Improvement of perioperative outcomes of gastric gastrointestinal stromal tumour (GIST) resections and the influence of minimal invasive surgery

Background: Safety of minimally invasive surgery (MIS) for gastrointestinal stromal tumours (GISTs) is still under debate since it might increase the risk of tumour rupture, especially in larger tumours. The aim of this study was to investigate trends in treatment and perioperative outcomes of patients undergoing resections of gastric GISTs over time. Methods: This was a multicentre retrospective study of consecutive patients who underwent wedge resection or partial gastrectomy for localized gastric GIST at five GIST reference centres between January 2009 and January 2022. To evaluate changes in treatment and perioperative outcomes over time, patients were divided into four equal periods. Perioperative outcomes were analysed separately and as a novel composite measure textbook outcome (TO). Results: In total 385 patients were included. Patient and tumour characteristics did not change over time, except for median age (62-65-68-68 years, p = 0.002). The proportion of MIS increased (4.0%-9.8%-37.4%–53.0 %, p &lt; 0.001). Postoperative complications (Clavien Dindo ≥2; 22%-15%-11%–10 %, p = 0.146), duration of admission (6-6-5-4 days, p &lt; 0.001) and operating time (92-94-77-73 min, p = 0.007) decreased over time while TO increased (54.0%- 52.7%-65.9%–76.0 %, p &lt; 0.001). No change was seen in perioperative ruptures (6.0%- 3.6%-1.6%–3.0 %, p = 0.499). MIS was correlated with less CD ≥ 2 complications (p = 0.006), shorter duration of admission (p &lt; 0.001) and more TO (p &lt; 0.001). Similar results were observed in tumours ≤5 cm and &gt;5 cm. Conclusion: A larger percentage of gastric GIST were treated with MIS over time. MIS was correlated with less complications, shorter duration of admission and more TO. Tumour rupture rates remained low over time.</p

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

Importance Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity.Objective To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity.Design, setting, and participants The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020.Interventions The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks.Main outcomes and measures As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects.Results Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%.Conclusions and relevance The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers.Trial registration ClinicalTrials.gov Identifier: NCT02106312

Local treatment in metastatic GIST patients: A multicentre analysis from the Dutch GIST Registry

Background: The 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. Methods: A 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. Results: The 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. Conclusion: Local 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