Vincent Launay-Vacher

Background: The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear. Methods: Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using serum creatinine levels and using adverse events reported by investigators. The impact of baseline estimated glomerular filtration rates (eGFRs) on progression-free survival (PFS) and overall survival (OS) was investigated. Pooled estimates of the impact of AKI on dose intensity, treatment duration, PFS and OS were obtained following a meta-analytic process. Results: Nine trials were included in this study, totalling 2872 metastatic patients with various tumour types and various systemic treatment types. Baseline eGFR had homogeneously no impact on PFS or OS. Most Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) events occurred early during the course of the treatment. AKI was not associated with an increased rate of treatment discontinuation, while it decreased the study treatment dose intensity. Occurrence of a first RIFLE event significantly and homogeneously reduced PFS (pooled hazard ratio = 1.18, 95% confidence interval 1.07–1.30; P = 0.0012), while its impact on OS was more heterogeneous across trials. Conclusion: AKI is associated with reduced treatment dose intensity and reduced PFS. Therefore, close monitoring of the kidney function during the first months of treatment should be included in clinical trial protocols and probably also in daily practice to enable early AKI diagnosis and management. Collaboration between oncologists and nephrologists is needed to reduce the risk of undertreatment of patients experiencing AKI.

The French National Authority for health recommends that the adjustment of the dosage of drugs in patients with renal insufficiency be carried out on the basis of an estimate of renal function using the Cockcroft-Gault formula, while the estimation of the glomerular filtration rate using the Modification of Diet in Renal Disease or CKD-EPI formula is recommended for the diagnosis and monitoring of renal insufficiency. The argument put forward is that the recommendations for dosage adjustment of the summaries of product characteristics would have been established on the basis of the use of this formula. Service ICAR aimed at verifying the evidence supporting this argument. In all, 2447 summaries of product characteristics were analyzed to identify the renal function criterion specified for dose adjustment recommendations. When no formulas were found in the summary of product characteristics, the firms were contacted to obtain information on renal function estimation methods used in developmental studies. Their responses were analyzed. Of the 2447 summaries of product characteristics studied, 438 (17.9%) propose a dosage adjustment in case of renal insufficiency. No formula is mentioned in the summarie of product characteristics for 90.0% of them. The Cockcroft-Gault and Modification of Diet in Renal Disease/CKD-EPI formulas are found in 8.7% and 0.7% respectively of these 438 summaries of product characteristics. After contacting pharmaceutical companies and analysis of the data available in the studies on which the summaries of product characteristics were based, the information cannot be found for 63.0% of the summaries of product characteristics, in spite they mention the need to adjust the dosage in case of renal insufficiency. The majority of summaries of product characteristics do not mention the Cockcroft-Gault formula and in the majority of cases it is not possible to identify the formula or technique used in the studies on which is based the reference to dosage adjustment in the summarie of product characteristics. In addition, there are discrepancies between the wording of the summaries of product characteristics and the data from development studies. The use of Cockcroft-Gault for dosage adjustment is to be questioned, especially since the Isotope-dilution mass spectrometry, or IDMS, standardization of creatinine dosage makes obsolete studies based on Cockcroft-Gault formula and a non-standardized dosage, and thus the use of Cockcroft-Gault not transposable to current clinical practice.

Concurrent chemoradiotherapy with high-dose cisplatin (100 mg/m² every 3 weeks) is the preferred regimen with curative intent for patients with unresected locally advanced squamous cell carcinoma of the head and neck (LA SCCHN). This treatment is associated with acute and late toxicities, including myelosuppression, severe nausea/vomiting, irreversible renal failure, hearing loss, and neurotoxicity. Because of cisplatin's safety profile, treatment adherence to high-dose cisplatin can be suboptimal. Patients commonly receive less than the total cumulative target dose of 300 mg/m² or the minimum recommended dose of 200 mg/m², which can have a negative impact on locoregional control and survival. Alternatively, cetuximab plus radiotherapy may be most suitable for patients at high risk of non-adherence to high-dose cisplatin. We discuss the baseline characteristics dictating the unsuitability/borderline unsuitability of cisplatin and the available alternative evidence-based treatment regimens for patients with LA SCCHN. We non-systematically reviewed published phase II and III trials and retrospective analyses of high-dose cisplatin-based chemoradiation in LA SCCHN conducted between 1987 and 2018, focusing on recent key phase III studies. We defined the baseline characteristics and associated prescreening tests to determine unsuitability and borderline unsuitability for high-dose cisplatin in combination with radiotherapy in patients with LA SCCHN. Patients with any pre-existing comorbidities that may be exacerbated by high-dose cisplatin treatment can be redirected to a non-cisplatin-based option to minimize the risk of treatment non-adherence. High-dose cisplatin plus radiotherapy remains the preferred treatment for fit patients with unresected LA SCCHN; patients who are unsuitable or borderline unsuitable for high-dose cisplatin could be identified using available tests for potential comorbidities and should be offered alternative treatments, such as cetuximab plus radiotherapy.

L’essor des techniques de radiologie interventionnelle conduit à exposer régulièrement les patients au potentiel néphrotoxique des produits de contraste iodés. Face à ce risque de néphrotoxicité, les produits de contraste à base de gadolinium pour rehausser l’imagerie à résonance magnétique ont longtemps été considérés comme une alternative sécurisante aux produits de contraste iodés, en particulier chez les sujets sensibles ou à risque. Cependant, ils sont eux-mêmes non dénués de néphrotoxicité et présentent un nouveau risque, dont la physiopathologie est également liée à l’insuffisance rénale, qui est la fibrose systémique néphrogénique. Les recommandations européennes et américaines des agences de santé se sont rapprochées récemment, définissant des groupes de patients à risque de fibrose systémique néphrogénique en fonction de leur niveau de fonction rénale et du type de produit de contraste à base de gadolinium utilisé. Quels sont les réels risques rénaux encourus face à ces produits ? Comment évaluer la balance bénéfice-risque du patient pour lui choisir un examen radiologique, informatif, efficace et sûr ? Cet article s’attache à la description des risques liés aux produits de contraste à base de gadolinium, fait le point sur les recommandations et les bonnes pratiques existantes afin de guider le choix des cliniciens. The development of interventional radiology techniques regularly exposes patients to the potential renal toxocity of iodinated contrast media. Faced with this risk of nephrotoxicity, gadolinium-based contrast agents have long been considered as a safe alternative to iodinated contrast media, especially in sensitive or at risk patients. However, these gadolinium-based contrast agents are not devoid of nephrotoxicity and present another risk, a complication related to renal failure, the nephrogenic systemic fibrosis. European and US recommendations from health agencies have recently come closer, defining groups of patients at risk of nephrogenic systemic fibrosis according to their level of renal function and the type of gadolinium-based contrast agent used. What are the real renal risks for these products? How to evaluate the benefit-risk balance of the patient to choose a radiological examination in an informative, effective and safe way? This article focuses on the description of the risks of gadolinium-based contrast agents, reviews existing recommendations and best practices to guide the choice of clinicians.

Onconephrology is a rapidly evolving subspeciality that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management administered by a dedicated team. Since there is an increasing need to address the needs of this population in dedicated outpatient clinics, it is critical to highlight basic characteristics and to suggest areas of development. In this brief perspective article, we analyse the requirements of an onconephrology clinic in terms of logistics, critical mass of patients and building a multidisciplinary team. We will further discuss which patients to refer and which conditions to treat. The last part of the article is dedicated to education and performance indicators and to analysis of the potential advantages of applying the hub-and-spoke model to this field. The ultimate aim of this experience-based article is to initiate debate about what an onconephrology outpatient clinic might look like in order to ensure the highest quality of care for this growing population of patients.