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Background: Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas. Methods: We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016. Results: Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4–73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5–4.6] and 5 months (95% CI 2.6–33.1), respectively (p = 0.0147). Conclusion: In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially. [ABSTRACT FROM AUTHOR]

The aim of the current study was to evaluate the effects of a short inspiratory muscle training (IMT) program results in functional capacity, inspiratory muscle strength and quality of life in physically active elderly people. Twenty-six physically active elderly subjects were assigned to either a 6-week IMT program (13 subjects) or a placebo-IMT (P-IMT; 13 subjects). The following parameters were measured before and after intervention: 6-minute walk test (6MWT) distance, inspiratory muscle strength (PImax) and quality of life scores. Between-groups analysis of functional capacity was not statistically significant, but showed a tendency to improvement in the IMT group from 469.4 m (IQR: 418-532 m) at baseline to 516.4 m (IQR: 462.5-560.1 m) during follow-up. The IMT program induced significant improvement in inspiratory strength between the groups from 55 cm H2O (IQR: 45-71.25 cm H2O) at baseline to 90 cm H2O (IQR: 76.25-107.5 cm H2O) during follow-up, whereas the P-IMT group had a slight decrease from 75 cm H2O (IQR: 67.5-95 cm H2O) at baseline to 67.5 cm H2O (IQR: 65-75 cm H2O; p = 0.010). The quality of life questionnaire did not improve after the IMT program. The present study demonstrates that a short-term 6-week IMT program results in improvement in inspiratory muscle strength and a tendency to improvement in functional capacity in physically active elderly people. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite progress in the biology and upfront treatment of childhood medulloblastoma, relapse is almost universally fatal. No standardized treatment has so far been established for these patients. By determining which characteristics are prognostic after relapse, treatment strategies may be optimized for each of these children. We demonstrated that molecular subgroup at diagnosis is a relevant prognostic factor of outcome after relapse. Moreover, we showed that time to relapse and the use of salvage radiotherapy at relapse might have a potential impact on post-relapse survival. Our data suggest that ongoing efforts toward a better understanding of the biology, timing and type of relapse would be important to understand the determinants of tumor behavior at relapse. This could help us address more specific questions on the best surveillance strategies after completion of the treatment and the introduction of risk-stratified second-line treatment strategies. Given the very poor prognosis for children with recurrent medulloblastoma, we aimed to identify prognostic factors for survival post-relapse in children with childhood medulloblastoma. We retrospectively collected clinico-biological data at diagnosis and main clinical characteristics at relapse of children newly diagnosed with a medulloblastoma between 2007 and 2017 at Gustave Roussy and Necker Hospital. At a median follow-up of 6.6 years (range, 0.4–12.3 years), relapse occurred in 48 out 155 patients (31%). The median time from diagnosis to relapse was 14.3 months (range, 1.2–87.2 months). Relapse was local in 9, metastatic in 22 and combined (local and metastatic) in 17 patients. Second-line treatment consisted of chemotherapy in 31 cases, radiotherapy in 9, SHH-inhibitor in four and no treatment in the remaining four. The 1-year overall survival rate post-relapse was 44.8% (CI 95%, 31.5% to 59.0%). While molecular subgrouping at diagnosis was significantly associated with survival post-relapse, the use of radiotherapy at relapse and time to first relapse (>12 months) might also have a potential impact on post-relapse survival. [ABSTRACT FROM AUTHOR]

The established role of morphological evaluation of tumour-infiltrating lymphocytes (TILs) with immune checkpoint inhibitors (ICIs) in non–small cell lung cancer (NSCLC) is unknown. We aimed to determine TIL association with the outcome for ICIs and for chemotherapy in advanced NSCLC. This is a multicenter retrospective study of a nivolumab cohort of 221 patients treated between November 2012 and February 2017 and a chemotherapy cohort of 189 patients treated between June 2009 and October 2016. Patients with available tissue for stromal TIL evaluation were analysed. The presence of a high TIL count (high-TIL) was defined as ≥10% density. The primary end-point was overall survival (OS). Among the nivolumab cohort, 64% were male, with median age of 63 years, 82.3% were smokers, 77% had performance status ≤1 and 63% had adenocarcinoma histology. High-TIL was observed in 22% patients and associated with OS (hazard ratio [HR] 0.48; 95% confidence interval [95% CI]: 0.28–0.81) and progression-free survival [PFS] (HR = 0.40; 95% CI: 0.25–0.64). Median PFS was 13.0 months (95% CI: 5.0–not reached) with high-TIL versus 2.2 months (95% CI: 1.7–3.0) with the presence of a low TIL count (low-TIL). Median OS for high-TIL was not reached (95% CI: 12.2–not reached) versus 8.4 months (95% CI: 5.0–11.6) in the low-TIL group. High-TIL was associated with the overall response rate (ORR) and disease control rate (DCR) (both, P <.0001). Among the chemotherapy cohort, 69% were male, 89% were smokers, 86% had performance status ≤1 and 90% had adenocarcinoma histology. High-TIL was seen in 37%. Median PFS and OS were 5.7 months (95% CI: 4.9–6.7) and 11.7 months (95% CI: 9.3–13.0), respectively, with no association with TILs. High-TIL was associated with favourable outcomes in a real-world immunotherapy cohort of patients with NSCLC, but not with chemotherapy, suggesting that TILs may be useful in selecting patients for immunotherapy. • High–tumour infiltrating lymphocyte (TIL) density was associated with immunotherapy benefit in non–small cell lung cancer (NSCLC) patients. • No correlation with outcome was observed in chemotherapy-treated patients with NSCLC. • TILs may be useful in selecting patients for immunotherapy. [ABSTRACT FROM AUTHOR]