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Background: Sustained clinical complete remissions were reported in all of 23 mismatch repair deficient/microsatellite instable (dMMR/MSI) locally advanced rectal cancer (LARC) patients treated with dostarlimab alone in a recent phase II study. These results led to off-label use of dostarlimab or other immune checkpoint inhibitors (ICIs) in dMMR/MSI-LARC even before regulatory approval. The present study [STAR(t)-IT-REDUCE] describes the outcome of dMMR/MSI-LARC patients treated with ICI in Italy., Materials and Methods: Investigator-initiated, observational, retrospective-cohort, multicentric study of ICI treatment in dMMR/MSI-LARC. Patients were eligible if treated with ≥1 ICI dose from July 2022 to December 2023 (date of approval of dostarlimab for this indication in Italy)., Results: Seventeen dMMR/MSI-LARC patients (13 of 17 treatment-naïve) were eligible. Fourteen patients completed 6 months of treatment, two discontinued after four doses and one after five doses because of immune-related pneumonia, social constraints, or non-oncological bowel obstruction, respectively. Overall, 16 of 17 assessable patients [94.1%; 95% confidence interval (CI) 69.24% to 99.69%, 'ITT analysis'] achieved complete clinical response (cCR). Ten of 11 treatment-naïve patients completing 6 months of treatment had cCR (90.9%; 95% CI 57.12% to 99.52%, 'per-protocol analysis'). One patient with near-CR underwent rectal surgery and minimal residual intramucosal tumor was found. With a median follow-up of 9.5 months, no local relapse occurred. One patient developed unconfirmed lung metastases. Two grade 3 and no grade 4 adverse events were reported., Conclusion: The present STAR(t)-IT-REDUCE study documents the immunoablative and curative activity of ICI monotherapy in dMMR/MSI-LARC. Toxicity and compliance issues inherent to real-world practice are limited and do not affect achievement of initial complete tumor response but may limit response duration., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Temporary ileostomy is a valuable aid in reducing the severity of complications related to rectal cancer surgery. However, it is still unclear what is the best timing of its closure in relation to the feasibility of an adjuvant treatment, especially considering patient-reported outcomes and health system costs. The aim of the study is to compare the results of an early versus late closure strategy in patients with indication to adjuvant chemotherapy after resection for rectal cancer., Methods and Analysis: This is a prospective multicentre randomised trial, sponsored by Rete Oncologica Piemonte e Valle d'Aosta (Oncology Network of Piedmont and Aosta Valley-Italy). Patients undergone to rectal cancer surgery with temporary ileostomy, aged >18 years, without evidence of anastomotic leak and with indication to adjuvant chemotherapy will be enrolled in 28 Network centres. An early closure strategy (between 30 and 40 days from rectal surgery) will be compared with a late one (after the end of adjuvant therapy). Primary endpoint will be the compliance to adjuvant chemotherapy with and without ileostomy. Complications associated with stoma closure as well as quality of life, costs and oncological outcomes will be assessed as secondary endpoints., Ethics and Dissemination: The trial will engage the Network professional teams in a common effort to improve the treatment of rectal cancer by ensuring the best results in relation to the most correct use of resources. It will take into consideration both the patients' point of view (patient-reported outcome) and the health system perspective (costs analysis). The study has been approved by the Ethical Review Board of Città della Salute e della Scienza Hospital in Turin (Italy). The results of the study will be disseminated by the Network website, medical conferences and peer-reviewed scientific journals., Trial Registration Number: NCT04372992., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To evaluate health-related quality of life (HRQOL), faecal continence and bowel function of patients with rectal cancer who underwent preoperative chemoradiotherapy (pCRT) in a cross-sectional setting., Methods: Out of 185 consecutive patients who underwent pCRT for rectal cancer from 1994 to 2004 at a single institution, 101 were eligible for the study. Causes of exclusion were: death (n = 38), not radical surgery or recurrence (n = 21), presence of stoma at the time of the survey (n = 15), lost to follow-up (n = 6) and miscellaneous (n = 4). Eligible patients were asked to complete: the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, the disease specific colorectal module (EORTC QLQ-CR38) and faecal incontinence and bowel function questionnaires. HRQOL outcomes were compared with reference data from the general population, and the association among clinical variables and HRQOL was also investigated with linear regression analyses., Results: Questionnaires were completed by 80% of eligible patients. Compared to population-based norms, patients showed clinically meaningful worse outcomes in terms of constipation and diarrhoea. Stool fractionation (p < 0.01) and use of enema/laxative (p < 0.01) were negatively associated with global health status/QOL. Urgency negatively affected physical (p < 0.01), role (p < 0.01) and social functioning (p < 0.01). Sensation of incomplete evacuation negatively affected social functioning (p < 0.01)., Conclusions: Although HRQOL profile of these patients is broadly similar to that of healthy subjects, there are still important limitations in terms of key symptoms. The use of validated questionnaires is crucial to provide standardised information on relevant health status areas.

Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment., Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status., Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04)., Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

Concomitant radiochemotherapy in patients with locally advanced rectal carcinoma has been shown to be useful in improving local control and survival in operated patients and in favoring sphincter preservation when administered before surgery. Together with the search for less toxic combinations, cost-analysis of radiochemotherapy has become topical also in consideration of new generation drugs. In this study the analysis was carried out by comparing the costs for 4 different combined modalities in the dual perspective of the payer (the National Health Service) and the provider (the Hospital). Based on their characteristic of treatment and innovative aspects, the following combinations were examined: external beam radiotherapy (ERT) 50.4 Gy + 5FU bolus; ERT 50.4 Gy + 5FU protracted infusion; ERT 50.4 Gy + 5FU continuous infusion, week 1 and 5; ERT 50.4 Gy+ Tomudex bolus. Costs were evaluated based on the frequency and type of specific services provided in therapeutic protocols: the positioning of central venous catheter, time of stay in day-hospital or hospital ward and the cost of drugs. Calculations were carried out based on an "ideal" patient of 1.7 sqm body surface. Costs were based on out patient rates, DRGs and the official drug list valid to September 1999. As for day-hospital costs afforded by the payer it is observed that the most expensive combinations are bolus and continuous infusion followed by protracted infusion; Tomudex, is the most economic. As for hospital costs afforded by the provider, it is observed that the most expensive combination is continuous infusion followed by protracted infusion, bolus administration and Tomudex. In conclusion, doctors are increasingly involved in the economic and organizational aspects of therapeutic decisions; however, the patient's needs should be kept in mind; apart from the therapeutic benefits, lower toxicity and ready use of treatments are amongst the patient's needs. The analysis of the patient's satisfaction is still lacking suitable means of evaluation, however it should be defined and carefully studied for an exhaustive evaluation of the impact of combined modality therapy.