Improving the treatment of localized rectal cancer, impact of the immunotherapy and new avenues of research

Despite the fact that colon and rectal cancer are frequently treated as one entity, we show that there are subtle biological differences between the two. We argue that for this reason, in this age of targeted treatment the two cancers should be dealt with separately. Rectal cancer is the 7th most common cancer in the word. Localized disease is treated with surgery. When at risk of local or distant relapse patients receive a neo-adjuvant chemoradiotherapy (CRT) or short course radiotherapy (SCRT). Recently, total neo-adjuvant treatment (TNT, combining induction or consolidation chemotherapy with CRT or SCRT) has been shown to improve clinical outcomes. One of the major issues during the management of rectal cancer is the reduction of treatment-related side effects (e.g fecal incontinence due to sphincter removal or damage secondary to surgery or the low anterior syndrome following radiotherapy, particularly in patients who derive little or no benefit from them). Currently there is no routine test capable of predicting the benefit of neoadjuvant treatments; this is part of one of our lines of inquiry. Recently, a dozen patients with localized rectal cancer and harboring a MSI-H tumor have been treated with an anti-PD1 immunotherapy. After a short follow-up, all showed clinical complete response without the need for neo-adjuvant therapy or surgery, allowing the preservation of the organ and its function with a minimum of toxicity. These results suggest that we should select patients molecularly in order to use targeted therapies such as immunotherapy’. In rectal cancer, unlike in colon cancer, MSI-H and POLE mutated tumors are rare, accounting for 1-5% of patients. Although transcriptomic signatures such as CMS point towards a larger subgroup sensitive to immunotherapy, this remains to be clinically confirmed. For MSS rectal cancer patients, a combination of immunotherapy with neo-adjuvant treatments (CRT or TNT but not SCRT) has been tested in six trials. Although the results of the combination with TNT have been disappointing, with pCR ranging from 32% to 46%, the trials reporting on the combination with CRT seem more promising, with pCR ranging from 30% to 33%. Based on some preclinical data, we believe that immunotherapy could be more effective if associated with SCRT. To test this theory, we have designed a trial PEMREC NCT: NCT04109755, which is currently running. Our translation investigations on the effect of neo adjuvant treatment on the tumor microenvironment have led us to believe that this treatment segment, in addition to being clinically beneficial for some patients, can also be used as a molecular target enhancer. Indeed, early results show that immune content change following neoadjuvant treatment in the case of, for example CRT treated patients exhibited lower stromal T helper, T reg, and T cytotoxi

Squamous rectal carcinoma: a rare malignancy, literature review and management recommendations

Squamous cell carcinoma of the rectum is a rare malignancy (0.3% of all rectal cancers), with no known risk factor. These tumours are assessed as rectal cancer using immunohistochemical and radiological tests, and certain criteria (localisation, relationship with neighbouring structures) have to be fulfilled to make the diagnosis. Some clinicians used to stage them with the anal cancer TNM (tumour-node-metastasis), whereas others used the rectal cancer TNM. When localised, the tendency nowadays is to treat those tumours like squamous anal cancers with definitive chemoradiotherapy (5-fluorouracil and mitomycin) and to skip surgery. For metastatic disease there is no clearly validated regimen and treatment should be based on recommendations of squamous anal cancers because of their common histology. Concerning follow-up after a curative approach, techniques should follow those for anal cancer as well, evaluating a delayed response

Emerging Trends for Radio-Immunotherapy in Rectal Cancer

Rectal cancer is a heterogeneous disease at the genetic and molecular levels, both aspects having major repercussions on the tumor immune contexture. Whilst microsatellite status and tumor mutational load have been associated with response to immunotherapy, presence of tumor-infiltrating lymphocytes is one of the most powerful prognostic and predictive biomarkers. Yet, the majority of rectal cancers are characterized by microsatellite stability, low tumor mutational burden and poor T cell infiltration. Consequently, these tumors do not respond to immunotherapy and treatment largely relies on radiotherapy alone or in combination with chemotherapy followed by radical surgery. Importantly, pre-clinical and clinical studies suggest that radiotherapy can induce a complete reprograming of the tumor microenvironment, potentially sensitizing it for immune checkpoint inhibition. Nonetheless, growing evidence suggest that this synergistic effect strongly depends on radiotherapy dosing, fractionation and timing. Despite ongoing work, information about the radiotherapy regimen required to yield optimal clinical outcome when combined to checkpoint blockade remains largely unavailable. In this review, we describe the molecular and immune heterogeneity of rectal cancer and outline its prognostic value. In addition, we discuss the effect of radiotherapy on the tumor microenvironment, focusing on the mechanisms and benefits of its combination with immune checkpoint inhibitors

Gastric squamous cell carcinoma : A rare malignancy, literature review and management recommendations (Review)

Gastric cancer serves a major role in the global cancer burden, being the fourth most frequent cause of mortality among all types of cancer. Gastric squamous cell carcinoma (GSCC) is a rare histological variant accounting for 0.04-0.5% of all gastric cancer cases. Diagnostic work-up of GSCC is essential and involves multiple criteria: i) Tumour not located in the cardia, ii) no oesophageal extension of the tumour, and iii) no evidence of SCC in any other part of the body. Little is known about this rare variant in terms of pathogenesis, risk factors or evolution. Consequently, neither the European Society of Medical Oncology nor the National Comprehensive Cancer Network societies have published recommendations for GSCC. The aim of the present review is to provide an in-depth analysis of the current literature on this pathology, from pathophysiological hypothesis and clinical presentation to diagnostic work-up and treatment trends, in order to establish a possible management algorithm

Rôle de l’échocardiographie avant, pendant et après un traitement anticancéreux

Cardiologists increasingly must face not only the cardiotoxicity of certain cancer therapies, but also the burden of morbidity related to previous chemotherapy in cancer survivors. Due to the formidable effectiveness of novel oncology treatments, cancer patients are treated with drugs with limited experience of their use and systemic toxicity profile, notably their cardiotoxic effects. Echocardiography is recognized as a must in the evaluation of patients before, during and after their potentially cardiotoxic treatment. We discuss how certain echocardiographic parameters, including the evaluation of left ventricular ejection fraction but also other factors that can help guide the management of cancer patients throughout their treatment and beyond.Avec l’amélioration générale du pronostic des cancers, les cardiologues sont de plus en plus confrontés non seulement à la cardiotoxicité immédiate de certaines thérapies oncologiques, mais également à la survenue de complications tardives chez les patients en rémission. Devant l’efficacité redoutable de certaines nouvelles thérapies, les patients bénéficient souvent précocement de molécules pour lesquelles nous manquons de recul quant à leur toxicité potentielle systémique et cardiaque. L’échocardiographie est actuellement reconnue comme un moyen incontournable dans l’évaluation avant, pendant et après un traitement potentiellement cardiotoxique. Nous discutons dans cet article des paramètres échocardiographiques, incluant l’évaluation de la fraction d’éjection du ventricule gauche, mais aussi d’autres facteurs qui peuvent aider à orienter la prise en charge des patients oncologiques tout au long de leur traitement

Physical activity programmes for patients undergoing neo-adjuvant chemoradiotherapy for rectal cancer: A systematic review and meta-analysis

Background: Patients diagnosed with localized rectal cancer should undergo Neoadjuvant Radio-Chemotherapy (NACRT) followed, a few weeks later, by surgical resection. NACRT is known to cause significant decline in the physical and psychological health of patients. This literature review aims to summarize the effects of a prehabilitation programme during and/or after NACRT but before surgery. Methods: Articles included in this review have been selected by two independent researchers on Pubmed, Google Scholar, and Cochrane databases with the following terms: “Rectal Cancer AND Physical Activity” and “Exercise AND Rectal Cancer.” Results: We obtained 560 articles. We selected 12 of these, representing 7 series but only one randomized study, constituting 153 patients in total. Most studies included have considerable variation in their prehabilitation programmes, in terms of supervision, training content, frequency, intensity, duration, and temporality, in regard to NACRT and surgery. Implementing a prehabilitation programme during NACRT seems feasible and safe, with adherence ranging from 58% to 100%. VO2max (maximal oxygen consumption during incremental exercise) was improved in three of the studies during the prehabilitation programme. No significant difference in the step count, 6-minute-walk test, or quality of life was seen. Conclusions: Prehabilitation programmes during NACRT for localized rectal cancer patients are safe and feasible; however, due to considerable variation in the prehabilitation programmes and their small size, impact on fitness, quality of life, and surgical outcome are unknown. Larger randomized studies are needed

Epidémiologie, prise en charge et suivi des polypes colorectaux

Colorectal polyps are frequent in the general population. The diagnostic is made by endoscopy. Polyp's characteristics determine the technic to be used to remove them. Transanal endoscopic microsurgery offers an alternative to radical surgery for large rectal polyps or rectal tumors with low risk of node invasion. One peace resection is necessary to evaluate the resection margins. Lymphatic invasion, ≥ 1 mm submucosae invasion, tumor budding and poorly differentiated tumor are the four main risk factors for node invasion. In case of high risk of lymph node invasion a radical surgery is recommended. Surveillance must be adapted to the polyp type, their number, size, presence of a carcinomatous component as well as age and clinical status of the patient

Cancer colorectal : révolution technologique

Colorectal cancer represents 4500 incidental cases in Switzerland per year, with an incidence increasing among the youngest patients. Technological innovation guides the management of colorectal cancer. Artificial intelligence in endoscopy optimizes the detection of small colonic lesions. Submucosal dissection allows treating extensive lesions at an early stage of the disease. The improvement of surgical techniques, notably robotic surgery, allows limiting complications and optimizing organ preservation. Molecular tools are leading to the development of promising targeted therapies for localized or advanced disease. The development of reference centers tends to bring together this expertise.Le cancer colorectal représente 4500 nouveaux cas par an en Suisse. Son incidence chez les sujets de plus de 50 ans semble se stabiliser, mais chez les plus jeunes elle est en augmentation. La révolution technologique guide sa prise en charge. L’intelligence artificielle en endoscopie optimise la détection de petites lésions coliques. La dissection sous-muqueuse permet de traiter des lésions parfois étendues à un stade précoce de la maladie. L’amélioration des techniques chirurgicales, notamment par robot, vise à limiter les complications et à optimiser la conservation d’organes. Les outils moléculaires aboutissent au développement de thérapies ciblées prometteuses pour les maladies localisées ou celles avancées. Le développement des centres de référence tend à rassembler cette expertise