CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.

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The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established radiation injury, for example in the case of radiation accidents or acts of terrorism.

The aim of this study was to compare two different tomographs for the evaluation of the role of semiquantitative PET/CT parameters and radiomics features (RF) in the prediction of thyroid incidentalomas (TIs) at 18F-FDG imaging. A total of 221 patients with the presence of TIs were retrospectively included. After volumetric segmentation of each TI, semiquantitative parameters and RF were extracted. All of the features were tested for significant differences between the two PET scanners. The performances of all of the features in predicting the nature of TIs were analyzed by testing three classes of final logistic regression predictive models, one for each tomograph and one with both scanners together. Some RF resulted significantly different between the two scanners. PET/CT semiquantitative parameters were not able to predict the final diagnosis of TIs while GLCM-related RF (in particular GLCM entropy_log2 e GLCM entropy_log10) together with some GLRLM-related and GLZLM-related features presented the best predictive performances. In particular, GLCM entropy_log2, GLCM entropy_log10, GLZLM SZHGE, GLRLM HGRE and GLRLM HGZE resulted the RF with best performances. Our study enabled the selection of some RF able to predict the final nature of TIs discovered at 18F-FDG PET/CT imaging. Classic semiquantitative and volumetric PET/CT parameters did not reveal these abilities. Furthermore, a good overlap in the extraction of RF between the two scanners was underlined.

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Objective: To assess the feasibility and activity of a combination schedule with irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients. Methods: Fifty consecutive patients were treated with CPT-11 125 mg/m² as a 90-min intravenous infusion, followed by FA 20 mg/m² as an intravenous bolus, and 5-FU 500 mg/m² over a 2-hour intravenous infusion on days 1 and 8. L-OHP was administered at 85 mg/m² over 2 h on day 15, in combination with a FA 60 mg/m² intravenous bolus and 5-FU 600 mg/m² as a 2-hour intravenous infusion on days 15–16. The treatment was repeated every 4 weeks for a maximum of 9 cycles. Results: Twenty-five of 50 assessable patients achieved a complete (n = 5) or partial (n = 20) response, leading to a response rate of 50% (95% CI 35–64%). Eighteen (36%) patients showed stable disease. The median time to tumor progression was 10.3 months (95% CI 9.6–10.9 months). After a median follow-up of 16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade 3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events. Conclusion: This alternating three-drug regimen is very well tolerated, manageable and effective in terms of activity and time to progression.

Immune checkpoint inhibitors have gained an established role in the treatment of different tumors. Indeed, their use has dramatically changed the landscape of cancer care, especially for tumor types traditionally known to have poor outcomes. However, stimulating anticancer immune responses may also elicit an unusual pattern of immune-related adverse events (irAEs), different from those of conventional chemotherapy, likely due to a self-tolerance impairment featuring the production of autoreactive lymphocytes and autoantibodies, or a non-specific autoinflammatory reaction. Ionizing radiation has proven to promote both positive pro-inflammatory and immunostimolatory activities, and negative anti-inflammatory and immunosuppressive mechanisms, as a result of cross-linked interactions among radiation dose, the tumor microenvironment and the host genetic predisposition. Several publications argue in favor of combining immunotherapy and a broad range of radiation schedules, based on the recent evidence of superior treatment responses and patient survival. The synergistic modulation of the immune response by radiation therapy and immunotherapeutics, particularly those manipulating T-cell activation, may also affect the type and severity of irAEs, suggesting a relationship between the positive antitumor and adverse autoimmune effects of these agents. As yet, information on factors that may help to predict immune toxicity is still lacking. The aim of our work is to provide an overview of the biological mechanisms underlying irAEs and possible crosslinks with radiation-induced anticancer immune responses. We believe such an overview may support the optimization of immunotherapy and radiotherapy as essential components of multimodal anticancer therapeutic approaches. Challenges in translating these to clinical practice are discussed.