RESUMEN
Background: Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most prevalent skin cancers in western countries. Surgery is the standard of care for these cancers and conventional external radiotherapy (CONV-RT) with conventional dose rate (0.03-0.06 Gy/sec) represents a good alternative when the patients or tumors are not amenable to surgery but routinely generates skin side effects. Low energy electron FLASH radiotherapy (FLASH-RT) is a new form of radiotherapy exploiting the biological advantage of the FLASH effect, which consists in delivering radiation dose in milliseconds instead of minutes in CONV-RT. In pre-clinical studies, when compared to CONV-RT, FLASH-RT induced a robust, reproducible and remarkable sparing of the normal healthy tissues, while the efficacy on tumors was preserved. In this context, we aim to prospectively evaluate FLASH-RT versus CONV-RT with regards to toxicity and oncological outcome in localized cutaneous BCC and SCC. Methods: This is a randomized selection, non-comparative, phase II study of curative FLASH-RT versus CONV-RT in patients with T1-T2 N0 M0 cutaneous BCC and SCC. Patients will be randomly allocated to low energy electron FLASH-RT (dose rate: 220-270 Gy/s) or to CONV-RT arm. Small lesions (T1) will receive a single dose of 22 Gy and large lesions (T2) will receive 30 Gy in 5 fractions of 6 Gy over two weeks.The primary endpoint evaluates safety at 6 weeks after RT through grade ≥ 3 toxicity and efficacy through local control rate at 12 months. Approximately 60 patients in total will be randomized, considering on average 1-2 lesions and a maximum of 3 lesions per patients corresponding to the total of 96 lesions required. FLASH-RT will be performed using the Mobetron® (IntraOp, USA) with high dose rate functionality.LANCE (NCT05724875) is the first randomized trial evaluating FLASH-RT and CONV-RT in a curative setting.
RESUMEN
FLASH radiation therapy (RT) is a promising new paradigm in radiation oncology. However, a major question that remains is the robustness and reproducibility of the FLASH effect when different irradiators are used on animals or patients with different genetic backgrounds, diets, and microbiomes, all of which can influence the effects of radiation on normal tissues. To address questions of rigor and reproducibility across different centers, we analyzed independent data sets from The University of Texas MD Anderson Cancer Center and from Lausanne University (CHUV). Both centers investigated acute effects after total abdominal irradiation to C57BL/6 animals delivered by the FLASH Mobetron system. The two centers used similar beam parameters but otherwise conducted the studies independently. The FLASH-enabled animal survival and intestinal crypt regeneration after irradiation were comparable between the two centers. These findings, together with previously published data using a converted linear accelerator, show that a robust and reproducible FLASH effect can be induced as long as the same set of irradiation parameters are used.
