National Comprehensive Cancer Network Criteria Research Articles

MP54-12 IMPLEMENTATION AND OUTCOMES OF A UNIVERSAL GERMLINE SCREENING PROGRAM IN A COMMUNITY UROLOGY PRACTICE

You have accessJournal of UrologyCME1 Apr 2023MP54-12 IMPLEMENTATION AND OUTCOMES OF A UNIVERSAL GERMLINE SCREENING PROGRAM IN A COMMUNITY UROLOGY PRACTICE Neil Mendhiratta, Herman Hauver, Whitley Hatton, Andrew Ostrusky, Devika Sathe, Patricia Rice, Sandeep Gurram, and Heather Chalfin Neil MendhirattaNeil Mendhiratta More articles by this author , Herman HauverHerman Hauver More articles by this author , Whitley HattonWhitley Hatton More articles by this author , Andrew OstruskyAndrew Ostrusky More articles by this author , Devika SatheDevika Sathe More articles by this author , Patricia RicePatricia Rice More articles by this author , Sandeep GurramSandeep Gurram More articles by this author , and Heather ChalfinHeather Chalfin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003307.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The role of germline genetic testing in urologic oncology has expanded in recent years. However, implementation of genetic testing in community practices remains a challenge, often due to limited access to qualified genetics trained providers. In this study, we report outcomes of a universal germline screening program in a community urology practice. METHODS: Between August 1st, 2021 and September 19th, 2022, all patients referred for urology clinic visits at Frederick Health (Frederick, MD, USA) were provided an online genetics screening questionnaire prior to the visit. Responses were compared against National Comprehensive Cancer Network (NCCN) criteria for germline testing. Those who met criteria were provided educational materials at the end of the questionnaire, and then counselled by a trained urologic oncologist (HC) in the clinic or referred to a genetic counselor prior to testing. Testing was performed with a 36-gene pan-cancer panel (CancerNext) or a 14-gene targeted prostate cancer panel (ProstateNext), with or without additional RNA analysis (RNAinsight) (Ambry Genetics, CA, USA). Demographic and clinical parameters, as well as genetic testing results, were retrospectively collected under IRB approval. RESULTS: In the study period, 846 patients were seen over 1,580 clinic visits. Of these, 540 patients (63.8%) completed the screening questionnaire. The majority were completed via email (59.7%) with the remainder (40.3%) via text message. Of the patients who completed screening, 136/540 (25.2%) met NCCN criteria for germline testing. 49/136 patients (36%) who met criteria underwent germline testing, of whom 6/49 (12.2%) had distinct pathogenic mutations identified. These included actionable mutations in BRCA1 (c.4616dupT), BRCA1 (c.4964_4982del19), BRCA2 (p.D2723H; c.8167G>C), and CHEK2 (1100delC); additional pathogenic mutations were found in LZTR1 (c.774delT;p.F258Lfs*93) and NBN (p.S706,c.2117c>G). Variants of unknown significance were identified in 8/49 patients (16.3%) in 9 total genes. Challenges to implementation of this program included meeting institutional requirements for genetic testing consent, facilitating specimen collection in clinic, and integration of results into the electronic health record. CONCLUSIONS: Genetic risk assessment for high-risk individuals is feasible as part of a universal screening program in a community urology practice. Approximately 12% of tested patients were found to have pathogenic germline mutations, which is consistent with contemporary tertiary referral cohorts. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e758 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neil Mendhiratta More articles by this author Herman Hauver More articles by this author Whitley Hatton More articles by this author Andrew Ostrusky More articles by this author Devika Sathe More articles by this author Patricia Rice More articles by this author Sandeep Gurram More articles by this author Heather Chalfin More articles by this author Expand All Advertisement PDF downloadLoading ...

PD21-11 REAL WORLD IMPACT OF GERMLINE GENETIC TESTING ON CLINICAL DECISION MAKING FOR PROSTATE CANCER PATIENTS

PD21-11 REAL WORLD IMPACT OF GERMLINE GENETIC TESTING ON CLINICAL DECISION MAKING FOR PROSTATE CANCER PATIENTS

Access disparities and underutilization of germline genetic testing in Chilean breast cancer patients

Latin American reports on genetic cancer risk assessments are scarce. In Chile, current breast cancer (BC) guidelines do not define strategies for germline genetic testing. Our study sought to quantify the disparities in access to genetic testing in Chilean BC patients, according to international standards and their clinical characteristics to explore improvement strategies. Retrospective analysis of invasive BC databases including patients treated in a Public Hospital (PH) and in an Academic Private Center (AC) in Santiago, Chile between 2012 and 2021. Of 5438 BC patients, 3955 had enough data for National Comprehensive Cancer Network (NCCN) categorization. From these, 1911 (48.3%) fulfilled NCCN criteria for germline testing, of whom, 300 were tested for germline mutations and 268 with multigene panels. A total of 65 pathogenic variants were found in this subset. As expected, BRCA1/2 mutations were the most frequent (17.7%). Access to genetic testing was higher in AC versus PH (19.6% vs. 10.3%, p = 0.0001). Other variables associated with germline genetic testing were BC diagnosis after 2018, being 45years old or younger at diagnosis, BC family history (FH), FH of ovarian cancer, non-metastatic disease, and triple-negative subtype. In our cohort, 15% of BC patients who met NCCN criteria for germline testing were effectively tested. This percentage was evenlower at the PH. Current recommendations encourage universal genetic testing for BC patients; however, our findings suggest that Chile is far from reaching such a goal and national guidelines in this regard are urgently needed. To our knowledge, this is the first study of its kind in Chile and Latin America.

Assessment of a Peer Physician Coaching Partnership Between a Designated Cancer Center Genetics Service and a Community Cancer Network Hospital

Patients with cancer seen in rural and underserved areas disproportionately face barriers to access genetic services. Genetic testing is critical to inform treatment decisions, for early detection of another cancer, and to identify at-risk family members who may benefit from screening and prevention. To examine medical oncologists' genetic testing ordering trends for patients with cancer. This prospective quality improvement study was performed in 2 phases over 6 months between August 1, 2020, and January 31, 2021, at a community network hospital. Phase 1 focused on observation of clinic processes. Phase 2 incorporated peer coaching from cancer genetics experts for medical oncologists at the community network hospital. The follow-up period lasted 9 months. The number of genetic tests ordered was compared between phases. The study included 634 patients (mean [SD] age, 71.0 [10.8] years [range, 39-90 years]; 409 women [64.5%]; 585 White [92.3%]); 353 (55.7%) had breast cancer, 184 (29.0%) had prostate cancer, and 218 (34.4%) had a family history of cancer. Of the 634 patients with cancer, 29 of 415 (7.0%) received genetic testing in phase 1, and 25 of 219 (11.4%) received genetic testing in phase 2. Of the 29 patients who received testing in phase 1, 20 (69.0%) had germline genetic testing; 23 of 25 patients (92.0%) had germline genetic testing in phase 2. Uptake of germline genetic testing increased by 23.0% between phases, but the difference was not statistically significant (P = .06). Uptake of germline genetic testing was highest among patients with pancreatic cancer (4 of 19 [21.1%]) and ovarian cancer (6 of 35 [17.1%]); the National Comprehensive Cancer Network (NCCN) recommends offering genetic testing to all patients with pancreatic cancer and ovarian cancer. This study suggests that peer coaching from cancer genetics experts was associated with an increase in ordering of genetic testing by medical oncologists. Efforts made to (1) standardize gathering of personal and family history of cancer, (2) review biomarker data suggestive of a hereditary cancer syndrome, (3) facilitate ordering tumor and/or germline genetic testing every time NCCN criteria are met, (4) encourage data sharing between institutions, and (5) advocate for universal coverage for genetic testing may help realize the benefits associated with precision oncology for patients and their families seeking care at community cancer centers.

Abstract P6-02-12: Underutilization and disparities in germline genetic testing for breast cancer patients diagnosed in Chile

Abstract Introduction 10% of Breast Cancer (BC) cases are thought to carry a germline pathogenic variant (PV) in a susceptibility gene. Most clinicians utilize the National Comprehensive Cancer Network (NCCN) guidelines criteria to both identify these patients and, in those who test positive, to provide adequate follow-up and/or surgery recommendations. In Chile, BC Guidelines, established in 2004, defined treatment strategies for invasive BC (iBC) which significantly reduced mortality. However, these guidelines do not define strategies for germline genetic testing nor contemplate coverage for those who needs them. Thus, we face many obstacles to genetic testing implementation such as out-of-pocket cost and lack of genetic counsellors. The aim of the study is to determine how many BC Chilean patients are at risk according to international guidelines, how many are being tested and what are their clinical characteristics. Methods Retrospective analysis of a prospective database of iBC patients treated in a public hospital (PH) and in an Academic Private Centre (AC) in Santiago, Chile from January 2012 to March 2022. All patients who had enough information (age, family history (FH), BC subtype) for NCCN Version 2.2022 categorization were included. Patients whose only indication for germline testing was the potential use of PARP-inhibitors were excluded. Clinical characteristics were extracted from clinical charts. Results 4,365 iBC patients met criteria. 51.1% were treated in PH and 49.9% in a AC. 2,260 patients (51.8%) fulfilled NCCN criteria for germline testing, distributed unevenly between PH (46.0%) vs. AC (56.9%, p=0.0001). Compared to PH, patients in AC were diagnosed at younger age (54 vs 56 years, p=0.0001) and were more likely to report FH (69.4% vs. 53.7%, p=0.0001). No difference between BC subtypes was reported. Considering only those fulfilling criteria, germline genetic testing was performed in 326 patients (14.4%) with a significant difference according to UH vs AC (18.7% vs. 9.1%, p= 0.0001). 58% of these tests were performed in the last 3 years. Multivariate logistic regression showed that being diagnosed before 46 (HR=5.3, p=0.0001); FH (HR=2.2, p=0.0001); localized vs. metastatic disease (HR=3.7, p=0.001); triple negative (TN) BC (HR=1.8, p=0.0001) and being treated in AC (HR=1.9, p=0.0001) were independently associated with germline genetic testing being performed in patients fulfilling NCCN criteria. 82 PV were documented, being the most frequent BRCA1/2 (18.1%) followed by PALB2 (1.8%) and ATM (1.2%). Being diagnosed with TNBC (HR=3.8, p=0.0001) and having a first-degree relative with cancer (HR=4.4, p=0.0001) were the only factors associated with carrying a pathogenic BRCA1/2 mutation. Conclusion In Chile, less than 20% of iBC patients who meet NCCN criteria for germline testing are being tested. In this sample of our Public Health System, where over 80% of the Chilean population is treated, fewer than 1 in 10 individuals fulfilling criteria have undergone testing. New evidence suggests that probably a wider span than suggested by NCCN of patients should be counselled and tested, deepening even further the underutilization of germline testing in Chile. Lack of knowledge and training in oncology providers and out-of-pocket costs might influence these results. National guidelines are urgently needed. Citation Format: FRANCISCO ACEVED, Benjamin Walbaum, Lidia Medina, Tomas Merino, Paula Reyes, Militza Petric, Francisco Dominguez, Paulina Gonzalez, CÉSAR SÁNCHEZ. Underutilization and disparities in germline genetic testing for breast cancer patients diagnosed in Chile [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-12.

Abstract P5-03-19: Frequency of germline TP53 p.R337H variant among women at risk of hereditary breast cancer in a public health system of Central-West of Brazil

Abstract Background: Breast Cancer (BC) is one of the most common cancers diagnosed in Li-Fraumeni Syndrome (LFS). Most studies about the frequency of germline pathogenic variant (PV) TP53 p.R337H have been conducted in the South and Southeastern regions of Brazil reaching rates as high as 8% of detection. There is a lack of data on the frequency of this germline PV in other Brazilian regions, especially among patients without access to genetic tests. Objective: This study aims to evaluate the detection rate of TP53 p.R337H in patients (pts) at risk of hereditary breast cancer (HBC) and describe the clinical and demographic profile of the study cohort. Methodology: Hereditary cancer risk assessment based on the National Comprehensive Cancer Network Criteria (NCCN), version 1.2020, was performed in women with BC who were being followed in a public hospital (DF, Brazil) between January 2021 and January 2022. All pts eligible for germline genetic testing according to HBC NCCN criteria were referred for genetic counseling and genetic testing. For those patients who could not afford a comprehensive genetic test, a real time PCR test specifically searching for TP53 p.R337H variant was performed. In case of TP53 p.R337H detection in the proband, genetic counseling and familial variant testing were offered to family members. Results: Among 221 pts eligible for this study, 180 pts performed germline testing, including 100 pts tested only for the TP53 p.R337H variant (real-time PCR) and 80 pts performed out of pocket BC multigene panel testing (including TP53 sequencing). This cohort was mostly represented by pts from Central-West (47%) and Northeast (35%) regions of Brazil. The median age of BC diagnosis was 44 y.o. (18 - 78). Invasive ductal carcinoma represented 92% (n=203) of the tumors, 50% were ER/PR+ HER2-, 25% HER2 +, 25% ER/PR- HER2- (triple negative). Regarding stage at diagnosis, 59% (n=130) were stages IIB-IIIC and 13% IV. The detection rate of TP53 p.R337H was 1.1% (2/180). Among the pts who met the revised Chompret criteria for LFS, this frequency was 5% (2/40). One of them was diagnosed with a stage IIIB IDC ER/PR+HER2- at 28 y.o. and had no relevant family history of cancer. The other pt was diagnosed with a stage IV IDC ER/PR+HER2- at 44 y.o. and the family history revealed four sisters and one niece with BC, and one nephew with brain tumor at 4 y.o. The family members from these two families received genetic counseling and genetic testing. Cascade testing was able to identify 12 additional carriers. All carriers were referred for post-testing follow-up. Conclusion: According to these results, we expect to identify at least one p.R337H carrier in each 90 BC pts treated in the Federal’s District Public Health setting who fulfill HBC NCCN criteria. In a limited resources setting, in Brazil, testing the TP53 p.R337H variant with PCR is a low-cost test that should be considered at least for pts that meet the revised Chompret criteria. The overall detection rate of TP53 p.R337H carriers was lower in comparison to other Brazilian studies from the South/Southeast of the country. Both cases identified in this cohort had advanced local disease or metastatic disease at BC diagnosis, raising the concern about the importance of LFS diagnosis, and high-risk surveillance and risk reduction strategies in this subgroup of pts. Despite the low detection rate of TP53 p.R337H in this cohort, there was a high familial impact through cascade testing. Citation Format: Tatiana S. Correa, Renata L. Sandoval, Eduarda S. Oliveira, Ana Carolina R. Leite, Luiza Nardin Weis, Maria Isabel Achatz, Claudiner P. Oliveira, Paula Fontes Asprino, Romualdo Barroso-Sousa. Frequency of germline TP53 p.R337H variant among women at risk of hereditary breast cancer in a public health system of Central-West of Brazil [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-19.

Abstract P6-02-03: Breast Health Assessment: A family health history tool using the electronic health record and clinical decision support to facilitate guidelines-driven hereditary breast cancer genetic testing at the time of screening mammogram

Abstract Background: Genetic testing (GT) is recommended for women who have a personal or family history of breast cancer and are at increased risk of carrying an inherited breast cancer risk gene pathogenic variant (PV) as defined by the National Comprehensive Cancer Network (NCCN) guidelines. Data shows that traditional GT workflows do not reach a large proportion of women eligible for GT. NorthShore University HealthSystem previously implemented the Genetic Wellness Assessment, a family health history (FHH) screening tool utilizing the electronic health record (EHR) and clinical decision support, to identify individual and familial risks to health conditions and personalize screening and prevention practices in primary care. To increase access to hereditary breast cancer GT, we implemented a similar FHH screening tool called the Breast Health Assessment (BHA) for patients completing routine screening mammogram. We describe uptake and results from implementation of the BHA in conjunction with routine screening mammogram. Methods: Patients scheduled for screening mammogram were assigned the BHA prior to their mammogram via the EHR portal. BHA questions addressed personal and family history of breast cancer and other cancer types associated with hereditary breast cancer syndromes. Upon completion of the BHA, patients who screened positive, i.e. identified as having a high-risk personal or family cancer history based on NCCN guidelines, were offered a comprehensive hereditary cancer panel (HCP). HCP included 38 genes associated with common cancer types, including all high and moderate risk breast cancer genes for which there are NCCN management guidelines. Individuals who were not identified as high-risk were offered a genetic health screen, which consisted of 148 genes associated with common cancer types, genetic forms of heart disease, medication response, and other health conditions. Saliva sample collection for GT occurred at the time of the patient’s screening mammogram appointment. Results: From August 2021 through May 2022, 32,438 patients were assigned the BHA prior to screening mammogram. Of these patients, 14,128/32,438 (44%) completed the BHA questionnaire. Based on BHA reponse, 3,490/14,128 (25%) screened positive and met NCCN criteria for GT for hereditary breast cancer risk genes and 529/3,490 (15%) completed GT. Additionally, 713/10,638 (7%) patients who screened negative on the BHA completed testing. In total, 1,242/14,128 patients (9%) completed GT and 78/1,242 (6%) were found to carry an inherited PV in a cancer risk gene, 35 of which were in an NCCN guidelines breast cancer risk gene. Of the 78 patients with a positive GT result, 57/78 (73%) had not been previously recommended for a genetics evaluation and/or received a genetics referral. Conclusion: The BHA is a novel FHH tool which increases access to hereditary breast cancer GT at the time of screening mammogram. Nearly half of women who completed screening mammogram completed the BHA and learned valuable information about their breast cancer risk and were invited to complete GT. Genetic testing completed through the BHA identified 78 patients with an actionable inherited PV in a cancer risk gene. This invaluable information will lead to potentially lifesaving personalized cancer screening and risk reduction and help identify additional at risk family members. Notably, 73% of patients who carried an inherited PV had not been previously recommended by their medical teams for genetic counseling and/or testing. The BHA has the potential to help close the care gap in GT for women at increased risk of breast cancer. Citation Format: Allison DePersia, Sarah Choi, Katharine Yao, Henry Dunnenberger, Peter Hulick. Breast Health Assessment: A family health history tool using the electronic health record and clinical decision support to facilitate guidelines-driven hereditary breast cancer genetic testing at the time of screening mammogram [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-03.

The Michigan Genetic Hereditary Testing (MiGHT) study’s innovative approaches to promote uptake of clinical genetic testing among cancer patients: a study protocol for a 3-arm randomized controlled trial

BackgroundAlthough most cancers are sporadic, germline genetic variants are implicated in 5–10% of cancer cases. Clinical genetic testing identifies pathogenic germline genetic variants for hereditary cancers. The Michigan Genetic Hereditary Testing (MiGHT) study is a three-arm randomized clinical trial that aims to test the efficacy of two patient-level behavioral interventions on uptake of cancer genetic testing.MethodsThe two interventions being tested are (1) a virtual genetics navigator and (2) motivational interviewing by genetic health coaches. Eligible participants are adults with a diagnosis of breast, prostate, endometrial, ovarian, colorectal, or pancreatic cancer who meet the National Comprehensive Cancer Network (NCCN) criteria for genetic testing. Participants are recruited through community oncology practices affiliated with the Michigan Oncology Quality Consortium (MOQC) and have used the Family Health History Tool (FHHT) to determine testing eligibility. The recruitment goal is 759 participants, who will be randomized to usual care or to either the virtual genetics navigator or the motivational interviewing intervention arms. The primary outcome will be the proportion of individuals who complete germline genetic testing within 6 months.DiscussionThis study addresses patient-level factors which are associated with the uptake of genetic testing. The study will test two different intervention approaches, both of which can help address the shortage of genetic counselors and improve access to care.Trial registrationThis study has been approved by the Institutional Review Board of the University of Michigan Medical School (HUM00192898) and registered in ClinicalTrials.gov (NCT05162846).

Beyond BRCA: Patterns of risk-reducing surgery for non-BRCA, homologous recombination repair pathway gene variant carriers

ObjectiveThe real-world management of patients with non-BRCA, homologous recombination repair pathway variants with increased or uncertain risks of ovarian cancer is unknown. The objective was to determine the adoption of risk-reducing salpingo-oophorectomy (RRSO) for carriers of variants with increased or uncertain risks of ovarian cancer beyond BRCA. MethodsThis was a retrospective cohort study of patients at three hospitals with non-BRCA, homologous recombination repair pathway variants with increased risk (BRIP1, RAD51C, RAD51D) and uncertain risk (ATM, BARD1, NBN, PALB2) of ovarian cancer. Outcomes of interest were adoption of RRSO and factors associated with adoption of RRSO. Wilcoxon rank-sum, chi-square, and logistic regression were performed with p < 0.05. ResultsOf 318 patients, 76 (24%) had pathogenic variants with increased risks of ovarian cancer (BRIP1, 45; RAD51C, 20; RAD51D, 11), and 242 (76%) had variants with uncertain risks of ovarian cancer (ATM, 145; PALB2, 69; NBN, 23; BARD1, 5). Of 64 patients eligible for RRSO by National Comprehensive Cancer Network (NCCN) criteria or family history, 31 (48%) underwent RRSO. Among eligible patients who did not undergo RRSO, 24 (73%) were not referred for gynecologic oncology consultation. Older age at testing (adjusted odds ratio [aOR] 1.08, 95% confidence interval [CI] 1.03–1.13) and referral to gynecologic oncology (aOR 33.48, CI 8.10–138.39) were associated with increased adoption of RRSO when adjusting for personal and family history of breast and ovarian cancer. ConclusionHalf of RRSO-eligible patients by NCCN criteria beyond BRCA did not undergo RRSO. Opportunities exist for improving education to increase referrals to facilitate RRSO for these patients.

Evolving Landscape of Practice Patterns in the Management of Localized Low-Risk Prostate Cancer: A NCDB Study

Introduction: Most patients with low-risk prostate cancer (LRPC) are candidates for active surveillance (AS) or definitive local treatment, including radical prostatectomy (RP), external beam radiotherapy (EBRT), or prostate seed implant (PSI). In this study, we analyzed the treatment pattern of patients with LRPC using a large patient population provided by the National Cancer Database (NCDB). Methods: Patients with LRPC, as defined by the National Comprehensive Cancer Network criteria, between 2004 and 2015 from the NCDB were analyzed. Patients, with no or minimal comorbidity, were categorized according to treatment modalities, including RP, EBRT, PSI, and no local therapy (NLT). Chi-square tests were used to analyze the association among demographic variables and treatments. Multivariate logistic regression analyses were conducted to determine the likelihood of choosing NLT. Results: In total, 195,452 patients diagnosed with LRPC between 2004 and 2015 were identified. There was a significant change in practice patterns with increased utilization of NLT over time, from 11.3% in 2004 to 53.5% in 2015, with a turning point in 2009. RP utilization peaked at 41.6% in 2008, EBRT peaked at 24.3% in 2006, and PSI peaked at 35.3% in 2004. However, it dropped to 17.6%, 18.1%, and 10.8%, respectively, in 2015. Academic/research programs (A/RP), older age, lower income, poorer education, lack of insurance, African Americans, and other races were associated with increased NLT use. The difference between White and African American, and older and younger patients in odds ratios were less after 2010. Conclusions: There was a significant shift in treatment patterns between 2004 and 2015. AS, as represented by the NLT in this study, has become the dominant treatment of choice for patients with LRPC. A/RPs were leading this trend, particularly in younger patients. Socioeconomic factors played roles in choosing NLT, but the racial difference became less apparent after 2010.

Missed opportunities in the real-world genetic testing in BRCA gene variant carriers with cancers meeting NCCN criteria

ObjectiveThe objective of this study was to determine the proportion of patients meeting the National Comprehensive Cancer Network (NCCN)’s BRCA genetic testing criteria prior to a diagnosis of a BRCA-related cancer. MethodsThis was a cross-sectional study of patients with BRCA pathogenic variants and a diagnosis of a BRCA-related cancer. Patients were included if they had known dates of genetic testing and cancer diagnosis. NCCN criteria (version 2.2021) were applied to determine if patients met criteria for testing before a BRCA-related cancer diagnosis. The outcome of interest was the proportion of patients undergoing genetic testing following a diagnosis of a BRCA-related cancer who qualified for genetic testing based on NCCN criteria. Chi-square, Mann-Whitney U test, and logistic regression were performed with significance at p < 0.05. ResultsOf 270 patients with a BRCA-related cancer, 229 (85%) underwent genetic testing after a cancer diagnosis. Most patients (97%) met at least one NCCN criteria for BRCA testing; 166 (73%) of patients who were tested following a BRCA-related cancer diagnosis also met the criteria for testing by family history. Publicly insured or uninsured patients were three times more likely to undergo BRCA testing after a diagnosis of cancer (odds ratio [OR] 3.03, 95% confidence interval [CI] 1.09–8.40). Patients with a family history of pathogenic variants were more likely to undergo testing before a cancer diagnosis (OR 0.10, 95% CI 0.05–0.23). ConclusionMost patients with BRCA-associated cancers undergo genetic testing after their cancer diagnosis. Increased education on genetic testing criteria and novel methods to improve testing are desperately needed.

Abstract P043: A precision medicine gap: limited recognition of colorectal patients eligible for germline testing in molecular residual disease testing setting

Abstract Background: Germline testing for hereditary colorectal cancer (CRC) has traditionally been offered to patients with strong cancer family histories, whose colon tumors revealed mismatch repair deficiency (dMMR), and/or individuals diagnosed with CRC under age 50. Underdiagnosis of hereditary cancer syndromes is often attributed to the complexity or unawareness of family history or phenotypic criteria.1,2 The National Comprehensive Cancer Network (NCCN) guidelines for CRC were recently updated (v. 1.2022) to consider germline multigene panel testing (MGPT) evaluation for all individuals with CRC.3,4 Our goal was to evaluate documentation of MGPT in CRC patients referred for molecular residual disease (MRD) testing. Methods: This retrospective cohort study reviewed clinical data submitted to a commercial laboratory for consecutive CRC patients referred from non-academic medical facilities for MRD testing during a two-month study period. Medical diagnoses, treatment history, family history and germline genetic evaluation status were obtained from the test requisition form and pathology reports. Clinical notes were reviewed in 77/80 cases. Results: Of the 80 patients who met criteria for inclusion, 65/80 (81%) had documented MMR testing of their colorectal tumor. Whereas five had abnormal immunohistochemistry, only two (40%) had documented germline results. 19/80 (24%) met NCCN criteria solely based on a personal CRC diagnosis &amp;lt;50 years, but only 1/19 (5.3%) had documented MGPT. Only 5/80 (6%) of all CRC patients had documented MGPT. Conclusion: Our real-world data from the community oncology precision medicine setting suggests that a majority of CRC patients who received MRD testing and met the prior NCCN criteria for MGPT may not have received evaluation beyond routine MMR status. Process and educational improvements are needed in community health settings to increase access and uptake of germline testing in CRC patients regardless of age at diagnosis or MMR status. Citation Format: Suzanne Schrock-Kelley, Vivienne Souter, Michael Hall, Jeffrey N. Weitzel. A precision medicine gap: limited recognition of colorectal patients eligible for germline testing in molecular residual disease testing setting. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P043.

Lower-Intensity CPX-351 + Venetoclax for Patients with Newly Diagnosed Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy: Post Hoc Analysis By Disease Risk Subgroups

Background: CPX-351 (United States: Vyxeos®; European Union/United Kingdom: Vyxeos® liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. CPX-351 is approved for the treatment of newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in patients who are candidates for intensive chemotherapy (IC) and aged ≥1 year in the United States and adults in the European Union/United Kingdom. However, the appropriate dosage of CPX-351 in patients unfit for IC may be different from the label dosage. Venetoclax (VEN; BCL-2 inhibitor) + low-dose cytarabine has demonstrated efficacy in unfit patients with AML, and drug synergism/additivity in preclinical studies provided a rationale for combining CPX-351 + VEN. Our analysis evaluates the safety and efficacy of lower-intensity CPX-351 + VEN, based on disease risk classification, in adults with newly diagnosed AML (primarily de novo AML) who are unfit for IC. Methods: This is an open-label, phase 1b study (NCT04038437). Patients who achieve at least partial remission after 1 or 2 cycles may receive up to 4 similar cycles of CPX-351 + VEN in the dose-exploration phase or up to 8 similar cycles in the expansion phase. Patients received CPX-351 dose levels of 20 units/m2 (dose level 1; n = 4), 40 units/m2 (dose level 2; n = 7), or 30 units/m2 (dose level 1b [recommended phase 2 dose]; n = 24) intravenously on Days 1 and 3 in combination with VEN 400 mg/day orally on Days 2 to 21 of each 28-day cycle. Patients are assessed for response (morphology, measurable residual disease [MRD]) and monitored for safety and survival. Patients were categorized into disease risk subgroups based on National Comprehensive Cancer Network criteria. Results: This analysis included data from 35 patients enrolled across dose levels as of the data cutoff date of March 23, 2022, including 16 (46%) with favorable/intermediate and 19 (54%) with poor disease risk. Of the patients with favorable/intermediate disease risk, median age was 74 (range: 60, 90); 50% were male; 81% had a diagnosis of de novo AML. Of the patients with poor disease risk, median age was 74 years (range: 59, 89); 68% were male; 74% had a diagnosis of de novo AML; and 42% had mutated TP53. Patients were considered unfit for IC based on age ≥75 years (n = 8 [50%] for favorable/intermediate and n = 9 [47%] for poor disease risk) or ECOG performance status of 2 or 3 or comorbidities (n = 8 [50%]; n = 10 [53%]). Treatment-emergent adverse events (TEAEs) in ≥25% of patients with favorable/intermediate disease risk included febrile neutropenia (38%) and neutropenia (25%) and in those with poor disease risk included nausea (42%), febrile neutropenia (37%), thrombocytopenia (32%) and diarrhea (26%). The majority of patients with favorable/intermediate (94%) or poor (79%) disease risk experienced a grade ≥3 TEAE, primarily myelosuppression. Serious AEs were experienced by 11/16 (69%) and 14/19 (74%) patients, respectively, and the most common serious AE was febrile neutropenia (25% and 37%). There were no deaths in either group on or before Day 30; early mortality by Day 60 was 12% and 11%, respectively. Among patients with an evaluable remission assessment, complete remission (CR) or CR with incomplete neutrophil or platelet recovery (CRi) was achieved by 10/13 (77%) patients with favorable/intermediate and 8/18 (44%) patients with poor disease risk (Table); all patients who achieved CR or CRi did so after Cycle 1. Among evaluable patients with poor disease risk, 1/8 (13%) with and 7/10 (10%) without a TP53 mutation achieved CR. In patients with CR or CRi, MRD negativity was achieved by 7/10 (70%) patients with favorable/intermediate and 7/8 (88%) with poor disease risk; of these, 5 and 4 patients achieved MRD negativity after Cycle 1, respectively. Median (interquartile range) recovery times to neutrophils ≥500/μL and platelets ≥50,000/μL, respectively, were 30 (28, 36) and 21.5 (21, 28) days for patients with favorable/intermediate disease risk in CR or CRi and 32.5 (21, 38) and 21 (21, 28.5) days for those with poor disease risk in CR or CRi. Conclusion: The combination of lower-intensity CPX-351 + VEN demonstrated efficacy in both the favorable/intermediate and poor disease risk subgroups, without excessive myelosuppression. These data also provide further insights into outcomes on CPX-351 combination therapies for the treatment of AML. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Evaluation of family history in individuals with heterozygous BRCA pathogenic variants diagnosed with breast or ovarian cancer in a single center in Italy.

BRCA1 and BRCA2 gene mutations are responsible for 5% of breast cancer (BC) and 10-15% of ovarian cancer (EOC). The presence of a germline mutation and therefore the identification of subjects at high risk of developing cancer should ideally precede the onset of the disease, so that appropriate surveillance and risk-reducing treatments can be proposed. In this study, we revisited the family history (FH) of women who tested positive for BRCA mutations after being diagnosed with BC or EOC. The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines®), and the Italian Association of Medical Oncology (AIOM) guidelines were applied to the FH of 157 women who were referred to San Gerardo Hospital for genetic counseling. Almost 85% of women had an FH of BRCA-related cancer. 63.7% and 52.2% of women could have undergone genetic testing according to NCCN and AIOM testing criteria (p < .05) before tumor diagnosis. An FH of EOC was the most frequent NCCN criterion, followed by BC diagnosed <45 years old. Sixty-five percent of deceased women could have undergone genetic testing before developing cancer. FH is a powerful tool to identify high-risk individuals eligible for genetic counseling and testing. Testing of healthy individuals should be considered when an appropriately affected family member is unavailable for testing.

Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)—a randomized phase II trial of the AIO pancreatic cancer group

Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

External Beam Radiation Therapy With or Without Brachytherapy Boost in Men With Very-High-Risk Prostate Cancer: A Large Multicenter International Consortium Analysis

Very-high-risk (VHR) prostate cancer (PC) is an aggressive subgroup with high risk of distant disease progression. Systemic treatment intensification with abiraterone or docetaxel reduces PC-specific mortality (PCSM) and distant metastasis (DM) in men receiving external beam radiation therapy (EBRT) with androgen deprivation therapy (ADT). Whether prostate-directed treatment intensification with the addition of brachytherapy (BT) boost to EBRT with ADT improves outcomes in this group is unclear. This cohort study from 16 centers across 4 countries included men with VHR PC treated with either dose-escalated EBRT with ≥24 months of ADT or EBRT+BT boost with ≥12 months of ADT. VHR was defined by National Comprehensive Cancer Network (NCCN) criteria (clinical T3b-4, primary Gleason pattern 5, or ≥2 NCCN high-risk features), and results were corroborated in a subgroup of men who met Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) trials inclusion criteria (≥2 of the following: clinical T3-4, Gleason 8-10, or PSA ≥40 ng/mL). PCSM and DM between EBRT and EBRT+BT were compared using inverse probability of treatment weight-adjusted Fine-Gray competing risk regression. Among the entire cohort, 270 underwent EBRT and 101 EBRT+BT. After a median follow-up of 7.8 years, 6.7% and 5.9% of men died of PC and 16.3% and 9.9% had DM after EBRT and EBRT+BT, respectively. There was no significant difference in PCSM (sHR, 1.47 [95% CI, 0.57-3.75]; P=.42) or DM (sHR, 0.72, [95% CI, 0.30-1.71]; P=.45) between EBRT+BT and EBRT. Results were similar within the STAMPEDE-defined VHR subgroup (PCSM: sHR, 1.67 [95% CI, 0.48-5.81]; P=.42; DM: sHR, 0.56 [95% CI, 0.15-2.04]; P=.38). In this VHR PC cohort, no difference in clinically meaningful outcomes was observed between EBRT alone with ≥24 months of ADT compared with EBRT+BT with ≥12 months of ADT. Comparative analyses in men treated with intensified systemic therapy are warranted.

EP02.01-004 Application of a Genomic Assay for Risk Stratification of Resected NSCLC in a Community Cancer Center Setting, a Pilot Study

30 to 50% of patients with resected, early stage, non-small cell lung cancer (NSCLC) will recur within 5 years of surgery. DetermaRx, a 14-gene molecular assay can be used to better risk stratify patients with stage I-IIA non-squamous NSCLC who may benefit from adjuvant chemotherapy. This assay more accurately identifies patients at high-risk for recurrence than the current National Comprehensive Cancer Network (NCCN) criteria for early-stage NSCLC. In a prospective validation study, DetermaRx high-risk patients who were treated with adjuvant chemotherapy had a 91.7% 5-year disease-free survival (DFS) compared to 48.9% for the same molecular high-risk patients who did not receive adjuvant treatment.

Eligibility, uptake and response to germline genetic testing in women with DCIS.

BackgroundDuctal carcinoma in situ (DCIS) is a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for recurrence. Uptake of genetic testing and subsequent surgical intervention in women with DCIS has not been well-studied. The aim of this study was to evaluate test eligibility parameters, uptake of clinical testing, impact on surgical decision making and second cancer events (SCE) in women with DCIS.MethodsFour-hundred eighty-four women diagnosed with unilateral DCIS 2001-2020 were eligible for this study. Demographic, commercial genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research laboratory across 94 cancer predisposition genes. Statistical analyses were performed using Fisher’s exact tests and Chi-square analyses with p < 0.05 defining significance.ResultsForty-four percent of women were test-eligible at diagnosis of which 63.4% pursued genetic testing before definitive surgery; 9.9% pursued testing only after a second cancer event. Bilateral mastectomy (BM) was significantly higher (p<0.001) in women who had testing before definitive surgery (46.9%) compared to those who had testing afterword (10.8%) and in women who underwent testing before definitive surgery with PV (75%) compared to those without PV (37.5%. p=0.045). Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 7 (17.9%) of these women not eligible for genetic testing based on NCCN criteria. In women who did not undergo BM at diagnosis, SCE were significantly higher (p=0.001) in women with PV (33.3%) compared to those without PV (11.9%).ConclusionPursuit of genetic testing and subsequent use of risk-reducing surgeries in women with PV was suboptimal in women with a primary diagnosis of DCIS. In conjunction, >50% of PV were detected only in the research setting. Because omission of genetic testing in women with DCIS may represent a lost opportunity for prevention, genetic testing at the time of diagnosis should be standard for all women with DCIS.

Identifying Patients Who Meet Criteria for Genetic Testing of Hereditary Cancers Based on Structured and Unstructured Family Health History Data in the Electronic Health Record: Natural Language Processing Approach.

BackgroundFamily health history has been recognized as an essential factor for cancer risk assessment and is an integral part of many cancer screening guidelines, including genetic testing for personalized clinical management strategies. However, manually identifying eligible candidates for genetic testing is labor intensive.ObjectiveThe aim of this study was to develop a natural language processing (NLP) pipeline and assess its contribution to identifying patients who meet genetic testing criteria for hereditary cancers based on family health history data in the electronic health record (EHR). We compared an algorithm that uses structured data alone with structured data augmented using NLP.MethodsAlgorithms were developed based on the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing for hereditary breast or ovarian and colorectal cancers. The NLP-augmented algorithm uses both structured family health history data and the associated unstructured free-text comments. The algorithms were compared with a reference standard of 100 patients with a family health history in the EHR.ResultsRegarding identifying the reference standard patients meeting the NCCN criteria, the NLP-augmented algorithm compared with the structured data algorithm yielded a significantly higher recall of 0.95 (95% CI 0.9-0.99) versus 0.29 (95% CI 0.19-0.40) and a precision of 0.99 (95% CI 0.96-1.00) versus 0.81 (95% CI 0.65-0.95). On the whole data set, the NLP-augmented algorithm extracted 33.6% more entities, resulting in 53.8% more patients meeting the NCCN criteria.ConclusionsCompared with the structured data algorithm, the NLP-augmented algorithm based on both structured and unstructured family health history data in the EHR increased the number of patients identified as meeting the NCCN criteria for genetic testing for hereditary breast or ovarian and colorectal cancers.

Cancer risk assessment models versus National Comprehensive Cancer Network guidelines: What is the most comprehensive method to assess cancer risk and triage for genetic testing? (373)

Cancer risk assessment models versus National Comprehensive Cancer Network guidelines: What is the most comprehensive method to assess cancer risk and triage for genetic testing? (373)