Combined Germline and Mosaic SDHA Mutation Is Associated With a Multicancer Syndrome Including Neuroblastoma, Renal Cancer, and Multifocal GI Tumor.

Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.

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

Background: 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. Objective: To examine medical oncologists' genetic testing ordering trends for patients with cancer. Design, Setting, and Participants: 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. Main Outcomes and Measures: The number of genetic tests ordered was compared between phases. Results: 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. Conclusions and Relevance: 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.

Multiple Primary Cancers in Patients Undergoing Tumor-Normal Sequencing Define Novel Associations.

BACKGROUND: Cancer survivors are developing more subsequent tumors. We sought to characterize patients with multiple (≥2) primary cancers (MPC) to assess associations and genetic mechanisms. METHODS: Patients were prospectively consented (01/2013-02/2019) to tumor-normal sequencing via a custom targeted panel (MSK-IMPACT). A subset consented to return of results of ≥76 cancer predisposition genes. International Agency for Research on Cancer (IARC) 2004 rules for defining MPC were applied. Tumor pairs were created to assess relationships between cancers. Age-adjusted, sex-specific, standardized incidence ratios (SIR) for first to second cancer event combinations were calculated using SEER rates, adjusting for confounders and time of ascertainment. Associations were made with germline and somatic variants. RESULTS: Of 24,241 patients, 4,340 had MPC (18%); 20% were synchronous. Most (80%) had two primaries; however, 4% had ≥4 cancers. SIR analysis found lymphoma-lung, lymphoma-uterine, breast-brain, and melanoma-lung pairs in women and prostate-mesothelioma, prostate-sarcoma, melanoma-stomach, and prostate-brain pairs in men in excess of expected after accounting for synchronous tumors, known inherited cancer syndromes, and environmental exposures. Of 1,580 (36%) patients who received germline results, 324 (21%) had 361 pathogenic/likely pathogenic variants (PV), 159 (44%) in high penetrance genes. Of tumor samples analyzed, 55% exhibited loss of heterozygosity at the germline variant. In those with negative germline findings, melanoma, prostate, and breast cancers were common. CONCLUSIONS: We identified tumor pairs without known predisposing mutations that merit confirmation and will require novel strategies to elucidate genetic mechanisms of shared susceptibilities. IMPACT: If verified, patients with MPC with novel phenotypes may benefit from targeted cancer surveillance.