Olivier Gaide, MD, PhD Principal Investigator Centre Hospitalier Universitaire Vaudois Jean Bourhis, MD, PhD Study Chair Centre Hospitalier Universitaire Vaudois
1. Frequency of ≥ grade 3 skin toxicity adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Time Frame - up to 6 weeks after radiotherapy): To evaluate the safety of FLASH radiotherapy measured by the collection of ≥ grade 3 skin toxicity AEs according to CTCAE version 5.0. The severity of a specific event is graded i.e. mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5) using the CTCAE Grading Table.
2. Hierarchically tested efficacy measured by local control rate (Time Frame - From Day 1 up to 12 months post-treatment): At day 1, 21, 28, 42, and months 3, 6, and 12 post-treatment, the investigator will measure (with a caliper) the largest diameter of selected lesions for irradiation.
Tumor response of each irradiated lesion will be assessed by the investigator as follow:
Complete Response: the irradiated lesion is no more visualized
Partial Response: the irradiated largest lesion dimension decreased by 30% at least from baseline (day 1)
Progressive Disease: the irradiated largest lesion dimension increased by 20% at least from baseline (day 1)
Stable Disease: no Complete Response, no Partial Response, no Progressive Disease
Secondary outcome:
1. Frequency of acute side effects observed "in radiation field" (Time Frame - up to 3 months after radiotherapy)
2. Frequency of late side effects observed "in radiation field" (Time Frame - from ≥ 3 months after radiotherapy until 12 months post-treatment start)
3. Evaluation of tumor response (Time Frame - From Day 1 up to 12 months post-treatment): Blinded Imaging Central Review (BICR) of photographs will evaluate tumor response by grading the size of the residual tumor in comparison to the size of the tumor on the day of irradiation (in percentage). 0% means no residual tumor and treatment success, 100% or more indicate a total lack of tumor response.
A baseline photograph will be taken the day of the treatment (day 1) in a pre-therapeutic setting with skin delineation of the lesion. Then photos will be repeated at day 21 (+/-2d), day 28 (+/-2d), day 42 (+/-3d) after treatment, then at 3 (+/-7d), 6 (+/-14d), 12 (+/-14d) months after treatment, and at progression.
4. Evaluation of "in radiation field" normal tissues reaction around the treated tumors (Time Frame - From Day 1 up to 12 months post-treatment): Blinded Imaging Central Review (BICR) of photographs will evaluate "in radiation field" normal tissues reaction around the treated tumors by grading radiation induced skin reactions, grade 1-5, using the CTCAE scale.
A baseline photograph will be taken the day of the treatment (day 1) in a pre-therapeutic setting with skin delineation of the lesion. Then photos will be repeated at day 21 (+/-2d), day 28 (+/-2d), day 42 (+/-3d) after treatment, then at 3 (+/-7d), 6 (+/-14d), 12 (+/-14d) months after treatment, and at progression.
5. Epidermis thickness measured by Optical coherence tomography (OCT) (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Epidermis thickness in micrometer will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
6. Epidermis roughness measured by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Epidermis roughness in micrometer will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
7. Plexus depth measured by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Plexus depth in micrometer will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
8. Vessel density measured by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Vessel density, expressed as percent of the surface covered by the vessels in the examined area, will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
9. Size of vessels measured by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Mean size (in micrometer) of all vessels in the examined area will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
10. Number of hairs counted by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Number of hairs in the examined area will be counted by OCT and compared between irradiated skin and normal non-irradiated skin
11. Size of hairs measured by OCT (Time Frame - at baseline, at 4 weeks, at 6 months, and at 12 months post-treatment): Mean size (in micrometer) of all hairs in the examined area will be measured by OCT and compared between irradiated skin and normal non-irradiated skin
