Simple Summary: Mucosal melanoma (MM) is rare and entails a poor prognosis. MM is biologically different from cutaneous melanoma (CM). For advanced CM, overall survival has improved since the... Show moreSimple Summary: Mucosal melanoma (MM) is rare and entails a poor prognosis. MM is biologically different from cutaneous melanoma (CM). For advanced CM, overall survival has improved since the introduction of immune and targeted therapy. In contrast, little is known about the effect of their introduction on the survival of MM. This study presents the incidence, clinical characteristics, treatment characteristics, and survival of MM over 30 years (1990-2019) in the Netherlands. We conclude that the incidence of MM remained stable, and survival has slightly improved when comparing the timeframe 2014-2019 with previous years. However, the prognosis of MM remains poor as compared to CM. Future studies addressing the effect of immune and targeted therapy in MM are needed to improve outcomes for patients with MM. Background: Mucosal melanoma (MM) is a rare tumour with a poor prognosis. Over the years, immune and targeted therapy have become available and have improved overall survival (OS) for patients with advanced cutaneous melanoma (CM). This study aimed to assess trends in the incidence and survival of MM in the Netherlands against the background of new effective treatments that became available for advanced melanoma. Methods: We obtained information on patients diagnosed with MM during 1990-2019 from the Netherlands Cancer Registry. The age-standardized incidence rate and estimated annual percentage change (EAPC) were calculated over the total study period. OS was calculated using the Kaplan-Meier method. Independent predictors for OS were assessed by applying multivariable Cox proportional hazards regression models. Results: In total, 1496 patients were diagnosed with MM during 1990-2019, mostly in the female genital tract (43%) and the head and neck region (34%). The majority presented with local or locally advanced disease (66%). The incidence remained stable over time (EAPC 3.0%, p = 0.4). The 5-year OS was 24% (95%CI: 21.6-26.0%) with a median OS of 1.7 years (95%CI: 1.6-1.8). Age >= 70 years at diagnosis, higher stage at diagnosis, and respiratory tract location were independent predictors for worse OS. Diagnosis in the period 2014-2019, MM located in the female genital tract, and treatment with immune or targeted therapy were independent predictors for better OS. Conclusion: Since the introduction of immune and targeted therapies, OS has improved for patients with MM. However, the prognosis of MM patients is still lower compared to CM, and the median OS of patients treated with immune and targeted therapies remains fairly short. Further studies are needed to improve outcomes for patients with MM. Show less
Aim: Follow-up strategies for high-grade bone sarcomas have been optimized to facilitate early detection of local recurrence and distant metastasis. The ideology is that early detection enables... Show moreAim: Follow-up strategies for high-grade bone sarcomas have been optimized to facilitate early detection of local recurrence and distant metastasis. The ideology is that early detection enables early treatment presuming better survival. However, the clinical value for each individual patient remains questionable. This study aims to evaluate oncological events after initial treatment in order to assess current follow-up strategies for high-grade bone sarcomas in the Netherlands.Patients and Methods: A retrospective cohort study was conducted based on a national registry. All cases were retrieved from the Netherlands Cancer Registry. Our study consisted of 393 patients treated between 2007 and 2011 with complete follow-up data. Baseline characteristics were analysed for all entities. Local recurrence and distant metastasis was analysed along with overall survival for high-grade chondrosarcoma, high-grade osteo-sarcoma, Ewing sarcoma and chordoma.Results: Median follow-up was 8,3 years for high-grade chondrosarcoma, 4,9 for high-grade osteosarcoma, 3,8 for Ewing sarcoma and 7,5 for chordoma. Median time to local recurrence and distant metastasis was 1,2 years for high-grade osteosarcoma and 1,5 years for Ewing sarcoma. For high-grade osteosarcoma with localized disease at presentation, 0.09 new distant metastatic events per patient per year were seen after five years of follow-up with 11,1 patients needed to follow-up for any event. Five-year overall survival was 60,0% for high-grade chon-drosarcoma, 50,0% for high-grade osteosarcoma, 45,3% for Ewing sarcoma and 71,4% for chordoma.Conclusions: This nationwide study shows a plateau in local recurrences and distant metastatic events after four years of treatment for patients with high-grade osteosarcoma and Ewing sarcoma. Due to a lack of reliable ev-idence however, we were not able to provide additional guidance on follow-up intervals and duration. Collab-orative research with larger groups is needed in order to provide a solid scientific recommendation for follow-up in the heterogenous patient population with bone sarcoma. Show less
Melis, A.S.; Vos, M.; Schuurman, M.S.; Dalen, T. van; Houdt, W.J. van; Hage, J.A. van der; ... ; Dutch Sarcoma Grp (DSG) 2022
Introduction: Timely recognition of soft tissue sarcomas (STS) remains challenging, potentially leading to unplanned excisions (also known as 'whoops procedures'). This population-based study... Show moreIntroduction: Timely recognition of soft tissue sarcomas (STS) remains challenging, potentially leading to unplanned excisions (also known as 'whoops procedures'). This population-based study charted the occurrence of unplanned excisions and identified associated patient, tumour, and treatment-related characteristics. Furthermore, it presents an overview of the outcomes and clinical management following an unplanned excision. Methods: From the Netherlands Cancer Registry (NCR) database, information was obtained on 2187 adult patients diagnosed with STS in 2016-2019 who underwent surgery. Tumours located in the mediastinum, heart or retroperitoneum were excluded, as well as incidental findings. Differences between patients with planned and unplanned excisions were assessed with chi-square tests and a multivariable logistic regression model. Results: Overall, unplanned excisions comprise 18.2% of all first operations for STS, with a quarter of them occurring outside a hospital. Within hospitals, the unplanned excision rate was 14.4%. Unplanned excisions were more often performed on younger patients, and tumours unsuspected of being STS prior to surgery were generally smaller (<= 5 cm) and superficially located. Preoperative imaging was omitted more frequently in these cases. An unplanned excision more often resulted in positive margins, requiring re-excision. Patients who had an unplanned excision outside of a sarcoma centre were more often discussed at or referred to a sarcoma centre, particularly in case of residual tumour. Discussion: Potential improvement in preventing unplanned excisions may be achieved by better compliance to preoperative imaging and referral guidelines, and stimulating continuous awareness of STS among general surgeons, general practitioners and private practices. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Background Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international... Show moreBackground Molecular analysis of KIT and PDGFRA is critical for tyrosine kinase inhibitor treatment selection of gastrointestinal stromal tumors (GISTs) and hence recommended by international guidelines. We performed a nationwide study into the application of predictive mutation testing in GIST patients and its impact on targeted treatment decisions in clinical practice. Methods Real-world clinical and pathology information was obtained from GIST patients with initial diagnosis in 2017-2018 through database linkage between the Netherlands Cancer Registry and the nationwide Dutch Pathology Registry. Results Predictive mutation analysis was performed in 89% of the patients with high risk or metastatic disease. Molecular testing rates were higher for patients treated in expertise centers (96%) compared to non-expertise centers (75%, P < 0.01). Imatinib therapy was applied in 81% of the patients with high risk or metastatic disease without patient's refusal or adverse characteristics, e.g., comorbidities or resistance mutations. Mutation analysis that was performed in 97% of these imatinib-treated cases, did not guarantee mutation-tailored treatment: 2% of these patients had the PDGFRA p.D842V resistance mutation and 7% initiated imatinib therapy at the normal instead of high dose despite of having a KIT exon 9 mutation. Conclusion In conclusion, nationwide real-world data show that over 81% of the eligible high risk or metastatic disease patients receive targeted therapy, which was tailored to the mutation status as recommended in guidelines in 88% of cases. Therefore, still 27% of these GIST patients misses out on mutation-tailored treatment. The reasons for suboptimal uptake of testing and treatment require further study. Show less
Martin, E.; Coert, J.H.; Flucke, U.E.; Slooff, W.B.M.; Ho, V.K.Y.; Graaf, W.T. van der; ... ; Verhoef, C. 2020
Background: Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors... Show moreBackground: Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands.Methods: Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age <= 18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs.Results: A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival.Conclusion: In localized MPNSTs, risk stratification for survival can be done using several patient-and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear. (C) 2019 The Author(s). Published by Elsevier Ltd. Show less
Aims: Chondrosarcoma, osteosarcoma and Ewing sarcoma form the majority of malignant primary tumours of bone. High-grade bone sarcomas require intensive treatment due to their rapid and invasive... Show moreAims: Chondrosarcoma, osteosarcoma and Ewing sarcoma form the majority of malignant primary tumours of bone. High-grade bone sarcomas require intensive treatment due to their rapid and invasive growth pattern and metastasising capabilities. This nationwide study covers overall incidence, treatment and survival patterns of bone sarcomas in a 15-year period (2000-2014) in the total population of the Netherlands.Patients and methods: Data for this study were derived from the Netherlands Cancer Registry, which receives primary notification from the national pathology database. Classification and categorisation was based on the ICD-O-3 classification and the WHO classification 2013 applied according to our clinicopathological expertise. Overall incidence over the 15-year-period was calculated as a rate per 100,000 person-years (using the European Standardised Rate, ESR). Survival was analysed with Kaplan-Meier curves and Cox proportional hazards regression.Results: Incidence for high-grade chondrosarcoma (n = 429) was estimated at 0.15 per 100,000 ESR, and 5-year overall survival at 65.9% (95% confidence interval (CI): 61.0%-70.4%). Incidence for high-grade central osteosarcoma (n = 605) was estimated at 0.25 per 100,000 ESR and 5-year survival at 53.9% (95% CI: 49.7%-58.0%). Ewing sarcoma incidence (n = 334) was estimated at 0.15 per 100,000 ESR and 5-year survival at 59.3% (95% CI: 53.5%-64.6%). For high-grade central osteosarcoma, treatment at a bone tumour centre was associated with better survival (HR 0.593).Conclusions: This study provides comprehensive incidence estimates for all the main primary bone sarcomas over a 15-year time period in a Northern European country with little migration. Centralisation of bone sarcoma care improves the clinical outcome in osteosarcoma. Show less
