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Background: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response., Patients and Methods: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified. Data on patient, disease, treatment, and response-specific factors were explored for potential risk factors. Overall treatment numbers were used to estimate incidence., Results: Nine patients from eight European centres were included. Common features were hepatic flexure location (5/9), T4 radiological staging (6/9), annular shape (8/9), radiological stricturing (5/9), and endoscopic obstruction (6/9). All received pembrolizumab and obstructed between 45 and 652 days after starting treatment. Seven patients underwent surgical resection; one was managed with a defunctioning stoma; and one was managed conservatively. One patient died from obstruction. Radiological response was seen in eight patients, including two complete responses. Pathological response was seen in all seven who underwent resection, including four complete responses. The overall incidence of immunotherapy response-related obstruction in these centres was 1.51%., Conclusions: Bowel obstruction associated with immunotherapy response may represent a rare treatment-related complication in dMMR CC. Clinicians must recognise this safety signal and share experience to maintain patient safety., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Mismatch repair (MMR) deficient (dMMR) colon cancer (CC) is distinct from MMR proficient (pMMR) CC, yet the impact of MMR status on radiological staging is unclear. The purpose of this study was to investigate how MMR status impacts CC CT staging., Methods: We retrospectively compared CT staging accuracy between dMMR and pMMR CC patients undergoing curative resection. Accuracy was assessed as individual tumour (T)/nodal (N) stages and as dichotomous "statuses" (T1/2 vs T3/4; N0 vs N1/2). Patient characteristics were analysed for factors to support staging., Results: There was no significant difference in overall staging accuracy between the dMMR (44 patients) and pMMR (57 patients) groups. dMMR tumours with incorrect N stage/"status" were more likely to be overstaged than pMMR tumours (90% vs 59%; p = 0.023 for "N status"). Platelet count, CRP and neutrophil count (AUC 0.76 ( p = 0.0078), 0.75 ( p = 0.034) and 0.70 ( p = 0.044), respectively) were associated with "N status" in dMMR tumours., Conclusion: Whilst overall staging accuracy was similar between groups, incorrectly N staged dMMR tumours were more likely to be overstaged than pMMR tumours, risking inappropriate surgical or neoadjuvant treatment. We describe novel relationships between several inflammatory markers and pathological "N status" in dMMR CC, which if integrated into routine practice may improve CT staging accuracy., Advances in Knowledge: Compared to pMMR CC, dMMR CC is at significant risk of N overstaging. Platelet count, CRP and neutrophil count are higher in dMMR CC patients with nodal metastases than those without, and their role in refining clinical staging requires further investigation.

Aim: The international FOxTROT trial, recently published in the Journal of Clinical Oncology is the first randomized controlled trial testing neoadjuvant chemotherapy (NAC) with oxaliplatin and 5-fluorouracil in locally advanced, but operable, colon cancer. The trial met its primary endpoint with fewer patients experiencing recurrent or residual disease at 2 years with NAC compared with the control (16.8% vs. 21.2%, risk ratio = 0.74, p  = 0.042). Translating the findings of the FOxTROT trial into improved patient outcomes is dependent on implementation of new neoadjuvant chemotherapy (NAC) pathways in colorectal cancer., Method: We describe our experience implementing a novel neoadjuvant treatment pathway in colorectal cancer at a large UK teaching hospital., Results: To date 64 patients have been commenced on the novel pathway following presentation and adoption of the FOxTROT trial results. We present key lessons and strategies developed across the multidisciplinary team to minimize impact on person hours, service capacity and budget, whilst building patient safety and confidence., Conclusion: Use of NAC for locally advanced colon cancer has been shown to improve surgical outcomes and longer term cancer outcomes. Provision of NAC requires some modifications to current treatment pathways but can be delivered with team working and without the requirement for additional resources., (© 2022 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Treating older adults with cancer is increasingly important in modern oncology practice. However, we currently lack the high-quality evidence needed to guide optimal management of this heterogeneous group. Principally, historic under-recruitment of older adults to clinical trials limits our understanding of how existing evidence can be applied to this group. Such uncertainty is particularly prevalent in the management of colon cancer (CC). With CC being most common in older adults, many patients also suffer from frailty, which is recognised as being strongly associated with poor clinical outcomes. Conducting clinical trials in older adults presents several major challenges, many of which impact the clinical relevance of results to a real-world population. When considering this heterogeneous group, it may be difficult to define the target population, recruit participants effectively, choose an appropriate trial design, and ensure participants remain engaged with the trial during follow-up. Furthermore, after overcoming these challenges, clinical trials tend to enrol highly selected patient cohorts that comprise only the fittest older patients, which are not representative of the wider population. FOxTROT1 was the first phase III randomised controlled trial to illustrate the benefit of neoadjuvant chemotherapy (NAC) in the treatment of CC. Patients receiving NAC had greater 2-year disease-free survival compared to those proceeding straight to surgery. Outcomes for older adults in FOxTROT1 were similarly impressive when compared to their younger counterparts. Yet, this group inevitably represents a fitter subgroup of the older patient population. FOxTROT2 has been designed to investigate NAC in a full range of older adults with CC, including those with frailty. In this review, we describe the key challenges to conducting a robust clinical trial in this heterogeneous patient group, highlight our strategies for overcoming these challenges in FOxTROT2, and explain how we hope to provide clarity on the optimal treatment of CC in older adults., Competing Interests: Disclosure ZC has received grants from Celgene, MSD, Amgen, and Takeda (via institution). MS has received a grant from Yorkshire Cancer Research to support provision of a clinical trial (via institution). MB has received payment/honoraria from Laboratoires Pierre Fabre, Amgen, and Servier, is Co-lead of Audit for the National Bowe Cancer Audit (England and Wales), and author of the National Institute for Health and Care Excellence (NICE) Colorectal Cancer Guideline. JR has received grants from Bristol Meyers Squibb, Laboratoires Pierre Fabre, Servier, HUB Organoids, and Cleara Biotech (via institution), consulting fees from Bayer, Bristol Meyers Squibb, Merck-Serono, Laboratoires Pierre Fabre, and Servier (via institution), payment/honoraria from Bristol Meyers Squibb, Laboratoires Pierre Fabre, and Servier (via institution), and support for attending meetings from Servier. JR is also a member of advisory boards for the PelvEx and MEND-IT trials, and a member of the ONCODE clinical advisory board. CP has received consulting fees from Nordic Pharma (via institution). JT has received payment/honoraria from Astellas Pharma Inc., Bristol Meyers Squibb, MSD, Merck & Co., Roche, Laboratoires Pierre Fabre, Novartis, and Servier, support for attending meetings from Laboratoires Pierre Fabre, MSD, and Servier, and is a member of advisory boards for Bristol Meyers Squibb, MSD, Merck & Co., Roche, Laboratoires Pierre Fabre, Novartis, and Servier. JB has received grants from Cancer Research UK, the National Institute for Health and Care Research, Medical Research Council, and Roche, and is Chair of the advisory board for the NIHR By-Band-Sleeve trial and the NIHR Health Technology Assessment General Funding Committee. DAC has received grants from Yorkshire Cancer Research (via institution) and support for attending meetings from Celgene. JFS has received consulting fees from Seagen, payment/honoraria from Laboratoires Pierre Fabre, Merck-Serono, and Servier, and support for attending meetings from Servier and Bristol Meyers Squibb. JFS is also a member of advisory boards for Elevation Oncology, Laboratoires Pierre Fabre, and Zentalis Pharmaceuticals. JFS, JB, and DM have received support from Yorkshire Cancer Research for the FOxTROT 2 trial, on which this manuscript is based (via institution). All other authors have declared no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)