutation. [KC1] 

• Screening guidelines vary depending on organization. The USPSTF recommends a screening mammogram performed every other year for women 50-74 years old.

• For those 40-49 years old, the decision for screening should be individualized, with higher value placed for those at higher risk, including those with a parent, sibling, or child with breast cancer.

• The American Cancer Society recommends yearly screening from ages 45-54 and then every 1-2 years until life expectancy is <10 years.

• MRI breast is great for certain indications but should be ordered with caution since it can result in false positive findings. Some common scenarios where you may want to order an MRI breast are if a patient presents with clinical node positive disease and you are looking for the primary tumor, patients with breast implants, or when there is a mass on exam, but no mammogram or ultrasound correlates.

• There is no numerical cutoff with respect to how far the tumor has to be from the edge of the resected specimen. This was established by the Society of Surgical Oncology and American Society for Radiation Oncology guidelines. If there was tumor on ink, the patient would need to go back for re-excision to achieve a margin negative resection. In our patient, since she was found to calcifications associated with her IDC and these was screen-detected, we would want to get a post-op mammo to ensure no residual suspicious calcifications. Another way to ensure there are no residual calcs is to obtain an intra-op radiographic.

• CALBG 9343 looked at women >= 70 with T1N0 HR+ tumors randomized to tam alone vs RT + tam after lumpectomy. The trial showed that women who receive RT reduced their 10 yr LRR from 10% to 2%; there was no impact on DM or OS. Similarly, PRIME II had broader eligibility criteria with larger tumors up to T2, younger women to 65+ and the presence of high grade dz or LVSI (but not both).  Again, 5-year LRR was decreased by 75%, from 4% to 1% for those who receive RT as well. The 10-year data was recently published in 2023 (linked above) and showed a more profound difference with in-breast LR of 10% for who don’t receive adjuvant RT versus 0.9% for women who received RT. These trials support endocrine alone after lumpectomy to be an appropriate treatment option in older women with favorable early-stage disease.

• To determine suitability for APBI, the ASTRO Clinical Practical Guideline is an excellent resource and was just recently updated in 2023 (linked above).  In patients with invasive disease, PBI is recommended for women >= 40, cT1, ER+, and tumors <=2 cm. In patients with DCIS, PBI is recommended for women >= 40, low to int grade DCIS spanning <=2 cm (Additional suitability criteria linked above)

• For CT simulation, in this case, a headfirst, supine setup on a breast board with the patient’s ipsilateral arm raised was performed. If a breast board is unavailable, a wingboard or vac-loc would be great alternatives for fixation. Consider wiring the scar and mark breast borders and given this is a left sided treatment, employ DIBH for heart avoidance. A prone setup can be considered as well.

• Follow up her 1-4 x per year for a H&P for up to 5 years, then annually, with a clinical exam. Consider obtaining a mammogram at 6 months, then yearly.

Acknowledgements

Thank you to Dr. Kim Corbin.

https://www.mayoclinic.org/biographies/corbin-kimberly-s-m-d/bio-20163919

Abbreviations:

• NSCLC: Non-Small Cell Lung Cancer

• SBRT: Stereotactic Body Radiation Therapy

• RTOG: Radiation Therapy Oncology Group

• PBT: Proximal Bronchial Tree

• DFS: Disease-Free Survival

• OS: Overall Survival

• cN2: Clinical N2 Lymph Node Involvement

• CRT: Chemoradiotherapy

• RFS: Recurrence-Free Survival

• LN: Lymph Node

• IMRT: Intensity-Modulated Radiation Therapy

• 3DCRT: Three-Dimensional Conformal Radiation Therapy

• PACIFIC Trial: A randomized controlled trial in stage III NSCLC

• ICI: Immune Checkpoint Inhibitor

• pCR: Pathologic Complete Response

Highlights:

• SBRT emerged as a revolutionary approach for treating early-stage NSCLC, especially in medically inoperable patients. RTOG 0236 was a landmark study that solidified its role, demonstrating efficacy in peripheral lesions.

• For central tumors, challenges arose due to proximity to the "No Fly Zone," a region around the Proximal Bronchial Tree. This zone's impact on toxicity led to refining treatment strategies.

• RTOG 0813 investigated SBRT for central lesions, revealing increased toxicity with higher dose levels. Similarly, the Nordic HILUS Trial highlighted risks near the trachea/main bronchus.

• The surgery vs. SBRT debate for operable early-stage NSCLC persisted. The Chang Pooled Analysis supported SBRT's non-inferiority, fostering ongoing research.

• RTOG 0618 examined medically operable patients, showcasing impressive local control rates with SBRT while paving the way for further studies.

• The iSABR Trial unveiled enhanced event-free survival with nivolumab and SBRT combination therapy, underscoring the synergy of immune checkpoint inhibitors and radiation.

• LA-NSCLC treatment choices were redefined by RTOG 0139, advocating for definitive CRT over trimodality therapy for cN2 patients.

• The PACIFIC Trial was a turning point, establishing the value of consolidation durvalumab after definitive CRT in stage III NSCLC, improving long-term survival rates.

• Checkmate 816 delved into neoadjuvant nivolumab + platinum doublet chemo, revealing significantly improved event-free survival and pCR rates in resectable lung cancer.

• The Auperin meta-analysis emphasized the survival benefit of concurrent CRT compared to sequential CRT, validating the standard approach.

• IMRT demonstrated its superiority over 3DCRT by reducing severe pneumonitis rates, enhancing treatment outcomes.

• RTOG 0617 reaffirmed 60 Gy in 30 fractions as the optimal dosing for CRT, preserving efficacy while mitigating adverse effects.

• The evolving landscape of lung cancer management involves immunotherapy, with the PACIFIC Trial showcasing extended survival benefits from consolidation durvalumab.

• Clinical studies like Checkmate 816 pave the way for innovative treatments, such as neoadjuvant immunotherapy, to improve outcomes for resectable lung cancer.

• Comprehensive research is addressing questions regarding dose escalation, optimal fractionation, and the integration of immunotherapy in lung cancer treatment.

• Stay informed about these pivotal studies, as they continue to shape the future of lung cancer management.

Show notes generated by ChatGPT4 

Acknowledgements

Thank you to Dr. Percy Lee

https://www.cityofhope.org/percy-lee

Abbreviations

• SCLC: Small Cell Lung Cancer

• NSCLC: Non-Small Cell Lung Cancer

• SVC: Superior Vena Cava

• RT: Radiation Therapy

• MRI: Magnetic Resonance Imaging

• CT C/A/P: CT Chest/Abdomen/Pelvis

• ES-SCLC: Extensive Stage Small Cell Lung Cancer

• PFS: Progression-Free Survival

• TTF1: Thyroid Transcription Factor 1

• IMpower133: Study investigating immunotherapy in SCLC

• CASPIAN: Study investigating immunotherapy in SCLC

• FDG-PET/CT: Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography

• RCT: Randomized Controlled Trial

• OS: Overall Survival

• AJCC: American Joint Committee on Cancer

• MRI Surveillance: Monitoring with Magnetic Resonance Imaging

• PCI: Prophylactic Cranial Irradiation

• Gy: Gray

Resource Links

• IMpower133 and CASPIAN studies: Studies investigating immunotherapy in SCLC.

https://www.nejm.org/doi/full/10.1056/nejmoa1809064

https://www.thelancet.com/article/S0140-6736(19)32222-6/fulltext

• RAPTOR/NRG LU007 Trial: Study investigating the benefit of consolidative thoracic RT with immunotherapy.

https://www.nrgoncology.org/Home/News/Post/the-raptor-trial-nrg-lu007-for-extensive-stage-small-cell-lung-cancer

Highlights

• SCLC differs from NSCLC clinically and histologically, with rapid cell division and neuroendocrine origin.

• SCLC often presents with metastatic disease; responsive to RT and chemotherapy.

• Key syndromes: SIADH, Eaton Lambert, Hypercalcemia of Malignancy.

• Patient with newly diagnosed extensive SCLC, large hilar mass, bilateral mediastinal lymphadenopathy.

• Staging crucial for treatment decisions; CT C/A/P and MRI brain needed.

• Patient has osseous metastases; unlikely neurosurgery; no immediate role for RT.

• Role of RT depends on systemic therapy response and reassessment scans.

• Options for ES-SCLC treatment: Immunotherapy plus platinum-based chemotherapy.

• IMpower133 and CASPIAN studies showed survival benefit of adding immunotherapy.

• Patient receives carboplatin, etoposide, atezolizumab, with good response.

• Consider consolidative thoracic RT to enhance cytoreduction.

• Data from Jeremic et al. and Dutch CREST Trial supports consolidative thoracic RT.

• Decision on RT dose and patient suitability personalized.

• Post-chemo areas of visible disease for iGTV; add sufficient PTV margin.

• Constraints: Lung V20Gy <30%, esophagus V24Gy <5cc, spinal cord protection.

• Acute and long-term side effects of thoracic RT.

• Controversy around PCI; recent trials and surveillance with MRI brain.

• Strategies for cognitive preservation after PCI.

• Outlook for ES-SCLC remains challenging; ongoing research in newer therapies.

Show notes generated by ChatGPT4 

Acknowledgements

Thank you to Dr. Drew Moghanaki at the University of California Los Angeles for helping review this case! https://www.uclahealth.org/providers/drew-moghanaki

Turrisi Regimen

https://www.nejm.org/doi/full/10.1056/nejm199901283400403

Staging 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266593/

SVC Grading

https://radiopaedia.org/articles/superior-vena-cava-obstruction-grading-2?lang=us

VALG Staging

https://www.wikidoc.org/index.php/Small_cell_carcinoma_of_the_lung_staging

Highlights

• SCLC is a high-grade neuroendocrine tumor which represents 15% of lung cancer cases. SCLC differs from NSCLC in that it is far less common than NSCLC and originates from neuroendocrine cells. Microscopically, these are classically described as sheets of small round blue cells with little cytoplasm, distinct nucleoli and high mitotic rates. The SCLC tumor cells are also known for being some of the most rapidly dividing cells. 

• SCLC occurs almost exclusively in former or current heavy smokers. Unlike in NSCLC, oncogenic driver mutations (such as EGFR, KRAS, ALK) do not seem to play a significant role in the carcinogenesis of SCLC.  

• Although LDH is a non-specific marker, elevated levels in patients with SCLC are associated with greater disease burden and worse overall survival. 

• the DDx can include any of the terrible T’s including teratoma, thymoma, thyroid tumors, “terrible lymphoma”, and of course mediastinal metastasis from lung cancer. We will need to obtain a biopsy of the. mass, preferably via endobronchial approach which can also evaluate the airways for a possible source of this tumor as CT scans are unreliable to rule out a tumor arising form the lining of the central airways. 

• Consider obtaining a FDG-PET/CT to assess for additional sites of disease including the supraclavicular and cervical LN stations and distant metastatic sites. All patients diagnosed with SCLC irrespective of stage should get some form of brain imaging (preferably with an MRI) since 1 in 5 patients can present with intracranial metastases. 

• A paraneoplastic syndrome that is classically associated with SCLC is Lambert-Eaton Syndrome, which is present in <5% of patients with SCLC. This is an auto-immune syndrome in which patients will present with weakness in the upper legs and hips, leading to difficulty walking, as well as weakness in the upper arms and shoulders, which can make self-care difficult. Patients with Lambert-Eaton develop an antibody to pre-synaptic calcium channels in the neuromuscular junction which clinically manifests this muscle weakness which characteristically improves with continued contraction (unlike myasthenia gravis). Remember, most patients (>50%) who present with Lambert-Eaton Syndrome have an underlying malignancy (most likely SCLC), but the minority of patients diagnosed with SCLC have Lambert-Eaton Syndrome. Another syndrome to look out for is SIADH which can cause euvolemic hyponatremia. 

• Patients with SCLC can also present with SVC syndrome which is when a mediastinal tumor can grow large enough to obstruct blood flow through the superior vena cava either via external compression or direct tumor invasion. About 10% of SCLC patients present with SVC syndrome which can clinically manifest as facial plethora, arm swelling, dyspnea and headaches, representing a clinical emergency that is best avoided 

• Historically, SCLC was designated as limited or extensive stage disease per the VA Lung Study Group’s 2 stage classification. In this definition, limited stage was cancer confined to the ipsilateral hemithorax, and disease can be safely encompassed within a single radiation field. Compare this to extensive stage, where disease has spread beyond the ipsilateral hemithorax. With more modern staging systems, NCCN combines both the VA and the TNM systems, where limited-stage SCLC is defined as stage I to III (T any ,N any, M0) that can be safely treated with definitive RT, excluding T3–4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Extensive stage Is defined as ANY M1 disease or T3-4 primaries. 

• In this patient with node positive limited stage SCLC and good PFS, I would treat with concurrent CRT. Chemo generally consists of Cisplatin 75 mg/m2 day 1 and etoposide 100 mg/m2 days 1, 2, 3, for at least 4 cycles. I patients with poor kidney function, carboplatin could be used instead of cisplatin. We would want to coordinate with med onc and treat with RT as soon as possible aiming to start with or during cycle 1 or 2 of chemotherapy. With respect to RT, I will treat to 45 Gy in 30 fx BID, at least 6 hours apart, per the Turrisi regimen. 

• the Turrisi regimen was established after a NEJM publication in 1999 that utilized accelerated RT to 45 Gy in 1.5 Gy fractions BID to take advantage of SCLC’s rapid turnover rate. It produced the best results to date and was significantly more effective than 45 Gy given in 1.8 Gy daily fractions, leading BID to become widely accepted as the standard of care for LS-SCLC. Over time, many started to question whether conventional daily radiation therapy prescribed to over 60 Gy per day would yield similar to better results, and it wasn’t until a pair of modern randomized Ph 3 trials (CONVERT and CALGB 30610/RTOG 0538) were unsuccessful in establishing superiority of conventionally fractionated once daily RT to 66 or 70 Gy (compared to Turrissi). 

• In the Turissi study, elective nodes were included, however recent data suggest that isolated nodal failures are uncommon (~2-3%) without elective nodal irradiation (ENI), thus ENI was not included in the more modern CALGB Trial 30610 and others. 

• If the patient already received CHT, it is OK to only target the post-induction primary tumor (ie. shrunken tumor) in the GTV but we would want to include the initially involved nodal regions in the GTV. 

• In patients who achieve a complete response after definitive CRT for limited stage SCLC, we should consider prophylactic cranial irradiation in patients who remain of good functional status in contrast to those who may be older, have poor PFS, or baseline neurocognitive function where surveillance MRI brains may be the preferred option in lieu of RT. 

• For follow up, unfortunately, all patients with SCLC remains at a high risk for local, regional, and distant metastases. Fortunately, that risk is highest in the first few years and then plateaus nicely, which means this patients like this can be cured. During the first 2 years, I would repeat H&P with restaging CTCAP q3 months. In regard to surveillance imaging of his brain, will obtain MRI brain q3 months in year 1 followed by q6 months in year 2. 

Acknowledgements

Thank you to Dr. Drew Moghanaki at the University of California Los Angeles for helping review this case! https://www.uclahealth.org/providers/drew-moghanaki

Title: Clinic Scaries: Prostate Literature Deep Dive
Series: Clinic Scaries (Season 2, Episode 5)
Release Date: 6/9/2023

Episode Description:

In this episode, our hosts are diving into the must-know prostate literature, unpacking studies behind prostate cancer treatments, the importance of ADT, and the role of dose escalation. Perfect for the night before your GU rotation!

Key Takeaways:

• ProtecT trial: low to int risk prostate cancer patients have similar disease-specific outcomes with surgery or RT/ADT.

• Dose escalation (>70 Gy) improves long-term biochemical failure. MDACC Trial and RTOG 0126 are key.

• FLAME trial utilized 77 Gy conventional fractionation with SIB up to 95 Gy, demonstrating better 5-year bDFS without additional toxicity.

• ASCENDE-RT: Adding LDR boost results in better long term bPFS but higher GU toxicity.

• PROFIT and CHHip Trials establish hypofractionation (60 Gy in 20 fx) as non-inferior to conventional fractionation.

• Ultrahypofractionation: HYPO-RT-PC compared standard fractionation to 42.7 Gy in 7 fractions, while PACE B investigated SBRT.

• Short course ADT beneficial as per RTOG 8610, RTOG 9408, and TROG 96.01.

• ADT still beneficial with dose escalation: EORTC 22991 and DART 01/05 GICOR.

• Long-term adjuvant ADT shows survival benefit for high-risk patients: EORTC 22863, RTOG 9202, EORTC 2291.

• POP-RT trial demonstrates WPRT has better bPFS, DMFS, and DFS for patients with node-negative prostate cancer but no impact on OS.

Show notes generated by ChatGPT4 

Acknowledgements

Thank you to Dr. Amar Kishan

https://www.uclahealth.org/providers/amar-kishan

At The Beam meet the Accelerators

https://accelerators.buzzsprout.com/

Thank you to Drs Brown, Parikh, and Spraker, for having us on!

https://twitter.com/jaguaranna27?lang=en

https://twitter.com/SprakerMDPhD

https://twitter.com/ParikhSimul

Abbreviations

GU- genitourinary

LN – lymph nodes

LVI- lymphovascular invasion

CTAP- CT abdomen and pelvis

CXR- chest X-ray

CHT- chemotherapy

BEP- bleomycin, etoposide, and cisplatin

EP- etoposide and cisplatin

GTV- gross tumor volume

APPA- anterior-posterior/posterior-anterior

IBD- inflammatory bowel disease

AFP- alpha-fetoprotein

bHCG- beta-human chorionic gonadotropin

LDH- lactate dehydrogenase

Highlights

• Seminoma is the most common solid tumor in men in their teens to mid 30s, representing 1% of male cancers.

•  Seminomas are classified as pure seminomas, with 100% seminoma cells, while non-seminomas contain different types of cells, including choriocarcinomas, teratomas, yolk sac carcinomas, and embryonal tumors.

•  The greatest risk factor for seminoma is a history of cryptorchidism, where one or both testicles fail to descend from the abdomen into the scrotum at birth.

•  When a patient presents with a testicular mass, the differential diagnosis includes tumor, torsion, epididymitis, and the “celes”—hydrocele, varicocele, and spermatocele.

•  Trans scrotal ultrasound and tumor markers (AFP, bHCG, LDH) are key in diagnosing seminoma.

•  Fertility planning is crucial before surgery, and sperm banking should be pursued if the patient wishes to preserve fertility.

•  Pathologic T staging is based on the extent of tumor invasion and presence of lymphovascular invasion.

•  Post-diagnostic workup includes a CTAP, CXR, and repeat tumor markers.

•  Staging is based on the extent of nodal or distant metastasis, with serum markers playing an important role.

•  Treatment options for stage IIA disease include RT to include the para-aortic and ipsilateral iliac lymph nodes or first line BEP or EP chemotherapy.

•  RT field design and targets are crucial in treatment, with a modified dog leg field used to cover the ipsilateral common, external and proximal internal iliac lymph nodes.

•  Side effects of treatment can include nausea, vomiting, diarrhea, fatigue, and secondary cancers.

•  Follow up includes regular health checks, imaging, and tumor marker tests.

•  For stage I seminoma, observation is strongly preferred due to the low risk of relapse and high survival rate after relapse and salvage therapy.

•  Adjuvant RT for stage I seminoma includes a dose of 20 Gy in 10 fractions to the para-aortic lymph nodes alone.

Show notes generated by ChatGPT4 

Acknowledgements

Thank you to Dr. Rachel Shenker, who was featured in this episode. 

https://radonc.duke.edu/personnel/rachel-shenker-md

Thank you to Dr. W Robert Lee for their review of this episode

https://www.dukehealth.org/find-doctors-physicians/w-robert-lee-md-med-ms

Acknowledgements

Thank you to Dr. Anna Lee at MD Anderson for proctoring this episode.

https://faculty.mdanderson.org/profiles/anna_lee.html

Episode features:

Kelsey Corrigan https://www.mdanderson.org/education-training/clinical-research-training/graduate-medical-education/residencies-fellowships/radiation-oncology-residency.html

Austin Iovoli https://www.roswellpark.org/austin-iovoli 

ARRO https://www.astro.org/Affiliate/ARRO

Abbreviations

SCC- squamous cell carcinoma

LN – lymph nodes

DOI- depth of invasion

TURBT- trans urethral resection of bladder tumor

CHT- chemotherapy

MIBC- muscle invasive bladder cancer

CRT- chemoradiation

MTX- methotrexate

5FU/MMC- 5-flurouracil and mitomycin C

CR- complete response 

Bladder Mapping 

https://twitter.com/NicholasZaorsky/status/1219388807814045696

Staging 

https://twitter.com/NicholasZaorsky/status/1593256300724465664

Contouring Tips 

https://twitter.com/NicholasZaorsky/status/1615706554552188928

MGH/Shipley CRT Regimen

https://twitter.com/NicholasZaorsky/status/1219387727524827138

BC2001 Trial 

https://www.nejm.org/doi/full/10.1056/nejmoa1106106

Highlights

• Bladder cancer is the second most common GU malignancy. Most patients are diagnosed in their 7th decade of life, and this disease predominately affects white men.  

• Risk factors include smoking (most important), chemical exposures to paint, metals, petroleum, and chronic irritation of the bladder. Infection with schistosoma haematobium can cause SCC (SCC is only 3% of all cases). 

• Urothelial carcinoma is the most common, >90% of cases. 

• The trigone is a triangular shape, connecting the 2 ureteral orifices and the urethral orifice. 

• Bladder layers are important to understand-- the inner layer is called the lamina propria which is coated by the detrusor muscle (muscularis propria). Bundling the bladder is perivesical fat. 

• cN+ disease is uncommon; however, LNs that might be involved include the external, internal, obturator, perivesical and presacral LNs. 

• Urine cytology and a cystoscopy key parts of the initial workup. Imaging should be with either a CT or MR urogram. 

• T staging depends on DOI. T1 invades the lamina propria, T2 invades the muscularis propria, T3 invades the perivesical fat, T4 invades adjacent organs. 

• N1 involves one LN, N2 multiple LNs, and N3 if common iliac LNs are involved. In the AJCC 8th edition, patients with N+ disease have stage III disease (compared to automatically stage IV in the 7th edition). 

• A full thickness TURBT is critical to fully evaluated DOI and staging. A single-dose of intravesical CHT (gemcitabine preferred) within 24 hours (per NCCN), can reduce the relative 5-year recurrence rate by 35% for selected patients. Do not give if there is concern for bladder perforation. 

• Any patient with MIBC (ie. T2 or greater), should get a CT chest +/- bone scan to rule out distant disease. 

• For any patient with up to cT4aN1M0 disease, there is category 1 evidence to support both treatment paradigms of 1) neoadjuvant chemotherapy followed by cystectomy or 2) bladder preservation with concurrent CRT.

• The preferred neoadjuvant CHT is DDMVAC which consists of dose dense MTX, vinblastine, doxorubicin, and cisplatin x3-6 cycles. An alternative regimen is gem/cis x4C. This would be followed by radical cystectomy and bilateral pelvic lymphadenectomy which would dissect the common, internal iliac, external iliac and obturator LNs.

• If going the bladder preservation route, advocate for maximum TURBT before starting CRT. 

• A common fractionation schedule is 45 Gy with concurrent cisplatin, low dose gemcitabine or 5FU/MMC, followed by interval cystoscopy; if CR, then boost to 64 Gy. Elective nodal irradiation should be offered on a case by case basis. 

• Sim with IV contrast, in a vacloc, with bladder empty. Consider also getting a full bladder scan at time of sim to aid with planning the boost. 

• The 45 Gy CTV should include the empty outer bladder wall with a 1.5 cm isotropic margin to form the PTV.

• If unable to localize the original tumor, boost the entire bladder with a tighter 0.5 cm margin to 64 Gy. If able to localize the original tumor bed, cone down to 54 Gy to the entire bladder but boost only the tumor bed to 64 Gy. 

• 55 Gy in 20 fx with concurrent CHT per BC2001 is another excellent option for patients. 

• Important constraints to keep in mind for hypofractionation are rectum V40<50% and small bowel V37<90 cc and V33<130 cc. 

• Acute side effects include fatigue, nausea, diarrhea, and urinary bother. In the long term, we monitor for radiation cystitis, proctitis, enteritis, and potential small bowel damage. 

• If the patient has T3 disease, we need to add a more generous PTV margin (2 cm rather than 1.5 cm). 

• If patient presents with cN+ disease, treat with standard fractionation and boost the gross node to 64 Gy, if dosimetric constraints permit. 

• Hydronephorsis at diagnosis is a poor prognostic sign and may be better suited with surgery. If CRT is pursued, stent the patient to relieve the hydronephrosis! 

• Patient goes to salvage cystectomy if there is persistent disease after hypofractionated RT. 

• Follow up plan should include a cystoscopy every 3 months, CT/MR urogram and CT chest and labs every 3-6 months, and urine cytology every 6-12 months. 

Acknowledgements

Thank you to Dr. Nicholas Zaorsky at University Hospitals Case Western for helping review this case! https://twitter.com/NicholasZaorsky

https://www.uhhospitals.org/doctors/Zaorsky-Nicholas-1073804373

Abbreviations

RO - Radiation Oncologist

RT - Radiotherapy

IR - Ionizing Radiation

CRT - Chemoradiotherapy

Intro to Rad Onc

https://www.astro.org/uploadedfiles/affiliates/arro/future_residents/introtoro.pdf

Highlights

• ROs (not to be confused with radiologists, or radiology oncology) are physicians who use therapeutic RT to largely treat cancer patients with either curative or palliative intent. 

• >60% of cancer patients will receive RT at some point during their cancer journey.

• IR in the context of RT simply means that electrically charged particles induce direct or indirect DNA damage which stops cells from proliferating. There are two common sources of ionizing RT—1. Photons and 2. Particle Beams. 

• Normal healthy cells may also be affected by RT but the key difference is that normal cells can recover and repair this damage, whereas think of cancer cells as generally defected and they lack the repair mechanisms to fix DNA damage and thus die off. Also, different radiation delivery techniques are used, such as intensity modulation, field shaping, and fractionation to limit normal tissue exposure to radiation.

• The concept of fractionation is a foundational concept of RT and basically means we are dividing the total prescribed dose into small daily “fractions” ie. treatments over the course of several weeks, this typically means the patient is getting 1.8-2 Gy per fraction. Gy is our unit of dose, which was formerly known as ‘rads’. Fractionation acts on a basic radiobiologic principle which allows normal tissues to repair and repopulate during treatment while malignant tissues are further damaged via redistribution and re-oxygenation. Of course, there is risk for inter-fraction tumor growth and this is balanced by the overall dose regimen.

• RT can be an effective and durable treatment for pain control, usually in the treatment of bone metastasis. Other reasons why we might get consulted are spinal cord compression from tumor, vascular compression, brain metastases, bleeding, or bronchial obstruction. 

• In patients who get palliative RT for bone metastasis, about 2/3 of patients will experience some degree of pain relief, and 1/4 of patients experience complete relief. Palliation may not be instant and the median onset to pain relief is about 3 weeks, which we often bridge with medical pain management. 

• A pain flare is a transient worsening of pain after RT, more likely to occur in patients with more severe pain at the offset. It usually develops about 1-3 days after RT and thought to be secondary to the inflammatory effects of radiotherapy. OTC NSAIDS can help with the transient pain flares, but a short course of steroids can be prescribed as well if the patient’s pain is refractory to NSAIDS.

• : A CT sim is a treatment planning scan that we usually obtain before each RT course. These scans are typically performed in a rad onc department, as special tables, devices, and localization tools are needed. These appointments usually lasts no longer than an hour. Our patients are usually immobilized using a vac loc, mask, etc, depending on our treatment sites, to ensure reproducible positioning before each fraction. For example, if a vac lock (which is essentially an airtight bean bag mold) is created at time of CT sim, the patient will lay in this same mold for each of their treatments and reproduce that position. After the scan is obtained, we will sometimes fuse the CT sim with other imaging such as a PET or MRI, which may offer better visualization of our targets, to help delineate treatment volumes. 

• that CT scans offer density information on how radiation will travel through different media in the body, such as air, bone, fat, muscle, and so on. We can use that personalized data for customized treatment planning.

• After contours are finalized, a dosimetrist or medical physicist helps create the RT plan. RT treatment planning is a careful and often time-consuming process. This is often why it takes several days to come up with a RT plan, because we want to be thoughtful in designing the best RT plan that achieves excellent coverage of the target, while minimizing dose to nearby organs at risk. After the plan is approved by the RO, the plan must be QA’d, which can be anything from double checking the dose calculations to running a phantom plan on the machines itself to ensure our planned treatments will play out like we intend. This typically occurs the night before a patient starts treatment, but ideally would be a few days before that. 

• We divide RT related toxicity or side effects into acute or chronic. Chronic toxicity is usually defined as at least 3 months after completion of RT, and the toxicity profile is often different from acute toxicity. 

Acknowledgements

Thank you to Hefei Liu, who was featured in this episode

https://www.goodmorningamerica.com/family/story/mom-son-celebrate-matching-residency-programs-98083134

Abbreviations

CHL - Classic Hodgkin's Lymphoma

HL - Hodgkin's Lymphoma

IPI -  International Prognostic Index 

NLPHL - Nodular Lymphocyte-predominant Hodgkin Lymphoma

FLIPI - Follicular lymphoma international prognostic index 

FNA - Fine Needle Aspiration 

Ann Arbor Staging System 

https://www.sciencedirect.com/topics/medicine-and-dentistry/ann-arbor-staging

Highlights

• Hodgkin’s Lymphoma is a malignancy of B-cell origin.

• Hodgkin’s lymphoma makes up about 10% of all lymphoma cases, not nearly as common as Non-Hodgkin’s. There are generally two populations that are commonly affected—those who are in the 20-30 age range and then those in their 50s.

• HL can be divided into classic HL and nodular lymphocyte predominant HL. In the US, Classic HL is far more common, comprising of 95% of cases.

• Classic HL can be divided into 4 sub-groups. These are 1) nodular sclerosing 2) mixed cellularity 3) lymphocyte-rich and 4) lymphocyte-depleted.

• In CHL, the classic histologic finding is the Reed Sternberg cell.

• On path review, it’s also important to know that immunohistochemistry can be helpful in identifying CHL vs NLPHL. Certain markers, such as CD15 is usually positive in classic HL, and CD30 is always positive. In NLPHL, CD20 will always be positive, while CD15 and CD30 are nearly always negative.

• Of the 4 types of classic HL, the most common would be nodular sclerosing, which makes up 70% of cases. This is most often seen in young adults who present with a mediastinal mass.

• B symptoms include fevers >100.4F, drenching night sweats, weight loss >10% of body weight within 6 months of dx.

• There are 3 prognostic groups—early stage favorable, early stage unfavorable, and advanced stage. Stage 1 or 2 are considered early stage, and 3 or 4 advanced stage. What distinguishes unfavorable from favorable disease? The presence of multiple involved nodal regions, bulky mediastinal disease, B sxs, EN involvement, or high ESR are considered unfavorable characteristics. Do note that the definition of unfavorable disease may differ depending on the institution.

• Both of the NCCN and EORTC definitions for unfavorable disease, 3 or more LN regions must be involved; whereas in the GHSG, 2 LN regions is enough to be considered unfavorable.

• MMR is the ratio of the maximum width of the mediastinal mass and the maximum intrathoracic diameter. Any MMR > 0.33 is considered ‘bulky’ disease.

• For early-stage unfavorable disease, we consider starting with ABVD x2 followed by a restaging PETCT.

• ABVD stands for doxorubicin, bleomycin, vinblastine, and dacarbazine.

• The Deauville score is a 5 point scoring system to describe uptake of lesions on a PET image. The FDG uptake of the lesions are compared against the mediastinum and liver—1- no uptake, 2 uptake <= mediastinum, 3 uptake > mediastinum but <=liver, 4 uptake moderately higher than the liver and visually above the adjacent background activity, and 5 is uptake markedly higher than the liver and/or appearance of new lesions.

• For the bulky disease, consider prescribing at least 30-36 Gy in 2 Gy fractions. For non-bulky disease, consider 30 Gy, also in 2 Gy fractions. 

• For simulation, consider a CT scan with IV contrast in the inclined supine position with arms up and utilize DIBH. It is critical that we fuse the pre-CHT and post-CHT PETCT scans to the CT sim and use these in delineation of our treatment volumes.

• Using all our scans, we should carefully delineate the pre-chemo GTV and post-chemo GTV. The CTV should be a 1.5 cm margin off the GTV, carving out uninvolved structures, with then a 1 cm axial and 1.5 cm cranial/caudal margin for a PTV.

• Important constraints to consider include ensuring that the heart mean is <8 Gy and LAD V15<10%. The lung mean dose should be <13.5 Gy, V20<30Gy, and V5<55%.

• In the acute period, patients may develop some fatigue and possibly skin irritation. However, it is the chronic toxicity we need to counsel on which include risk of a major cardiac adverse event, pericarditis, cardiomyopathy, valvular heart disease, hypothyroidism, and pneumonitis. Also, it is very important to counsel younger patients on the risk of developing a secondary malignancy in the future.

• For follow, patients are seen for a H&P q3-6 mos for the first 3 years. A complete response by PETCT should be documented within 3 months of completing treatment. Surveillance imaging with CT scans should be obtained no sooner than every 6 months the first 2 years.

Acknowledgements

Thank you to Dr. Ann Raldow

https://www.uclahealth.org/providers/ann-raldow

Abbreviations

NHL - Non-Hodgkin's Lymphoma

HL - Hodgkin's Lymphoma

IPI -  International Prognostic Index 

FLIPI - Follicular lymphoma international prognostic index 

FNA - Fine Needle Aspiration 

Relevance of Bone Marrow Biopsy in Follicular Lymphoma 

https://pubmed.ncbi.nlm.nih.gov/35787017/

Ann Arbor Staging System 

https://www.sciencedirect.com/topics/medicine-and-dentistry/ann-arbor-staging

Review on Follicular Lymphoma 

https://www.haematologica.org/article/view/10486 

FORT Trial 

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30686-0/fulltext

Highlights

• Lymphoma can be classified as Non-Hodgkins and Hodgkin's Lymphoma. NHL is more likely to present with extranodal disease, spread in a non-contiguous pattern and have more sites of disease involved at diagnosis. (Not Nodal, Non-contigious)

• Important details on the H&P include presence of B symptoms (fever >100.4F, >10% body weight loss in 6 months, or drenching night sweats; present in ~33% of patients), evaluate for other sites of LAD and extranodal disease. 

• The International Prognostic Index (IPI) is a prognostic assessment and used in aggressive forms of NHL. Use the pneumonic APLES which stands for age>60, PFS ECOG >=2, LDH >normal, >1 extranodal group, and stage III-IV disease.  

• The Follicular Lymphoma International Prognostic Index (FLIPI and FLIPI2) are only used in follicular lymphoma. Use the pneumonic BBLAH which stands for B2 microglobulin elevated, + marrow biopsy, LN>6 cm, age >60, Hg <12. 

• Gold standard for biopsy= excisional or incisional biopsy. 

• A bone marrow biopsy should generally be obtained for all lymphomas. 

• Follicular lymphoma is the most common type of NHL and is characterized by CD19+, CD20+ and t(14:18). 

• Lymphomas are staged via the Ann Arbor Staging System. Stage 1 (1 LN region or 1 site), stage 2 (2 more sites on the same side of the diaphragm), stage 3 (disease on both sides of the diaphragm), stage 4 (diffuse and widespread extra lymphatic disease). 

• The preferred treatment for stage 1 Follicular Lymphoma is definitive ISRT. Observation is an option if RT may result in a high toxicity risk. 

• The dose to treat indolent NHL is 24 Gy in 12 fractions. 

• When evaluating a plan, make sure there is adequate dose coverage and minimize/evaluate hotspots. 

• Obtain a restaging PETCT 3 months after completion of RT to assess treatment response. This is graded by the Lugano criteria (1: no uptake, 2: uptake <= mediastinum, 3: uptake > mediastinum, <=liver, 4: uptake >liver, and 5: uptake >> liver or new lesions)

• Surveillance follow-up consists of H&P and labs every 3-6 mos for 5 years, then lengthening after 5 years, and scans every 6 months for the first 2 years.  

• If there is progressive and new disease detected on restaging PETCT, you should be worried about transformation to more aggressive disease, which may also be evidenced by rising LDH levels, clinical progression, or new B symptoms. Re-biopsy to confirm. 

• Double-hit DLBCL means that both MYC and BCL2 translocations are detected by IHC or FISH. 

• DLBCL with double hit are at higher risk of CNS involvement and should be considered for CNS ppx (although controversial). 

• Use the GELF criteria to determine whether observation is appropriate for the patient. If there are >=3 nodal sites each 3 cm or larger, any site >=7 cm, + B sxs, pleural effusions, peritoneal ascites, cytopenias, leukemia, splenomegaly—it is more compelling to start treatment. 

• Palliative "boom boom" 4 Gy in 2 fractions confers in a response rate in >90% of patients, however freedom from local failure was only 66% in the FORT Trial. 

• First-line systemic therapy for Stage 3 or 4 FL can vary depending on the institution but include CHOP, CVP + obinutuzmab/rituximab, lenalidomide +rituximab, or bendamustine + Obinutuzumab or rituximab.

Acknowledgements

Thank you to Dr. Michael Binkley 

https://med.stanford.edu/profiles/michael-binkley

Abbreviations

CHF – Congestive Heart Failure

CNS – Central Nervous System

CPA – Cerebellopontine Angle

CTV – Clinical Tumor Volume

H&P – History and Physical

HPF – High Powered Field

HRT – Hormone Replacement Therapy

HTN – Hypertension

IMRT – Intensity Modulated Radiation Therapy

LC – Local control

MRI – Magnetic Resonance Imaging

NF-2 – Neurofibromatosis 2

OAR – Organs at Risk

OS – Overall Survival

PCP – Primary Care Physician

PTA – Pure Tone Average

PTV – Planning Tumor Volume

RCT – Randomized Controlled Trial

RT – Radiotherapy

SRS – Stereotactic Radiosurgery

VMAT – Volumetric Arc Therapy

VS – Vestibular Schwannoma

WHO – World Health Organization

Cranial Nerves

https://www.kenhub.com/en/library/anatomy/the-12-cranial-nerves

Risk Factors of Acoustic Neuroma: Systematic Review and Meta-Analysis

https://synapse.koreamed.org/articles/1032004

House-Brackmann Facial Nerve Grading System

https://i.pinimg.com/736x/6b/28/a9/6b28a9251d594fed762132ccf0793ea1.jpg

Gardner-Robertson scale

https://operativeneurosurgery.com/doku.php?id=gardner_robertson_scale

Koos Grading Scale

https://operativeneurosurgery.com/doku.php?id=koos_grading_scale#:~:text=The%20Koos%20classification%20of%20vestibular,not%20encroach%20on%20the%20brainstem

Highlights

• Vestibular schwanommas, also called acoustic neuromas, are schwann cell derived tumors that commonly arise from the vestibular portion of the eighth cranial nerve, specifically from the Obersteiner-Redlich Zone.

• These account for about 8% of intracranial tumors in adults and occurs in 1 per 100,000 people in the US, higher in Taiwan at 2.66 per 100,00 and lower in Hispanics and African Americans, at .7 and .4 per 100,000.

• The median age of diagnosis is about 50 years old. 90% are sporadic and unilateral, and some risk factors include childhood exposure to XRT, parathyroid adenomas, NF-2, which account for about 10% of VS, but often presents bilaterally- which is pathognomonic for NF-2. There have been some studies that suggest loud noise may have some positive associations with VS incidence, although this is controversial.

• ~ 95% of VS cases will present with some hearing loss and about 60% with tinnitus and imbalance. This is because most tumors arise from the vestibular portion of CN VIII. However, some other presenting symptoms may include facial numbness if CN V is impinged, as well as facial weakness and taste disturbance if CN VII is involved.

• A quick test for CN VII is to ask the patient to tighten their anterior neck to see if the platysma is working which is innervated by CN VII.

• The most common sxs (hearing loss/tinnitus/dysequilbrium) derive from CN VIII pathology, followed by CN V and VII. When the vestibular nerve is affected, patients will fall towards the side of the tumor

• The House-Brackmann Facial Nerve Grading System is widely used to characterize the degree of facial paralysis. It’s a 6 point system looking at static and dynamic facial symmetry, where 1 is normal symmetric function in all areas and 6 is no movement with loss of tone.

• Audiometry is the best initial screening laboratory test for the diagnosis of vestibular schwannoma, since only 5 percent of patients will have a normal test. Pure tone and speech audiometry should be performed in an acoustically shielded area. Test results typically show an asymmetric sensorineural hearing loss, usually more prominent in the higher frequencies. Just to note, hearing loss does not necessarily correlate with tumor size. The speech discrimination score is usually markedly reduced in the affected ear and out of proportion to the measured hearing loss.

• Deficits are scored on a Gardner-Robertson scale, looking at a “pure tone average” or PTA, average hearing threshold (>50% heard) between multiple frequencies, as well as exploring speech discrimination percentage (aka word recognition), by evaluating what percent of words recognized at a particular dB. The Gardner-Robertson scale is also performed on a 5 point scale, and the key item you are looking for is whether there is serviceable hearing or not, as this may alter your recommended treatment strategy. If the PTA is 50 dB or less and/or the speech discrimination % is 50% or less, hearing would be considered serviceable.

• The Koos grading scale is designed to stratify tumors based on extrameatal extension and compression of the brainstem. Grade 1 is when the lesion is confined to the internal auditory canal, grade 2 is when it extends into the CPA, grade 3 fills the CPA, and grade 4 compresses the brainstem and cranial nerves.

• In general, we consider observation, surgery, and SRS. Observation is considered in advanced age or if the patient has multiple co-morbidities, slow tumor growth, or asymptomatic cases. ~50% of these lesions will grow, with ~50% developing hearing loss and up to 80% requiring eventual treatment due to growth or symptoms. Surgery is considered for younger patients, larger lesions, and or symptomatic cases.

• In this case, it was recommended to treat with SRS. Although there are no RCTs comparing surgery to SRS, there are meta-analyses that show that tumor control is nearly identical to microsurgery with excellent hearing preservation rates. There can be large variations based on practice patterns and provider/patient preference, but I would recommend 18 Gy in 3 fractions, given that he has serviceable hearing.

• Given that we are taking an SRS approach, consider carefully delineating the GTV with a 1 mm margin for a PTV. Ensure coverage as close to 100% of my PTV receiving 100% dose as reasonably possible. Look for an ablative dose pattern with a HI of 1.25 and ensure good fall off of the low doses immediately outside of the PTV. For OAR constraints, ensure the brainstem V18 <0.5 cc, optic chiasm V15<0.2cc, and a Dmax of 17 for the cochlea.

• In regards to side effects, acutely, patients may experience fatigue, skin irritation, nausea, vomiting, dizziness, temporary worsening hearing, and headache. In the future, we will monitor for trigeminal and facial nerve neuropathies, and worsening hearing deficits.

• For follow up, perform another MRI 3-6mo post treatment, then yearly with an H&P.

• About 15-30% of cases will show pseudoprogression following RT, at a median onset of ~1 year, but can be as late as 3+ years. The majority of these will regress. If this is true progressive growth, we can consider re-treatment with SRS versus surgery, particularly if there are new or worsening symptoms, an impending mass effect, or impingement on critical structures.

Acknowledgements

Thank you to Dr. John Hegde

https://www.uclahealth.org/providers/john-hegde

Abbreviations

CNS – Central Nervous System

CTV – Clinical Tumor Volume

H&P – History and Physical

HPF – High Powered Field

HRT – Hormone Replacement Therapy

IMRT – Intensity Modulated Radiation Therapy

LC – Local control

MRI – Magnetic Resonance Imaging

NF-2 – Neurofibromatosis 2

OAR – Organs at Risk

OS – Overall Survival

PCP – Primary Care Physician

PTV – Planning Tumor Volume

RT – Radiotherapy

SRS – Stereotactic Radiosurgery

VMAT – Volumetric Arc Therapy

WHO – World Health Organization

WHO Grading

https://www.hopkinsmedicine.org/health/conditions-and-diseases/meningioma-grading

Simpson Grading

https://radiopaedia.org/articles/simpson-grade?lang=us

Hormonal Therapy and Meningioma

https://www.nejm.org/doi/full/10.1056/NEJMc071938

RTOG 0539

https://pubmed.ncbi.nlm.nih.gov/31786276/

Highlights

• Meningiomas are the most frequent primary brain tumor and account for about a third of all primary brain and spinal tumors.

• Although most are benign, their location in the CNS can cause serious morbidity and mortality. Their incidence increases progressively with age, with a median diagnosis age of 65.

• Meningiomas are more common in women, with a female to male ratio of 2-3:1, and spinal meningiomas, which is about 10% of all meningiomas, have even a larger female to male ratio of about 9:1.

• Meningiomas most commonly present as a headache, but seizures can occur in ~30% of patients. Keep in mind that these benign brain tumors can also be asymptomatic and detected incidentally.

• Common risk factors associated with meningiomas include a history of prior RT to the head, and a history of neurofibromatosis type 2 (NF-2). Hormonal therapy has been implicated with the development of meningiomas and thought to possibly be hormonally driven.

• About 60% of meningioma cases will have surrounding edema, although edema hasn’t been correlated with grade or size of the lesion. Some buzzwords that describe meningiomas on imaging are an ‘extra-cranial homogenous and enhancing mass’ with or without a ‘dural tail’. These tumors may be ‘T2 isointense’

• ~60% meningiomas have a dural tail and this is not exclusive to meningiomas. Dural tails can also be seen in lymphoma and chloroma.

• Meningiomas have 3 general treatment options-- observation, definitive radiotherapy, and surgery. Observation is usually reserved in small, asymptomatic cases without mass effect. About 40-60% of cases will remain stable, with skull base tumors having a higher predilection for stability. You want to monitor with serial MRI scans to ensure < 2mm growth per year. Any growth >3 mm annually may increase the patient’s risk of symptoms and concerning for high grade disease.

• RT results in excellent control for small grade 1 meningiomas and is a great option for tumors without any mass effect. This is typically delivered with SRS 14-16 Gy in a single fraction or with standard fractionation to 50-54 Gy for grade 1 tumors. Remember, the total RT dose depends largely on the grade and can range anywhere from 50-60 Gy. Both SRS and fractionated RT result in excellent LC of >90% at 5 years for grade 1 tumors, however, with SRS, you want to be cognizant of toxicities, particularly when considering peritumoral edema and tumor locations in the parasagittal, falcine, convexity, or skull base, which may lead to symptomatic edema, headache, or cranial nerve deficits.

• Surgery will be the mainstay of treatment for higher grade, and importantly, large symptomatic tumors. The goal is maximal safe resection and decompression, if applicable. The Simpson grading system helps classify the extent of surgical resection.

• Simpson grading is a 5-tiered system which can predict local failure rates based on extent of resection. Grade 1 represents total resection of the tumor, any dura attachments, and abnormal bone. Grade 2 - total resection of the tumor and coagulation of the dural attachments. Grade 3 – total resection of the tumor without resection or coagulation of dural attachments or extradural extensions. Grade 4- partial resection of the tumor, and Grade 5- simple decompression, such as a biopsy. You can multiply the grade number by 10 to estimate the local failure rate (without RT), so grade 1 would be roughly 10%, grade 2 ~20%, and so on.

• WHO grade is done on a 3 point scale. Grade 1 is benign (70-80% incidence), grade 2 will show atypical, clear cell, chordoid features and 4-19 mitoses per 10 HPF, and grade 3 will show anaplastic, rhabdoid, or papillary features and exhibit 20 or greater mitoses per 10 HPF. This would be considered a WHO grade 2.

• Brain invasion upgrades an otherwise grade 1 tumor to grade 2

• RTOG 0539 has 3 risk categories-- low, intermediate, and high, based on grade and resection. Low risk would be a WHO grade 1 tumor that underwent GTR or STR, intermediate includes a recurrent WHO grade 1 tumor or grade II that underwent GTR, and high risk would include any WHO grade 3 or a grade 2 that was recurrent or underwent an STR. In our patient’s case, she is a WHO grade 2 that underwent STR so we would consider consider her high risk.

• For low risk, observation is recommended. For intermediate, we would recommend adjuvant RT to 54 Gy, and in high risk, we would recommend adjuvant RT to 60 Gy to any residual tissue.

• For simulation, use a head mask, supine, with the head in a neutral position, arms to the side. Define the GTV as the tumor bed + any residual nodular enhancement, not including edema or the dural tail. The CTV would be a 5-7 mm margin on the GTV, reduced around anatomic barriers and uninvolved brain regions. With daily KVs, the PTV would be a 2-3 mm expansion.

• In regards to side effects, we would worry about recurrence of any heralding symptoms, in her case right foot paresthesias. This is usually due to treatment related inflammation, although not very common. Other side effects to counsel on are fatigue, skin irritation, patchy hair loss that may be permanent, headaches, and nausea.

• For follow up, perform a comprehensive H&P with a restaging MRI at 3 months, 6 months, and 1 year. Then consider an MRI every 3-12 months for the next 5 years, then every 1-3 years beyond 5 years post-treatment. If following a higher grade tumor, consider obtaining scans in closer intervals.

• Unfortunately, the likelihood for LC is worse for a recurrent WHO grade 2 versus a new Grade 3. Given this, there are active trials looking at observation vs standard fractionated treatments to 60Gy for grade 2 meningiomas that undergo a GTR to hopefully divert this issue. A post hoc analysis of RTOG 0539 shows a 3 year PFS of 45% in recurrent grade 2 vs 65% in an initial grade 3, as well as inferior OS and time to progression.

Acknowledgements

Thank you to Dr. Tania Kaprealian

https://www.uclahealth.org/providers/tania-kaprealian

Abbreviations  

BOS – Base of Skull

BOT – Base of Tongue

CN – Cranial Nerve

CRT – Chemoradiotherapy 

CTV – Clinical Tumor Volume

EBV - Epstein–Barr Virus

ENT – Otorhinolaryngology

FNA – Fine Needle Aspiration

H&P – History and Physical 

HPV – Human papilloma virus

ICA – internal carotid artery

IMRT – Intensity Modulated Radiation Therapy 

LAD – Lymphadenopathy 

LN – Lymph Nodes 

MRI – Magnetic Resonance Imaging 

NPC – Nasopharynx cancer

NPX – Nasopharynx

OAR – Organs at Risk 

OPX – Oropharynx

PET- positron emission tomography

PTV – Planning Tumor Volume 

RPN – Retropharyngeal Node

RT – Radiotherapy 

SCC – Squamous Cell Carcinoma

SCM – Sternocleidomastoid

SIB – Simultaneous integrated boost 

SMG – Submandibular glands

VMAT – Volumetric Arc Therapy 

WHO – World Health Organization

NPX Staging  

https://radiopaedia.org/articles/nasopharyngeal-cancer-staging?lang=us

NCCN guidelines 

https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf 

Head and Neck Anatomy 

https://www.kenhub.com/en/library/anatomy/head-and-neck-anatomy 

Highlights  

• Nasopharyngeal cancer is endemic to regions of Asia and Northern Africa.

• It is important to understand the anatomy of the nasopharynx. Picture the NPX as a box with the posterior choanae as the anterior border, the C1-2 vertebrae as the posterior border, the skull base as the superior extent, down to the soft palate. The lateral boundaries are the torus tubarius and the fossa of rosenmuller. Important to know that most NPC’s arise from the fossa of rosenmuller.

• CN palsies is present in about 10% of patients with NPC

• If the tumor extends superiorly, it can invade into the cavernous sinus and can compress/involve CN VI first then III-IV which can cause diplopia and oculomotor signs. This is known as petrosphenoidal syndrome. If there are bulky RPNs, these can push on CN IX-XII resulting in enophthalmos, ptosis, and miosis. This is known as retroparotidian syndrome. Facial numbness can be a result of V1-2 involvement which also reside in the cavernous sinus.

• Any of these clinical signs would indicate locally advanced disease and automatically be considered cT4 due to CN involvement.

• NPC can invade superiorly through the foramen lacerum or foramen ovale.

• Over 50% of patients present with a neck mass; other symptoms include epistaxis, headache, otalgia and nasal congestion.

• For workup, consider a scope to assess the anatomic tumor extent and evaluate for extension into the nasal cavity or OPX. On exam, assess for CN deficits and cervical LAD since a majority (anywhere from 60-90%) can present with palpable LAD, and up to 50% of patients will have bilateral neck involvement. For imaging, consider an MRI w and wo contrast to image the BOS, NPX and neck extending to the clavicles; PETCT for full staging, and EBV DNA titers.

• You can broadly divide NPC into 2 subtypes– keratinizing SCC and nonkeratinizing. Let’s talk about keratinizing SCC first. This is AKA WHO type 1 or the sporadic form and makes up about 25% of cases. It is associated with smoking and tends to have less of a propensity for DM but LC may be challenging. The second type is nonkeratinizing which can be further divided into differentiated and undifferentiated. Nonkeratinizing differentiated is AKA WHO grade II. The undifferentiated form is AKA WHO grade III and is endemic in regions such as Asia and strongly associated with EBV. As opposed to the differentiated counterpart, undifferentiated is more likely to have metastasize distantly.

• Treatments paradigms for head and neck cancers vary by subsite, including different variations of surgery, radiation, and or chemotherapy. For this patient with a locally advanced EBV associated NPC, it was recommended that induction CHT with gemcitabine/cisplatin followed by definitive CRT with concurrent cisplatin 100 mg/m2 q3 weeks take place. This included treating all sites of gross disease on exam and imaging (post-induction chemo) to 69.96 Gy, and the surrounding high-risk regions which would include a 5mm expansion upon the CTV69.96 to 59.4 Gy. In the high-risk volume, ensure the entire NPX and skull base were included plus the anterior clivus, pterygoid plates, pharyngeal space, inferior sphenoid sinus, retropharyngeal LNs, posterior nasal cavity/maxillary sinus, soft palate, bilateral neck levels IB-III and high level II. For the low-risk neck, treat bilateral level IV and Vb down to the clavicle to 54 Gy. All dose levels will be delivered via SIB in 33 fractions. In these types of cases, surgery is not routine, although it can be reserved for salvage in specific situations

• Before starting treatment, ensure that our patient sees their dentist prior to RT. They will have significant doses to parotids due to coverage of the nasopharynx, RP, and cervical nodes, so all will be at risk for xerostomia and related xerostomia-related caries.  Further, the maxilla (and likely mandible) will get significant dose that will limit extractions in the future.

• For our sim, we obtained a CT sim with contrast with the patient supine and the head slightly extended, immobilized with a long mask. To ensure the dose distribution doesn’t become variable upon delivery, we want to ensure the shoulders are stabilized with this mask and brought inferiorly as much as the patient can tolerate. I would also consider using a mouth-opening, tongue-depressing stent to separate the nasopharynx from the non-target oral structures, if the patient can tolerate. To help with target delineation, I would fuse the diagnostic MRI and PETCT scans.

• For this case, OARS included brainstem Dmax <54 Gy, SC Dmax <45 Gy, optic chiasm Dmax<54 Gy, cochlea V55<5%, parotid mean <=26 Gy in at least one gland.  However, if the patient had a T4 cancer with extensive intracranial extension or full-thickness clival involvement, we do have to weigh risks/benefits with taking critical structures to higher dose (versus under-coverage of target).

• In regards to side effects, in the acute setting, discuss xerostomia, dysgeusia, thick secretions, nasal and oral mucositis, dysphagia, odynophagia, fatigue, and nausea, related to the radiation.  From the chemotherapy, the patient is also at risk for nausea, neuropathy, renal dysfunction, and blood count issues.  Long term, these patients often do well.  However, there are long-term toxicities from chemoradiation, such as a risk for xerostomia, dental decay, dysphagia, dysgeusia, peripheral neuropathy, and hearing loss.  If the disease is extensive and requires/involves more critical structures, additional risks may exist.  

• For follow up, perform an H&P with nasolaryngoscope q3 mos for the first year and then lengthen gradually after the first year to eventually annually after year 5. Also consider a post-tx PETCT at 3 mos and another EBV titer after treatment as this can have some prognostic value

Acknowledgements  

Thank you to Dr. Beth Beadle 

https://profiles.stanford.edu/beth-beadle 

Abbreviations  

BOT – Base of Tongue 

CRT – Chemoradiotherapy  

ENT – Otorhinolaryngology 

H&P – History and Physical  

HPV – Human papilloma virus 

ICA – internal carotid artery 

IMRT – Intensity Modulated Radiation Therapy  

LAD – Lymphadenopathy  

LN – Lymph Nodes  

MRI – Magnetic Resonance Imaging  

OAR – Organs at Risk  

OPX – Oropharynx 

PET- positron emission tomography 

PTV – Planning Tumor Volume  

RT – Radiotherapy  

SCC – Squamous Cell Carcinoma 

SCM – Sternocleidomastoid 

SIB – Simultaneous integrated boost  

SMG – Submandibular glands 

VMAT – Volumetric Arc Therapy  

 P16+ OPX Staging  

https://radiopaedia.org/articles/hpv-mediated-p16-positive-oropharyngeal-cancer-staging?lang=us 

NCCN guidelines 

https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf 

Head and Neck Anatomy 

https://www.kenhub.com/en/library/anatomy/head-and-neck-anatomy 

Highlights  

• Evaluate your patient’s overall health, including comorbidities, and explore social history, with a specific focus on smoking and EtOH use. On exam, assess tongue mobility, look for trismus and palpate for cervical LAD. Although limited tongue mobility and trismus could indicate more extensive disease, this patient will be recovering from a tonsillectomy, so limitations may also be due to post-operative changes and swelling. Also, very important would be to assess swallowing function and nutritional status after the tonsillectomy, and whether there was otalgia at presentation, which can represent referred pain 

• SCC of the OPX is the most common HN cancer in the United States, which can affect both men and women, but more so in men. The OPX consists of several subsites including the soft palate, palatine tonsils, BOT, and pharyngeal wall. Historically, these cancers had the same risk factors as other head and neck SCC, such as alcohol and tobacco use.  However, most cancers in the US are now related to human papillomavirus (HPV), even in those with an alcohol or tobacco history.  HPV-related OPX most commonly develops in the BOT or tonsils.  HPV status is important for risk stratification, and it is now part of the staging system.   

• The first site of drainage for cancers that originate in the OPX is to the cervical LNs. That is why doing a physical exam is very important. Typically, the first site of involved LNs are at level II, which start at the base of the skull, bounded anteriorly by posterior border of the SMG, posteriorly by SCM, medially by ICA, down to the inferior border of the hyoid bone. 

• Disease can involve the level III and IV neck nodes, as well as IB. Distant disease is uncommon, but when it occurs, it can involve the lungs and bones as well as some unusual sites (soft tissue, thyroid, brain, liver). 

• Assessing tongue mobility and trismus is important in OPX cancer because if clinically present, that would automatically upstage the patient to cT4. 6 cm is the number we want to remember when thinking about LN size, and any LN >6 cm is automatically N3. The pathologic nodal staging is different; for example, if the patient gets a neck dissection and there are <= 4 LN positive, it’s pN1 and >4 LNs positive pN2. Remember this patient had a tonsillectomy upfront for diagnosis; this is equivalent to a biopsy.   

• Reviewing the path report in closer detail and see if there is mention of PNI or LVSI. The reason being these pathologic features would argue for the use of PORT if the patient goes back for an oncologic surgery. Other high-risk features include a pT3-4 tumor (size criteria >4 cm), close or positive margins, pN2-3 disease, or ECE. These would all warrant RT +/- CHT. CHT is added to PORT when there are positive margins or ECE. 

• In this case, a CT simulation scan with IV contrast, with the patient supine with a head and neck thermoplastic face mask for immobilization, neck extended and shoulders down was performed. To aid with target delineation, fuse any available diagnostic scans such as the PETCT. Prescribe 70 Gy to any suspicious sites for residual disease near the resected tonsil and gross FDG avid nodes. For areas at high risk for subclinical spread, I would treat to 60 Gy. For this patient this would include the adjacent parapharyngeal space, soft palate, superior tonsillar pillars, and ipsilateral level II-IV neck including high level II and the retrostyloid space and lateral retropharyngeal LN up to the skull base. The regions at low risk for spread, I would prescribe 54 Gy. This would include the contralateral level II-IV neck. The radiation would be delivered via dose modulation with IMRT or VMAT for SIB, all in 35 fractions. 

• If the patient is considered high risk, you can consider including level V and IB on the side with involved nodes. Also, OARS that we should be mindful of in HN are the mandible, parotid glands, spinal cord, brainstem, brachial plexus, pharyngeal constrictors, submandibular glands, cochlea. 

• Counsel to expect the side effects to predictably develop as treatment goes on. He will notice fatigue, dysgusia, mucositis, dysphagia, odynophagia, xerostomia, and dermatitis to the neck. For late toxicity, we will mostly monitor him for neck fibrosis, persistent xerostomia (and resultant risk for dental decay), dysgeusia, dysphagia, and hypothyroidism.  

• A rare but severe toxicity is osteoradionecrosis which can develop in <5% of patients. 

• Follow up with a scope about every 3 months for the first year, lengthening to 4-6-month intervals during the second-year post treatment. Once we hit the 5-year mark, patients can follow up annually. Additionally, it is important to check TSH since many patients may develop hypothyroidism after RT and require levothyroxine. For this patient, I would probably want to obtain a PETCT at 3 mos post treatment to assess response to CRT. 

Acknowledgements  

Thank you to Dr. Beth Beadle 

https://profiles.stanford.edu/beth-beadle 

Abbreviations 

3D-CRT – 3-Dimensional Conformal Radiation Therapy 

4D-CT – 4-Dimensional Computed Tomography 

CBC – Complete Blood Count 

CI – Common Iliac 

CMP – Complete Metabolic Panel 

CRT – Chemoradiotherapy 

DRE – Digital Rectal Exam 

FNA – Fine Needle Aspiration 

GI – Gastrointestinal 

H&P – History and Physical 

IMRT – Intensity Modulated Radiation Therapy 

LAD – Lymphadenopathy 

LARC – Locally Advanced Rectal Cancer 

LINAC – Linear Accelerator 

LN – Lymph Nodes 

MLC – Micro-Leaf Collimators 

MRI – Magnetic Resonance Imaging 

OAR – Organs at Risk 

PTV – Planning Tumor Volume 

RT – Radiotherapy 

SIB – Simultaneous integrated boost 

VMAT – Volumetric Arc Therapy 

Anal Cancer Staging 

https://radiopaedia.org/articles/rectal-cancer-staging?lang=us 

RAPIDO 

https://www.thelancet.com/article/S1470-2045(20)30555-6/fulltext 

OPRA 

https://pubmed.ncbi.nlm.nih.gov/35483010/ 

PRODIGE 23 

https://www.thelancet.com/article/S1470-2045(21)00079-6/fulltext 

STAR-TReC 

https://ro-journal.biomedcentral.com/articles/10.1186/s13014-020-01487-6 

RTOG 0822 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540628/ 

Highlights 

• Colorectal cancer is the second leading cause of cancer death with just shy of 35,000 new cases diagnosed each year in the United States. 

• NCCN recommends any “average risk” person start screening at age 45 for colorectal cancer. Screening modalities vary but most take form as a colonoscopy or stool-based testing. If negative, colonoscopies should be repeated every 10 years and stool-based testing annually. 

• When is a patient not considered “average risk”? If there is family history of CRC, they need to start screening earlier at age 40 or 10 years before earliest CRC diagnosis in a first-degree relative. Patients who have personal history of inflammatory BD, also need to start screening sooner and have their first colonoscopy 8 years after onset of symptoms. 

• The rectum is the part of the GIT (about 12-15 cm in length) spanning from the anorectal ring to the rectosigmoid junction. We can broadly divide the rectum into 3 sections—the lower third, middle third, and upper third. This is important because LN drainage and treatment management can differ based on where the index lesion is located. Tumors arising from the lower third of the rectum drain along the middle rectal artery to the IILNs, vs. tumors in the upper third of the rectum drain along the superior rectal artery to the presacral and sigmoidal LNs. We mentioned this during the anal cancer episode but don’t forget that if the tumor extends into the anal canal, this puts the inguinal LNs at risk. If the patient does have a positive non-regional inguinal LN, that is considered metastatic disease.  

• In this case, we treated with total neoadjuvant therapy starting with CRT 45 Gy to the pelvic LNs with a seq boost to 50.4 Gy to the primary tumor and positive nodes with concurrent capecitabine. After completion of CRT, he will receive consolidation CHT, likely with FOLFOX, followed by LAR with TME technique.  

• For planning, obtain a CT sim with IV contrast with the patient supine in a vac loc with a BB placed at the anal verge and a comfortably full bladder. To aid with target delineation, fuse the pelvis MRI. For the elective nodes, the superior border will be at the CI bifurcation, moving down to include the IILN, pre-sacral, obturators, perirectal nodes, the entire mesorectum and rectum. Laterally, stop at the pelvic sidewall and anteriorly, cover about 1 cm into the bladder to account for variations in bladder filling.  The CTV would stop at the pelvic floor making sure it covers at least 2 cm below the most inferior extent of the tumor. Sequentially boost the mesorectum to 50.4 Gy. Use your MR fusion to delineate the primary tumor and make sure this is receiving 50.4 Gy as well.  

• For field arrangements, create a 3 field arrangement with 2 lats and a PA field. Ensure you are getting at least a 5mm to 1 cm margin from my PTV to block edge. The posterior border would include the entire sacrum and anteriorly, cover to the back of the symphysis, for T3 disease. 

• IMRT is so commonly utilized but important to recognize the 3DCRT remains standard of care for these patients given negative IMRT toxicity studies such as RTOG 0822. 

• Ideally, we want to make sure the small bowel V35 <150 cc so I would ask if we could reduce the bowel dose. We can consider re-arranging our fields or blocks, or perhaps even simulating in a prone position, which can sometimes help to propel the bowel forward and away from our targets. Other OARs I’m interested in are the femoral heads making sure the V40<35% and bladder V40<35%. Importantly, we want to ensure 95% of the PTV is receiving at least 95% of the dose rx.  

• For concurrent CHT, Capecitabine (or commonly known as Xeloda) is 825 mg/m2 BID only on days of RT. He should start on his first day of RT. 

Acknowledgements 

Thank you to Dr. Ramez Kouzy, who was featured in this episode. 

https://www.linkedin.com/in/ramez-kouzy-b2329761/ 

Thank you to Dr. Emma B. Holliday 

https://faculty.mdanderson.org/profiles/emma_holliday.html 

Abbreviations

3D-CRT – 3-Dimensional Conformal Radiation Therapy

4D-CT – 4-Dimensional Computed Tomography

5FU – Fluorouracil

APR – Abdominal Perineal Resection

CBC – Complete Blood Count

CEA - Carcinoembryonic Antigen

CMP – Complete Metabolic Panel

CRT – Chemoradiotherapy

DRE – Digital Rectal Exam

FNA – Fine Needle Aspiration

GI - Gastrointestinal

H&P – History and Physical

HIV – Human Immunodeficiency Virus

HPV - Human Papillomavirus

IMRT – Intensity Modulated Radiation Therapy

LAD - Lymphadenopathy

LINAC – Linear Accelerator

LN – Lymph Nodes

MLC – Micro-Leaf Collimators

MMC – Mitomycin C

MRI – Magnetic Resonance Imaging

MU – Monitor Units

OAR – Organs at Risk

pCR – Pathologic Complete Response

PTV – Planning Tumor Volume

RT – Radiotherapy

SCC – Squamous Cell Carcinoma

SIB – Simultaneous integrated boost

STD – Sexually Transmitted Disease

VMAT – Volumetric Arc Therapy

Anal Cancer Staging

https://radiopaedia.org/articles/anal-cancer-staging-1?lang=us

Nigro Regimen

https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19830515)51:10%3C1826::AID-CNCR2820511012%3E3.0.CO;2-L

RTOG 8704

https://pubmed.ncbi.nlm.nih.gov/8823332/

ACTII

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70086-X/fulltext

Highlights

• Anal cancer affects around 8000 patients each year.

• Anal cancer is twice as common in females and frequently diagnosed in the 6th decade of life. Risk factors are any immunocompromised state which would include HIV infection, long-term use of immunosuppressive medications, smoking, history of STDs, HPV, or receptive anal intercourse. In fact, >75% of cases are associated with HPV infection. Don’t forget, the high-risk strains are 16, 18, 31, 33 and 35.

• Anal Canal Anatomy: It all starts at the anal margin. When you hear anal margin, think perianal skin which extends around the anal verge. The anal verge is the palpable junction between the internal and external sphincters, and this is where the squamous epithelium transitions from keratinized to non-keratinized. Finally, the anal canal is approximately a 4 cm segment extending from the anal verge towards the rectum and stops at the dentate line. The dentate line is important because mucosa changes from squamous epithelium to columnar epithelium at this junction. 

• If we are thinking in terms of histology. We first start with keratinized squamous epithelium from the outside (‘keratinized’ so think skin) to non-keratinized squamous epithelium at the anal verge, to columnar mucosa at the dentate line.

• The dentate line is an important landmark because nodal drainage is different. Below the dentate line, the path of drainage travels to the inguinal and femoral LNs. Above the dentate line, drainage goes to the obturators, peri-rectal and ILLNs. Which if you recall, is the pattern of drainage for rectal cancer. This is important to understand because it could influence our treatment volumes.

• About a quarter to a third of patients will present with N+ disease. However, keep in mind that if you palpate LNs on exam, that doesn’t necessarily mean they are malignant and often times, palpable LAD is a sign of reactive hyperplasia. If you have any suspicious LNs, we should obtain an FNA or biopsy.

• For workup, obtain an anoscopy with biopsy of the mass and order labs/imaging. For labs, a CBC, CMP, CEA, and HIV testing. For imaging, obtain an MRI abdomen/pelvis with contrast to best determine local extent of disease and staging scans either with CT or PET-CT. 

• Anal cancer is one of few select cancers where definitive CRT is commonly the primary treatment. This was established in the 1970s with the Nigro Regimen. Before the 1970s, patients received abdominal perineal resection with permanent colostomy. The Nigro trial employed neoadjuvant RT to 30 Gy in 15 fx with 5FU and MMC followed by an APR. Before performing the APR, the patients on trial would get a post-CRT biopsy where 5 of first 6 patients had negative biopsies suggesting a pathologic complete response. Due to these high pCR rates, the protocol was amended to mandate surgery only if the post-tx biopsy returned positive. >80% on this trial achieved a pCR with 30Gy plus CHT and avoided surgery, thus establishing definitive CRT as the gold standard for care.

• There other treatment options besides CRT for early-stage anal cancer: Generally, patients with small T1 lesions (remember that is <2 cm), <40% circumferential involvement, favorable histology, and no sphincter involvement can get away with local excision alone if negative margins are achieved. Another option is to omit concurrent CHT and treat with RT alone for a T1N0 lesions.

• In this case, we treated the pelvic LNs to 42 Gy with SIB to the primary tumor to 50.4 Gy in 28 fractions. This would be given concurrently with 5-FU and MMC. 5FU is given 1,000 mg/m2/day on days 1-4 and then a second round on days 29-31. MMC’s dose is 10 mg/m2 bolus on the first day of each round of 5-FU so days 1 and 29.

• MMC is a hypoxic cell radiosensitizer and there have been several trials questioning whether MMC (which is a relatively outdated CHT and really only relevant in anal cancer) can be omitted (RTOG 8704) or replaced with cisplatin (ACTII), however the data continues to support the use of MMC in anal cancer as an option.

• Note there are variable techniques to simulate patients for anal cancer. In this case, we obtained a CT sim with IV contrast and place her supine in a vac loc, frog-legged, with arms on chest and place a BB marker at the anal verge. Using data from her MRI AP fusion, scope and DRE, create a GTVp. This would be expanded 2.5 cm S/I and 1.5 cm radially to form the CTVp. For elective nodal volumes, start at the CI bifurcation and include the IILN, EILN, presacral, mesorectal and inguinal LNs, covering the inguinals all the way down to the inferior border of the lesser trochanter. PTV expansions can slightly differ, but I would add a 1 cm expansion pulling back at the skin.

• For plan eval, aside from appropriate target coverage and controlled hotspots, the dose constraints most important are the small bowel V35<150cc, V30<200 cc and femoral heads V40<35% V30<50%. Ensure there aren’t any hot spots by the external genitalia.

• Counsel on fatigue, dermatitis, pain and pain with bowel movements, diarrhea, urinary bother and importantly skin toxicity. During treatment, it’s important to encourage good skin care and check her skin to assess the degree of desquamation and prescribe steroid cream as necessary. She may also experience nausea/vomiting and neutropenia from the CHT. In the long term, I will discuss the risk of vaginal stenosis and importance of vaginal dilator use after completion of CRT.

• See the patient about 3 months after treatment for exam, scope and possibly restaging PET-CT. The scope is the most important piece and ideally, this is performed by the same physician who initially scoped her at diagnosis. Her first restaging imaging will be informative to assess for clinical response however if there is still residual FDG uptake at the tumor, that does not mean she has recurrent or progressive disease. A radiologic response can take up to 1 year! She should be followed with H&P, exam, q3-6 months for 5 years. In conjunction with this, she should be getting an anoscopy about 1-2 times a year for the first 3 years.

• Tumor regression on exam/imaging can take some time (up to 12 months). 30% of anal cancers will recur and most commonly within the first 2 years after completing treatment, so consistent, continued follow up will be important. If there is suspicion for disease recurrence down the line, we would want to obtain a biopsy first to confirm, restage and then consider treatment options such as APR.

 Acknowledgements

Thank you to Dr. Emma B. Holliday

https://faculty.mdanderson.org/profiles/emma_holliday.html

Abbreviations

3D-CRT – 3-Dimensional Conformal Radiation Therapy

4D-CT – 4-Dimensional Computed Tomography

CBCT – Cone Beam Computed Tomography

cGy – Centi-Gray

CI_ Conformality index

HDR – High Dose Rate

HI – Homogeneity index

IMRT – Intensity Modulated Radiation Therapy

LINAC – Linear Accelerator

MLC – Micro-Leaf Collimators

MRI – Magnetic Resonance Imaging

MU – Monitor Units

OAR – Organs at Risk

TPR – Tissue Phantom Ratio

TPS – Treatment Planning system

VMAT – Volumetric Arc Therapy

DVH

https://pubmed.ncbi.nlm.nih.gov/10192366/

CB-CHOPS

https://appliedradiationoncology.com/articles/cb-chop-a-simple-acronym-for-evaluating-a-radiation-treatment-plan

CI

https://www.redjournal.org/article/S0360-3016(05)02719-7/fulltext

HI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532749/

Highlights

• First and foremost you want to ensure you have the correct patient, medical number and so on. You want to ensure that you are looking at the right scan and plan Some patients may have multiple plans in a course, or plans that were created but not treated, such as teaching plans or trial plan. As the evaluator, it’ll be your job to ensure the appropriate uploaded patient, scan, and plans are the correct one to be evaluated.

• It can be helpful to mark off the scan you want to use for planning by re-naming the image set to highlight this is the scan to use.

• Evaluate isocenter placement and field arrangements as well. See where your isocenter is relative to the triangulation point.

• In regards to prescriptions, some TPS operate in Grays, and others in Centigrays. Ensure you know the scale of your prescription in your planning system as it can change your MU output considerably.

• If you normalize a specific coverage to a structure, the entire plan will scale, in proportion to each field’s output, to meet that objective. It’s the same if you normalize to a point in space. It will detect what dose % is received to that point, and scale the entire plan accordingly. Think carrots.

• Overmodulated plans are not robust, are sensitive to small treatment delivery changes, and won’t deliver efficiently[MOU1] . Visually, look for the MLCs to be open generally around the tumor as it goes around.

• If you want minimal or no low dose spill[MOU2] , ensure your fields are not traversing through the areas of avoidance or consider the appropriate tx technique. If VMAT gives you too high of a low dose spread in a particular area, you can always consider static angle IMRT as an option.

• Generally, your total MU’s for all fields should be about 2-3x the daily rx dose in vmat or imrt plans, as a rough rule of thumb. This is because most of the dose is blocked with the MLC patterns, but if over modulated, there will be far more segments blocked, requiring an escalation in the MU’s.

• Your dose volume histogram will graphically annotate your doses relative to your structures, whether as a percentage or volume. Its important to keep in mind that anything displayed on this DVH is completely contingent on the contouring you or your team performed.

• A conformity index is the ratio of the volume of your prescription cloud compared to the volume of your target, ideally close to 1 but ideally not greater than 1.5.

• HI indicates the ratio between the maximum and minimum dose in the target volume and a lower value indicates better homogenous dose distribution within your target. You want this small, typically less than 1.1, but sometimes, like in SABR planning, you want to make sure this is above 1.25 or even 1.3.

• Sign your plan and make sure to tip your dosimetrist. Please remember that these plans have to go through a quality assurance process that only starts once you’ve approved the plan, and this process can take some significant time. Please consider your physics teams and sign plans early if you can.

• Think CB-CHOP. C-contours, B-Beam arrangements/Fields, C-coverage, H-hotspots, O-OARs, P-prescription.

 Acknowledgements

Thank you to Ontida Apinorasethkul, MS, CMD

https://www.linkedin.com/in/ontida/

Abbreviations

3D-CRT – 3-Dimensional Conformal Radiation Therapy

4D-CT – 4-Dimensional Computed Tomography

CBCT – Cone Beam Computed Tomography 

cGy – Centi-Gray 

HDR – High Dose Rate 

IMRT – Intensity Modulated Radiation Therapy 

kV – KiloVoltage 

LINAC – Linear Accelerator 

LDR – Lose Dose Rate 

MLC – Micro-Lead Collimators 

MRI – Magnetic Resonance Imaging 

MU – Monitor Units 

OAR – Organs at Risk

ODI – Optical Distance Indicator

TPR – Tissue Phantom Ratio 

VMAT – Volumetric Arc Therapy 

What is IMRT 

https://www.youtube.com/watch?v=eZS6DVGBx0k&ab_channel=TheNCIHospital 

What is VMAT

https://vimeo.com/26858213

Radiation Therapy SRS 

https://www.youtube.com/watch?v=6d_dtVTs4CM&ab_channel=TED-Ed 

Simulations

https://www.youtube.com/watch?v=ePjvoqXeDow&ab_channel=TampaGeneralHospital

Highlights 

• Historically, simulations were a way of planning. Measurements were taken, specifically different patient separations using tools like calipers. Sometimes, the contour of patient surfaces were captured using wires or molds to help calculate and predict how radiation could be delivered throughout the body. This would be used in conjunction with 2D X-ray images to help localize treatments. These simulation appointments would be used to also help position patients in a way that was best for treatment delivery, generally simple, reproducible maneuvers

• Now CT based planning is the standard of care in radiation oncology, providing a 3-dimensional views of the patient, our treatment targets, and the surrounding internal healthy tissue

• CT scans are used in simulations because of its ability to measure density, tabulated as Hounsfield units. This helps with our dose calculations, to help account for the different densities of the different types of tissue that our radiation beams may go through.

• Sometimes it can be difficult to see our targets or organs at risk using CT alone, so MRI’s and PET scans, or any other helpful imaging can be used as an adjunct and superimposed on top of our CT scan. The term “fusion” describes this process of overlying additional diagnostic information.

• For cases with concern about internal organ movement, many facilities can capture ct scans in multiple phases throughout the breathing cycle, known as 4D-CT.

• 4D CT’s can offer reducing the amount of tissue we treat. If we know where a tumor will be at specific time point of the breathing cycle, we can also manipulate our beams to only deliver treatments during those specific cycles, as opposed to covering larger swaths of the tumor path during breathing. We can deliver this through gated treatments, where the field will close from delivering doses at certain points, and then open it when proper.

• BB are often these tiny radio-opaque markers that will show up on our CT scan to help us figure out where things are in space on the actual patient. These BB’s positions can be marked on patient’s skin, historically tiny tattoo marks were used but many institutions have been moving away from that and opting to use ink instead. We often use 3 points, at a minimum, to be able to triangulate a position. It helps us translate our virtual CT treatment planning data to true to life “directions” on an actual patient using a known point of reference. Additionally, these markers also help us figure out how to level and rotate a person on the treatment machine itself so we are able to set them up the same way every day and gives us a good starting reference points to those make shifts for where to place our isocenter.

• In terms of how locations for these BBs are selected, typically we will choose an area of skin that have the least mobility, such as the sternum and ribs, on head masks, or on the hips. Ideally these points will be placed exactly where your target is, so your isocenter could align there.

• The isocenter is a conceptual, not actual, point in air. You can find this point 100 cm from the “source” of radiation within the linac, falling down the center of the beam. The relevance for this is that this is the reference point for our dose calculations in our plan. Also, this point gives good mechanical data on issues like clearance, rotation for the fields and table, as well as provide the therapist with a verification point to assure your setup is played out like you planned.

• VMAT planning is nearly identical to IMRT inverse planning except that aside from setting up the total number of fields used, you also arrange the angles you want the beams to traverse. The biggest difference is that VMAT is a type of arc therapy where the linac gantry will rotate around the patient while also modulating the MLCS. Traditional arc therapy does not modulate the field dose as you swing the beam around the patient.

Acknowledgements  

Thank you to Diana No, CMD

https://www.linkedin.com/in/diana-kwa-no-3aa0a26/

Abbreviations  

3D-CRT – 3-Dimensional Conformal Radiation Therapy

CBCT – Cone Beam Computed Tomography 

cGy – Centi-Gray 

HDR – High Dose Rate 

IMRT – Intensity Modulated Radiation Therapy 

kV – KiloVoltage 

LINAC – Linear Accelerator 

LDR – Lose Dose Rate 

MLC – Micro-Lead Collimators 

MRI – Magnetic Resonance Imaging 

MU – Monitor Units 

TPR – Tissue Phantom Ratio 

VMAT – Volumetric Arc Therapy 

How do LINACs Work   

https://www.youtube.com/watch?v=jSgnWfbEx1A&ab_channel=Elekta 

What is IMRT 

https://www.youtube.com/watch?v=eZS6DVGBx0k&ab_channel=TheNCIHospital 

Radiation Therapy SRS 

https://www.youtube.com/watch?v=6d_dtVTs4CM&ab_channel=TED-Ed 

Protons vs Photons 

https://www.youtube.com/watch?v=QM1PPplvYDQ&ab_channel=ProtonTherapyCenter 

Highlights

• Radiation therapy is the deposition of energy delivered in a local manner to kill cells 

• Internal radiation (brachytherapy) often uses radiation sources that emit energy that is then shielded and only exposed when needed, using its emission rate and time as the two factors to help deliver dose. Brachytherapy can further be classified as LDR or HDR, depending on the emission rate. Radiation sources are often put into place through a procedure, whether intercavitary, interstitial, or adjoined superficially to a target. 

•  External beam radiation is typically produced electromagnetically but there are some exceptions such as cobalt based linacs, gamma knife, etc. 

• EBRT modalities include electrons, photons and protons. 

• To produce radiation, you can more or less imagine these machines are producing electrons on the back end and accelerating them. Electrons exit the machine through a scattering foil which helps spread the electrons out to treat a nice wide blanket of area you want to treat. 

• If you want to produce photons, a "target" of high-density material, typically tungsten, is placed in the electron beam path and struck to produce photons through different interactions. 

• 3DCRT, IMRT and VMAT are different techniques to modulate your beam. 

• In 3DCRT, you know the shape of the beam you want, and YOU can set specific angles you want your beams to travel through, accounting for where the target sites are and the organs you want to avoid. You can also change the angle of the table the patient is lying on, as well as the angle of the collimator, to rotate those mini slit MLC blocks, to help sculpt a nice dose output. 

• In IMRT and VMAT, you can use MLCs to shape not only the external shape of the target, but account for the different depths of your target. Imagine your overall field is partitioned into a grid. Using some complex calculations, we can designate each voxel of that grid with a different output. MLCs will then open and close, using the amount of time they need to open each voxel to treat that designated dose. 

Acknowledgements  

Thank you to Dr. Daniel Pham.

https://med.stanford.edu/medphysics/about/dosimetry-team.html 

Abbreviations 

CBC – Complete Blood Count 

CHT - Chemotherapy 

CT – Computed Tomography 

CT CAP – CT of the Chest Abdomen and Pelvis 

CTV – Clinical Tumor Volume 

CXR – Chest X-Ray 

EBRT – External Beam Radiation Therapy 

FIGO - International Federation of Gynecology and Obstetrics (FIGO) 

GTV – Gross Tumor Volume 

H&P – History and Physical 

HNPCC - Hereditary nonpolyposis colorectal cancer 

HPV – Human Papilloma Virus 

IMRT – Intensity Modulated Radiation Therapy 

LN – Lymph Nodes 

LVSI - Lymph-Vascular Space Invasion 

MRI – Magnetic Resonance Imaging 

N stage – Nodal Staging 

NCCN – National Comprehensive Cancer Network 

OAR – Organs at Risk 

PA – Para-Aortic 

PTV – Planning Tumor Volume 

RT – Radiation Therapy 

T stage – Tumor Staging 

TNM – Tumor Node Metastasis 

TVUS – Trans Vaginal Ultra Sound 

V20 – Volume receiving 20 Gray 

VCB – Vaginal Cylinder Brachytherapy 

Staging 

https://radiopaedia.org/articles/cervical-cancer-staging-1?lang=us 

ACOG Screening Guidelines 

https://www.acog.org/womens-health/infographics/cervical-cancer-screening 

Radiation Therapy for Cervical Cancer: An ASTRO Clinical Practice Guideline 

https://www.practicalradonc.org/cms/10.1016/j.prro.2020.04.002/attachment/b3495c02-3020-4944-9248-122057abef3b/mmc1.pdf 

Consensus guidelines for delineation of clinical target volume for intensity-modulated pelvic radiotherapy for the definitive treatment of cervix cancer 

https://pubmed.ncbi.nlm.nih.gov/20472347/ 

Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group 

https://www.brachyacademy.com/wp-content/uploads/2016/03/GEC-ESTRO-Recom-I.pdf 

Highlights 

• There are 13,000 new cases of cervical cancer in the US annually 

• Most cervical cancers develop from the high-risk strains of HPV, notably HPV 16/18. Additional risk factors include immunosuppression (such as having HIV), smoking, and high-risk sexual behavior (multiple partners, and a history of STDs). 

• No PAP screening is performed if you are under 21 years old. For women 21-29, they only need a pap q3 years. Once 30 years of age, co-testing with a pap and HPV test is recommended q5 years—or you can continue doing a routine pap q3 years or HPV test alone every 5 years. For women 65 or older, generally, screening is not pursued if there are 3 negative paps in a row or 2 negative co tests. 

• For initial workup, consider a biopsy followed by a PET-CT, MRI pelvis, CBC/CMP and pregnancy test if the patient is pre- or peri-menopausal. Consider screening for HIV and hepatitis B.  On the CBC, ensure the patient is not anemic and on the CMP check renal functions in anticipation of cisplatin. 

• In this case, For patients staged above FIGO stage IB2 (patients with bulkier tumors >=4cm and those with lymph node involvement, in our case our patient is a T2b N1 (FIGO IIIC1) , consider definitive CRT with EBRT 45 Gy in 25 fx including the pelvic LNs with a sequential or SIB to gross nodes to 55-65 Gy based on size, location, brachytherapy contribution, your dose per fraction and normal tissue tolerances. This would then be followed by a brachytherapy boost. The brachy boost dose, volume and technique depend on how the patient responds to EBRT. If the patient demonstrates good radiographic response and has < =4 cm residual tumor remaining, our goal is to achieve an EQD2 of at least 80 Gy. If the patient is a non-responder or has > 4 cm remaining, we want to go higher and treat to an EQD2 of at least 85-90 Gy. 

• In this case, the patient will receive concurrent cisplatin 40 mg/m2 on a once weekly basis. 

• Total treatment time is important in cervical cancer  with possible worse outcomes if treatment is not completed with both EBRT and brachytherapy within 7 weeks.  

• There are several different ways to administer the brachytherapy boost which can consist of intracavitary, interstitial or hybrid techniques. The optimum technique is often determined by where the dose targets are and the volume of residual disease, and this is defined by the GEC-ESTRO guidelines. There are 2 CTV volumes to consider. First is the high risk CTV (HR-CTV) and includes any residual gross disease following EBRT, the entire cervix, and any grey zone areas on T2-weighted MRI.  The second CTV is the intermediate-risk CTV (IR-CTV) which is the volume that harbors significant microscopic disease, usually corresponding to the area of initial gross disease prior to the start of treatment from which disease has regressed.  While the goal EQD2 to the HR-CTV is >80Gy if <4cm and 85-90Gy if >4cm, the goal EQD2 for the IR-CTV is about 60Gy. 

• Considering the EBRT and brachy boost portions, the goal is to maintain a D2cc<90 for the bladder and D2cc<75 Gy for the rectum and sigmoid. With better image-guidance including growing use of MRI to guide treatment planning, these constraints can ideally be lowered to 80Gy for the bladder, 65Gy for the rectum and 70Gy for the sigmoid in order to reduce treatment-related morbidity.  The small bowel should be limited to 70Gy.  The recto-vaginal point should ideally also be kept to <65Gy to reduce risk of significant vaginal stenosis.  There are EQD2 calculators available online to help keep track of cumulative total dose to OARS from the EBRT and each brachytherapy fraction. 

Acknowledgements 

Thank you to Dr. Christine Chin. 

https://www.cancer.columbia.edu/profile/christine-chin-md 

Abbreviations

CHT - Chemotherapy

CT – Computed Tomography

CTV – Clinical Tumor Volume

GTV – Gross Tumor Volume

H&P – History and Physical

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MLC – Micro-Leaf Collimator

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

NCCN – National Comprehensive Cancer Network

OAR – Organs at Risk

PTV – Planning Tumor Volume

RT – Radiation Therapy

T stage – Tumor Staging

TNM – Tumor Node Metastasis

V20 – Volume receiving 20 Gray

CBC – Complete Blood Count

TVUS – Trans Vaginal Ultra Sound

CXR – Chest X-Ray

CT CAP – CT of the Chest Abdomen and Pelvis

HNPCC - Hereditary nonpolyposis colorectal cancer

TAH BSO - Total abdominal hysterectomy and bilateral salpingo-oophorectomy

FIGO - International Federation of Gynecology and Obstetrics (FIGO)

MMI - Myometrial Invasion

PA – Para-Aortic

VCB – Vaginal Cylinder Brachytherapy

IMRT – Intensity Modulated Radiation Therapy

EBRT – External Beam Radiation Therapy

Staging

https://radiopaedia.org/articles/endometrial-carcinoma-staging-2?lang=us

ESGO/ESTRO/ESP guidelines

https://ijgc.bmj.com/content/31/1/12

Molecular Classification

https://jcp.bmj.com/content/early/2022/05/29/jclinpath-2022-208345

FIRES Trial

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30068-2/fulltext

Substantial LVSI – significant risk factor for recurrence

https://pubmed.ncbi.nlm.nih.gov/26049688/

Fractionation in HDR Brachytherapy

https://www.americanbrachytherapy.org/ABS/document-server/?cfp=ABS/assets/File/public/consensus-statements/Brachy2.pdf

ABS Consensus Guidelines for adjuvant vaginal cuff brachytherapy

https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S1538472111003874?scrollTo=%23hl0000665

Highlights

• While routine staging scans are not necessary in endometrial cancer, one can consider getting a MRI to better characterize tumor origin/extent and a CXR to evaluate for distant metastatic disease. If the patient has high risk features such as grade 3 disease, consider getting a CT CAP for full metastatic staging. Importantly, ensure the patient is established with a gyn onc in anticipation of surgery.

• Type 1 tumors are often thought to be linked to excess estrogen and have evolved from endometrial hyperplasia into an endometroid carcinoma.  Most endometrial cancers are type 1 and represent a more favorable disease course given they are lower grade and estrogen responsive.  On the flip side, type 2 tumors are thought to develop from atrophic endometrium and many harbor TP53 mutations. These tumors are more aggressive and act independently of estrogen. Any tumor classified as grade 3, serous or clear cell histology is automatically a type 2 tumor.

• Grade is determined by the percent of glandular differentiation. A tumor with =<5% nonsquamous or nonmorular solid growth patterns is considered G1 and if it is >50%, it’s considered a G3. Anything in between is G2.

• Endometrial cancer can also be subcategorized through molecular classifications. There are 4 buckets—POLE ultramutated (7%), microsatellite unstable hypermutated (28%), copy-number low (39%) and copy-number high (26%). Prognosis and implications may vary based on subtype. For example, POLE mutated endometrial cancers carry the most favorable prognosis and MMRd/microsatellite instability may be candidates for anti-PD-1 antibody after first line platinum chemotherapy.

• When thinking about risk factors, consider sources for excess estrogen, which can increase a woman’s risk for type I endometrial cancer, which encompass about 80% of cases. Some main risk factors include, obesity, nulliparity, PCOS, T2DM, and exogenous estrogen such as tamoxifen. There are a few genetic syndromes to keep in mind such as Lynch syndrome and Hereditary nonpolyposis colorectal cancer (HNPCC), which also can increase the risk for endometrial cancer. Patients who are younger than 50yo and have significant family history of endometrial and/or CRC should be considered for genetic testing/counseling. Tumors should be tested for MMR (MLH1, MSH2/6) defects and patients with MMR abnormalities should also be offered genetic testing/counseling.

• Surgery is the primary treatment for endometrial cancer unless patients are deemed medically inoperable. Patients receive a total hysterectomy, sentinel lymph node dissection) and the surgeon may take peritoneal washings.  Of note peritoneal washings are typically reserved for higher risk histologies and no longer affect FIGO staging (previously FIGO IIIA until 2009) but may still influence adjuvant treatment recommendations.

• Staging of early disease confined to the uterus is determined by how much myometrium is involved. Think <50%-- stage IA and >50% stage IB. Any patient with cN+ disease is automatically FIGO stage IIIC—which can be further divided into IIIC1 which is pelvic LNS alone or IIIC2 which includes PA nodes.

• When considering VC Brachytherapy, start with a speculum exam and check to make sure the patient’s vaginal cuff is well-healed.  Treatments typically begin  at around 6 weeks post op and ideally no later than 12 weeks post op. To fit for a cylinder, ensure that the cylinder is of correct size/diameter for the patient, meaning it’s large enough to minimize air pockets within the vaginal canal but also comfortable for the patient. Simulate the patient at time of first fractionin a supine position, arms on chest, with the cylinder in place. No formal immobilization is needed. On the CT scan, I’m looking to make sure that the surface fits snug in the vaginal vault and there are no air gaps.

• With additional high-risk features such as older age >60 and LVSI—specifically substantial LVSII would consider treating with external beam radiation instead of VCB.

• In the post-op setting, patients should be receiving radiation using IMRT as it was shown to have reduced toxicity compared to 3DCRT in the TIME-C Trial. 

• Chemo should be considered for grade 3 tumors, serous/clear cell histology, or in patients with FIGO stage III/IV disease.

Acknowledgements

Thank you to Dr. Claire Baniel, who was featured in this episode.

https://radonc.stanford.edu/education/residency/therapyresidents1.html#pgy_iii_-_year_2

Thank you to Dr. Christine Chin.

https://www.cancer.columbia.edu/profile/christine-chin-md

Abbreviations

Bx - Biopsy

CTV- Clinical Tumor Volume

EDM- Electronic Dance Music

GIST- Gastrointestinal Stromal Tumor

GTV – Gross Tumor Volume

H&P – History and Physical

ITV- Internal Target Volume

IVC- Inferior Vena Cava

LN – Lymph Nodes

MRI – Magnetic Resonance Imaging

PTV- Planning Tumor Volume

PORT- Post-operative Radiation Therapy

RT- Radiation Therapy

RP- Retroperitoneal

SBO- Small Bowel Obstruction

STS – Soft Tissue Sarcoma

4D-CT- Four-dimensional Computed Tomography

NCCN Guidelines

https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf

Staging

https://jnccn.org/view/journals/jnccn/16/2/article-p144.xml 

Highlights

• In a patient with a new painless left tight mass, start off with a comprehensive history and physical paying close attention to the onset and pace of growth for the mass

• On physical exam, consider measuring the size and noting the appearance of the mass, as well as to evaluate for any signs of compression (ie. compartment syndrome) that may manifest as distal edema or paresthesias. Also assess for palpable lymphadenopathy within the regional LNs

• Obtain relevant PMHx that would could result in impaired wound healing, such as uncontrolled diabetes.

• Obtain imaging, preferably an MRI. This would help best figure out where the biopsy should be taken from in the mass. The goal is to obtain tissue where the highest grade may lie.

• There are two methods for biopsy, core needle bx and incisional bx. It is very important to ideally have the same surgical oncologist perform the bx and surgery since the bx should be longitudinal so that the scar or needle tract is resected at time of surgery.

• To complete staging, obtain a CT Chest.

• This is the only disease site where grade can alter staging and a small high-grade tumor would represent a more advanced stage than a large low grade tumor. Any tumor that is G2 is automatically stage II (think G2, stage 2). Another important thing to remember is that the presence of any LN involvement automatically makes the patient stage IV. 

• Nodal involvement is typically not common in these cases, usually <5%. Because it’s so uncommon, any nodal involvement has to reflect advanced disease and is thus, classified as stage IV.

• Histology can drive the risk of nodal involvement; the acronym CARE highlights those with an increased risk of nodal metastases-- around 20-30%. CARE stands for Clear cell, Angiosarcoma, Rhabdomyosarcoma, and Epithelioid.

• The mainstay of treatment for large, high-grade localized soft tissue sarcomas would be surgical resection with RT. We want to opt for limb preservation if possible, with a wide local excision. This would be performed with either pre-operative or post-operative radiation therapy to help improve local control.

• There are generally 5 types of surgical resection 1) intralesional 2) marginal- where the surg onc is resecting through the immediate reactive tissue around the tumor 3) simple—where narrow margins are obtained 4) wide—where margins of 2-3 cm are obtained within the compartment and 5) radical/compartmental—which is a en bloc resection of the entire anatomical compartment.

• In a pre-operative situation, we can often treat with lower doses, at 50Gy vs 60-66Gy and treat to smaller volumes given that there hasn’t been any tissue manipulation performed in a pre-operative setting. Additionally, oxygenation is also improved as blood supply is not manipulated in these situations. However, many clinical situations may not permit for pre-operative RT, as sometimes these sarcomas are discovered on pathologic evaluation after being removed, or the patient is at high risk of wound complication.

• Pre-operative RT does garner more wound healing complications, nearly double the rate at 35% versus ~17% if performed post-operatively. Post-operative RT often requires larger coverage fields and higher doses, leading to increased fibrosis rates, edema, and joint stiffness when compared to pre-operative RT. It is important for listeners to note that local control, recurrence free survival, and overall survival are equal between pre and post op RT. 

• Perform a CT sim with contrast in a supine, feet first position, with her right leg frog legged in a vac bag. Given that her left upper thigh is involved, the goal of this simulation is to ensure that treated thigh is away from the right thigh, and there are limited folds in the groin. We want to create an optimal position for our beam angles to appropriately cover our target without traversing the other leg and ensure that she can fit through our scanner in that position. We want to make sure the left leg is immobilized above and below the joint as well. We can also wire the biopsy site if that’s visible.

• For contouring, fuse in the MRI to help guide contours and have the primary lesion contoured as a GTV based on the T1 post contrast scan. Add a 1.5 cm radial expansion with a 3 cm longitudinal expansion as a CTV, however this would be a longitudinal expansion anatomically constrained within the compartment. Ensure to include any peri-tumoral edema and the biopsy tract site if possible. Add a 0.5 cm expansion to that as a PTV. During the contouring and planning process, ensure there is at least a 2 cm skin strip contoured where we would limit dose to prevent circumferential dose that may lead to compartment syndrome. Ensure the femur and joints are contoured as well.

• Ensure at least 95% of the PTV is getting 100% of the PTV dose without more than a 110% hotspot, but the lower the better. For the skin strip, I want to make sure the V20 is <50%. On the femur itself, I want to make sure the mean dose is <37 Gy and the V40 <64Gy. If there are joints in field, Ensure that the V50 is less than 50%.

• Acutely, discuss the expectation of fatigue, radiation dermatitis, pain, and edema. Ensure to discuss that there is an increased likelihood for wound healing complications in this pre-operative RT setting. Long term, discuss the expectation of fibrosis, joint stiffness, and edema, as well as a small chance of secondary malignancies.

• The indications for chemotherapy are controversial. In the adjuvant setting, there is some data suggesting a modest overall survival benefit with doxorubicin-based CHT, although typically reserved for large, grade 3 tumors. In this case, she will likely not receive benefit from chemotherapy.

Acknowledgements

Thank you to Dr. Everett Moding.

https://profiles.stanford.edu/everett-moding

Abbreviations

CTV- Clinical Tumor Volume

EDM- Electronic Dance Music

GIST- Gastrointestinal Stromal Tumor

GTV – Gross Tumor Volume

ITV- Internal Target Volume

IVC- Inferior Vena Cava

PTV- Planning Tumor Volume

PORT- Post-operative Radiation Therapy

RT- Radiation Therapy

RP- Retroperitoneal

SBO- Small Bowel Obstruction

4D-CT- Four-dimensional Computed Tomography 

The STRASS TRIAL 

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30446-0/fulltext

NCCN Guidelines
https://www.nccn.org/professionals/physician_gls/pdf/sarcoma.pdf

Highlights

• Keep in mind that 80% of retroperitoneal masses are malignant. The differential diagnosis includes sarcoma, GIST, lymphoma, germ cell tumor and benign etiologies such as desmoid tumor, lipoma, or peripheral nerve sheath tumor.

• Use the mnemonic SADPUCKER to remember retroperitoneal organs -- suprarenal glands (Adrenal), aorta, duodenum (2nd/3rd parts), pancreas, ureters, colon (ascending/descending), kidneys, esophagus, and rectum.

• Staging imaging includes CT chest +/- MRI abdomen.

• Pre-op biopsies are not necessary if clinical suspicion for retroperitoneal sarcoma is high and there is a plan for up front resection.

• Generally speaking, management options include upfront resection alone or pre-operative RT followed by resection. Observation would be appropriate in select cases (advanced age, not a surgical candidate, asymptomatic, slow pace of growth, etc).

• It is important to carefully review imaging to determine surgical candidacy. Contraindications to surgical resection include extensive vascular involvement, peritoneal implants, distant metastases, or involvement of the root of the mesenteric vessels or spinal cord.

• The goal of pre-operative RT is to decrease the likelihood of a local recurrence.

• An exploratory analysis of the STRASS Trial suggested a 10% absolute abdominal recurrence-free survival benefit with pre-operative RT followed by resection.

• Multiple additional retrospective studies have shown a decrease of about 50% in local recurrence. However, like extremity sarcomas there is no clear benefit on overall survival.

• Simulate the patient supine, headfirst, with a vac loc, and both arms raised with IV contrast.  A 4D-CT scan can be considered for motion management.  

• Contour the primary tumor as a GTV and check the 4D phases to account for any movement. If the overall movement is limited, within 5-7 mm, contour an ITV in a motion inclusive manner in all phases. If not, contour within the exhale phases and ensure to treat during those phases as well. Add a 1.5 cm CTV expansion[EJM1] [WTC2]  but edit around bone, the kidney, and bowel. Add a 0.5 cm margin to form the PTV.

• The pre-op prescription dose is 50.4 Gy in 28 total fractions.

• Make sure at least 95% of the PTV is getting a 100% dose. Try to keep hotspots <110%. Compromise on coverage to meet constraints for the bowel (Dmax 54 Gy, V55 is <20cc, V15 <150cc), kidney (V18 <15%), spinal cord (Dmax 50 Gy), and liver (mean <26 Gy).

• Acute toxicity includes fatigue, nausea, vomiting, loose stools, and possible exacerbation of abdominal pain. Chronic toxicity includes renal injury, loss of kidney function, bowel strictures leading to SBO, bowel perforation, fistulation, myelopathy, and a small chance of secondary malignancies.
  
  

Acknowledgements

Thank you to Dr. Everett Moding.

https://profiles.stanford.edu/everett-moding

Abbreviations

BCT – Breast Conservation Therapy

BI-RADS - Breast Imaging Reporting and Data System

CHT - Chemotherapy

CT – Computed Tomography

CTV – Clinical Tumor Volume

DCIS - Ductal carcinoma in situ

DIBH – Deep Inspiratory Breath Hold

ENE – Extranodal Extension

ER – Estrogen Receptor

GTV – Gross Tumor Volume

H&P – History and Physical

HER2 - Human Epidermal Growth Factor Receptor 2

HRT – Hormone Replacement Therapy

IDC – Invasive Ductal Carcinoma

IMN – Internal Mammary Nodes

Ki67 - percentage score defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed, commonly used measure of cellular proliferation in breast cancer tissue

LAD - Lymphadenopathy

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MLC – Microleaf Collimator

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

NAC – Neoadjuvant Chemotherapy

NCCN – National Comprehensive Cancer Network

OAR – Organs at Risk

PMRT – Post Mastectomy Radiation Therapy

PR – Progesterone Receptor

PTV – Planning Tumor Volume

RNI – Regional Nodal Irradiation

RT – Radiation Therapy

SLNB – Sentinel Lymph Node Biopsy

T stage – Tumor Staging

TNM – Tumor Node Metastasis

V20 – Volume receiving 20 Gray

Staging

https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging

Breast Screening Guidelines

https://www.komen.org/breast-cancer/screening/when-to-screen/average-risk-women/

DIBH

https://www.petermac.org/DIBH

Highlights

• When presenting with a new breast mass, start with a detailed history and physical exam, paying specific attention to family history of cancer, gynecologic history and history of any irregular mammograms. On physical exam, consider performing a bilateral breast exam, paying specific attention to size/mobility of breast mass, location in the breast, any suspicious skin changes and evaluate for any palpable lymphadenopathy.

• LN stations can be easier to remember if using the pectoralis minor as a landmark. As we work our way medially, level 1 LNs are inferior/lateral to pec minor, level 2 is deep to pec minor, level 3 is superior/medial to pec minor. Level 4 represents our supraclavicular LNs and then, there are the IMNs.

• To work this patient up who has a 7 cm breast mass and fixed axillary adenopathy, start with a bilateral diagnostic mammogram and ultrasound followed by core needle biopsy.

• T staging represents the index breast lesion– anything measuring 2 cm or less is T1, 2-5 cm T2, >5 cm T3, extension to the CW, adherence to the pec muscle, or skin involvement represents T4. If the patient has mobile level I or II LNs, that is N1; if those LNs are fixed OR there’s an isolated IMN, that’s N2; any level III or IV involvement or a + IMN with multistation LAD, is N3.

• In this case, with a 5.5 cm primary lesion and fixed adenopathy, her clinical stage is cT3N2.

• Per the NCCN guidelines, staging imaging should be considered if there is suspicion for metastatic disease. There are many indications to obtain genetic testing which can also be found on the NCCN guidelines but the main highlights are get testing for patients diagnosed with breast cancer any age 45 or younger, TNBC, any close blood relative with breast/ovarian/pancreatic cancer or deNovo high risk prostate cancer, Ashkenazi Jewish decent, or if the patient is a male.

• In this case, we advocated for neoadjuvant chemotherapy. There are a few different CHT regimens available but a commonly used one is dose dense doxorubicin/cyclophosphamide x4C followed by weekly paclitaxel x12C. The benefits of NAC include the opportunity to downstage prior to surgery (in the setting of initial unresectable disease or if BCT is desired/feasible), serves as an in vivo test of CHT efficacy, and may serve as a prognostic marker depending on the patient’s degree of pathologic response.

• In this patient with cT3N2 IDC with only a minimal response to NAC on restaging imaging, it’s clear that she will need PMRT. On surgical pathology, be aware of margin status, measure of treatment effect, how many LNs were positive, the total number of LNs removed in the dissection, whether there was ENE, and the tumor biology post NAC.

• In this case, we recommended LEFT PMRT to the reconstructed breast to 50.4 Gy in 28 fractions with bolus for the first 13 fractions. For comprehensive RNI, I would also treat the left level I-IV and IMNs to 50.4 Gy. 

• For our simulation, we would obtain imaging in a head first, supine setup on a breast board with the ipsilateral arm raised, and head turned to the contralateral side. We would wire her left breast, any scars, drain sites, and mark breast borders, placing the superior border at the level of the inferior clavicle head, medial at the patient’s midline, lateral at the mid-axillary line, and inferior 1-2 cm below the inframammary fold. I would also obtain a DIBH scan, if available to me.

• For the CW CTV, the superior border would be bottom of the clavicular head down about 2 cm inferior of the implant. My posterior border in PMRT will include the pectoralis major muscle and ribs. For the lymph nodes, contour the level I-IV axilla. The IMN contours will be located in the first 3 interspaces between the ribs, stopping at the 4th rib, including the thoracic vessels. Pertinent OARs to be mindful of are the heart, bilateral lungs, esophagus, spinal cord, and the contralateral reconstructed breast.

• For PMRT, you always include the pectoralis major and ribs in your CTV volumes. This is different than adjuvant RT in BCT, where you do not include the muscle.

• Key OAR constraints include mean heart < 4 Gy and ipsilateral lung V20 <30%.

• Our patient had significant residual disease after NAC, therefore she should also get 1 year of Olaparib in conjunction with endocrine therapy. Because she is post-menopausal, I would recommend letrozole.

Acknowledgements

Thank you to Dr. Ryan Morse, who was featured in this episode.

https://www.med.unc.edu/radonc/education/residency/current/meet-the-residents-dr-ryan-morse/

Thank you to Dr. Michael Xiang.

https://www.uclahealth.org/providers/michael-xiang

Abbreviations

BCT – Breast Conservation Therapy

CT – Computed Tomography

CTV – Clinical Tumor Volume

DCIS - Ductal carcinoma in situ

DIBH – Deep Inspiratory Breath Hold

ER – Estrogen Receptor

GTV – Gross Tumor Volume

H&P – History and Physical

HER2 - Human Epidermal Growth Factor Receptor 2

HRT – Hormone Replacement Therapy

IDC – Invasive Ductal Carcinoma

IMN – Internal Mammary Nodes

Ki67 - percentage score defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed, commonly used measure of cellular proliferation in breast cancer tissue

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MLC – Microleaf Collimator

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

NAC – Neoadjuvant Chemotherapy

OAR – Organs at Risk

PR – Progesterone Receptor

PTV – Planning Tumor Volume

RNI – Regional Nodal Irradiation

RT – Radiation Therapy

SLNB – Sentinel Lymph Node Biopsy

T stage – Tumor Staging

TDM1 - Trastuzumab emtansine

TNBC – Triple Negative Breast Cancer

TNM – Tumor Node Metastasis

USPSTF - United States Preventive Services Taskforce

V20 – Volume receiving 20 Gray

VATS - Video-assisted thoracoscopic surgery

WBI – Whole Breast Irradiation

Staging

https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging

Breast Screening Guidelines

https://www.komen.org/breast-cancer/screening/when-to-screen/average-risk-women/

DIBH

https://www.petermac.org/DIBH

NEOSPHERE

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70336-9/fulltext

Highlights

• On workup of a person who had prior “breast cancer surgery,” consider obtaining a more comprehensive history and physical– paying specific attention to receipt of neoadjuvant systemic therapy and on physical exam, note any surgical sites, palpable nodes, nipple discharge, and skin discoloration, along with a full bilateral breast exam. Assess menopausal status, if she were premenopausal, consider a pregnancy test. In anticipation of upcoming treatment. Consultation with a fertility specialist for consideration of future family planning should be considered as well. Obtain all historical data I could find, including workup imaging, surgical reports, and pathology reports.

• In this case, histology shows an IDC, 2.5 cm in size, grade 3 without any associated DCIS. There is LVSI present with negative margins. 1 of 3 removed sentinel nodes showed disease, the largest deposit of 5mm without any associated extracapsular extension. She is ER/PR negative, Her2 positive, Ki67 70%. The patient was considered a pT2pN1, stage IIb

• NCCN recommends NAC for HER2+/TNBC if >=cT2 or N+ at presentation. In this case, she likely fulfilled both criteria. The most common NAC for HER2+ disease include Adriamycin/cyclophosphamide followed by paclitaxel/herceptin OR TCHP.  Since this case did not receive NAC, consider adjuvant docetaxel, trastuzumab, and pertuzumab (NEOSPHERE trial).

• It was recommended to recieve whole breast radiotherapy that would include comprehensive regional nodal irradiation with 50.4 Gy in 28 fractions with a boost to the tumor bed with 10 Gy in 5 total fractions. The nodal basins would include level 1-4 axilla and IMNs.  

• When treating with regional nodal irradiation for patients with 1-2 positive SLNs. This is often a topic of discussion and there is no clear standard for patients with 1-2 positive SLNB. In this population, the patient’s overall risk profile for recurrence should be considered when deciding whether to include RNI. This patient had 1 SLN positive but she has other risky features for recurrence such as her young age, high grade, high Ki67, and +LVSI so very reasonable to include RNI in this case. If the patient had less aggressive tumor biology and more favorable features, one could consider treating WBRT alone with high tangents to cover the level 1 and 2 axilla.

• Simulation included a headfirst, supine setup on a breast board with the patient’s left arm raised and head turned to her right side. If a breast board is unavailable, a wingboard or vac-loc are alternatives for fixation. Consider wiring scars, and mark breast borders; given this is a left-sided breast cancer, also consider a Deep Inspiratory Breath Hold scan. 

• Breast borders are marked as: superior border at the level of the inferior clavicle head, medial border at the patient’s midline, lateral border at the mid-axillary line, and inferiorly mark 1-2 cm below the inframammary fold.

• Contour the tumor bed, adding a 1cm margin for a PTV. Also contour the ipsilateral axillary nodes levels 1-3, the ipsilateral supraclavicular nodes, and the ipsilateral IMN’s.

• For field arrangements, create opposing tangential fields with the isocenter placed at the level of my superior border to create a half beam block sup/inf. This is called a mono-isocentric technique  

• Set Beams eye view’s field borders to encompass those marked borders, with the tangent breast beam angles adjusted so the posterior field edges align on a straight edge. Also ensure atleast a 2-3cm flash anteriorly. Evaluate the lung and heart involved in the field and make adjustments as fit to reduce dose without too much compromise to coverage.

• Add a superior nodal anterior field, angled 5-10 degrees towards the opposing side to avoid the spinal cord. This field would be bordered to block the spinal cord medially, laterally just past the humeral head to cover the contoured level 1 and 2 axillary nodes, inferiorly to match the half beam blocked breast tangents border, and superiorly to cover the contours supraclavicular nodes.

• Adjust the MLC’s to block the humeral head, spinal cord, and thyroid, without compromising nodal coverage. A PA beam can be considered as well later in the planning process if the anterior fields alone do not adequately cover the axillary nodes. It would be dosed so the primary dose contribution would come from the anterior field.

• If the IMN’s are not properly covered and the heart and lung coverage permit, begin field adjustments with partially-wide tangents. If inadequate, a medial electron field can be brought it. This would require lateralization of our tangent fields to permit for a suitable electron field that is wide enough for clinical use. If the IMNs are too deep, an electron photon mix can be used for this field. When placing in an IMN electron field, ensure the gantry angle is matched your anterior breast tangent gantry angle but adjusted further anteriorly 5-7 degrees to account for the lateral bowing of the electron dose distribution. Feathering of this field with the tangent fields should be considered as well.

• For planning evaluation, ensure that the lung V20 is ideally less than 30%, although consider up to 35%. For the heart, ensure that <5% of the heart received no more than 40% of the prescription dose, but ideally as low as possible. Ensure the mean heart dose can be held to <5Gy, but the lower the better, ideally less than 2Gy. Also evaluate the thyroid dose and ensure there are no high doses in this region, looking for less than 3% of the Rx dose.

• Tumor boost plans are typically electron versus photon based boosts, with electrons selected for more superficial tumor beds, and mini tangents versus non-coplanar arrangements with photons for deeper tumor beds. The superficiality of the tumor doesn’t preclude either modality from being used, the overall goal is to minimize breast and OAR dose while ensuring appropriate tumor bed dose.

• With electron beam planning, you should adjust your energy to make sure you have adequate deep coverage, and ensure at least a 1.5 cm margin around your PTV, to account for the larger penumbra of electrons.

• In regards to side effects, acutely, discuss fatigue and skin changes. Long term, monitor for lymphedema, radiation pneumonitis, increased risk for rib fracture, thyroid toxicity, cardiotoxicity, breast edema/fibrosis, and a low risk for secondary malignancies.

• Follow up includes appointments 1-4 x per year for a H&P for up to 5 years, then annually with a clinical exam. Consider obtaining a mammogram at 6 months, then yearly

• In this case, if the patient presents to you initially, but has a 6 cm tumor, bulky fixed LAD and is ER/PR- HER2+, they would be considered cT3N2.

• Having residual disease after NAC is a poor prognostic sign. Consider additional HER2 directed therapy with TDM1 in this secondary case.

• What does a nosey pepper do? It gets jalapeño business

Acknowledgements

Thank you to Dr. Michael Xiang.

https://www.uclahealth.org/providers/michael-xiang

Abbreviations

BCT – Breast Conservation Therapy

BI-RADS - Breast Imaging Reporting and Data System

CT – Computed Tomography

CTV – Clinical Tumor Volume

DCIS - Ductal carcinoma in situ

DIBH – Deep Inspiratory Breath Hold

ER – Estrogen Receptor

FNA – Fine Needle Aspiration

GTV – Gross Tumor Volume

H&P – History and Physical

HER2 - Human Epidermal Growth Factor Receptor 2

HRT – Hormone Replacement Therapy

IDC – Invasive Ductal Carcinoma

IMN – Internal Mammary Nodes

Ki67 - percentage score defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed, commonly used measure of cellular proliferation in breast cancer tissue

LN – Lymph Nodes

LVSI - Lymph-Vascular Space Invasion

MLC – Microleaf Collimator

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

OAR – Organs at Risk

OCP - Oral Contraceptive Pills

PBI – Partial Breast Irradiation

PCP – Primary Care Physician

PR – Progesterone Receptor

PTV – Planning Tumor Volume

RT – Radiation Therapy

SLNB – Sentinel Lymph Node Biopsy

T stage – Tumor Staging

USPSTF - United States Preventive Services Taskforce

V20 – Volume receiving 20 Gray

VATS - Video-assisted thoracoscopic surgery

WBI – Whole Breast Irradiation

Staging

https://www.cancerresearchuk.org/about-cancer/breast-cancer/stages-types-grades/tnm-staging

Breast Screening Guidelines

https://www.komen.org/breast-cancer/screening/when-to-screen/average-risk-women/

USPSTF Breast Cancer Screening

https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening

BIRADs Scoring

https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/mammograms/understanding-your-mammogram-report.html

DIBH

https://www.petermac.org/DIBH

Choosing Wisely

https://www.choosingwisely.org/societies/society-of-surgical-oncology/

FAST FORWARD

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30932-6/fulltext

Highlights

• Screening guidelines vary depending on organization. The USPSTF recommends a screening mammogram performed every other year for women 50-74 years old.

• For those 40-49 years old, the decision for screening should be individualized, with higher value placed for those at higher risk, including those with a parent, sibling, or child with breast cancer.

• The American Cancer Society recommends yearly screening from ages 45-54 and then every 1-2 years until life expectancy is <10 years.

• “BI-RADS” is an acronym for the Breast Imaging Reporting and Data System score. It’s a scoring system radiologists use to describe mammogram results on a 7-point scale 0-6. A BI-RADS 0 represents an incomplete test requiring additional imaging. A BI-RADS 1-3 represent negative, benign, and probably benign findings. A BI-RADS 3 will likely buy you a short interval follow up imaging (~6 months). BI-RADS 4 is the start of our suspicious findings that likely will warrant further workup. Finally, a BI-RADS 5 indicates a very high suspicion of malignancy. BI-RADS 6 are for lesions we already know are cancer and biopsy proven.

• When pursuing a biopsy, consider a core needle biopsy performed with image guidance. FNA’s or excisional biopsies are not ideal.

• In this case, the patient gets a core needle biopsy and it shows invasive ductal carcinoma, ER+/PR+/HER2-, grade 2.

• If the patient were premenopausal, consider a pregnancy test. In anticipation of upcoming treatment, should the patient be pre-menopausal and amenable to it, consider consultation with fertility specialists for future family planning.

• Breast MRI or whole body staging, without symptoms, would not be indicated in this case.

• For treatment options, broadly, surgery will be the mainstay of treatment, including breast conservation therapy as well as mastectomy. BCT will include lumpectomy and a SLNB +/- adjuvant RT, depending on the patient’s age and features on surgical pathology. Mastectomy would be considered if she exhibited multi-centric disease, required repeat margin excisions after lumpectomy, had contraindications to RT, or if this was the patient’s preferred approach. Given her age is 72, as per choosing wisely, routine SLNB is not indicated for those over age 70 who are clinically N0.

• In this case, the patient was pT1c pN0 M0, stage IA. She would be classified as a Luminal A as this is estrogen receptor-positive and progesterone receptor-positive, HER2-negative, and has low level Ki-67.

• Adjuvant treatment options include adjuvant whole breast radiotherapy, adjuvant accelerated partial breast, and hormone therapy alone.

• For CT simulation, in this case, a headfirst, supine setup on a breast board with the patient’s left arm raised was performed. If a breast board is unavailable, a wingboard or vac-loc would be great alternatives for fixation. Consider wiring the scar and mark breast borders and given this is a left sided treatment, employ DIBH for heart avoidance. A prone setup can be considered as well.

• Breast borders are marked with superior border at the level of the inferior clavicle head, medial border at the patient’s midline, lateral border at the mid-axillary line, and inferiorly, 1-2 cm below the inframammary fold.

• Ensure relevant OARs were contoured such as the heart, lungs, and contralateral breast but the breast CTV itself does not necessarily need to be contours. Using the same borders that had been marked off, create opposing tangential fields and ensure the glandular breast tissue is well covered. This can be performed by setting the isocenter along the posterior border of the field to create a half beam block effect. If there are clearance or set up issues, the isocenter can be placed more anteriorly as well, with the beam angles adjusted so the posterior field edges align on a straight edge. Ensure there is at least a 2-3cm flash anteriorly. Evaluate how much lung and heart are involved in the field and adjust as fit to reduce dose without much compromise to coverage.

• With treatment, acutely, discuss toxicities including fatigue and skin changes. Long term, monitor for radiation pneumonitis, increased risk for rib fracture, cardiotoxicity, changes in breast cosmesis, and a low risk for secondary malignancies.

• Follow up her 1-4 x per year for a H&P for up to 5 years, then annually, with a clinical exam. Consider obtaining a mammogram at 6 months, then yearly.

• Generally speaking, a tumor boost should be included in younger patients 50 or younger or older patients with grade 3 disease, positive margins. Other cases require individual patient decision making taking into account other parameters such as tumor biology, tumor size, close margins, etc.

Acknowledgements

Thank you to Dr. Michael Xiang.

https://www.uclahealth.org/providers/michael-xiang

Abbreviations

CABG - Coronary Artery Bypass Graft

CBC – Complete Blood Count

CMP – Complete Metabolic Panel

COPD - Chronic Obstructive Pulmonary Disease

CT – Computed Tomography

CTV – Clinical Tumor Volume

DLCO - Diffusing capacity for carbon monoxide (measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries)

Dmax – Dose Maximum

EBUS - Endobronchial Ultrasound

FEV1 - Forced expiratory volume in the first second (Volume that has been exhaled at the end of the first second of forced expiration)

GTV – Gross Tumor Volume

H&P – History and Physical

ITV – Internal Target Volume

IV – Intravenous

LN – Lymph Nodes

LUL – Left Upper Lobe

MRI – Magnetic Resonance Imaging

N stage – Nodal Staging

NSCLC – Non Small Cell Lung Cancer

PET - Positron emission tomography

PFS – Progression Free Survival

PFT – Pulmonary Function Test

PORT – Post Operative Radiation Therapy

PTV – Planning Tumor Volume

SABR – stereotactic ablative radiotherapy

SBRT - stereotactic body radiation therapy

TTF-1 - Thyroid transcription factor 1 (used as a diagnostic marker for lung adenocarcinoma and small cell carcinoma)

USPSTF - United States Preventive Services Taskforce

V20 – Volume receiving 20 Gray

VATS - Video-assisted thoracoscopic surgery

Staging

https://www.jto.org/action/showPdf?pii=S1556-0864%2815%2900017-9

Anatomy

https://www.ncbi.nlm.nih.gov/books/NBK532863/

https://www.ncbi.nlm.nih.gov/books/NBK532863/figure/article-24847.image.f2/?report=objectonly

USPSTF Lung Cancer Screening

https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening

4D-CT imaging

https://www.aapm.org/meetings/06ss/documents/ClincalUseof4DCT_Low.pdf

Lung Tumor Location and Toxicity

https://ascopubs.org/doi/figure/10.1200/JCO.2006.07.5937

https://www.lungcancerjournal.info/article/S0169-5002(15)00232-9/fulltext

CALGB 9366

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652093/pdf/7795.pdf

LungART

https://www.thelancet.com/article/S1470-2045(21)00606-9/fulltext

Highlights

• Lung Cancer is the leading cause of cancer related death in the US. About 15-20% of patients present with early stage disease. Smoking is the #1 risk factor; additional risk factors include occupational exposures, radon, asbestos, and family history.

• The USPSTF recommend low dose screening CT chest for anyone ages 50 to 80 with a 20+ pack year smoking history and has not quit greater than 15 years ago.

• For workup, begin with a detailed H&P paying attention to unintentional weight loss, CBC, CMP, diagnostic CT chest with IV contrast, and PFTs. On the CT chest, IV contrast would help identify pathologic lymph nodes which are defined, on a size criteria, as >1 cm in the short axis. Consider a biopsy +/- EBUS/mediastinoscopy.

• TTF-1 is associated with adenocarcinoma, adenocarcinoma in situ, and neuroendocrine tumors.

• In this case, our patient presented with clinical stage T1bN0M0 disease (stage IA2). Since he was medically inoperable, SABR was recommended.

• Reasonable to obtain a PET-CT for tumors >8 mm. An MRI brain is usually indicated for stage II disease or greater as part of standard workup.

• Mediastinal nodal evaluation is indicated if there is radiographic nodal disease, for all superior sulcus tumors, T3 primaries, or a central T1-2 lesions.

• If patients need to have their nodes assessed, this is typically done via mediastinoscopy to evaluate stations 2, 4, 7 or EBUS to sample stations 3 and 10. The best way to evaluate stations 5 and 6 is through a VATS or anterior mediastinotomy procedure.

• Simulate the patient head first supine with arms up +/- use of a vac loc. Obtain a 4DCT to help with motion management. If 4DCT is unavailable, other motion management strategies include abdominal compression, breath hold, or active breathing control.

• For SABR planning, for GTV contouring, use a lung window with PET fusion if available. No CTV extension would be required. The ITV would include tumor movement on the 4DCT scan. This would typically be encompassed on the expiratory phases, 30%-70% but if the tumor moves<3-5 mm, we could also use a motion inclusive approach where we contour an ITV in all phases of the breathing cycle. Add a 5 mm margin to form the PTV.

• Treatment recommendation for SABR dosing was 54 Gy in 3 fractions. There is no indication for elective nodal coverage in this case.

• An alternative fractionation schema would be 34 Gy in 1 fraction.

• For plan evaluation, ensure our 100% isodose line remains well constrained around the PTV, with the center increased to at least 20% of our RX dose as we are taking an ablative approach. Ensure our low dose fall off is controlled and that ideally the 50% isodose line is within 1-2 cm from the periphery of our PTV, while avoiding >50% of the prescription dose circumferentially surrounding any nearby tubular structures, such as the vessels, esophagus, and airways.

• Monitor for the Dmax of the esophagus is <27 Gy and brachial plexus <24 Gy, as well as V20<15% for the lungs.  For a single fraction approach, ensure not to exceed a Dmax of 15.4 Gy for esophagus, 17.5 Gy for brachial plexus and Lung-GTV V20<15%, although ideally less than 10%.

• Central tumors are lesions within 2 cm of the proximal bronchial tree. Consider treatment of central tumors to 50 Gy in 5 fractions. Ultracentral tumors directly abut the proximal bronchial tree or touch mediastinal structures such as the esophagus or great vessels. For  ultracentral tumors, consider treatment to 60 Gy in 8 fractions.

• Short term toxicities can include develop cough, esophagitis, chest wall pain and fatigue. For late toxicity, monitor for radiation pneumonitis, esophageal stricture, or uncommonly rib fracture.

• Follow patients with a CT chest every 6 months for 2 years, but opting for every 3 months the first year would be within reason. Then lengthen to annual scans after 2 years if they remain clear of disease or progression.

• Surgery is the standard of care for medically operable patients with an early-stage NSCLC. There are 3 different types of resection– a wedge (ie. segmental resection), lobectomy, or pneumonectomy. One of the benefits of surgery include the ability for mediastinal lymph node dissection being performed to obtain pathologic nodal staging. Radiation treatment, as described, remains a treatment option as well if the patient refuses surgery

• In CALGB 9366, there is suggestion that stage IB with tumors >4 cm may benefit from adjuvant carbotaxol.

• LungART did not show a PFS benefit in PORT for pN2 disease.

Acknowledgements

Thank you to Dr. Lucas Vitzthum.

https://profiles.stanford.edu/lucas-vitzthum

Abbreviations

CBC – Complete Blood Count

CMP – Complete Metabolic Panel

CRT – Chemotherapy and Radiation Therapy

CT – Computed Tomography

CTAP – Computed Tomography of the Abdomen and Pelvis

CTV – Clinical Tumor Volume

DLCO - Diffusing capacity for carbon monoxide (measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries)

Dmax – Dose Maximum

EGFR - Epidermal Growth Factor Receptor

FEV1 - Forced expiratory volume in the first second (Volume that has been exhaled at the end of the first second of forced expiration)

GTV – Gross Tumor Volume

H&P – History and Physical

ITV – Internal Target Volume

IV – Intravenous

LAD - Lymphadenopathy

LLL – Left Lower Lobe

LN – Lymph Nodes

MIP – Maximum Intensity Projection

MLD – Mean Lung Dose

MRI – Magnetic Resonance Imaging

N stage – Nodal stage

NSCLC – Non Small Cell Lung Cancer

PE – Physical Examination

PET - Positron emission tomography

PFS – Progression Free Survival

PFT – Pulmonary Function Test

PTV – Planning Tumor Volume

SCC – Squamous Cell Carcinoma

SVC – Superior Vena Cava

TKI – Tyrosine Kinase Inhibitors

V20 – Volume receiving 20 Gray

Staging

https://www.jto.org/action/showPdf?pii=S1556-0864%2815%2900017-9

Anatomy

https://www.ncbi.nlm.nih.gov/books/NBK532863/

https://www.ncbi.nlm.nih.gov/books/NBK532863/figure/article-24847.image.f2/?report=objectonly

USPSTF Lung Cancer Screening

https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-screening

4D-CT imaging

https://www.aapm.org/meetings/06ss/documents/ClincalUseof4DCT_Low.pdf

PACIFIC Trial

https://www.nejm.org/doi/full/10.1056/nejmoa1709937

Highlights

• 30% of patients with NSCLC present with stage IIIA disease.

• Workup includes H&P, CBC, CMP, and CT chest with contrast +/- CTAP.

• This discussed case presented with enlarged ipsilateral hilar LNs on imaging, this patient needs a biopsy either via EBUS/mediastinoscopy or a CT guided approach.

• Common signs and symptoms of advanced lung cancer include SOB, hemoptysis, anorexia, and weight loss.

• Paraneoplastic syndromes can include Horner’s Syndrome, presenting with a triad of ptosis, miosis, and anhidrosis; Pancoast syndrome which is the result of an apical tumor invading the thoracic inlet causing Horner’s syndrome, brachial plexopathy, shoulder pain, and occasionally SVC syndrome. Other paraneoplastic syndromes are hypercalcemia of malignancy due to parathyroid hormone related peptide (PTHrP) seen only with SCC and Lambert-Eaton. Voice hoarseness may present due to recurrent laryngeal nerve involvement from a Pancoast tumor.

• In advanced stage disease, consider obtaining a PET CT and MRI brain to complete staging, as well as PFTs to determine if the patient is a surgical candidate. Of importance, the FEV1 and DLCO should ideally both be >80% predicted to be a surgical candidate.

• In this case, a lobectomy and mediastinal lymphadenectomy was performed and the patient is upstaged to pN2 disease with a positive microscopic margin. Given the positive margin, concurrent CRT to 60 Gy with cisplatin/etoposide or weekly carboplatin/paclitaxel was recommended.

• With N3 disease, the stage is IIIB, and the recommended course would include definitive CRT to 60 Gy in 30 fractions with concurrent cisplatin/etoposide or weekly carboplatin/paclitaxel followed by durvalumab for one year per the PACIFIC Trial.

• For cisplatin/etoposide, the dose is 50 mg/m2 for both agents, every 4 weeks. For weekly carboplatin, AUC is 2.0 and paclitaxel is also 50 mg/m2.

• Trials in dose escalation beyond 60 Gy have been negative.

• Simulation includes a supine position with arms up with 4DCT acquisition if available with IV contrast.

• For treatment volumes, fuse the most recent PET CT to aid in GTV delineation, which would include the primary lung lesion and pathologic nodal disease.

• For the GTV contour on the MIP imaging with a 3-8 mm margin to form the ITV, cropping out uninvolved organs. Add an additional 5 mm margin to form the PTV.

• Elective nodal coverage is not indicated as locoregional improvement has not been demonstrated.

• For constraints, MLD ≤ 20 Gy, lung V20 < 35%, mean esophagus ≤ 34 Gy, and mean heart ≤ 20 Gy. Dmax 66 Gy for brachial plexus.

• Acutely, patients may develop fatigue, cough, esophagitis, SOB. In the long term, monitor for pneumonitis, lung fibrosis, brachial plexopathy and signs of cardiac toxicity.

• Neoadjuvant CRT can be considered for patients minimal, non-bulky N2 disease and importantly should be candidates for lobectomy. Patients with a superior sulcus tumor are also an ideal neoadjuvant CRT patient. These patients are treated to 45 Gy with conventional fractionation and concurrent cisplatin/etoposide leading up to surgery.

• In NSCLC, an EGFR mutation in exon 19 and 21 is seen in about 10% of cases and importantly predict for excellent clinical response with use of TKIs such as Osimertinib. EGFR is more commonly mutated in SCC.

Acknowledgements

Thank you to Dr. Lucas Vitzthum.

https://profiles.stanford.edu/lucas-vitzthum

Abbreviations

ADT – Androgen Deprivation Therapy

AS – Active Surveillance

CTV – Clinical Tumor Volume

DRE – Digital rectal examination

EBRT – External Beam Radiation Therapy

ECE – Extra-Capsular Extension

EPE – Extra-Prostatic extension

GnRH - Gonadotropin hormone-releasing hormone

H&P – History and Physical

HDR – High Dose Rate

LDR – Low Dose Rate

LN – Lymph Nodes

MRI – Magnetic Resonance Imaging

NCCN – National Comprehensive Cancer Network

PET – Positron Emission Tomography

PSA – Prostate Specific Antigen

PSMA – Prostate Specific Membrane Antigen

PTV – Planning Tumor Volume

RALP – Robotic-Assisted Laparoscopic Prostatectomy

RT – Radiation Therapy

SBRT – Stereotactic Body Radiation Therapy

SV – Seminal Vesicles

SVI – Seminal Vesicle Invasion

Staging

https://www.ncbi.nlm.nih.gov/books/NBK279042/table/prostate-cancer-det.primarytum/

Gleason Scoring

https://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/grading.html

NCCN Risk Categories

https://www.uptodate.com/contents/image?imageKey=ONC%2F118962

Anatomy

https://training.seer.cancer.gov/prostate/anatomy/

Decipher Genomic Testing

https://decipherbio.com/prostate/

The Decipher® Prostate Cancer Test (GenomeDx Biosciences, San Diego, CA) is a genomic test that serves as a prognostic marker of cancer control outcomes in patients newly diagnosed with localized PCa at the time of biopsy, as well as patients who have undergone radical prostatectomy.

STAMPEDE

http://www.stampedetrial.org/centres/eligibility-randomisation/

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)32486-3/fulltext

Phoenix definition

https://www.redjournal.org/article/S0360-3016(06)00663-8/fulltext

Highlights

• Intermediate and high-risk prostate cancer comprises of 10-20% of new cases.

• About 5% are associated with genetic mutations. The NCCN now recommends genetic testing for any patient with high-risk disease or family history of prostate cancer.

• For favorable risk patients, hard indications that upgrade to unfavorable intermediate risk are a GS 4+3 score and >50% cores positive. Also, if there are 2 or more risk factors– which include palpable disease crossing midline, GS 7 disease, or PSA of 10-20.

• Treatment options for favorable intermediate risk prostate cancer include AS, RALP or primary RT.

• SBRT—36.25 Gy in 5 fx to the PTV and 40 Gy in 5 fractions to the CTV—delivered every other day. The CTV would include the prostate alone and PTV expansions would be anisotropic with a 3 mm posterior expansion and 5 mm in all other planes.

• With SBRT, for rectum/bladder, ensure D50% <18-20 Gy and Dmax<42 Gy

• For the rectum, ensure less than half of the rectum is receiving 24 Gy and V38 < 2cc.

• For the urethra, ensure the Dmax is <42 Gy. 

• Common acute side effects of RT include urgency, frequency, dysuria, and loose stools. For late side effects, monitor for cystitis, proctitis and sexual dysfunction.

• NCCN-defined unfavorable intermediate risk category, which would warrant short course ADT, which include 6 months of Lupron in conjunction with definitive RT.

• Unfavorable intermediate risk prostate cancer calls for initial staging scans such as CT and bone scan or a PSMA PET—however, for unfavorable intermediate risk disease, this is unlikely to upstage and change management.

• In unfavorable intermediate prostate cancer, target volume would include adding the proximal 1 cm of the seminal vesicles in the CTV.

• Any PSA >20 can upstage to high risk. Other high-risk features include cT3a (which is disease leaving the prostate through EPE or SVI), and grade group 4 or 5 disease (which is GS 8 or 9).

• With high-risk disease, staging imaging is warranted.

• PSMA PET is far more sensitive than conventional imaging, however, it is unknown if upstaging from scan findings, such as newly detected nodal disease, that wouldn’t have been detected on CT otherwise would warrant a change in management. Furthermore, since staging and prognostication was developed in an era without PSMA availability, it is unknown if upstaging by PSMA PET translates into a change in prognosis.

• For high risk disease, treatment options include RALP or definitive RT with long course ADT.

• For high risk disease, definitive RT includes fractionated EBRT to 46 Gy to the prostate/SV and pelvic LN followed by a HDR brachy boost (single implant, 15 Gy).

• Pelvic lymph node volumes begin at the L4 and L5 spine levels, including the external and internal iliac, presacral, and obturator LNs.

• Alternatively, SBRT to the prostate and LN is also an option with long term ADT—40 Gy in 5 fx to the prostate/SV and 25 Gy in 5 fx to the pelvic LNs.

• Recommend for 1-3 years of combined ADT with a GnRH agonist such as lupron and a non-steroidal antiandrogen like Bicalutamide-- to start at the same time of RT, and then continue adjuvantly.

• An alternative ADT approach is use of a GnRH antagonist, such as relugolix—these are often associated with a quicker onset of testosterone suppression and fewer cardiovascular risks.

• Observation is appropriate for high risk disease if life expectancy is <5 years.

• For any patient with node positive prostate cancer, treatment of choice would include definitive RT rather than RALP + PLND, targeting the prostate/SV to 60 Gy in 20 fx and elective LN to 46 Gy in 20 fx with SIB to 54 Gy to gross nodes. Importantly, for regional N1 disease, patients should receive at least 2 years of advanced ADT with abiraterone + prednisone.

• Common side effects of ADT include fatigue, weight gain, hot flashes, decreased libido and impotence. In the long term, monitor for depression and bone health since osteoporosis can develop. ADT may also confer in cardiotoxicity so be mindful in patients with pre-existing cardiac co-morbidities.

• For follow up, check PSA q6 months at first. If the PSA starts to rise after being on surveillance, disease recurrence concerns heighten once the PSA surpasses nadir +2 (known as the Phoenix Definition for biochemical recurrence). Recommend to obtain restaging imaging at that point.

• With ultrasensitive PSMA PET scan, if the PSA rises to >0.2, consider obtaining a PSMA PET to evaluate for recurrent disease, or any restaging scan if there are signs or concerns for clinical recurrence.

Acknowledgements

Thank you to Dr. Amar Kishan.

https://www.uclahealth.org/providers/amar-kishan

Abbreviations

AS – Active Surveillance

BPH – Benign Prostatic Hyperplasia

CTV – Clinical Tumor Volume

DRE – Digital rectal examination

EBRT – External Beam Radiation Therapy

EPE – Extra-Prostatic extension

H&P – History and Physical

HDR – High Dose Rate

IPSS - International Prostate Symptom Score

LDR – Low Dose Rate

LUTS - Lower urinary tract symptoms

MRI – Magnetic Resonance Imaging

NCCN – National Comprehensive Cancer Network

OAR – Organ at Risk

PSA – Prostate Specific Antigen

PTV – Planning Tumor Volume

RALP – Robotic-Assisted Laparoscopic Prostatectomy

ROS – Review of Systems

RT – Radiation Therapy

SBRT – Stereotactic Body Radiation Therapy

SHIM – Sexual Health Inventory for Men

SVI – Seminal Vesicle Invasion

TRUS – Trans-Rectal Ultrasound

TURP – Trans-Urethral Resection of the Prostate

Staging

https://www.ncbi.nlm.nih.gov/books/NBK279042/table/prostate-cancer-det.primarytum/

Gleason Scoring

https://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/grading.html

NCCN Risk Categories

https://www.uptodate.com/contents/image?imageKey=ONC%2F118962

Anatomy

https://training.seer.cancer.gov/prostate/anatomy/

Highlights

• For men 55-69, the American Urology Association is currently suggesting PSA q1-2 years if life expectancy is >10 years.

• Benign causes of high PSA: Prostatitis, urinary retention, BPH, ejaculation, recent trauma to the prostate such as DRE, TRUS biopsy and TURP.

• 5-alpha reductase inhibitors, most commonly finasteride, can artificially lower the PSA. So if your patient is on a 5-alpha reductase inhibitor, to account for these effects, multiply the PSA level by 2 to normalize the PSA values.

• RT simulation: Supine with a full (but comfortable) bladder and empty rectum. Employ intraprostatic fiducial markers placed prior to the sim scan to aid with image-guidance.

• SBRT—36.25 Gy in 5 fx to the PTV and 40 Gy in 5 fractions to the CTV—delivered every other day. The CTV would include the prostate alone and PTV expansions would be anisotropic with a 3 mm posterior expansion and 5 mm in all other planes.

• Other dosing regimens include 70 Gy/28 fractions and 60 Gy/20 fractopms

• Brachytherapy, either LDR or HDR monotherapy are treatment options as well.

• No ADT is indicated for low risk disease.

• With SBRT, for rectum/bladder, ensure D50% <18-20 Gy and Dmax<42 Gy

• For the rectum, ensure less than half of the rectum is receiving 24 Gy and V38 < 2cc.

• For the urethra, ensure the Dmax is <42 Gy. 

• Common acute side effects of RT include urgency, frequency, dysuria, and loose stools. For late side effects, monitor for cystitis, proctitis and sexual dysfunction.

• With favorable intermediate risk disease, staging scans are not necessary (this should only be considered starting with unfavorable intermediate disease). The RT plan would remain the same.

Acknowledgements

Thank you to Dr. Amar Kishan.

https://www.uclahealth.org/providers/amar-kishan