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PURPOSE: Guidelines recommend germline genetic testing (GT) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aims to evaluate the utilization and outcomes of multigene panel GT in patients with PDAC. METHODS: This retrospective, multisite study included patients with PDAC diagnosed between May 2018 and August 2020 at Mayo Clinic Arizona, Florida, and Minnesota. Discussion, uptake, and outcomes of GT were compared before (May 1, 2018-May 1, 2019) and after (August 1, 2019-August 1, 2020) the guideline update, accounting for a transition period. RESULTS: The study identified 533 patients with PDAC, with 321 (60.2%) preguideline and 212 (39.8%) postguideline. Patient characteristics did not differ between the preguideline and postguideline periods. GT was discussed in 34.3% (110 of 321) of preguideline and 39.6% (84 of 212) of postguideline patients (odds ratio [OR], 1.26 [95% CI, 0.88 to 1.80]) and subsequently performed in 80.9% (89 of 110) of preguideline and 75.0% (63 of 84) of postguideline patients (OR, 1.10 [95% CI, 0.75 to 1.61]). Of 152 tested patients, 26 (17.1%) had a pathogenic variant (PV), of whom 17 (11.2%; 17 of 152) were PDAC-associated. Over the entire study period, GT was more likely in younger patients (65 v 70 years; P <.001), those seen by a medical oncologist (82.9% v 69.0%; P <.001), and those surviving more than 12 months from diagnosis (70.4% v 43.4%; P <.001). Demographics and personal/family cancer history were comparable between patients with and without a PDAC PV. CONCLUSION: GT remains underutilized despite National Comprehensive Cancer Network guideline recommendations. Given the poor prognosis of PDAC and potential implications of GT, efforts to increase utilization are needed to provide surveillance and support to both patients with PDAC and at-risk family members. Underutilization of genetic testing in pancreatic cancer. Time for action! #PancreaticCancer #GeneticTesting [ABSTRACT FROM AUTHOR]

Prognosis is generally poor for patients with pancreatic ductal adenocarcinoma. However, patients with germline BRCA1 or BRCA2 mutations (gBRCAm) may benefit from first-line platinum-based chemotherapy and maintenance therapy with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib following at least 16 weeks of first-line platinum-based chemotherapy without disease progression. Germline breast cancer gene (BRCA) testing is therefore important to ensure that patients receive the most effective treatment. In addition, testing for other DNA damage response gene mutations beyond gBRCAm may also guide treatment decisions. However, clinical pathways for genetic testing are often suboptimal, leading to delays in treatment initiation or missed opportunities for personalized therapy. Barriers to testing include low rates of referral and uptake, delays to referral and slow result turnaround times, cost, and biopsy and assay limitations if somatic testing is performed, leading to the requirement for subsequent dedicated germline testing. Low rates of referral may result from lack of awareness among physicians of the clinical value of testing, coupled with low confidence in interpreting test results and poor availability of genetic counseling services. Among patients, barriers to uptake may include similar lack of awareness of the clinical value of testing, anxiety regarding the implications of test results, lack of insurance coverage, fear of negative insurance implications, and socioeconomic factors. Potential solutions include innovative approaches to testing pathways, including 'mainstreaming' of testing in which BRCA tests are routinely arranged by the treating oncologist, with the involvement of genetic counselors if a patient is found to have a gBRCAm. More recently, the utility of multigene panel analyses has also been explored. Access to genetic counseling may also be improved through initiatives such as having a genetic counseling appointment for all new patient visits and telemedicine approaches, including the use of telephone consultations or DVD-assisted counseling. Educational programs will also be beneficial, and cost effectiveness is likely to improve as the number of targeted treatments increases and when the earlier detection of tumors in family members following cascade testing is considered. [ABSTRACT FROM AUTHOR]

A 46-year-old female presents with a pelvic mass and is diagnosed as having a high-grade endometrial stromal sarcoma. During surgery, she is noted to have areas of intussusception of the small bowel secondary to large hamartomatous polyps. The patient had a previous history of small bowel obstruction secondary to what had been thought to be hyperplastic polyps but represented hamartomatous polyps on further review. Additional examination revealed the presence of subtle hyperpigmented macules on the fingers leading to a diagnosis of Peutz-Jeghers Syndrome (PJS). The diagnosis was confirmed by the presence of a germ-line STK11 mutation. Immunohistochemistry analysis of the tumor showed decreased expression of STK-11 as compared to one of the patient&apos;s hamartomatous polyps. Next generation sequencing of the tumor specimen failed to demonstrate a "second hit" somatic mutation in STK-11. This case represents the first case of endometrial stromal sarcoma associated with PJS and illustrates the importance of increased awareness of this condition among oncologists. PJS is associated with dysregulation of the mTOR pathway; treatment with an mTOR inhibitor was not effective in this case. Keywords: Peutz-Jeghers syndrome, Endometrial stromal sarcomas, Soft tissue sarcomas, Gynecologic oncology, Everolimus, Author(s): Maria Fernanda Noriega-Iriondo[sup.1] , Gerardo Colon-Otero[sup.2] , Benjamin R Kipp[sup.7] , John A Copland[sup.6] , Matthew J Ferber[sup.7] , Laura A Marlow[sup.6] , Maegan E Roberts[sup.2] , Matthew W [...]

Abstract Background Cancer risk and Lhermitte-Duclos disease (LDD) risk estimates for Cowden syndrome (CS) are broad and based on a small number of patients. Risk estimates are vital to the development of diagnostic criteria, genetic counseling, and cancer surveillance. To further elaborate and estimate the risks associated with CS, a large cohort of patients was evaluated. Methods CS patients were identified from the medical literature and the Mayo Clinic's records. All patients met accepted diagnostic criteria for CS. Results A total of 211 CS patients (age 44 ± 16 years, 64% female, 46% PTEN mutation) were included (published literature 90% and Mayo Clinic series 10%). The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%), and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS. Seven percent of breast and thyroid cancers occurred in patients who were younger than the recommended age to commence radiographic cancer screening. There was a trend for patients with a family history of CS and PTEN mutations to have a lower cancer risk than those without. Conclusions This study confirms CS patients are at increased risk for cancer and quantitative data is provided to guide clinical care. Based on a different tumor spectrum, separate male and female clinical CS diagnostic criteria may be indicated.

Background Patients with familial adenomatous polyposis (FAP) are known to have an increased risk for gastric adenomas. The clinical features of gastric adenomas in FAP have not been well characterized, and there is a lack of standardized approaches to the management of these lesions. Aims To study the endoscopic appearance, risk factors, clinical course, and response to therapy of gastric adenomas in patients with FAP. Methods We retrospectively reviewed the records of 97 patients with FAP who underwent esophagogastroduodenoscopy (EGD) at Mayo Clinic (Florida, Rochester and Arizona) between 2004 and 2013. Results Nine patients (9%) had biopsy-proven gastric adenomas. Adenomas were located in the antrum (five patients), in the body and fundus in the setting of background fundic gland polyps (FGP) (three patients), and in the body not associated with FGP (one patient). Adenoma size was 3-40 mm and the number of adenomas per patient ranged from one to 20. Adenomas in the antrum were flat and subtle, whereas those in the gastric body or fundus were polypoid and difficult to differentiate from the cystic FGPs seen in patients with FAP. The performing endoscopists reported difficulty with identifying adenomas, and six patients had at least one EGD within the previous three years where gastric adenomas were not reported. Adenomas were classified as tubular in eight patients and tubulovillous in one patient. High grade dysplasia was noted in one patient. After a median follow-up of 63 months (interquartile range: 20-149 months), no patient in our entire cohort (with or without gastric adenomas) developed gastric cancer. The patients in whom gastric adenoma developed, compared to those without gastric adenoma, were more likely to be younger [36 [+ or -] 12 vs. 48 [+ or -] 15 years, p = 0.02], have concomitant chronic gastritis [22% vs. 0%, p = 0.008], and have desmoid tumors [5 (56%) vs. 19 (22%), p = 0.04]. Conclusions Gastric adenomas are not uncommon in patients with FAP and are often difficult to identify endoscopically. Endoscopists should have a high degree of suspicion for gastric adenomas in these patients and a low threshold to biopsy. Given the benign clinical course, recommended initial management is conservative with endoscopic therapy and periodic surveillance. Keywords: Gastric adenoma, Stomach neoplasm, Familial adenomatous polyposis, Author(s): Saowanee Ngamruengphong[sup.1] , Lisa A Boardman[sup.2] , Russell I Heigh[sup.3] , Murli Krishna[sup.4] , Maegan E Roberts[sup.5] and Douglas L Riegert-Johnson[sup.1,5] Background Familial adenomatous polyposis (FAP) is an inherited [...]