MRI-Based Radiomics Input for Prediction of 2-Year Disease Recurrence in Anal Squamous Cell Carcinoma

International audiencePurpose: Chemo-radiotherapy (CRT) is the standard treatment for non-metastatic anal squamous cell carcinomas (ASCC). Despite excellent results for T1-2 stages, relapses still occur in around 35% of locally advanced tumors. Recent strategies focus on treatment intensification, but could benefit from a better patient selection. Our goal was to assess the prognostic value of pre-therapeutic MRI radiomics on 2-year disease control (DC). Methods: We retrospectively selected patients with non-metastatic ASCC treated at the CHU Bordeaux and in the French FFCD0904 multicentric trial. Radiomic features were extracted from T2-weighted pre-therapeutic MRI delineated sequences. After random division between training and testing sets on a 2:1 ratio, univariate and multivariate analysis were performed on the training cohort to select optimal features. The correlation with 2-year DC was assessed using logistic regression models, with AUC and accuracy as performance gauges, and the prediction of disease-free survival using Cox regression and Kaplan-Meier analysis. Results: A total of 82 patients were randomized in the training (n = 54) and testing sets (n = 28). At 2 years, 24 patients (29%) presented relapse. In the training set, two clinical (tumor size and CRT length) and two radiomic features (FirstOrder_Entropy and GLCM_JointEnergy) were associated with disease control in univariate analysis and included in the model. The clinical model was outperformed by the mixed (clinical and radiomic) model in both the training (AUC 0.758 versus 0.825, accuracy of 75.9% versus 87%) and testing (AUC 0.714 versus 0.898, accuracy of 78.6% versus 85.7%) sets, which led to distinctive high and low risk of disease relapse groups (HR 8.60, p = 0.005). Conclusion: A mixed model with two clinical and two radiomic features was predictive of 2-year disease control after CRT and could contribute to identify high risk patients amenable to treatment intensification with view of personalized medicine

Oligometastatic renal cell carcinoma: radiotherapy as a new standard of care?

International audienceThe prognosis of metastatic renal cell carcinoma is poor, with a median 5-year survival of 9·5%. 1In patients with localised renal tumours, surgery remains the reference treatment, whereas radiotherapy plays a key role in the palliative care of patients with metastatic disease. However, during the past 20 years, a better understanding of biology has allowed targeted molecular therapies 1to emerge as a new standard of care in the metastatic setting. Regarding the role of radiotherapy in this setting, the sparing of surrounding healthy tissues has improved substantially thanks to the increasing use of stereotactic body radiotherapy (SBRT). A higher and more accurate dose per fraction is delivered with SBRT than with standard radiotherapy, which results in a large dose gradient around the target volume. In addition, new sophisticated imaging modalities have made identifying patients with oligometastatic renal cell carcinoma—namely patients with five or fewer metastatic lesions—possible. But, in oligometastatic disease, the role of radiotherapy and systemic treatment in the therapeutic arsenal has not yet been establishe

Comparison of electromagnetic neuronavigation system and free-hand method for ventricular catheter placement in internal shunt

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Challenges in radiobiology – technology duality as a key for a risk-free α/β ratio

International audienceSince radiotherapy discovery, prediction of biological response to ionizing radiation remains a major challenge. Indeed, several radiobiological models appeared through radiotherapy history. Nominal single dose so popular in the 1970s, was tragically linked to the dark years in radiobiology by underestimating the late toxicity of the high-dose fractions. The actual prominent linear-quadratic model continues to prove to be an effective tool in radiobiology. Mainly with its pivotal α/β ratio, which gives a reliable estimate of tissues sensitivity to fractions. Despite these arguments, this model experiences limitations with substantial doubts of α/β ratio values. Interestingly, the story of radiobiology since X-ray discovery is truly instructive and teaches modern clinicians to refine fractionation schemes. Many fractionation schemes have been tested with successes or dramas. This review retraces radiobiological models’ history, and confronts these models to new fractionation schemes, drawing a preventive message

Brain metastases from non-small cell lung carcinoma: Changing concepts for improving patients’ outcome

International audienceThe management of Non Small Cell Lung Cancer (NSCLC) brain metastases is challenging, as this frequent complication negatively impacts patients’ quality of life, and can be a life-threatening event. Through a review of the literature, we discuss the main therapeutic options and the recent developments that improved (and complicated) the management of NSCLC brain metastases patients. Most current validated approaches are local with exclusive or combined surgery, whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRT). At the same time, there is a growing role for systemic treatments that might significantly postpone WBRT. Targeted therapies efficacy/toxicity profile remains to be defined but predictive and prognostic molecular factors integration could help to select treatments fully adapted to life expectancy and progression risk

Altération de la réparation de l’ADN et cancer

International audienceMaintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA. In addition to its impact on carcinogenesis, the DNA damage repair system is now considered as a therapeutic target of choice for cancer treatment, as monotherapy or in combination with other cytotoxic therapies, such as chemotherapies or radiotherapy. PARP inhibitors are nowadays the best known, but other agents are emerging in the field of clinical research. The enthusiasm in this area is coupled with promising results and a successful collaboration between clinicians and biologists would allow to optimize treatment plans in order to take full advantage of the DNA repair system modulation.Le maintien de l’intégrité génétique est un processus central de la viabilité cellulaire qui est permis par un large réseau de voies de réparation. Lorsque ce système de réparation est défectueux, il génère une instabilité génomique et entraîne une accumulation d’aberrations chromosomiques et de mutations qui peuvent alors être responsables de divers phénotypes cliniques dont la susceptibilité à développer un cancer. En effet, ces défauts peuvent favoriser non seulement l’initiation du cancer, mais aussi permettre aux cellules tumorales d’acquérir rapidement des mutations pendant leur évolution. Plusieurs gènes sont impliqués dans ces systèmes de réparations et des polymorphismes particuliers sont prédictifs d’apparition d’un cancer, le mieux décrit d’entre eux étant BRCA. En plus de son impact sur la carcinogenèse, le système de réparation des lésions de l’ADN est aujourd’hui considéré comme une cible thérapeutique de choix pour lutter contre le cancer, en monothérapie ou en association avec d’autres thérapies cytotoxiques comme certaines chimiothérapies ou la radiothérapie. Les inhibiteurs de PARP sont aujourd’hui les plus connus, mais d’autres agents voient le jour dans le domaine de la recherche clinique. L’engouement dans ce nouveau pan de traitements anticancéreux est associé à des résultats prometteurs, et un mariage réussi entre cliniciens et biologistes permettrait d’optimiser au mieux les plans de traitement afin de tirer pleinement profit de la modulation du système de réparation de l’ADN