National Comprehensive Cancer Network Criteria Research Articles

Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among high risk breast Cancer patients: a retrospective chart review study

BackgroundTesting for BRCA variants can impact treatment decisions for breast cancer patients and affect surveillance and prevention strategies for both patients and their relatives. National Comprehensive Cancer Network (NCCN) guidelines recommend testing for patients at heightened risk of BRCA pathogenic variant. We examined the BRCA testing rate among high risk breast cancer patients treated in community oncology practices.MethodsWe conducted a retrospective medical chart review among community-based US oncologists using a physician panel approach. High risk breast cancer patients with a known family history of cancer and diagnosis with breast cancer at age ≥ 18 years between January 2013–October 2017 were included. We assessed the proportions of patients tested for BRCA variants in accordance with NCCN guidelines.ResultsCharts from 63 physicians, averaging 16 years of practice, were included; 97% were medical oncologists and 66.7% had a genetic counselor in their practice. We analyzed data for 410 randomly-selected patients with mean age of 52 years; 95% were female, 74% were White, and 19% had Ashkenazi Jewish ancestry. Among all patients, 94% were tested for BRCA variants. The testing rate ranged from 78 to 100% in various high risk groups; lower rates were observed among Black patients (91%), men (92%), and patients meeting NCCN criteria based on family history of male breast cancer (78%) and prostate cancer (87%). We observed a higher testing rate in patients treated by physicians with a genetic counselor in their practice (95% versus 91%).ConclusionsAdherence to NCCN BRCA testing guidelines is high in this group of predominantly medical oncologists with extensive experience, with a high proportion having a genetic counselor in practice. Testing rates can be improved in patients with risk factors related to male relatives. High level of compliance to guidelines in a community setting is possible with a delivery model for genetic counseling and testing.

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

Points to consider: is there evidence to support BRCA1/2 and other inherited breast cancer genetic testing for all breast cancer patients? A statement of the American College of Medical Genetics and Genomics (ACMG)

Racial disparities in breast cancer hereditary risk assessment referrals.

For poorly understood reasons, Black non-Hispanic (BNH) women meeting National Comprehensive Cancer Network (NCCN) criteria for genetic testing for breast cancer risk are less likely than White non-Hispanic (WNH) women to undergo testing (Armstrong, Micco, Carney, Stopfer, & Putt, JAMA, 293, 1729 and 2005). We compared physician referral rates and uptake for genetic testing of BNH and WNH women meeting select NCCN criteria (breast cancer under age 50, two primary breast cancers, triple-negative disease under age 60) in the Cancer Center at George Washington University (GWCC) between 2015 and 2018. Of the 723 BNH and WNH patients treated for breast cancer at GWCC, 28% met study criteria for genetic counseling referral (n=252; BNH n=115, WNH n=137). Physician referral rates to genetic counseling differed significantly by race (BNH 75.7%, n=87 and WNH 92.7%; n=127; χ2 =14.19, p-value<.01). Once referred, though, there was no significant difference in uptake of genetic counseling by race (BNH 95.4%, n=83; WNH 97.6%, n=124, χ2 =1.33, p-value=.25) for patients appropriately referred.

Performance of prostate multiparametric MRI for prediction of prostate cancer extra-prostatic extension according to NCCN risk categories: implication for surgical planning.

Prediction of extra-prostatic extension (EPE) in men undergoing radical prostatectomy (RP) is of utmost importance. Great variability in the performance of multiparametric magnetic resonance imaging (mpMRI) has been reported for prediction of EPE. The present study aimed to determine the diagnostic performance of mpMRI for predicting EPE in different National Comprehensive Cancer Network (NCCN) risk categories. Overall 664 patients who underwent radical prostatectomy with a staging mpMRI were enrolled in this single-center, retrospective study. Patients with mpMRI report non-compliant with PI-RADSv2.0, were excluded. Patients were stratified according to NCCN criteria: very low/low (VLR-LR) to High Risk (HR) in order to assess final pathology EPE rates (focal and established). Sensitivity, specificity, positive and negative predictive values of staging mpMRI were computed in each group. Univariable and multivariable analysis were used to evaluate predictors of positive surgical margins. Pathological evaluation demonstrated established and focal EPE in 60 (9%) and 106 (16%) patients, respectively, while mpMRI suspicion for EPE was present in 180 (27%) patients. Age, preoperative PSA, PSA density, number of positive cores, NCCN groups, prostate volume, mpMRI suspicion for EPE, PIRADSv2.0 and lesion size differed significantly between the patients with any EPE and without EPE (all P≤0.05). The sensitivity of mpMRI in detecting any EPE varied from 12% (95% CI: 0.6-53%) in VLR-LR to 83% (66-93%) in HR while the corresponding values for the specificity were 92% (85-96%) and 63% (45-78%), respectively. Patients with false-negative mpMRI EPE prediction were more likely to have positive surgical margins in univariable (OR: 2.14; CI: 1.18, 3.87) as well as multivariable analysis adjusting for NCCN risk categories (OR: 1.97; CI: 1.08, 3.60). The performance of mpMRI for prediction of EPE varies greatly between different NCCN risk categories with a low positive predicting value in patients at low to favorable intermediate risk and a low negative predictive value in patients at Unfavorable intermediate to high risk PCa. Given that mpMRI EPE misdiagnosis could have a negative impact on oncological and functional outcomes, NCCN risk categories should be considered when interpreting mpMRI findings in PCa patients.

Adherence to the National Comprehensive Cancer Network Criteria of Complete Circumferential Peripheral and Deep Margin Assessment in Treatment of High-Risk Basal and Squamous Cell Carcinoma.

The National Comprehensive Cancer Network (NCCN) has established guidelines for the treatment of keratinocyte carcinomas (KCs). Complete circumferential peripheral and deep margin assessment (CCPDMA) is recommended for "high-risk" tumors that cannot be closed primarily. If flap or grafts are needed and CCPDMA was not used, it is recommended that reconstruction be delayed until achieving clear margins. To measure provider utilization rates of the NCCN guidelines for high-risk KCs and assess barriers that are limiting adherence. A ten-item questionnaire was distributed to NCCN nonmelanoma skin cancer panel members and physicians participating in KC treatment at academic institutions. Response rate was 49% (57/116). Responses were categorized by practice area: Mohs surgery, pathology, and other specialties: General Dermatology, Otolaryngology, Plastic Surgery, Surgical Oncology, Radiation Oncology, and Oral and Maxillofacial Surgery. Mohs surgeons were most likely to use CCPDMA for tumors meeting NCCN criteria with 14/15 using this technique in a majority of their cases, versus 2/6 pathologists and 10/16 specialists from other fields. Reasons cited for not using CCPDMA included deference to pathologists to determine the appropriate method for margin assessment and logistical difficulty. Further efforts are needed to increase adherence to NCCN's guidelines regarding CCPDMA in KCs.

Genetic risk assessment for hereditary RCC: Report from the consensus panel meeting.

615 Background: While many genes are now known to be associated with hereditary kidney cancer syndromes, there is a paucity of guidelines or uniform consensus on genetic testing for these patients. An expert panel was organized to assess who, what, when and how patients should be evaluated and what testing should be initiated. Methods: A national, multidisciplinary, panel of experts in urology, medical oncology, clinical geneticists, genetic counselors and patient advocates with background and knowledge in hereditary syndromic kidney cancer convened in person in September 2019. A renal cell carcinoma (RCC) genetic risk assessment questionnaire consisting of 52 questions was compiled prior to the meeting using modified Delphi methodology. The questions were then discussed and reviewed with uniform consensus defined as a minimum of 85% agreement in accordance with the National Comprehensive Cancer Network criteria. Results: The panel consisted of twenty-six attendees represented by urologists (43%), medical oncologist (23%), genetic counselors (13%), clinical geneticists (7%), and patient advocates (3%). The questionnaire consisted of fifty-five statements focusing on who, what, when and how genetic testing should be performed in a patient suspected of hereditary RCC syndrome. A &gt;85% agreement was reached on 30/52 statements with 18/25 (72%) achieving consensus addressing “who”, 2/6 (33%) achieving consensus in “what’ category, 2/7 (29%) in ‘when’ and 4/6 (67%) on how. The questions with least consensus were found in the “what/when?” category with only 4/13 questions with minimum 85% agreement. Specific areas of debate included an age cutoff for prompting a genetic risk assessment as well as need for familial testing in patients with variants of unknown significance. Conclusions: Despite experience of the panel in management of hereditary RCC, the consensus was reached only on 66% of genetic testing. While many issues will need to be discussed further, those statements with consensus may be used to guide physicians and patients on who, what, when and how genetic RCC risk assessment should be performed.

Abstract P6-08-01: Comparison of recommendations for germline genetic testing in an unselected cohort of patients with breast cancer

Abstract Purpose: To determine the sensitivity of germline hereditary cancer genetic testing recommendations for detection of pathogenic mutations in breast cancer predisposition genes in an unselected cohort of breast cancer patients. Patients and Methods: The study population included patients enrolled in a prospective breast cancer registry after being seen at Mayo Clinic for newly diagnosed breast cancer between 2004 and 2016. All patients were subjected to germline mutation testing for 12 known breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D and TP53). Results from testing of all breast cancer patients according to American Society of Breast Surgeons (ASBrS) genetic testing recommendations and patients meeting National Comprehensive Cancer Network (NCCN) criteria for BRCA1/2 testing, based on age at diagnosis and personal and family history of cancer, were compared. Results: Among the 4516 patients in the cohort, the median age at diagnosis of breast cancer was 57 years, 80.5% had estrogen receptor positive tumors, and 43% had a family history of breast cancer. All patients in the cohort met ASBrS criteria for hereditary cancergenetic testing, 2050 (45.4%) met NCCN criteria, 1892 (41.9%) did not meet NCCN criteria, and 574 (12.7%) patients could not be fully evaluated for NCCN testing criteria due to missing data. The frequencies of pathogenic variants in the cohort are shown in Table 1. Patients meeting NCCN criteria were more likely to carry a pathogenic variant compared to those who did not (9.8% vs. 3.8%, p&amp;lt;0.001, Table 1). However, 72 (26.5%) out of the 272 patients with mutations in 12 breast cancer predisposition genes and 15 (12.4%) out of 121 with mutations in BRCA1/2 were overlooked when NCCN selection criteria alone were applied. When testing was expanded to include all patients with breast cancer diagnosed at age ≤65 and/or meeting NCCN testing criteria, only 20 (7.4%) out of 272 mutation carriers in 12 breast cancer genes and 2 (1.6%) out of 121 BRCA1/2 mutation carriers were overlooked. However, this increased the number tested to detect one mutation carrier on average from 17 to 25 for BRCA1/2 and from 9 to 12 for the 12 breast cancer predisposition genes. In total, this age cutoff led to an increase in the number of patients tested by 28% while the number of patients in the cohort that need not undergo germline genetic testing was 20%. Conclusions: Although NCCN criteria for BRCA1/2 germline genetic testing detect the majority of predisposition gene mutation carriers, a significant number of carriers are missed in an unselected cohort of breast cancer patients using these criteria. Expanding the current NCCN criteria to include all women with breast cancer diagnosed ≤ 65 years of age, will substantially improve the sensitivity of mutation testing, without the need for evaluation of all breast cancer patients. Table 1: Comparison of frequency of germline mutations between patients who met and did not meet NCCN guidelines for germline genetic testing#Total, Meets ASBrS guidelines N=3942Meets NCCN guidelines, N=2050Did not meet NCCN guidelines, N=1892P-value€ NCCN vs non-NCCNPercent mutation carriers missed by NCCN criteria* BRCA1/2121 (3.1%)106 (5.2%)15 (0.8%)&amp;lt;0.00112.4%6 High risk genes$150 (3.8%)120 (5.8%)30 (1.6%)&amp;lt;0.00120.0%12 Breast cancer genes:272 (6.9%)200 (9.8%)72 (3.8%)&amp;lt;0.00126.5%ATM45 (1.1%)32 (1.56%)13 (0.69%)28.9%BARD16 (0.2%)5 (0.24%)1 (0.05%)16.7%BRCA158 (1.5%)53 (2.59%)5 (0.26%)8.6%BRCA263 (1.6%)53 (2.59%)10 (0.53%)15.9%CDH16 (0.2%)3 (0.15%)3 (0.16%)50.0%CHEK267 (1.7%)41 (2.00%)26 (1.36%)38.8%NF10 (0.0%)0 (0.00%)0 (0.00%)0.0%PALB216 (0.4%)7 (0.34%)9 (0.48%)56.3%PTEN1 (0.0%)1 (0.05%)0 (0.00%)0.0%RAD51C6 (0.2%)6 (0.29%)0 (0.00%)0.0%RAD51D4 (0.1%)2 (0.10%)2 (0.11%)50.0%TP537 (0.2%)3 (0.15%)4 (0.21%)57.1%#: Patients who did not meet NCCN criteria excluded from analysis$: BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53;€: Fisher exact test comparing frequency of germline mutations between those who met NCCN guidelines and those who did not;*: Denominators for percentages are the total mutation carriers in respective categories. Citation Format: Siddhartha Yadav, Chunling Hu, Steven N. Hart, Nicholas Boddicker, Eric C. Polley, Jie Na, Rohan Gnanaolivu, Kun Y. Lee, Janet E. Olson, Kathryn J. Ruddy, Fergus J. Couch. Comparison of recommendations for germline genetic testing in an unselected cohort of patients with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-01.

Abstract P6-08-39: Hereditary cancer risk assessment using a chatbot in women presenting to obstetrics and gynecology practices across the U.S.

Abstract Background: Hereditary cancer risk assessment is standard of care in the obstetrics and gynecology (ob/gyn) practice. Historical data indicates 1 in 12 individuals have a family history consistent with hereditary cancer(1), however recent data from a small community practice found that 1 in 4 women met National Comprehensive Cancer Network (NCCN) criteria for genetic testing(2). The aim of this study was to assess the number of women who meet NCCN criteria for genetic testing in a diverse population across the United States (US) by using a computer program that conducts conversations with patients (a.k.a. chatbot) for risk assessment(3). Method: We partnered with Clear Genetics Inc. (San Francisco, CA) to use a HIPAA compliant chatbot for collecting personal and family history of cancer from women in 28 ob/gyn practices across the US. Patients received a text message or email asking them to complete the chatbot five days before their scheduled appointment. Reminders were sent at three days and again one day prior if not completed. After history collection was complete, an algorithm determined if the patient had a known familial variant or met NCCN guidelines for hereditary cancer testing, including BRCA-Related Breast and/or Ovarian Cancer, Lynch, and Polyposis syndromes(3). Incomplete chats, minors under age 18 or those who declined to provide information were excluded. Additionally, some ob/gyn practices elected to exclude pregnant patients. Results: Over 15,000 chatbots were sent to patients. Overall, 65% of patients completed the chatbot and 26% of these patients met NCCN criteria or had a known familial variant(3). 14.5% of completed assessments were excluded (1.2% declined, 1.4% minors and 11.9% pregnant patients). Some patients received the chatbot less than five days before their appointment due to administrative delays at the ob/gyn practice, and 15% of intended recipients did not receive the chatbot due to incorrect contact information. Patients reviewed their experience with an average rating of 4.6 out of 5. Conclusions: A novel chatbot tool was used to collect pertinent cancer history and provide NCCN criteria assessment to identify patients for inherited cancer risk. This study population was nearly four times the size of the most recent study identifying 1 in 4 women met NCCN criteria for genetic testing. In addition, this study was more diverse - examining multiple ob/gyn practices across the US compared to a single community practice. Results of this study were consistent with newly reported data indicating 1 in 4 patients meet NCCN criteria for hereditary cancer testing. There is a need for increased education and tools to help ob/gyn practices identify these patients consistent with ACOG Practice Guideline 634(4), in light of a higher number of patients who need genetic testing.

Abstract P6-08-14: Assessing the effectiveness of the NCCN genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations

Abstract Purpose: Approximately 10% of breast cancers are hereditary. Identifying women at high risk for hereditary breast and ovarian cancer allows for early detection, prevention, and individualized disease management for those diagnosed with breast cancer. There is limited data about breast cancer genetic risks among African Americans (AA) as the majority of the large studies have been conducted in European Americans. We examined the distribution of deleterious genetic mutations in AA breast cancer patients, and evaluated the effectiveness of the National Comprehensive Cancer Network (NCCN) guidelines for identifying AA women at high risk for deleterious genetic mutations. Methods: AA participants with breast cancer underwent an interview regarding health and family history, and a 30-gene saliva test. Medical records were accessed to determine whether participants had received prior genetic testing as part of usual care, results of previous testing, and cancer characteristics. Results: Two hundred and fifty participants were enrolled between February 2016 and May 2018. Twenty (8.0%) had a deleterious mutation in one of the 30 genes; BRCA2 had the highest frequency (40.0%). 187 (74.8%) met eligibility for testing based on NCCN guidelines. Only 110 (58.8%) of participants eligible for genetic testing, according to guidelines, had received prior testing as part of routine care. Using the 30-gene test, we identified deleterious mutations in 17 of 187 (9.1%) of those who met NCCN criteria for testing, and three of 63 (4.8%) of those who did not meet criteria for testing nonetheless had a deleterious mutation associated with breast cancer. Conclusions: Our results indicate that a large proportion of African American breast cancer patients who meet criteria for genetic testing do not receive it as part of routine care. Even in women who do not meet testing guidelines, nearly 5% have a known deleterious mutation associated with breast cancer. Citation Format: Foluso O Ademuyiwa, Patricia Salyer, Yinjiao Ma, Sherri Fisher, Graham Colditz, Katherine Weilbaecher, Laura J Bierut. Assessing the effectiveness of the NCCN genetic testing guidelines in identifying African American breast cancer patients with deleterious genetic mutations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-08-14.

Abstract P5-08-03: Creation of a high volume, proactive high-risk breast cancer prevention program

Abstract Introduction: Approximately one out of eight women get breast cancer in their lifetime, and the National Cancer Institute estimates 268,600 new diagnoses in 2019. About 5-10% of breast cancers can be attributed to a genetic predisposition. Identifying women with genetic predispositions is significant because they qualify for more intense breast cancer screening or risk reducing strategies. Unfortunately, genetic testing is often not offered until cancer is diagnosed. This traditional genetic testing model is reactive rather than proactive, and it fails to identify a large proportion of unaffected genetic mutation carriers in the United States. Purpose: Our goal was to create a proactive system for identifying women at high risk for breast cancer. We integrated an online family history software, Progeny, into our mammography center to screen unaffected women for high-risk status (Tyrer-Cuzick (TC) score ≥ 20%) and National Comprehensive Cancer Network (NCCN) genetic testing criteria. Methods: Patients undergoing breast imaging were given a computer tablet with a preprogrammed Progeny questionnaire. Progeny collects the patient’s gynecological and family history, calculates a TC risk score, and assesses NCCN genetic testing criteria. Progeny was integrated into the mammography center on 1/10/2019 and this preliminary data was collected through 6/6/2019. Summary statistics were tabulated. Results: A total of 3,129 patients were invited to complete the questionnaire. 2,474 (79.1%) completed the questionnaire and 540 (21.8%) met NCCN genetic testing criteria. The average age of those meeting NCCN criteria was 60.3 years (range: 21-94). Of the patients who completed the questionnaire, 148 (6.0%) patients were found to be high-risk due to a TC score ≥20%. Clinical Impact: We found 540 patients who qualified for genetic counseling/testing. Under the previous, reactive genetic testing model, most of these patients would not have been selected for testing unless they received a cancer diagnosis. We recommended pretest genetic counseling to all these high-risk patients. Typical oncology genetic counselors see 10.2 new patients a week and our clinic can see 15 new patients per week. It would take 36 weeks with our current clinic system for all the patients identified during the initial questionnaire trial period to see a genetic counselor for pretest counseling. This demand alone would require two full time genetic counselors to accommodate. Conclusion: Our initial experience integrating a genetic screening questionnaire into our mammography center shows that 22% of patients need genetic testing and 6% need follow-up in a high-risk breast cancer clinic. Given current staffing constraints, it would take about 9 months to genetic test and counsel the patients identified after just 6 months of screening. This estimate does not include the demand placed on genetic counselors from current referral sources, so actual wait times could be longer than 9 months. This long wait time could increase anxiety for patients and dissatisfaction for patients and providers. A new approach to offering genetic testing and counseling to these patients is needed. Future Directions: In response to this increased clinical demand, we are partnering with Progeny and Ambry Genetics to create a novel program that allows patients to receive preliminary genetic education by video and genetic testing the same day as their mammogram appointment. Ultimately, the hope is that this new, high volume, proactive high-risk prevention program will allow a larger proportion of women with a genetic predisposition to receive diagnoses of their mutations and to initiate risk reducing and life-saving treatments. With this partnership, we will better accommodate the increased patient demand for genetic testing and avoid long wait times for counseling. Citation Format: Rebecca C Luiten, Vilert A Loving, Jennifer Siettmann, Beverly Reyes, Lida A Mina. Creation of a high volume, proactive high-risk breast cancer prevention program [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-03.

The Role of Radiological Parameters in Assessing Response to Neoadjuvant Therapy in Borderline Resectable Pancreatic Cancer

Background: Surgery in pancreatic cancer remains the curative option, consequently drawing attention to the importance of an indeterminate group of patients potentially curable by undergoing this procedure, Borderline Resectable Pancreatic Cancer (BRPC). Despite this seemingly positive outlook the outcome of these patients remains undefined. Aim: To assess the response of BRPC patients to neoadjuvant treatment and the accuracy of radiological constraints in their selection. Methods: Data extraction from a university hospital filing system from September 2015 to September 2018 was performed to select patients with BRPC. The National Comprehensive Cancer Network (NCCN) criteria to define BRPC were used. Clinical, surgical and radiological parameters were collected pre/ post-operative for all cases and correlated to outcome. Results: Sixty patients with BRPC were identified. The outcome of neoadjuvant treatment was partial response in 6 (10%) patients, stable disease in 49 (81.7%) and progressive disease in 5 (8.3%). The majority (78.3%) of patients underwent pancreatectomy. In patients who underwent resection a median overall survival of 31 months (95% CI: 29.180 - 32.820) was achieved vs. 17 months (95% CI: 15.625 - 18.375) in non-resected cases (p < 0.001). Response to neoadjuvant therapy was found to be favorable for overall survival (p = 0.014) and progression-free survival (p = 0.006). Response Evaluation Criteria in Solid Tumors (RECIST) criteria did not predict operative potential. Conclusion: RECIST criteria lacked predictive potentiality for surgical intervention after neoadjuvant chemotherapy in a cohort of BRPC patients. The significant positive outcome observed in BRPC patients who underwent surgery emphasizes that the decision for this procedure should not depend on the response to neoadjuvant treatment per se.

Prospective Evaluation of Universal BRCA Testing for Women With Triple-Negative Breast Cancer.

BackgroundLimited published literature exists on women with triple-negative breast cancer (TNBC) diagnosed over the age of 60 years with breast cancer gene (BRCA) pathogenic variants. Our study determined whether the rate of BRCA pathogenic variants in a prospective cohort of TNBC patients outside the definition of current clinical genetic testing (GT) guidelines warrants a change in recommendations.MethodsA prospective study of 395 women with TNBC underwent genetic counseling and 380 (96.2%) underwent clinical BRCA GT regardless of age of diagnosis beginning January 2014 to October 2015 at The University of Texas MD Anderson Cancer Center, Houston. TNBC patients older than 60 years who did not meet clinical GT guidelines had comprehensive sequencing and large rearrangement GT as part of the research protocol.ResultsFifty-one of 380 (13.4%) women with TNBC who underwent clinical BRCA GT were BRCA positive. Of the 86 patients diagnosed at age over 60 years and underwent GT, only two (2.3%) were positive for BRCA. These two patients would have met clinical testing criteria due to family or ancestral history.ConclusionsOur study does not support universal BRCA testing for TNBC patients diagnosed older than 60 years as their only risk factor for a BRCA pathogenic variant. Both of the positive BRCA patients older than 60 years identified would have met current National Comprehensive Cancer Network criteria for testing. Therefore, our study demonstrates that the National Comprehensive Cancer Network guidelines provide sufficient criteria for identifying BRCA pathogenic variants in women with TNBC at 60 years or younger.

Low-risk prostate cancer in India: Is active surveillance a valid treatment option?

Introduction and Objective:Carcinoma prostate is considered highly aggressive in Asian countries such as India. This raises an argument whether active surveillance (AS) gives a false sense of security as opposed to upfront radical prostatectomy (RP) in Indian males with low-risk prostate cancer (PCa). We analyzed our prospectively maintained robot-assisted RP (RARP) database to address this question.Materials and Methods:Five hundred and sixty-seven men underwent RARP by a single surgical team from September 2013 to September 2019. Of these, 46 (8.1%) were low risk considering the National Comprehensive Cancer Network criteria. Gleason grade group and stage were compared before and after surgery to ascertain the incidence of upgrading and upstaging. Preoperative clinical and pathological characteristics were analyzed for association with the probability of upstaging and upgrading.Results:The mean age was 60.8 ± 6.8 years. Average prostate-specific antigen level was 6.7 ± 2.0 ng/mL. 40 (86.9%) patients had a T1 stage disease and 6 (13%) patients were clinically in T2a stage. A total of 25 (54.3%) cases were either upstaged or upgraded, 19 (41.3%) showed no change, and the remaining 2 (4.3%) had no malignancy on the final RP specimen. Upstaging occurred in 8 (17.4%) cases: 5 (10.9%) to pT3a and 3 (6.5%) to pT3b. Upgrading occurred in 23 (50%) cases: 19 (41.3%) to Grade 2; 3 (6.5%) to Grade 3; and 1 (2.2%) to Grade 4.Conclusions:There is a 50% likelihood of upstaging or upgrading in Indian males with low-risk PCa eligible for AS. Decision to proceed with AS should be taken carefully.

Gemcitabine/nab-paclitaxel with pamrevlumab: a novel drug combination and trial design for the treatment of locally advanced pancreatic cancer

PurposePancreatic ductal adenocarcinomas exhibit a high degree of desmoplasia due to extensive extracellular matrix deposition. Encasement of mesenteric vessels by stroma in locally advanced pancreatic cancer (LAPC) prevents surgical resection. This study sought to determine if the addition of a monoclonal antibody to connective tissue growth factor, pamrevlumab, to neoadjuvant chemotherapy would be safe and lead to improved resectability in this surgically adverse patient population.MethodsIn this phase I/II trial, 37 patients with LAPC were randomised 2:1 to gemcitabine/nab-paclitaxel plus (Arm A, n=24) or minus (Arm B, n=13) pamrevlumab. Those who completed six cycles of treatment were assessed for surgical eligibility by protocol-defined criteria. Resection rates, progression-free and overall survival were evaluated.ResultsEighteen (75%) patients in Arm A and seven (54%) in Arm B completed six cycles of therapy with similar toxicity patterns. In Arms A and B, carbohydrate antigen 19–9 response, as defined by ≥50% decline from baseline, occurred in 13 (65%) and 5 (42%), respectively. Sixteen (16%) per cent of patients were radiographically downstaged by National Comprehensive Cancer Network criteria (5 in Arm A (21%) and 1 (8%) in Arm B). Positron emission tomography normalised in 9 (38%) vs 3 (23%) of patients in Arm A vs Arm B, respectively, and correlated with surgical exploration. Eligibility for surgical exploration was 17 (71%) vs 2 (15%) (p=0.0019) and resection was achieved in 8 (33%) vs 1 (8%) of patients in Arm A vs Arm B (p=0.1193), respectively. Postoperative complication rates were not different between arms.ConclusionsNeoadjuvant chemotherapy with pamrevlumab holds promise for enhancing resection rates in patients with LAPC without added toxicity. This combination merits evaluation in a larger patient cohort.

Race is not prognostic in unfavorable prostate cancer: an NCDB analysis

Introduction: It is commonly held that race serves as a significant prognosticator in prostate cancer. We sought to analyze whether race impacted overall survival (OS) of men receiving standard of care treatment. Materials and Methods: All data was obtained from the NCDB (National Cancer Database) and initially contained 1,294,126 cases of prostate cancer diagnosed between 2004 and 2013. Patients were excluded if they had metastatic or nodal disease, received chemotherapy, or had noninvasive disease. Patients were grouped into 2 cohorts as per NCCN (National Comprehensive Cancer Network) criteria: favorable risk and unfavorable risk. All patients received risk-appropriate radiation therapy or surgery, and were subsequently analyzed. Black and white men were also matched 1:1 within each risk cohort using propensity scores, and multivariate analysis was conducted on these matched cohorts. Results: The final cohort 77,448 patients. Median follow-up 58.7 months (range, 48–143.5). In the favorable risk cohort, white men had superior OS compared with black men, 77.63% versus 80.57% at 10 years (hazard ratio, 0.644; 95% confidence interval, 0.536–0.773; P&lt;0.001). In the unfavorable cohort, race was not a significant prognostic factor for OS on unmatched analysis; 10-year survival 73.6% and 71.3% (hazard ratio, 0.941; 95% confidence interval, 0.848–1.044; P=0.249), and significant interaction existed with age. Results were unchanged in propensity score matched cohorts. Conclusion: The prognostic value of race-related biological differences of prostate cancer may hold less value in higher risk disease than is commonly believed.

Role of Intraoperative Clean Surgical Margin Determined With Lesion Size and Duration to Obtain Apropriate Histological Clean Surgical Margin in High-Risk Basal Cell Carcinoma Patients, According to National Comprehensive Cancer Network Criteria.

We aimed to elucidate the role of intraoperative clean surgical margin (iCSM) determined according to lesion size and duration to obtain appropriate histological clean surgical margin (hCSM) in high-risk basal cell carcinoma (BCC) patients evaluated according to National Comprehensive Cancer Network (NCCN) criteria considering the tumor size and/or location. The contribution of lesion area to determine iCSM was also evaluated. Patients with high-risk BCC requiring surgical management were included. iCSM, hCSM, and clinical variables including sec, age, longest edge, location and area, and follow-up duration were recorded. In total, 96 lesions were evaluated. Lesions were mostly located in the mask area and other face region (93.8%). Lesions located on the nose comprised 50%, 34.1%, and 26.3% in the BCC-5, BCC-7, and BCC-10 lesions, respectively. The hCSMs were positive in 11.5%, 9.1%, and 3.8% of the BCC-5, BCC-7, and BCC-10 lesions, respectively. The deep surgical margin was positive in 15.4%, 4.5%, and 7.7% of the BCC-5, BCC-7, and BCC-10 lesions, respectively. The calculated risk for the positive surgical margin if the BCC-10 lesions were done like the BCC-7 was 15.4%. No recurrence was during follow-up duration. As supported by the findings of the present study, to obtain an adequate hCSM in the high-risk BCC lesions, the iCSM determined according to NCCN recommendations may not be optimal. Nevertheless, after their categorization according to lesion size and disease duration for excision with 5-, 7-, and 10-mm iCSMs, it is possible to obtain a small but important improvement in the outcome of patients.

Pathological upgrading and upstaging at radical prostatectomy in Jamaican men with low-risk prostate cancer.

Several studies suggest race-based health disparities in men with low-risk prostate cancer (PCa), with African American males having poorer oncological outcomes. We sought to determine the prevalence and predictors of pathological upgrading and upstaging in Jamaican men with low-risk PCa treated with radical prostatectomy (RP). Data on 141 men who met the National Comprehensive Cancer Network criteria for low-risk PCa and underwent RP at a single institution were reviewed. All men had a transrectal ultrasound-guided biopsy. Pre-operative clinical and final pathological data were obtained. Data were summarised as means and standard deviations or percentages as appropriate. Bivariate analyses such as independent samples t-tests and chi-square tables were conducted and logistic regression models were estimated to predict upgrading (>Gleason 6) and upstaging (p ≥ T3).The mean age was 59.5 ± 7.8 years with mean prostate specific antigen (PSA) of 6.6 ± 2 ng/mL. A total of 48.3% of men were upgraded and 11.4% were upstaged. Bivariate analyses indicated that PSA (p = 0.008) and percentage positive cores (p = 0.002) were associated with upgrading. PSA (p = 0.042) and percentage positive cores (p = 0.003) were significantly associated with upstaging. The odds of upgrading increased with increased PSA levels (OR 1.40, 95% CI 1.05–1.87, p = 0.021) or increased percentage positive cores (OR 8.27, 95% CI 2.19–31.16, p = 0.002). The odds of upstaging increased with increased PSA levels (OR 1.4, 95% CI 1.01–1.96, p = 0.046) and with increased percentages positive cores (OR 11.4; 95% CI 2.06–63.09, p = 0.005). Jamaican men with low-risk PCa are at high risk of pathological upgrading and upstaging at RP. These findings should be taken into consideration when discussing treatment options with these patients.

302 Increasing Appropriate Referrals to Genetic Counseling at the Time of Endoscopy

INTRODUCTION: The ACG recommends an initial assessment of family history of cancer and premalignant conditions be performed for all patients evaluated in gastroenterology practices to develop a preliminary determination of risk of familial cancer predisposition. Due to the fast-paced nature of practice and a knowledge gap, providers often miss referring high-risk patients for genetic counseling. For example, less than 2% of the projected 830,000 Lynch syndrome patients in the US are aware of their mutation status. In this quality improvement project, we implemented a one-page, patient-administered survey to identify those at high risk of common hereditary cancer syndromes and facilitate appropriate referral to genetic counseling. METHODS: We created a four-question survey based on National Comprehensive Cancer Network (NCCN) guidelines for genetic testing for several hereditary cancer syndromes, including Lynch syndrome and Hereditary Breast and Ovarian Cancer syndrome. It was provided to all English-speaking patients presenting for outpatient endoscopy, who voluntarily completed the survey in the waiting area. Completed surveys were assessed for meeting criteria for referral for genetic testing. The survey was implemented on April 1, 2019, and we assessed its initial impact by comparing the number of positive surveys (i.e. meeting NCCN guidelines for referral to genetic counseling) over two months post-implementation (Apr-May 2019) with the number of genetic counseling referrals by gastroenterology providers at our institution over two months pre-implementation (Feb-Mar 2019). RESULTS: In February-March 2019, 13 genetic counseling referrals were made by gastroenterology providers at our institution. In April-May 2019, 874 surveys were completed. 330 surveys (37.8%) had responses meeting NCCN guidelines for referral for genetic counseling and a high risk of familial cancer predisposition. 481 (55%) did not meet criteria for high-risk family history, and 63 (7.2%) had indeterminate responses, requiring additional evaluation to determine risk. CONCLUSION: We created a simple, self-administered survey that identified a far larger number of endoscopy patients meeting NCCN criteria for genetic counseling referral than the number of referrals placed over a comparable timeframe prior to implementation. To address the large gap in appropriate genetic counseling referrals, we aim to create a sustainable workflow for referral from endoscopy, and plan to assess patient follow-through on these referrals.

Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing

BackgroundPersonal cancer diagnosis and family cancer history factor into which individuals should undergo genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome. Family history is often determined in the research setting through kindreds with disease clusters, or clinically from self‐report. The population prevalence of individuals with diagnostic characteristics and/or family cancer history meeting criteria for HBOC testing is unknown.MethodsUtilizing Surveillance, Epidemiology, and End Results (SEER) cancer registry data and a research resource linking registry records to genealogies, the Utah Population Database, the population‐based prevalence of diagnostic and family history characteristics meeting National Comprehensive Cancer Network (NCCN) criteria for HBOC testing was objectively assessed.ResultsAmong Utah residents with an incident breast cancer diagnosis 2010‐2015 and evaluable for family history, 21.6% met criteria for testing based on diagnostic characteristics, but the proportion increased to 62.9% when family history was evaluated. The proportion of cases meeting testing criteria at diagnosis was 94% for ovarian cancer, 23% for prostate cancer, and 51.1% for pancreatic cancer. Among an unaffected Utah population of approximately 1.7 million evaluable for family history, 197,601 or 11.6% met testing criteria based on family history.ConclusionsThis study quantifies the population‐based prevalence of HBOC criteria using objectively determined genealogy and cancer incidence data. Sporadic breast cancer likely represents a portion of the high prevalence of family cancer history seen in this study. These results underline the importance of establishing presence of a deleterious mutation in an affected family member, per NCCN guidelines, before testing unaffected relatives.

Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections

IntroductionBRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations. Patients and MethodsGreek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests. ResultsOf 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups. ConclusionsThese data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.