8 research outputs found
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High Rate of Actionable Variants Identifed by Multigene Testing for Pancreas Cancer Patients in a High Risk Clinic 24
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Yttrium-90 Radioembolization: An Unusual Cause of Radiating Abdominal Pain
Mo1725 ADVANCED AGE IS AN INDEPENDENT RISK FACTOR OF ADVANCED NEOPLASIA RECURRENCE AT COLORECTAL CANCER SURVEILLANCE
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Metachronous Advanced Neoplasia on Surveillance Colonoscopy in Patients With Young- vs Older-onset of Colorectal Cancer
The incidence of colorectal cancer (CRC) and cancer-related mortality has increased in patients <55 years old.1 Consensus on optimal intervals for post-CRC surveillance colonoscopy in young patients is lacking. The primary endpoint of this study was comparison of rates of metachronous advanced neoplasia (AN) in patients diagnosed with CRC at <50 and 50–75 years. The secondary aim was to evaluate risk factors of metachronous AN
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DNA damage repair deficiency as a predictive biomarker for FOLFIRINOX efficacy in metastatic pancreatic cancer
Patients with pathogenic germline and somatic variants in DNA damage repair (DDR) genes may derive greater benefit with platinum-based chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC). This study investigates the role of DDR genes as a predictive biomarker for response to first-line platinum chemotherapy with FOLFIRINOX in metastatic PDAC patients. Demographic, clinical, and pathologic variables were collected for patients with metastatic PDAC who received FOLFIRINOX as frontline treatment and who had germline and somatic genetic testing. Kaplan-Meier analysis of overall survival (OS) and progression free survival (PFS) were correlated to the presence of DDR pathogenic variants. Forty patients with metastatic PDAC met inclusion criteria. Germline genetic testing revealed germline pathogenic variants in DDR genes in 5 patients (12%), and somatic pathogenic variants in DDR genes in 4 patients (10%). Median PFS was significantly longer in patients with any (germline or somatic) pathogenic variant in DDR genes than in those without alterations 18.5
vs.
6.9 months (log-rank P=0.003). When restricted to the presence or absence of germline pathogenic variants in DDR genes, the median PFS was 18.5
vs.
7.4 months (log-rank P=0.005). The median OS for the entire cohort was 11.5 months was not statistically different between the two groups, however there were no deaths in the subgroup with germline pathogenic variants in DDR genes treated with frontline FOLFIRINOX. A subset of patients with metastatic PDAC and germline or somatic pathogenic variants in DDR genes have a statistically superior PFS when treated with the platinum containing regimen FOLFIRINOX. The role of DDR gene alterations as a predictive biomarker for FOLFIRINOX benefit should be further evaluated in prospective trials
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Deleterious alterations in DNA-damage repair (daDDR) genes as a predictive biomarker for platinum-based chemotherapy in metastatic pancreatic ductal adenocarcinoma (mPDAC)
266 Background: Germline genetic testing and somatic genomic profiling using commercial multigene panels are now routine in mPDAC. A subset of these patients have deleterious alterations in genes involved with DDR. Herein we investigate the role of daDDR as a predictive biomarker for response to first-line platinum-based chemotherapy. Methods: Utilizing the IRB-approved pancreas cancer and genetics clinic databases at the University of Miami, we identified all patients with mPDAC who had germline and/or somatic mutation testing. We performed a retrospective chart review to extract demographic and clinical characteristics including treatments received, response and survival. Results: Between 2012 and 2018, 116 patients with mPDAC underwent germline (using Invitae, Ambry Counsyl or Myriad) and/or somatic testing (using FoundationOne CDx). Among these, 40 received first-line therapy with FOLFIRINOX (95%) or gemcitabine/cisplatin (5%). The median age was 59 years and 15 (38%) were female. The majority (70%) were Hispanic and 63% had de-novo mPDAC (treatment-naïve). Germline testing revealed daDDR in 5 patients and somatic NGS found an additional 4 patients with daDDR (total of 9 (23%), including 5 with BRCA2, one each with BRCA1, RAD51C, ATM and MUTYH). The median progression-free survival (PFS) was significantly longer in patients with daDDR than without (17.3 vs 7.8 months, log-rank p = 0.01). The median overall survival (OS) was not statistically different between the two groups. Three patients with daDDR had complete or near-complete radiological and tumor marker responses to FOLFIRINOX and were treated with olaparib (a PARP inhibitor) as maintenance and remain progression-free after 7, 12.4 and 13.6 months respectively. Conclusions: daDDR appears to define a subset of patients with mPDAC who may be more sensitive to platinum agents. There are currently no biomarkers for selection of first-line therapy in patients with mPDAC and we demonstrate that this composite biomarker which is easily done via commercially available assays may be able to inform treatment selection
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Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening
Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome.
We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses.
Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P = .02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P < .01). On multivariate analysis, African American race, older age, and medical center were independently associated with lack of referral for genetic evaluation and genetic testing.
In a retrospective analysis, we found that despite similar rates of colorectal tumor analysis, minority patients are less likely to be recommended for genetic evaluation or to undergo germline testing for Lynch syndrome. Improvements in institutional practices in follow up after tumor testing could reduce barriers to diagnosis of Lynch diagnosis in minorities