The rapid evolution of oncological treatments in patients with lung cancer has led to the emergence of targeted therapies (TT), immune checkpoint inhibitors (ICI), and antibody-drug conjugates (ADC), which are significantly transforming the management of cancer. However, these advances are associated with complex adverse effects that affect multiple organ systems. This review explores the etiopathogenic mechanisms underlying therapy-related toxicity and describes the major adverse effects: immune-related toxicity of ICIs, "on-target" and "off-target" effects of TTs, and systemic toxicity of ADCs. Systemic toxicities are discussed, with a focus on monitoring strategies and management approaches. A multidisciplinary approach is critical to optimize therapeutic efficacy while minimizing toxicity.

New anticancer strategies increasingly rely on targeted therapies, which maximize anticancer activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) mainly include immune checkpoint inhibitors (ICIs), antibody drug conjugates (ADCs) and targeted anticancer therapies (TATs) which inhibit signal transduction pathways. These new molecules are associated with a wide range of ocular adverse events (OAEs), of varying severity: from ocular surface irritation to irreversible vision loss. ICIs can trigger autoimmune responses in all eye tissues. ADCs mainly cause ocular surface toxicity, the most specific of which being microcyst-like epithelial changes (MECs). TATs cause a wide range of OAEs, depending on their class. Oncologists and ophthalmologists will be increasingly confronted to these OAEs - some of which are still poorly characterized - as the number of prescribed NTAs increases. Close collaboration between specialists is essential for their early identification and management, which helps reduce visual and quality of life consequences for these patients. This review addresses the clinical characteristics of the main OAEs linked to MATs, the description of the suspected underlying pathophysiological mechanisms and the key points of their management.

This article reports on new findings on integrative and complementary medicine published in 2024. The implementation of guidelines for the management of pain in cancer patients is discussed. Then, a literature review is presented, that aims to clarify the role of complementary approaches in the management of chemotherapy-induced nausea and vomiting and provides a concrete example of how recommendations are established. Finally, a meta-analysis focusing on the efficacy of Echinacea in the treatment of upper respiratory tract infections is summarized. These articles illustrate the complexity of the path from science to practice and underscore the importance of identifiable centers of reference to support the dissemination of knowledge to health care professionals and promote broad patient access to well-coordinated therapies.

The covalent Bruton tyrosine kinase inhibitors (iBTKs) have profoundly transformed the management of B-cell lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). These targeted therapies, with ibrutinib as the pioneer, have paved the way for significant improvement in the prognosis of many patients. With second-generation iBTKs such as acalabrutinib and zanubrutinib, the therapeutic landscape has expanded, offering potential new options for patients with CLL. This review focuses on the cardiovascular adverse effects associated with these treatments. It delves into the underlying pathophysiological mechanisms of these effects, highlighting the complex interactions between these molecules and the cardiovascular system. Additionally, it examines the frequency of adverse effects according to the type of iBTK, drawing on data from clinical trials and real-world clinical practice. Finally, the importance of close cardio-oncological monitoring is emphasized, with essential collaboration between hematologists and cardiologists. Strategies for screening and managing cardiovascular adverse effects are also discussed, emphasizing the need for a proactive approach in managing these complications. Experts propose a pragmatic follow-up of these patients, through a central illustration and a figure adapted from European cardio-oncology guidelines, to simplify hematologists' practice.

A large body of literature highlights the importance of energy metabolism in the response of haematological malignancies to therapy. In this review, we are particularly interested in acute myeloid leukaemia, where mitochondrial metabolism plays a key role in response and resistance to treatment. We describe the new concept of mitohormesis in the response to therapy-induced stress and in the initiation of relapse in this disease.

Therapeutic options for breast cancer have recently been enriched by new antibody-drug conjugates (ADC), which are now being utilized across all known molecular subtypes. ADCs represent a groundbreaking class of therapies that combine a cytotoxic agent with a monoclonal antibody via a combination molecule (linker). The primary objective is to selectively deliver chemotherapy to cells expressing the target antigen, thereby enhancing the therapeutic index. Trastuzumab-emtansine marked the pioneering use of this approach for HER2-overexpressed breast cancer. More recently, trastuzumab-deruxtecan and sacituzumab-govitecan have demonstrated efficacy in progression-free survival and overall survival in HER2-overexpressed and HER2-low breast cancer for the former, and HER2-non-overexpressed (including HER-low) for the latter. Numerous other ADCs are currently under development in breast cancer. While ADCs were initially designed to widen the therapeutic index and mitigate toxicities, managing ADC-related adverse events in the clinical setting remains a challenge. This review article aims to provide an overview of the toxicity profiles of these drugs already in current clinical practice or under development, drawing from results observed in various studies.

Evaluating the benefits and risks of prolonged hormonal treatment with aromatase inhibitors (AIs) for treating hormone-dependent breast cancer.

The treatment of chronic myeloid leukemia relies on orally available tyrosine kinase inhibitors targeting the BCR::ABL1 oncoprotein. Bosutinib is a second generation adenosine triphosphate-competitive inhibitor approved for use in frontline adult chronic phase-chronic myeloid leukemia and all phases-chronic myeloid leukemia in the second line setting or beyond. Its efficacy was demonstrated in several pivotal clinical trials at 400mg once daily in the first line context and at 500mg once daily beyond first line. Bosutinib-related adverse events frequently occur early after treatment initiation and include gastro-intestinal symptoms and cytolytic hepatitis. These drug-related adverse events must be properly managed in order to preserve safety, efficacy and treatment acceptability. The French chronic myeloid leukemia study group gathered a panel of experts in hematology, pharmacology and hepatology in order to elaborate practical recommendations on the management of bosutinib treatment. These recommendations aim at optimizing the short and long-term tolerance and benefit/risk balance of bosutinib, mainly focusing at gastro-intestinal and liver toxicities.

Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia. It has improved response rates to chemotherapy. However, this is not without consequences. Therapeutic efficacy is sometimes achieved at the expense of toxicities that can lead to treatment discontinuation. Among them, patients can develop hyperammonemia which can sometimes be symptomatic leading to neurological disorders that can go as far as hyperammonemic coma or even death. Through a review of the current state of the literature, the objective is to understand the disparity of ammonia values as well as the clinical heterogeneity for a given ammonia concentration. A review of the literature including more than eighty publications was performed. The glutaminase activity of asparaginase seems to play an important role in the development of hyperammonia. At present, no risk factors have been identified for the development of hyperammonemia. On the other hand, the question of the impact of pre-analysis phase arises. Indeed, asparaginase continues to exert its activity in vitro, which leads to an artefactual increase in ammonia.

Immune checkpoint inhibitors (ICI) are the standard of care for many solid tumors with specific physiopathology mechanisms and adverse events. While the percentage of elderly patients increase from years to years, these patients are underrepresented in clinical trials. Immunosenescence and inflammaging, two main components of the aging of our immune system, and their consequences on the safety and the efficacy are today major focus of clinical research. However, there are still no risk assessment score specific to ICI in elderly patients. In this review we showed the global reassuring data on safety from several retrospective and subgroup analysis, in elderly patients. In summary, impairment of the general state is an independent factor of occurrence of adverse events treatment related whatever the age. Here, we highlight the necessity to use of geriatric evaluation screening test in clinic, the need of specific risk score ICI use in the erdely population and mostly the inclusion of elderly patients in clinical trial to generate specific data.

Myelodysplastic syndromes (MDS) are clonal stem cell diseases that primarily affect the elderly. They are classified into low- and high-risk MDS according to prognostic scoring systems. In high-risk patients, treatment should aim to modify the course of the disease by preventing progression to acute myeloid leukemia, and thus improve survival. Stem cell transplantation remains the only curative treatment when possible, but this concerns a small minority of patients. Treatment is mainly based on hypomethylating agents (HMA). Our understanding of the biology of MDS has led to the development of drugs targeting key cellular processes such as apoptosis or post-translational modifications of proteins, the microenvironment and genetic mutations. Currently, new drugs are mainly tested in combination with HMAs in several clinical trials and, although none has yet obtained marketing authorization, many molecules seem promising.

Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management.

High-grade serous ovarian carcinoma (HGSOC), the most frequent and aggressive form of epithelial ovarian cancer is characterized in half of cases by homologous recombination deficiency (HRD). This molecular alteration is defined by distinct causes and consequences. The main and most characterized cause is the presence of an alteration affecting BRCA1 and BRCA2 genes. Regarding consequences, a specific genomic instability leads to increased sensitivity to platinum salts and poly (ADP-ribose) polymerase (PARPi) inhibitors. This latter point enabled the advent of PARPi in first and second line maintenance. As such, the initial and rapid evaluation of HRD status with molecular tests is a key step in the management of HGSOC. Until recently, the range of tests offered proved to be very limited and suffered from technical and medical limitations. This has recently led to the development and validation of alternatives, including academic ones. This "state of the art" review will bring a synthesis concerning the assessment of HRD status in HGSOCs. After a brief introduction of HRD (including main causes and consequences) and of its predictive value regarding PARPi, we will discuss the limitations of current molecular tests and the existing alternatives. Finally, we will contextualize this to the situation in France, with special consideration concerning the positioning and the financial coverage of these tests, with the perspective of optimizing patient management .

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities.

For therapeutic purposes, the development of new anti-cancer drugs requires their evaluation in terms of activity, cytotoxicity and pharmacokinetics. The candidate drugs are tested in vitro on cell lines and primary cells isolated from patients, and in vivo, often, using xenografts in immuno-compromised mice. In recent years, administrative constraints have become increasingly stringent and the 3R rule (reduce, refine, replace) requires the elaboration of alternative models capable to replace mouse models or at least to limit their use. Among them, xenograft on chick embryo chorioallantoic membrane (CAM assay) seems particularly efficient. It makes it possible to monitor and quantify tumor growth and tumor-associated parameters such as neoangiogenesis, invasion and migration. It allows the screening of drugs effective both on tumor cells and their microenvironment. Finally, the model seems adapted to the development of personalized medicine to which current research in cancerology is tending. In this context, this review focuses on the technique itself and its advantages.

Radiotherapy and targeted therapies play a major role in the management of cancers. Unfortunately, the toxicity and efficacy data regarding their association are tenuous and not centralized. Thus, we propose a literature review about the risks and opportunities of combining radiotherapy with targeted therapies.

Standard treatment consisting of chemoradiotherapy followed by radical surgery with total mesorectal excision, results in good oncologic local control but high morbidity and poor functional results. Since chemoradiotherapy results in 15% pathological complete response, even reaching up to 30% in case of association with neoadjuvant chemotherapy, radical surgery has been recently debated for good responders. Therefore, a de-escalation strategy, by omitting radical surgery in good responders, has recently been developed with two different options: a watch and wait strategy, requiring an accurate clinical and radiological definition of complete response and a local excision strategy including patients with sub-complete response. Ongoing trials focus on response optimization by chemotherapy intensification or radiotherapy dose escalation. However, many questions are still to be answered regarding definition of complete response, follow-up strategy, morbidity of salvage surgery in case of recurrence as well as long-term oncological and functionnal results.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

Alopecia, although long considered an unavoidable consequence of cancer therapy, currently presents a multifaceted challenge. The knowledge of the physiology of the hair and consequently of the pathophysiology of alopecia has led to show that there is not one but several types of alopecia. Transposed to the world of oncology, different types of alopecia and subsequently molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. Thus, in patients with cancer, alopecia can be iatrogenic (chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy, surgery) or directly the consequence of the disease itself (malnutrition, scalp metastases, paraneoplastic syndromes). Knowledge of the incriminated mechanism(s) could thus make it possible to deploy an appropriate care component, whether on the preventive or curative sides or in terms of supportive care. These are particularly essential regarding the psychological repercussions caused by alopecia, with significant consequences on the quality of life of patients and with a potential impact on treatment compliance. On the preventive side, the last few years have seen the advent of the automated scalp cooling therapy, supported by several randomized clinical trials. On the curative side, several therapeutic proposals are currently deployed or under development in order to provide relevant treatments.