Episodes

Episodes List

Episode 11 - Cervical Cancer

Episode 11 Show Notes

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

Episode 10 - Endometrial Cancer

Episode 10 Show Notes

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

Episode 9 - Extremity Sarcoma

Episode 9 Show Notes

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

Episode 8 - Retroperitoneal Sarcoma

Episode 8 Show Notes

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

Episode 7 - Locally Advanced Breast Cancer 2

Episode 7 Show Notes

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

Episode 6 - Locally Advanced Breast Cancer

Episode 6 Show Notes

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

Episode 5 - Early Stage Breast Cancer

Episode 5 Show Notes

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

Episode 4 - Early Stage Lung Cancer

Episode 4 Show Notes

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

Episode 3 - Locally Advanced Lung Cancer

Episode 3 Show Notes

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

Episode 2 - Intermediate Risk Prostate Cancer

Episode 2 Show Notes

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

Episode 1 - Low Risk Prostate Cancer

Episode 1 Show Notes

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

Disclaimer: The information provided in this podcast and all associated content is for educational and entertainment purposes only and should not be used for diagnosing or treating a health problem or disease. Those seeking personal medical advice should consult with their licensed physician(s) . Please consult a medical professional or healthcare provider if you are seeking medical advice, diagnoses, or treatment. These scenarios also do not represent real oral boards cases.