Germline pathogenic variants in patients with early-onset neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a rare group of cancers with heterogeneous behaviour and mostly of unknown aetiology. Excluding some infrequent hereditary cancer syndromes, the extent and clinical significance of mutations in other cancer predisposing genes (CPGs) are not known. We aimed to investigate the frequency of pathogenic and likely germline pathogenic variants (GPVs) in known CPGs in young adults with NEN and the clinical and molecular characteristics of these patients. We recruited 108 patients with lung or digestive NEN diagnosed between 18 and 50 years and performed targeted sequencing of 113 CPGs on germline DNA. For some patients, tumour features such as loss of heterozygosity (LOH), tumour mutation burden and microsatellite instability were evaluated. GPVs were detected in 17 patients (15.7%). Median age, sex, stage at diagnosis, family history of NENs or any personal history of neoplasm were similar between patients with or without GPVs. GPV carriers had more gastric (P = 0.084), functioning NEN (P = 0.041), positive family history of cancer (P = 0.015) and exclusively well-differentiated histology. Genes affected were mostly involved in DNA repair (CHEK2, ERCC2, ERCC3, XPC, MSH6, POLE and SLX4), with most GPVs found in MUTYH (four cases). LOH was performed in eight tumours and detected only in an SLX4-positive case. Overall, our findings indicate a role of inherited genetic alterations, particularly in DNA repair genes, in NEN carcinogenesis in young adults. These patients more often had a family history of cancer and functioning NENs.

A Prospective Cohort Study of Biomarkers in Squamous Cell Carcinoma of the Anal Canal (SCCAC) and their Influence on Treatment Outcomes.

Background: Although Chemoradiation (CRT) is the curative treatment for SCCAC, many patients present primary resistance. Since it is a rare tumor, response predictors remain unknown. Methods: We performed a prospective cohort study to evaluate biomarkers associated with CRT response, progression-free survival (PFS), and overall survival (OS). The primary endpoint was response at 6 months (m). Tumor DNA and HPV were analyzed by next-generation sequencing, while KI-67 and PD-L1 by immunohistochemistry in tumor tissue. Results: Seventy-eight patients were recruited between October/2011 and December/2015, and 75 were response evaluable. The median age was 57 years, 65% (n=49) were stage III and 12% (n=9) were HIV positive (HIV+). At 6m, 62.7% (n=47) presented CR. On multivariate analyses, stage II patients were 4.7 more likely to achieve response than stage III (OR, 4.70; 95%CI, 1.36-16.30; p=0.015). HIV+ was associated with a worse response (OR, 5.72; 95%CI, 2.5-13.0; p<0.001). 5-year PFS and OS rates were 63.3% and 76.4%, respectively, with a median follow up of 66m. On multivariate analyses, older age (HR 1.06, p=0.022, 95%IC 1.01-1.11) and absence of CR at 6m (HR 3.36, p=0.007, 95%IC 1.39-8.09) were associated with inferior OS. The 5-year OS rate was 62.5% in HIV+ group compared to 78% among HIV- pts, although this difference was not statistically significant (p=0.4). PIK3CA, MET and TP53 mutations, HPV, Ki-67 expression, and PD-L1 expression, were not associated with PFS and OS. Conclusions: Clinical stage III and HIV+ were associated with worse response to CRT at 6m. The absence of CR was the main factor associated with poor 5-year OS.

Potential for drug interactions in hospitalized cancer patients.

OBJECTIVES: To quantify the frequency of potential drug interactions unrelated to chemotherapy in cancer patients admitted to our institution, and to define risk factors for such interactions. METHODS: Charts of 100 consecutive hospitalized cancer patients were reviewed. Patients receiving chemotherapy and/or hormone therapy were excluded, as were patients admitted for intensive care. Drug-drug interactions were screened with Drug Interaction Facts software, and manually by the authors. Potential interactions were graded by levels of severity (severe, moderate, minor) and significance (one to five, with one representing the highest level of evidence). RESULTS: The median age of the patients was 67 years, and the length of hospital stay and the number of drugs per patient were 6 days and eight drugs, respectively. In 63 patients 180 potential interactions were detected. Of the potential interactions, 18.3% were severe, 56.7% were moderate, and 25% were minor. Approximately 7%, 18% and 13% of potential interactions were graded as level 1, 2 and 3, respectively. In multivariate analysis, prescriptions with eight or more drugs (P=0.0004) and six or more days of hospital stay (P=0.014) were independent risk factors for potential interactions. CONCLUSION: Potential drug interactions are common among hospitalized cancer patients. Length of hospital stay and number of prescribed drugs are risk factors.

Acinar cell carcinoma of the pancreas.

Acinar cell carcinoma of the pancreas is a rare tumor for which the best chemotherapy regimen has not been clearly established. Here, we report on a female patient with an unusually long survival and a remarkable response to weekly paclitaxel. To our knowledge, this is the first time that paclitaxel has been associated with an objective response in this disease. The patient recurred after initial resection and failed multiple prior chemotherapeutic regimens. She received weekly paclitaxel at 80 mg/m2 and responded after eight doses, maintaining controlled disease for a total of 4 mo. We present her case in detail and review the available literature regarding this rare type of tumor.