[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.

[Does high-dose intravenous vitamin C has anti-cancer activity ?] / La vitamine C haute dose intraveineuse a-t-elle un effet antitumoral ?

High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.

La vitamine C administrée par voie intraveineuse (IV) chez les patients atteints de cancer est controversée. De nombreux travaux effectués sur des lignées cellulaires cancéreuses et des modèles animaux montrent que des concentrations plasmatiques pharmacologiques (≥ 15 mmol/l) de vitamine C sont capables de diminuer la viabilité des cellules cancéreuses. Chez les patients atteints de cancer, l'administration d'une haute dose IV de vitamine C seule ne montre pas de signe d'activité antitumorale. Elle a également été étudiée en association avec de la chimiothérapie, mais les essais cliniques réalisés ne permettent pas de conclure à un bénéfice pour les patients en termes de contrôle de la maladie oncologique ou de survie. Des études randomisées contre placebo et en double aveugle sont indispensables.

SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2.

INTRODUCTION: The safety of first-line (1L) durvalumab in patients with advanced nonsmall-cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (PS2) is unknown. This is an interim unplanned safety analysis of the study SAKK 19/17 for patients with metastatic NSCLC with programmed death-ligand 1 (PD-L1) expression in ≥ 25% of tumor cells and an ECOG PS2 treated with 1L durvalumab. This safety analysis was triggered by the SAKK data and safety monitoring board due to a high mortality rate observed after the recruitment of the first 21 patients. METHODS: This single-arm phase II study recruited patients with metastatic NSCLC with PD-L1 in ≥ 25% and ECOG PS2. Patients received durvalumab 1500 mg every four weeks. The trial aims to recruit 48 patients in total. This report includes safety analyses only. Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 5.0. Efficacy data including the primary endpoint overall survival at 6 months and secondary endpoints (objective response rate, progression-free survival, and quality of life) will be reported at a later time point. RESULTS: The data from 21 patients were available at this interim safety analysis. Among these, 13 deaths (13/21; 62%) were reported, including one treatment-related fatal colonic perforation at 9 months after treatment initiation (1/13; 8%). Twelve deaths were not treatment-related (12/13; 92%), and mostly attributed to tumor progression (10/13; 77%). Of note, seven deaths (7/13; 54%) occurred during the first 5 weeks (range 0.6-4.7 weeks) after treatment initiation. Four (4/7; 57%) were respiratory failures attributed to tumor progression. One of these patients (25%) had pre-existing COPD, and three (75%) had baseline dyspnea grade 2-3 related to the tumor. Grade ≥ 3 treatment-related AEs (TRAEs) included colonic perforation (grade 5), abdominal pain, and colitis (grade 3 each) in one patient, and fatigue (grade 3) in another. Other Grade ≥ 3 AEs unrelated to treatment were all of pulmonary origin: lung infections (19%), dyspnea (24%), cough (5%), and bronchial obstruction (5%). CONCLUSIONS: 1L durvalumab in patients with ECOG PS2 and metastatic NSCLC with PD-L1 expression ≥ 25% resulted in an unexpectedly high number of fatal early events due to rapid tumor progression. We recommend to avoid treatment with 1 L durvalumab of patients who are highly symptomatic from the tumor, particularly those with respiratory symptoms. The study is continuing its accrual after an amendment excluding these patients.

[Non-small cell lung cancer: a target biology]. / Cancer pulmonaire non à petites cellules : une biologie prête à cibler.

Lung cancer is divided into two categories: small cell cancer and non-small cell lung cancer (NSCLC). Management of NSCLC has evolved considerably since the advent of immunotherapies and targeted therapies, both for the localized stages and for the advanced stages. NSCLC are no longer only subdivided by their histological characteristics but also by their molecular characteristics which constitute therapeutic targets.

Les cancers pulmonaires sont divisés en deux catégories: le cancer à petites cellules et le cancer non à petites cellules (Non Small Cell Lung Cancer (NSCLC)). La prise en charge de ce dernier a beaucoup évolué depuis l'avènement des immunothérapies et des thérapies ciblées, tant pour les stades localisés que pour les stades avancés. Les NSCLC ne sont plus seulement subdivisés par leurs caractéristiques histologiques, mais aussi par leurs caractéristiques moléculaires qui constituent des cibles thérapeutiques.

[Immunotherapy with immune checkpoint inhibitors and hepatitis]. / Immunothérapie par inhibiteurs de points de contrôle immunitaire et hépatite.

Immunotherapy, with « checkpoint ¼ inhibitors (CPIs), has become an essential therapeutic weapon against cancer. Autoimmune disorders related to overactivation of the immune system are well known side effects. The risk of reactivation of the hepatitis B and C viruses and exacerbation of the hepatitis, known from the introduction of immunosuppressive drugs such as chemotherapy, is poorly documented under immunotherapy. In this article, we discuss the issue of immunotherapy in patients presented with hepatitis using two approaches: the risks of immunotherapy in these situations and the management by disruption of liver tests under immunotherapy.

L'immunothérapie, avec les inhibiteurs de points de contrôle immunitaire « immune checkpoint inhibitors ¼, est devenue une arme thérapeutique essentielle contre de nombreux cancers. Les troubles autoimmuns liés à la suractivation du système immunitaire sont des effets secondaires bien connus. Le risque de réactivation des virus de l'hépatite B et C ou d'exacerbation de l'hépatite, connu lors de l'introduction de médicaments immunosuppresseurs telles les chimiothérapies, est peu documenté sous immunothérapie. Dans cet article, nous aborderons la question de l'immunothérapie chez des patients présentant une hépatite B ou C selon deux approches : les risques encourus à introduire une immunothérapie dans ces situations et la gestion d'une perturbation des tests hépatiques sous immunothérapie.

Evolving Therapeutic Scenario of Stage III Non-Small-Cell Lung Cancer.

Lung cancer remains the leading cause of cancer-related death with an incidence that continues to increase in both sexes and all ages. However, 80% to 90% of lung cancers are non-small cell lung cancer (NSCLC) and the remaining 10% to 20% are small cell lung cancer. Adenocarcinoma is the most common histologic subtype of lung cancer worldwide. More frequently, lung cancer diagnosis is made in advanced stages. Stage III NSCLC refers to locoregionally advanced disease without metastases and represents about 30% NSCLC cases. Despite the absence of metastases at diagnosis, the outcome is generally poor. Stage III comprises a heterogeneous group and optimal management requires the input of a multidisciplinary team. All modalities of oncologic treatment are involved: surgery, chemotherapy, radiotherapy, and more recently, immunotherapy and targeted therapy. We will discuss the different therapeutic options in stage III NSCLC, both in operable and inoperable scenarios, and the role of immunotherapy and targeted therapy.

Immunotherapy and Gastrointestinal Toxicities.

Gastrointestinal toxicities secondary to immune checkpoint inhibitors are very frequent. Because in some instances this can be severe or fatal, it is essential to be able to identify immune-related adverse events rapidly. Prompt initiation of systemic immunosuppression can improve outcomes. A biopsy is often necessary to confirm the diagnosis of immune-related adverse events. Moderate or severe irAEs need an interruption of ICI. After the resolution of the toxicities, the rechallenge of immune checkpoint inhibitors must be discussed case by case.

Home-deliverable antitumoral treatments in the age of COVID-19: the Portsmouth experience and a narrative review.

Background and Objective: During the coronavirus disease 2019 (COVID-19) pandemic, risks and priorities of oncologic care have required a thorough reassessment. The chance that fragile patients have exposure to infection during frequent hospital visits is an additional consideration for all therapeutic decisions. Patients with cancer, particularly those with lung cancer, have a greater chance of developing a severe form of COVID-19. Their increased risk is due to the immunosuppression associated with the chemotherapy itself, the underlying pulmonary compromise, which often accompanies lung malignancy or their general poor health. Oncology societies have given precise recommendations on the treatment modalities to be favoured, such as giving up specific palliative or adjuvant treatments, preferring shorter and less cytopenic therapies. In this review, we discussed how some of these curative treatments could be given by administering them at home. In this narrative review, we aim to see if it is safe and feasible to deliver home-administered oncologic intravenous treatments. Methods: By narrative review, we looked for all the articles written in English describing home delivery chemotherapy or immunotherapy programs since 2019 that emerged or evolved during the COVID-19 pandemic. We added real-life data regarding the initiation of home immunotherapy in Portsmouth. Key Content and Findings: There is a growing body of evidence supporting the safety and feasibility of home-administered chemotherapy and immunotherapy treatments. Conclusions: Home-administered chemotherapy and immunotherapy treatments are safe and feasible despite financial challenges, particularly about reimbursement by insurance companies and the loss of earnings for hospitals. Home treatments also require the careful selection of eligible patients and the training and organisation of specialised teams capable of managing the expected complications. It would be interesting to assess the risk-reduction in terms of infections and potential survival gains obtained by these programmes during the COVID pandemic.