BackgroundThe added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of... Show moreBackgroundThe added value of local treatment in selected metastatic GIST patients is unclear. This study aims to provide insight into the usefulness of local treatment in metastatic GIST by use of a survey study and retrospective analyses in a clinical database.MethodsA survey study was conducted among clinical specialists to select most relevant characteristics of metastatic GIST patients considered for local treatment, defined as elective surgery or ablation. Patients were selected from the Dutch GIST Registry. A multivariate Cox-regression model for overall survival since time of diagnosis of metastatic disease was estimated with local treatment as a time-dependent variable. An additional model was estimated to assess prognostic factors since local treatment.ResultsThe survey's response rate was 14/16. Performance status, response to TKIs, location of active disease, number of lesions, mutation status, and time between primary diagnosis and metastases, were regarded the 6 most important characteristics. Of 457 included patients, 123 underwent local treatment, which was associated with better survival after diagnosis of metastases (HR = 0.558, 95%CI = 0.336–0.928). Progressive disease during systemic treatment (HR = 3.885, 95%CI = 1.195–12.627) and disease confined to the liver (HR = 0.269, 95%CI = 0.082–0.880) were associated with worse and better survival after local treatment, respectively.ConclusionLocal treatment is associated with better survival in selected patients with metastatic GIST. Locally treated patients with response to TKIs and disease confined to the liver have good clinical outcome. These results might be considered for tailoring treatment, but should be interpreted with care because only specific patients are provided with local treatment in this retrospective study. Show less
Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint... Show moreBackground: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM). Methods: We included patients with advanced AM and CM treated with first-line anti -programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS. Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8-5.6) than patients with CM (10.1 months; 95%CI: 8.5-12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26-2.11 ; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15-2.06; P Z 0.004) than CM. Conclusions: This study shows lower effectiveness of anti-PD-1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies. 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR,... Show moreBackground: Little is known about outcomes of adjuvant-treated melanoma patients beyond the clinical trial setting. Since 2019, adjuvant-treated melanoma patients have been registered in the DMTR, a population-based registry to monitor the quality and safety of melanoma care in the Netherlands. This study aims to describe treatment patterns, relapse, and toxicity rates of adjuvant-treated melanoma patients beyond the clinical trial setting.Methods: Analyses were performed on adjuvant-treated melanoma patients included in the DMTR. Descriptive statistics were used to analyse patient-, and treatment characteristics. A baseline registration completeness analysis was performed, and an analysis on trial eligibility in clinical practice patients. Recurrence-free survival (RFS) at 12-months was estimated with the Kaplan-Meier method.Results: A total of 641 patients were treated with adjuvant anti-PD-1 therapy. RFS at 12-months was 70.6% (95% CI, 66.9-74.6) with a median follow-up of 12.8 months. Sex, stage of disease and Breslow thickness were associated with a higher hazard for RFS. Eighteen per cent of the anti-PD-1-treated patients developed grade >= 3 toxicity. Sixty-one per cent of patients prematurely discontinued anti-PD-1 therapy.Conclusion: Adjuvant anti-PD-1 treatment of resected stage III/IV melanoma in daily practice showed slightly higher toxicity rates and more frequent premature discontinuation but similar RFS rates compared to trials. (C) 2021 The Authors. Published by Elsevier Ltd. Show less
IJzerman, N.S.; Mohammadi, M.; Tzanis, D.; Gelderblom, H.; Fiore, M.; Fumagalli, E.; ... ; Smith, M. 2020
Background: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the managementmay influence outcome, but there is a lack of understanding regarding contemporary... Show moreBackground: Rectal gastrointestinal stromal tumours (GISTs) are rare tumours. Variability in the managementmay influence outcome, but there is a lack of understanding regarding contemporary variancein care. A multicenter, international, retrospective cohort study was performed to elucidate characteristicsand outcomes of rectal GIST in European practice, with particular reference to surgical approach.Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five Europeandatabases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meiermethod. Possible confounders were identified using Cox regression analyses.Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumourresection (LTR, n ¼ 46), low anterior resection (LAR, n ¼ 31) and abdomino-perineal resection (APR,n ¼ 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Localrecurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences werefound in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours weresmaller, while LAR and APR patients more often received perioperative imatinib. General hospitalstreated smaller GISTs, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for localrecurrence was higher age (HR 1.06, CI 1.00e1.12, p ¼ 0.048).Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable localcontrol. Multimodal approach is higher and tumour rupture less frequent in specialist centres comparedto general hospitals. Show less
IJzerman, N.S.; Mohammadi, M.; Tzanis, D.; Gelderblom, H.; Fiore, M.; Fumagalli, E.; ... ; Smith, M. 2020
Background: Rectal gastrointestinal stromal tumours (GISTS) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary... Show moreBackground: Rectal gastrointestinal stromal tumours (GISTS) are rare tumours. Variability in the management may influence outcome, but there is a lack of understanding regarding contemporary variance in care. A multicenter, international, retrospective cohort study was performed to elucidate characteristics and outcomes of rectal GIST in European practice, with particular reference to surgical approach.Methods: All rectal GIST patients diagnosed between 2009 and 2018 were identified from five European databases. Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier method. Possible confounders were identified using Cox regression analyses.Results: From 210 patients, 155 patients had surgery. The three main types of surgery were local tumour resection (LTR, n = 46), low anterior resection (LAR, n = 31) and abdomino-perineal resection (APR, n = 32). Most patients received neoadjuvant (65%) and/or adjuvant imatinib therapy (66%). Local recurrence rate after surgery was 15% and overall recurrence rate 28%. No significant differences were found in terms of RFS nor OS between LTR, LAR and APR. However, locally resected tumours were smaller, while LAR and APR patients more often received perioperative imatinib. General hospitals treated smaller GISTS, offered imatinib less frequently, and had a higher tumour rupture rate. In the multivariate analysis in the group having LTR, APR or LAR, the only significant prognostic factor for local recurrence was higher age (HR 1.06, CI 1.00-1.12, p = 0.048).Conclusions: In European clinical practice for rectal GIST, LTR, LAR and APR have comparable local control. Multimodal approach is higher and tumour rupture less frequent in specialist centres compared to general hospitals. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
