[Treatment of localized rectal cancer in 2024]. / Prise en charge du cancer du rectum localisé en 2024.

The management of localized rectal cancer has evolved significantly over the last two years. On one hand, intensification of treatments (radio-chemotherapy, chemotherapy, then surgery) for the most advanced tumors has shown an improvement in clinical results compared to less intense regiments. On the other hand, the possibility, as for prostate cancers, of opting for active surveillance without surgery in patients presenting a complete clinical response after a treatment phase, is now accepted. More recently, the Swiss recommendations for the surveillance of rectal cancer have been modified and now differ from those of colon cancers, by incorporating pelvic MRI and rectoscopy in addition, as well as special guidelines for tumors under active surveillance.

La prise en charge du cancer du rectum localisé a beaucoup évolué ces deux dernières années. D'un côté, l'intensification des traitements (radio-chimiothérapie, chimiothérapie, puis chirurgie) pour les tumeurs les plus avancées a montré une amélioration des résultats cliniques par rapport aux traitements moins intenses. De l'autre côté, la possibilité, comme pour les cancers de la prostate, d'opter pour une surveillance active sans chirurgie chez les patients présentant une réponse clinique complète après une phase de traitement est aujourd'hui acceptée. Plus récemment, les recommandations suisses pour la surveillance du cancer du rectum ont été modifiées et se différencient maintenant de celles des cancers du côlon, en incorporant IRM pelvienne et rectoscopie en sus, de même qu'un suivi spécial pour les tumeurs en surveillance active.

Artificial intelligence for characterization of colorectal polyps: Prospective multicenter study.

Background and study aims Optical diagnosis poses challenges to implementation of "resect and discard" strategies. This study aimed to assess the feasibility and performance of a new commercially available system for colorectal polyps. Patients and methods Nine expert endoscopists in three centers performed colonoscopies using artificial intelligence-equipped colonoscopes (CAD EYE, Fujifilm). Histology and predictions were compared, with hyperplastic polyps and sessile serrated lesions grouped for analysis. Results Overall, 253 polyps in 119 patients were documented (n=152 adenomas, n=78 hyperplastic polyps, n=23 sessile serrated lesions). CAD EYE detected polyps before endoscopists in 81 of 253 cases (32%). The mean polyp size was 5.5 mm (SD 0.6 mm). Polyp morphology was Paris Ip (4 %), Is (28 %), IIa (60 %), and IIb (8 %). CAD EYE achieved a sensitivity of 80%, specificity of 83%, positive predictive value (PPV) of 96%, and negative predictive value (NPV) of 72%. Expert endoscopists had a sensitivity of 88%, specificity of 83%, PPV of 96%, and NPV of 72%. Diagnostic accuracy was similar between CAD EYE (81%) and endoscopists (86%). However, sensitivity was greater with endoscopists as compared with CAD EYE ( P <0.05). CAD EYE classified sessile serrated lesions as hyperplasia in 22 of 23 cases, and endoscopists correctly classified 16 of 23 cases. Conclusions The CAD EYE system shows promise for detecting and characterizing colorectal polyps. Larger studies are needed, however, to confirm these findings.

[Abdominal surgery: what's new in 2023]. / Chirurgie viscérale: ce qui a changé en 2023.

In 2023, robotic surgery has witnessed an expansion in the number of surgical procedures and in the number of platforms on the market. We illustrate the phenomenon, by exploring parietal, œso-gastric and liver robotic surgery. Surgical innovation aligns with advancements in oncology. Immunotherapy now enables "watch and wait" strategies for patients with colorectal cancer, and decreases recurrence rate and improves survival after liver surgery for hepatocellular carcinoma and œso-gastric surgery. The multidisciplinary field of obesity management has seen the development of new medications, diversifying the treatment options, while surgery continues to deliver the best weight-loss outcomes.

En 2023, la chirurgie robotique a poursuivi son expansion avec une augmentation du nombre d'interventions et la mise sur le marché de nouvelles plateformes. Ce phénomène est illustré dans cet article par la description des chirurgies robotique pariétale, œsogastrique et hépatique. L'innovation en chirurgie accompagne aussi celle de l'oncologie. L'immunothérapie permet maintenant une stratégie « watch and wait ¼ chez les patients avec un cancer colorectal, diminue le risque de récidive et améliore la survie après chirurgie hépatique pour un carcinome hépatocellulaire et chirurgie œsogastrique. Le domaine multidisciplinaire de la prise en charge de l'obésité a aussi vu l'arrivée de nouveaux traitements médicamenteux, qui viennent diversifier les options thérapeutiques, où la chirurgie continue d'apporter les meilleurs résultats en termes de perte de poids.

Feasibility, criterion and construct convergent validity of the 2-minute walk test and the 10-meter walk test in an oncological context.

Objective: To examine the feasibility, the criterion, and the construct convergent validity of the 2-Minute Walk Test (2MWT) and the 10-Meter Walk Test (10MeWT) against the 6-Minute Walk Test (6MWT) to assess walking capacity in people with cancer. The criterion concurrent validity of a self-test version of the 10MeWT (10MeWTself-test) was also evaluated against the 10MeWT. Methods: Fifty-six people with cancer performed the 2MWT, the 10MeWT at comfortable and fast speeds, the 6MWT, and the 10MeWTself-test. The feasibility of the tests was assessed using safety, adverse events, space requirements, time taken to administer and interpret the tool, equipment or training required, cost, and portability as criteria. Validity was assessed using Pearson correlation coefficients and Bland Altman plots. Results: The 2MWT, 6MWT, 10MeWT, and 10MeWTself-test were feasible for people with cancer. The 2MWT and the 10MeWT results were moderately to strongly correlated with the 6MWT results (0.61 < r < 0.84, p < 0.001). The 10MeWTself-test results were strongly correlated with the 10MeWT results at comfortable and fast speeds (r = 0.99, p < 0.001). Conclusions: The 2MWT, 10MeWT, and 10MeWTself-test are simple, rapid, and feasible tests for use in people with cancer. The strong correlation between the 2MWT and 6MWT results indicates that the 2MWT can be used as an alternative walking capacity assessment tool. The 10MeWT results moderately correlated with those of the other two tests, suggesting that it partially measures the same construct of walking capacity in walking-independent outpatients with cancer. The 10MeWTself-test showed promising results but needs further investigations in ecological settings.

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.

In Vivo Thermal Ablation of Deep Intrahepatic Targets Using a Super-Convergent MRgHIFU Applicator and a Pseudo-Tumor Model.

BACKGROUND: HIFU ablation of liver malignancies is particularly challenging due to respiratory motion, high tissue perfusion and the presence of the rib cage. Based on our previous development of a super-convergent phased-array transducer, we aimed to further investigate, in vivo, its applicability to deep intrahepatic targets. METHODS: In a series of six pigs, a pseudo-tumor model was used as target, visible both on intra-operatory MRI and post-mortem gross pathology. The transcostal MRgHIFU ablation was prescribed coplanar with the pseudo-tumor, either axial or sagittal, but deliberately shifted 7 to 18 mm to the side. No specific means of protection of the ribs were implemented. Post-treatment MRI follow-up was performed at D7, followed by animal necropsy and gross pathology of the liver. RESULTS: The pseudo-tumor was clearly identified on T1w MR imaging and subsequently allowed the MRgHIFU planning. The peak temperature at the focal point ranged from 58-87 °C. Gross pathology confirmed the presence of the pseudo-tumor and the well-delineated MRgHIFU ablation at the expected locations. CONCLUSIONS: The specific design of the transducer enabled a reliable workflow. It demonstrated a good safety profile for in vivo transcostal MRgHIFU ablation of deep-liver targets, graded as challenging for standard surgery.

[Colorectal cancer: technological revolution]. / 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.

Platform combining statistical modeling and patient-derived organoids to facilitate personalized treatment of colorectal carcinoma.

BACKGROUND: We propose a new approach for designing personalized treatment for colorectal cancer (CRC) patients, by combining ex vivo organoid efficacy testing with mathematical modeling of the results. METHODS: The validated phenotypic approach called Therapeutically Guided Multidrug Optimization (TGMO) was used to identify four low-dose synergistic optimized drug combinations (ODC) in 3D human CRC models of cells that are either sensitive or resistant to first-line CRC chemotherapy (FOLFOXIRI). Our findings were obtained using second order linear regression and adaptive lasso. RESULTS: The activity of all ODCs was validated on patient-derived organoids (PDO) from cases with either primary or metastatic CRC. The CRC material was molecularly characterized using whole-exome sequencing and RNAseq. In PDO from patients with liver metastases (stage IV) identified as CMS4/CRIS-A, our ODCs consisting of regorafenib [1 mM], vemurafenib [11 mM], palbociclib [1 mM] and lapatinib [0.5 mM] inhibited cell viability up to 88%, which significantly outperforms FOLFOXIRI administered at clinical doses. Furthermore, we identified patient-specific TGMO-based ODCs that outperform the efficacy of the current chemotherapy standard of care, FOLFOXIRI. CONCLUSIONS: Our approach allows the optimization of patient-tailored synergistic multi-drug combinations within a clinically relevant timeframe.

Immunotherapy in Urological, Gynecological and Gastrointestinal Cancers - Current Landscape.

Immunotherapy is becoming increasingly important in the management of urological, gynecological, and gastrointestinal cancers. Immune checkpoint inhibitor-based combinations have become a standard of care for patients with metastatic renal and liver cancers, as well as for many patients with bladder, cervical, gastric, and esophageal cancers, based on various biomarkers. Some tumor types are less responsive to immunotherapy, such as prostate and colon cancer. In these tumors, however, a subgroup of patients with a microsatellite-instability-high/DNA-mismatch repair deficient molecular phenotype significantly benefits from immunotherapy. Molecular characterization is therefore essential to identify patients who may benefit from these treatments. One of the major challenges is the search for new predictive biomarkers and novel combinations or strategies to further improve patient outcome.

Surgical Prehabilitation in Patients with Gastrointestinal Cancers: Impact of Unimodal and Multimodal Programs on Postoperative Outcomes and Prospects for New Therapeutic Strategies-A Systematic Review.

The advantages of prehabilitation in surgical oncology are unclear. This systematic review aims to (1) evaluate the latest evidence of preoperative prehabilitation interventions on postoperative outcomes after gastrointestinal (GI) cancer surgery and (2) discuss new potential therapeutic targets as part of prehabilitation. Randomized controlled trials published between January 2017 and August 2022 were identified through Medline. The population of interest was oncological patients undergoing GI surgery. Trials were considered if they evaluated prehabilitation interventions (nutrition, physical activity, probiotics and symbiotics, fecal microbiota transplantation, and ghrelin receptor agonists), alone or combined, on postoperative outcomes. Out of 1180 records initially identified, 15 studies were retained. Evidence for the benefits of unimodal interventions was limited. Preoperative multimodal programs, including nutrition and physical activity with or without psychological support, showed improvement in postoperative physical performance, muscle strength, and quality of life in patients with esophagogastric and colorectal cancers. However, there was no benefit for postoperative complications, hospital length of stay, hospital readmissions, and mortality. No trial evaluated the impact of fecal microbiota transplantation or oral ghrelin receptor agonists. Further studies are needed to confirm our findings, identify patients who are more likely to benefit from surgical prehabilitation, and harmonize interventions.

Promises and Challenges of Predictive Blood Biomarkers for Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy.

The treatment of locally advanced rectal cancer (LARC) requires a multimodal approach combining neoadjuvant radiotherapy or chemoradiotherapy (CRT) and surgery. Predicting tumor response to CRT can guide clinical decision making and improve patient care while avoiding unnecessary toxicity and morbidity. Circulating biomarkers offer both the advantage to be easily accessed and followed over time. In recent years, biomarkers such as proteins, blood cells, or nucleic acids have been investigated for their predictive value in oncology. We conducted a comprehensive literature review with the aim to summarize the status of circulating biomarkers predicting response to CRT in LARC. Forty-nine publications, of which forty-seven full-text articles, one review and one systematic review, were retrieved. These studies evaluated circulating markers (CEA and CA 19-9), inflammatory biomarkers (CRP, albumin, and lymphocytes), hematologic markers (hemoglobin and thrombocytes), lipids and circulating nucleic acids (cell-free DNA [cfDNA], circulating tumor DNA [ctDNA], and microRNA [miRNA]). Post-CRT CEA levels had the most consistent association with tumor response, while cfDNA integrity index, MGMT promoter methylation, ERCC-1, miRNAs, and miRNA-related SNPs were identified as potential predictive markers. Although circulating biomarkers hold great promise, inconsistent results, low statistical power, and low specificity and sensibility prevent them from reliably predicting tumor response following CRT. Validation and standardization of methods and technologies are further required to confirm results.

The first comprehensive genomic characterization of rectal squamous cell carcinoma.

BACKGROUND: Rectal cancers represent 35% of colorectal cancers; 90% are adenocarcinomas, while squamous cell carcinoma accounts for 0.3% of them. Given its rarity, little is known concerning its pathogenesis, molecular profile and therapeutic management. The current treatment trend is to treat rectal squamous cell carcinoma by analogy to anal squamous cell carcinoma with definitive chemo-radiotherapy, setting aside surgery in case of local recurrence. METHODS: We performed an in-depth genomic analysis (next-generation sequencing, copy number variation, and human papilloma virus characterization) on 10 rectal squamous cell carcinoma samples and compared them in silico to those of anal squamous cell carcinoma and rectal adenocarcinoma. RESULTS: Rectal squamous cell carcinoma shows 100% HPV positivity. It has a mutational (PIK3CA, PTEN, TP53, ATM, BCL6, SOX2) and copy number variation profile (3p, 10p, 10q, 16q deletion and 1q, 3q, 5p, 8q, 20p gain) similar to anal squamous cell carcinoma. PI3K/Akt/mTOR is the most commonly affected signaling pathway similarly to anal squamous cell carcinoma. Most commonly gained or lost genes seen in rectal adenocarcinoma (FLT3, CDX2, GNAS, BCL2, SMAD4, MALT1) are not found in rectal squamous cell carcinoma. CONCLUSION: This study presents the first comprehensive genomic characterization of rectal squamous cell carcinoma. We confirm the existence of this rare histology and its molecular similarity with anal squamous cell carcinoma. This molecular proximity confirms the adequacy of therapeutic management based on histology and not localization, suggesting that rectal squamous cell carcinoma should be treated like anal squamous cell carcinoma and not as a rectal adenocarcinoma.

FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells.

FOLFOXIRI, i.e., the combination of folinic acid, 5-fluorouracil, oxaliplatin, and irinotecan, is a first-line treatment for colorectal carcinoma (CRC), yet non-personalized and aggressive. In this study, to mimic the clinical situation of patients diagnosed with advanced CRC and exposed to a chronic treatment with FOLFOXIRI, we have generated the CRC cell clones chronically treated with FOLFOXIRI. A significant loss in sensitivity to FOLFOXIRI was obtained in all four cell lines, compared to their treatment-naïve calls, as shown in 2D cultures and heterotypic 3D co-cultures. Acquired drug resistance induction was observed through morphometric changes in terms of the organization of the actin filament. Bulk RNA sequencing revealed important upregulation of glucose transporter family 5 (GLUT5) in SW620 resistant cell line, while in the LS174T-resistant cell line, a significant downregulation of protein tyrosine phosphatase receptor S (PTPRS) and oxoglutarate dehydrogenase-like gene (OGDHL). This acquired resistance to FOLFOXIRI was overcome with optimized low-dose synergistic drug combinations (ODCs) acting via the Ras-Raf-MEK-ERK pathway. The ODCs inhibited the cell metabolic activity in SW620 and LS174T 3Dcc, respectively by up to 82%.

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin.

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.

Study protocol of a phase II study to evaluate safety and efficacy of neo-adjuvant pembrolizumab and radiotherapy in localized rectal cancer.

BACKGROUND: Reshaping the tumor microenvironment by novel immunotherapies represents a key strategy to improve cancer treatment. Nevertheless, responsiveness to these treatments is often correlated with the extent of T cell infiltration at the tumor site. Remarkably, microsatellite stable rectal cancer is characterized by poor T cell infiltration and, therefore, does not respond to immune checkpoint blockade. To date, the only available curative option for these patients relies on extensive surgery. With the aim to broaden the application of promising immunotherapies, it is necessary to develop alternative approaches to promote T cell infiltration into the tumor microenvironment of these tumors. In this regard, recent evidence shows that radiotherapy has profound immunostimulatory effects, hinting at the possibility of combining it with immunotherapy. The combination of long-course chemoradiotherapy and immune checkpoint inhibition was recently shown to be safe and yielded promising results in rectal cancer, however short-course radiotherapy and immune checkpoint inhibition have never been tested in these tumors. METHODS: Our clinical trial investigates the clinical and biological impact of combining pembrolizumab with short-course radiotherapy in the neo-adjuvant treatment of localized rectal cancer. This phase II non-randomized study will recruit 25 patients who will receive short-course preoperative radiotherapy (5 Gy × 5 days) and four injections of pembrolizumab starting on the same day and on weeks 4, 7 and 10. Radical surgery will be performed three weeks after the last pembrolizumab injection. Our clinical trial includes an extensive translational research program involving the transcriptomic and proteomic analysis of tumor and blood samples throughout the course of the treatment. DISCUSSION: Our study is the first clinical trial to combine short-course radiotherapy and immune checkpoint inhibition in rectal cancer, which could potentially result in a major breakthrough in the treatment of this cancer. Additionally, the translational research program will offer insights into immunological changes within the tumor and blood and their correlation with patient outcome. Taken together, our work will help optimizing future treatment combinations and, possibly, better selecting patients. TRIAL REGISTRATION: This study was registered with www. CLINICALTRIAL: gov : NCT04109755 . Registration date: June, 2020.

Highlights from the 2022 ASCO gastrointestinal cancer symposium: An overview by the EORTC gastrointestinal tract cancer group.

Recently, we have witnessed impressive diagnostic and therapeutic changes for gastrointestinal cancer patients. New challenges brought by the COVID-19 pandemic have led us to re-evaluate our work priorities. Thanks to the commendable resilience of both investigators and patients, however, clinical research never stopped. In addition to conducting cutting-edge research and serving patients' needs, as EORTC Gastrointestinal Tract Cancer Group, we are committed to pursuing educational initiatives beneficial to the entire European oncology community and beyond. In this regard, we have been providing critical discussions of new data from major international meetings. In this article, we discuss results of important selected studies presented at the 2022 ASCO Gastrointestinal Cancer Symposium, putting them in perspectives and highlighting potential implications for routine practice. With the number of in-person attendees and practice-changing/informing trials presented, this meeting represented a milestone in the return to normality as well as in the fight against cancer.

[Intraperitoneal therapy for carcinomatosis in ovarian cancer: proposed treatment algorithm]. / Traitements intrapéritonéaux de la carcinose ovarienne : proposition d'algorithmes décisionnels.

Ovarian cancer is the first cause of death by gynecological cancer. Most of the patients are diagnosed with peritoneal carcinomatosis that represents a therapeutic challenge. Its management implies maximal cytoreductive surgery with survival benefit. Over the last three decades, several strategies of intra-peritoneal chemotherapy have been investigated. This includes intra-peritoneal adjuvant chemotherapy that is used mainly in North America, hyperthermic intraperitoneal chemotherapy (HIPEC) and more recently pressurized intraperitoneal aerosol chemotherapy (PIPAC). In the current article, we review the evidence in favor of each therapeutic approach, and we propose treatment algorithms depending on the clinical situation of ovarian cancer patients: upfront, platinum-sensitive and platinum-resistant relapse.

Le cancer de l'ovaire est la première cause de décès par cancer gynécologique. La plupart des patientes sont diagnostiquées au stade de carcinose péritonéale qui représente un défi thérapeutique. Sa prise en charge chirurgicale implique une cytoréduction maximaliste. Au cours des 30 dernières années, plusieurs stratégies de chimiothérapie intrapéritonéale ont été testées afin d'améliorer le contrôle de la carcinose péritonéale. Il s'agit des chimiothérapies intrapéritonéale adjuvante utilisée surtout en Amérique du Nord, hyperthermique intrapéritonéale (CHIP) et intrapéritonéale pressurisée en aérosols (PIPAC). Dans cet article, nous reprenons les données de la littérature sur chacune de ces trois approches thérapeutiques et proposons des algorithmes décisionnels selon la situation clinique des patientes traitées pour un cancer de l'ovaire : au diagnostic, récidive platine-sensible et platine-résistante.

Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?

OPINION STATEMENT: Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3-6 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors. Therapeutic strategies are driven by the number and localisation of the lesion, consisting in local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. Novel treatment modalities are slowly finding their way into this shy unconsented armatorium including immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors, or a combination of those, among others.This article reviews the pioneering strategies aiming at understanding, diagnosing, and managing this disease, and discusses future directions, challenges, and potential innovations in each of these domains. HIGHLIGHTS: • With the increasing survival in CRC, brain and other rare/late-onset metastases are rising. • Distal colon/rectal primary location, long-standing progressive lung metastases, and longer survival are risk factors for BM development in CRC. • Late diagnosis and lack of consensus treatment strategies make BM-CRC diagnosis very dismal. • Liquid biopsies using circulating tumor cells might offer excellent opportunities in the early diagnosis of BM-CRC and the search for therapeutic options. • Multi-modality treatment including surgical metastatic resection, postoperative SRS with/without WBRT, and chemotherapy is the best current treatment option. • Recent mid-sized clinical trials, case reports, and preclinical models show the potential of unconventional therapeutic approaches as monoclonal antibodies, targeted therapies, and immunotherapy. Graphical abstract.

Influence of chemotherapy on postural control and quality of life in women with gynaecological cancer: a protocol of a prospective observational study.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy is a frequent side effect of some chemotherapies that can cause postural control disorders and has a serious impact on quality of life (QoL). An enhanced understanding of postural control dysfunction could help build a systematic and accurate assessment as well as specific exercises to limit the impact on QoL. This study aims to assess the influence of chemotherapy on postural control and the QoL for women with gynaecological cancer. METHODS AND ANALYSIS: This prospective observational study will include 37 participants with cancer treated using neurotoxic chemotherapy. Their postural control in various conditions (rigid and foam surfaces, eyes open and closed, with and without tendon vibration, and dual tasks), limits of stability, QoL and modified Total Neuropathy Score will be assessed. A linear mixed model will compare postural control pre-chemotherapy and post-chemotherapy. ETHICS AND DISSEMINATION: This study was approved by an ethical review board in Geneva (CCER-2020-01639). The study findings will be disseminated through conference presentations and publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04692168.