Background Panel-based genetic testing has identified increasing numbers of patients with pancreatic ductal adenocarcinoma (PDAC) who carry germline mutations. However, small sample sizes or number of genes evaluated limit prevalence estimates of these mutations. We estimated prevalence of mutations in PDAC patients with positive family history. Methods We sequenced 25 cancer susceptibility genes in lymphocyte DNA from 302 PDAC patients in the Mayo Clinic Biospecimen Resource for Pancreatic Research Registry. Kindreds containing at least two first-degree relatives with PDAC met criteria for Familial Pancreatic Cancer (FPC), while the remaining were familial, but not FPC. Results Thirty-six patients (12%) carried at least one deleterious mutation in one of 11 genes. Of FPC patients, 25/185 (14%) were carriers, while 11/117 (9%) non-FPC patients with family history were carriers. Deleterious mutations (n) identified in PDAC patients were BRCA2 (11), ATM (8), CDKN2A (4), CHEK2 (4), MUTYH/MYH (3 heterozygotes, not biallelic), BRCA1 (2), and 1 each in BARD1, MSH2, NBN, PALB2, and PMS2. Novel mutations were found in ATM, BARD1, and PMS2. Conclusions Multiple susceptibility gene testing in PDAC patients with family history of pancreatic cancer is warranted regardless of FPC status, and will inform genetic risk counseling for families.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional—yet unsubstantiated—practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity.

Outcomes for patients with multiple myeloma (MM) have improved in recent years owing to use of novel agents and high-dose therapy followed by autologous stem cell transplant (ASCT). We analyzed the outcomes of 511 consecutive patients treated with novel therapies at our institution between 2006 and 2014 to determine the impact of relapse within 12 months of initiating treatment. A total of 82 patients (16.0%) experienced early relapse, with median time to relapse of 8.0 months (95% confidence interval (CI); 6.3, 8.9). Median overall survival (OS) was significantly worse for this group at 21.0 months (95% CI; 16.3, 27.2) vs not reached (NR) (95% CI; 96.3, NR) for those with late relapse (P<0.001). Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. In multivariate analysis, low albumin and high-risk cytogenetics predicted early relapse. Outcomes of early relapse from early ASCT were also considered; median OS from ASCT for those relapsing within 12 months was 23.1 months (95% CI; 15.7, 32.4) vs 122.2 months (95% CI; 111.5, 122.2) for the remaining patients (P<0.001). Early relapse remains a marker of poor prognosis in the current era, and such patients should be targeted for clinical trials.

Purpose Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes transcutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality. Methods The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner. Results To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive. Conclusion The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.

PURPOSE: There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS: We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS: Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older ( P = .002) and received more cycles of pembrolizumab ( P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION: Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.

p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

Over the past decade, use of novel agents, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has resulted in high response rates and improvement in overall survival (OS) for patients with multiple myeloma (MM); however, the prognostic significance of refractoriness to these agents when used as initial therapy has not been extensively studied. We reviewed the outcomes of 816 consecutive patients treated for MM at our institution since 2006 to evaluate the survival difference between those achieving at least a partial response (PR) to induction therapy and those who were primary refractory. The median OS from start of therapy was significantly shorter for the primary refractory group at 3.6 years vs 7.6 years for the responding patients (P < 0.001). The difference in median OS persisted when only patients receiving a novel agent as part of induction therapy were considered (3.6 years vs 7.9 years, P < 0.001) and in a four-month landmark analysis (4.2 years vs 7.6 years, P < 0.001). The median OS for patients achieving a complete response (CR), very good partial response (VGPR), PR, or less than PR was not reached (NR), 6.1, 6.4, and 4.2 years from the four-month landmark, respectively (P < 0.001). The comparatively poor outcomes of patients refractory to induction therapy in the current era of novel agents suggests that this high-risk sub-population must be further studied for predictors of resistance and, when identified, should be targeted for clinical trials.

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