Abstract
Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called "FLASH-RT" and irradiation delivered at a conventional dose rate called "Conv-RT." A clinical, phase I, single-dose escalation trial (25-41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients.See related commentary by Harrington, p. 3.
Highlights
Radiotherapy is an essential part of cancer treatment; more than half of patients with cancer are treated with radiotherapy, mostly with curative potential
Some doses were delivered with a conventional radiotherapy dose rate (%5 Gy/minute), each dose to a different skin patch, and the same doses were delivered to other skin patches with
The overall survival and metastatic dissemination were recorded by the veterinarian along with any acute or late toxicity. These endpoints were checked every day Reduced pig skin toxicity with FLASH-RT The film and alanine pellet in vivo dosimetry verified the doses delivered to the pig skin surface
Summary
Radiotherapy is an essential part of cancer treatment; more than half of patients with cancer are treated with radiotherapy, mostly with curative potential. Major advances in high precision treatment delivery and multimodal imaging allowed radiotherapy to be better tolerated with an increased proportion of patients living longer, free of tumor, and with fewer side effects. Despite these progresses, radiation resistance remains an unmet clinical need, because an important proportion of solid tumors can be resistant to conventional radiotherapy. Radiation resistance remains an unmet clinical need, because an important proportion of solid tumors can be resistant to conventional radiotherapy For patients harboring those tumors, a more effective radiotherapeutic strategy is needed.
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