Second cancers after radiotherapy: update and recommandations

While radio-induced cancers are well known since the first years of the xxth century, they did not represent a major concern for radiation oncologists for many decades. With better and better results of modern radiotherapy and prolonged follow-up of patients, secondary radio-induced cancers should now be systematically taken into account when irradiating patients. The analysis of the available literature allows to stress a few main points; (1) cancer patients are at a higher risk for developing secondary cancers than the general population, radiotherapy being only responsible for a (small) proportion of those second malignancies; (2) the clinical data emphasize the role of age, with children being much more susceptible to the carcinogenic effect of ionizing radiation than adults; (3) most radio-induced cancers occur in or close to the high-dose treatment volume; (4) the relative risk of radio-induced cancer appears to be different for different organs; (5) the relative risks of radio-induced cancers tend to be lower in the medical cohort studies than in the Japanese A-Bomb survivor studies; (6) several cofactors (genetic, lifestyle…) account for the risk of secondary and radiation-induced cancer. The exact shape of the dose/effect (carcinogenesis) curve is still debated, particularly for the high doses of radiotherapy, with a direct impact on risk calculations, which can be very different if using different radiobiological models. In spite of some uncertainties, a few main recommendations could be proposed to reduce as much as possible the risk of radio-induced cancer after radiotherapy: (1) adapting the irradiation technique; (2) reducing the target volumes; (3) adapting to patient’s age; (4) adapting to specific organs; (5) and optimizing the imaging dose. In conclusion, even if radio-induced cancers are rare, they must be kept in mind each time a radiotherapy is proposed in 2018

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412.

Current treatment guidelines for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) recommend multimodal treatment, including chemoradiation therapy (CRT) or surgery followed by radiation, with or without chemotherapy. The immune checkpoint inhibitor pembrolizumab has previously demonstrated antitumor activity in recurrent and/or metastatic HNSCC in large Phase III trials. For patients with locally advanced disease, Phase Ib data on the use of pembrolizumab in combination with chemoradiation have shown the approach to be safe and feasible. We describe here the design and rationale for KEYNOTE-412, a randomized, double-blind, Phase III trial investigating pembrolizumab or placebo administered concurrently with CRT and as maintenance treatment in patients with locally advanced HNSCC. Clinical Trial Registration: NCT03040999 (ClinicalTrials.gov)