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
Single-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying... Show moreSingle-agent Talimogene Laherparepvec (T-VEC) was developed for treatment of unresectable and injectable stage III-IV melanoma. Since its approval and reimbursement, studies have reported varying response rates. The purpose of this systematic review and meta-analysis was to investigate the efficacy and safety of T-VEC. Of 341 publications that were identified, eight studies with a total of 642 patients were included. In patients with stage IIIB-IVM1a, the pooled complete-and overall response rate (CRR and ORR) were 41% and 64%, respectively. In patients with stage IIIB-IVM1c, the pooled CRR and ORR were 30% and 44%, respectively. In patients with stage IVM1b and IVM1c, the pooled CRR and ORR were 4% and 9%, respectively. Adverse events (AEs) were seen in 41-100% of all patients and 0-11% of AEs were severe. In conclusion, single agent T-VEC achieves the highest response rates in patients with early metastatic melanoma and is well-tolerated with generally only mild toxicities. Show less
Lansu, J.; Houdt, W.J. van; Langevelde, K. van; Ende, P.L.A. van den; Graaf, W.T.A. van der; Schrage, Y.; ... ; Haas, R.L. 2021
Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that... Show moreIntroduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS.Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy. The primary endpoint was local progression free survival(LPFS). Secondary endpoints included postponement of systemic therapy, symptom reduction, radiological objective response, and toxicity.Results: Nine patients with a total of 25 lesions were included, with a median follow-up of 23 months. The median number of lesions per patient was three and the trunk wall and bone were the most frequently affected sites. In lesions treated with definitive RT(n = 21), LPFS rates at 1, 2, and 3 years were respectively 73%, 61%, and 40%. Radiological objective response and clinical symptom reduction were achieved in 8/15(53%) and 9/10(90%) of the evaluable lesions, respectively. No local recurrences occurred in lesions treated with RT and metastasectomy(n = 4). For the entire study population, the median postponement of systemic therapy was 10 months. Grade >= 2 toxicity was observed in 2/9(22%) of patients.Conclusions: This trial suggests that 36 Gy could possibly be effective to achieve local control, postpone systemic therapy and reduce symptoms in oMLS. Given the minimal toxicity this treatment could be reasonably considered in oMLS.(c) 2021 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 158 (2021) 33-39 Show less
Breugom, A.J.; Bastiaannet, E.; Guren, M.G.; Korner, H.; Boelens, P.G.; Dekker, F.W.; ... ; Velde, C.J.H. van de 2020
Background: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment... Show moreBackground: The potential benefit of surgery of the primary tumour in patients with asymptomatic metastatic colorectal cancer is debated. This EURECCA international comparison analyses treatment strategies and overall survival in the Netherlands and Norway in patients with incurable metastatic colorectal cancer.Methods: National cohorts (2007-2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer were compared on treatment strategy and overall survival. Using country as an instrumental variable, we assessed the effect of different treatment strategies on mortality in the first year.Results: Of 21,196 patients (16,144 Dutch and 5052 Norwegian), 38.6% Dutch and 51.5% (p < 0.001) Norwegian patients underwent resection of the primary tumour. In the Netherlands, 58.2% received chemotherapy compared with 21.4% in Norway. Radiotherapy was given in 9.5% of Dutch patients and 7.2% of Norwegian patients. Using the Netherlands as reference, the adjusted HR for overall survival was 0.96 (95% CI 0.93-0.99; p = 0.024). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.99-1.02; p = 0.741).Conclusions: Treatment strategies varied significantly between the Netherlands and Norway, with more surgery and less radiotherapy in Norway. Adjusted overall survival was better in Norway for all patients and patients <75 years, but not for patients >= 75 years. Instrumental variable analysis showed no benefit in one-year mortality for a treatment strategy with a higher proportion of surgery and a lower proportion of radiotherapy. Our findings emphasise the need for further research to select patients with incurable metastatic colorectal cancer for different treatment options. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
Bastiaannet, E.; Battisti, N.; Loh, K.P.; Glas, N. de; Soto-Perez-de-Celis, E.; Baldini, C.; ... ; Lichtman, S. 2019
Malignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined... Show moreMalignant melanoma is an aggressive cancer associated with a poor prognosis in patients with metastatic disease. As in many other cancers, the incidence of melanoma rises with age; and combined with the longer life expectancy, this led to an increasing prevalence of melanoma in the older population. Recently, immune checkpoint inhibitors significantly improved the treatment of melanoma given their efficacy and tolerability profile. Two major classes of agents include the anti-cytotoxic T lymphocyte-associated protein 4 (CFLA-4) inhibitors, such as ipilimumab, and the anti-programmed death-ligand 1 (PD-1) inhibitors, such as nivolumab and pembrolizumab. Treatment of metastatic disease with immune checkpoint inhibitors demonstrated improved efficacy and better safety profiles compared to cytotoxic drugs and appears to be an attractive treatment option. Nevertheless, there is a need for tools designed to better predict which older patients will benefit from its use and who will experience toxicities related to the treatment. Current data do not show a major increase in toxicity rates in older patients. However, patients above 75 are often under-represented and those who are included are not representative of the general population of older patients, thereby also stressing the need for real-life data. Ongoing research is aiming at maximizing the potential treatment efficacy and developing novel immune-targeting modalities. Future studies should include older patients and assess geriatric domains in these older patients to better guide decision-making. This review discusses published clinical trials and where known, the efficacy and toxicity in older patients. Moreover, the clinical implications and future perspectives are discussed, with current recommendations for older patients, management of toxicities, and a proposal for an initial approach to the treatment of older patients with metastatic melanoma. (C) 2018 Elsevier Ltd. All rights reserved. Show less
