Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial.

BACKGROUND: Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone. METHODS: MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants. FINDINGS: Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group. INTERPRETATION: Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone. FUNDING: National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).

Intensity modulated radiotherapy (IMRT) in the management of locally advanced oropharyngeal squamous cell carcinomata (SCC): disease control and functional outcome using the therapy outcome measure (TOM) score--report from a single U.K. institution.

INTRODUCTION: This paper evaluates tumour control and toxicity especially in relation to swallowing dysfunction in those patients with locally advanced oropharyngeal squamous cell carcinoma who have undergone either primary chemo-radiation or post-operative parotid sparing IMRT. The TOM scoring system was used to assess dysphagia. METHODS: All patients with locally advanced (stage 3/4) squamous cell oropharyngeal cancer and who required either primary or post-operative RT were identified. Toxicity was recorded prospectively. The TOM score (0-5 where 5 indicates that the patient is able to eat a normal diet and 0-2 varying degrees of enteral feeding dependency), weights and trismus was recorded immediately prior to and following radiotherapy. RESULTS: 24 patients were identified between 1/2003 and 11/2007. Median weight loss during radiotherapy was 9 kg. All but one patient had a gastrostomy (RIG) tube inserted prophylactically. With a mean follow-up of 37.1 months, 62.5% of pts had a TOM score of 5, 12.5% scored 3, 8% scored and 17% scored 0-2. For those patients whose swallowing function did recover, it took on average 8.7 months. 15% patients experienced trismus secondary to radiotherapy. 2 year overall survival was 92% and disease specific survival 96%. CONCLUSION: Excellent disease control with intensified schedules of radiotherapy with IMRT has been achieved in this patient population. Intermediate toxicity is significant but with longer follow-up, dysphagia continues to improve with 75% of patients not requiring any form of enteral or oral supplementation.