In-vivo and in-vitro impact of high-dose rate radiotherapy using flattening-filter-free beams on the anti-tumor immune response.

INTRODUCTION: Modern accelerators have the "flattening filter-free" (FFF) technique to deliver RT with a moderate high-dose rate, currently used in limited clinical indications. No scientifically established data are currently available on the possible effects of this high dose rate on the anti-tumor immune response. We therefore propose here to study these effects in a preclinical CT26 murine colorectal tumor model. MATERIAL AND METHODS: In-vitro, CT26 cells were irradiated on a Varian TrueBeam® linac at 3 different dose rates (4; 12 or 24 Gy/min) using the FFF mode. Activation of the anti-tumor immune response was evaluated by the analysis of induction of genes of the type I interferon pathway by RT-qPCR, and by the study of the induction of immunogenic death biomarkers. In-vivo, an efficacy study of RT delivering 16.5 Gy at 2 different dose rates was performed in immunocompetent Balb/c mice carrying CT26 syngeneic tumors, as well as an immunomonitoring analysed by flow cytometry and a transcriptomic analysis using RNA sequencing. Statistical analyzes were performed using non-parametric tests. RESULTS: In-vitro, no significant influence of an increase in FFF dose rate was shown for the induction of genes of the type I interferon pathway as well as for the studied immunogenic death markers (HMGB1 secretion). In-vivo, no difference in terms of tumor growth retardation between the 2 dose rates used was demonstrated, as well as for the composition of immune cell infiltrates within tumor microenvironment and the expression of immune checkpoints in immunomonitoring and RNAseq. CONCLUSION: In this study involving the CT26 model, no influence of a moderate high dose rate in FFF technique on the anti-tumor immune response was demonstrated, which would make studies of associations between RT and checkpoint inhibitors fit with this technique of RT. However, further explorations using other cellular models seem to be of interest.

Salvage brachytherapy as a modern reirradiation technique for local cancer failure: The Phoenix is reborn from its ashes.

The treatment of local recurrence of a previously irradiated cancer or a second cancer arising in-field remains challenging. Ultimately, the objective of salvage therapy is to control disease while ensuring minimal collateral damage, thereby optimizing both cancer and toxicity outcomes. Reirradiation has historically been associated with unacceptable toxicity and a limited benefit. Brachytherapy offers the best dose distribution and a high radiation dose to the target volume while better protecting surrounding previously irradiated healthy tissues. The management of local cancer recurrence in irradiated areas should be planned through multidisciplinary discussions and patients should be selected carefully. This overview of the literature describes brachytherapy as a reirradiation treatment in local recurrences of previously irradiated prostate, breast, head and neck and rectal cancers, or second primary cancers occurring in-field. For these cancers, the prognosis and therapeutic challenges are quite different and depend on the type of primary cancer. However, current data confirm that brachytherapy reirradiation is feasible and has acceptable toxicity.

[Quality control of dose delivered by in vivo dosimetry: can one tolerance be used for all localizations?]. / Contrôle qualité de la dose délivrée par dosimétrie in vivo : un critère de tolérance unique peut-il satisfaire toutes les localisations ?

PURPOSE: In vivo dosimetry measurements are accepted when the difference between measured and calculated dose is under 5%. A statistical analysis has been conducted to determine whether this tolerance matched the clinical practice for the studied localizations: pelvis, thorax, head and neck, breast. MATERIALS AND METHODS: The technical characteristics of the detectors were checked before being used in clinical practice. Then an automatic statistical analysis was implemented using the 2450 in vivo dosimetry measurements obtained during 1 year. MAIN RESULTS: The global average is 1.10%, the standard deviation 2.46% and the percentage of out of level measurements 4.09%. By distinguishing the localizations, the 5% tolerance appeared to be too narrow for the breast localization. DISCUSSION/CONCLUSION: Several investigations were initiated to justify the modification of the tolerance for the breast localization. They highlighted an underestimation of the calculated dose when high beam angles are set: a new correction factor was defined to take account this error. A specific tolerance was also specified for the breast localization.