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Contains fulltext : 287666.pdf (Publisher’s version ) (Open Access) There is no consensus on the optimal treatment duration of anti-PD-1 for advanced melanoma. The aim of our study was to gain insight into the outcomes of anti-PD-1 discontinuation, the association of treatment duration with progression and anti-PD-1 re-treatment in relapsing patients. Analyses were performed on advanced melanoma patients in the Netherlands who discontinued first-line anti-PD-1 monotherapy in the absence of progressive disease (n = 324). Survival was estimated after anti-PD-1 discontinuation and with a Cox model the association of treatment duration with progression was assessed. At the time of anti-PD-1 discontinuation, 90 (28%) patients had a complete response (CR), 190 (59%) a partial response (PR) and 44 (14%) stable disease (SD). Median treatment duration for patients with CR, PR and SD was 11.2, 11.5 and 7.2 months, respectively. The 24-month progression-free survival and overall survival probabilities for patients with a CR, PR and SD were, respectively, 64% and 88%, 53% and 82%, 31% and 64%. Survival outcomes of patients with a PR and CR were similar when anti-PD-1 discontinuation was not due to adverse events. Having a PR at anti-PD-1 discontinuation and longer time to first response were associated with progression [hazard ratio (HR) = 1.81 (95% confidence interval, CI = 1.11-2.97) and HR = 1.10 (95% CI = 1.02-1.19; per month increase)]. In 17 of the 27 anti-PD-1 re-treated patients (63%), a response was observed. Advanced melanoma patients can have durable remissions after (elective) anti-PD-1 discontinuation.

Background: Mucosal melanoma (MM) is rare and has a poor prognosis. Since 2011, new effective treatments are available for advanced melanoma. It is unclear whether patients with mucosal melanoma equally benefit from these new treatments compared with patients with cutaneous melanoma (CM).Methods: Patients with advanced MM and CM diagnosed between 2013 and 2017 were included from a nationwide population-based registry the Dutch Melanoma Treatment Registry. Overall survival (OS) was estimated with the Kaplan-Meier method (also for a propensity score-matched cohort). A Cox model was used to analyse the association of possible prognostic factors with OS.Results: In total, 120 patients with MM and 2960 patients with CM were included. Median OS was 8.7 months and 14.5 months, respectively. Patients with MM were older (median age 70 versus 65 years) and more often female (60% versus 41%), compared with CM. In total, 77% and 2% of the MM patients were treated with first-line immunotherapy and targeted therapy, respectively, compared with 49% and 33% of the CM patients. In contrast to CM, OS for MM did not improve for patients diagnosed in 2015-2017, compared with 2013-2014. ECOG performance score >= 1 (HR = 1.99 [1.26-3.15; p = 0.003]) and elevated LDH level (HR = 1.63 [0.96-2.76]; p = 0.069) in MM were associated with worse survival.Conclusions: Within the era of immune and targeted therapies, prognosis for patients with advanced MM has not improved as much as for CM. Collaboration is necessary to enlarge sample size for research to improve immunotherapeutic strategies and identify targetable mutations. (C) 2020 Elsevier Ltd. All rights reserved.

There is limited evidence on the costs associated with ipilimumab. We investigated healthcare costs of all Dutch patients with advanced cutaneous melanoma who were treated with ipilimumab. Data were retrieved from the nation-wide Dutch Melanoma Treatment Registry. Costs were determined by applying unit costs to individual patient resource use. A total of 807 patients who were diagnosed between July 2012 and July 2015 received ipilimumab in Dutch practice. The mean (median) episode duration was 6.27 (4.61) months (computed from the start of ipilimumab until the start of a next treatment, death, or the last date of follow-up). The average total healthcare costs amounted toOV0556;81 484, but varied widely (range:OV0556;18 131-OV0556;160 002). Ipilimumab was by far the most important cost driver (OV0556;73 739). Other costs were related to hospital admissions (OV0556;3323), hospital visits (OV0556;1791), diagnostics and imaging (OV0556;1505), radiotherapy (OV0556;828), and surgery (OV0556;297). Monthly costs for resource use other than ipilimumab wereOV0556;1997 (SD:OV0556;2629). Treatment-naive patients (n=344) had higher total costs compared with previously-treated patients (n=463;OV0556;85 081 vs.OV0556;78 811). Although patients with colitis (n=106) had higher costs for resource use other than ipilimumab (OV0556;11 426) compared with patients with other types of immune-related adverse events (n=90;OV0556;9850) and patients with no immune-related adverse event (n=611;OV0556;6796), they had lower total costs (OV0556;76 075 vs.OV0556;87 882 andOV0556;81 480, respectively). In conclusion, this nation-wide study provides valuable insights into the healthcare costs of advanced cutaneous melanoma patients who were treated with ipilimumab in clinical practice. Most of the costs were attributable to ipilimumab, but the costs and its distribution varied considerably across subgroups.

Introduction Vaginal (re)construction is essential for the psychological well‐being of biological women with a dysfunctional vagina and male‐to‐female transgender women. However, the preferred method for vagina (re)construction with respect to functional as well as aesthetic outcomes is debated. Regarding intestinal vaginoplasty, despite the asserted advantages, the need for intestinal surgery and subsequent risk of diversion colitis are often‐mentioned concerns. The outcomes of vaginal reconstructive surgery need to be appraised in order to improve understanding of pros and cons. Aims To review literature on surgical techniques and clinical outcomes of intestinal vaginoplasty. Methods Electronic databases and reference lists of published articles were searched for primary studies on intestinal vaginoplasty. Studies were included if these included at least five patients and had a minimal follow‐up period of 1 year. No constraints were imposed with regard to patient age, indication for vaginoplasty, or applied surgical technique. Outcome measures were extracted and analyzed. Main Outcome Measures Main outcome measures were surgical procedure, clinical outcomes, and outcomes concerning sexual health and quality of life. Results Twenty‐one studies on intestinal vaginoplasty were included (including 894 patients in total). All studies had a retrospective design and were of low quality. Prevalence and severity of procedure‐related complications were low. The main postoperative complication was introital stenosis, necessitating surgical correction in 4.1% of sigmoid‐derived and 1.2% of ileum‐derived vaginoplasties. Neither diversion colitis nor cancer was reported. Sexual satisfaction rate was high, but standardized questionnaires were rarely used. Quality of life was not reported. Conclusion Based on evidence presently available, it seems that intestinal vaginoplasty is associated with low complication rates. To substantiate these findings and to obtain information about functional outcomes and quality of life, prospective studies using standardized measures and questionnaires are warranted. Bouman M‐B, van Zeijl MCT, Buncamper ME, Meijerink WJHJ, van Bodegraven AA, and Mullender MG. Intestinal vaginoplasty revisited: A review of surgical techniques, complications, and sexual function. J Sex Med 2014;11:1835–1847.