The goal of this clinical investigation is to describe and compare the toxicity and efficacy of an experimental radiotherapy, named FLASH therapy, to conventional radiotherapy for subjects suffering from localized Cutaneous Squamous Cell Carcinoma (cSCC) and Basal Cell Carcinoma (BCC). FLASH therapy can deliver the irradiation dose within milliseconds instead of the minutes commonly required in conventional radiotherapy, with the aim of providing a curative dose while minimizing side effects on healthy tissue.

This is a phase II selection and monocentric clinical investigation with a 1 to 1 randomization. This clinical investigation will include approximately 60 participants aged ≥ 60 years old with one or more localized cSCC and BCC who either cannot undergo surgery or decline surgical resection.

The study design is the following:

• On day 1, either a single dose FLASH radiotherapy (22 Gy) will be delivered or a single dose conventional radiotherapy (22 Gy) will be delivered to the selected localized cSCC or BCC lesion(s) (up to maximum 3 per participant; all lesions distant of at least 4 cm from one-another).
• The surveillance period will be of 6 weeks post irradiation.
• Follow-up visits will take place at 3, 6, and 12 months post-treatment.

Inclusion Criteria:

1. Signed study Informed Consent Form
2. Karnofsky Performance Status (KPS) ≥ 60
3. Age ≥ 60 years
4. Participants with histologically proven cSCC; or participants with BCC either histologically proven or proven by non-invasive imaging: either OCT, LC-OCT or RCM
5. Participants requiring radiotherapy treatment according to the dermato-oncology tumor board: participants who cannot undergo surgical procedure or participants who decline surgical resection, and/or anatomical locations where surgery can compromise function or cosmesis.
6. T1-N0 lesions (TNM UICC, 8th Edition)
7. Lesions should be at least 4 cm apart if treated with 2 different modalities (including surgical treatment of lesions). Lesions should not be located on the face, except on the forehead, above a line situated 1 cm above the eyebrows. Lesions located on the scalp can be treated
8. In cases of prior intervention within the target area, the treated lesion must be located at a distance of > 4 cm from the previous site.

Exclusion Criteria:

1. Previous radiotherapy in the treated area or a history of radiation therapy within 4 cm of the lesion to be treated
2. Concomitant auto-immune disease with skin lesions
3. Concomitant use of radio-sensitizer drug
4. Cognitive disorders not compatible with the signature of informed consent or that may compromise compliance with the requirements of the study
5. Current, recent (within 10 days prior to start of study treatment), or planned participation in an experimental drug study (before EOT visit)
6. Concomitant use of systemic or immunochemotherapy for skin cancer(s)
7. Concomitant use of systemic chemotherapy for a cancer other than the skin cancer(s)
8. Topical antitumoral treatment is prohibited within the radiation field except after a mandatory 4-weeks washout period.
9. Any active cutaneous infection within the irradiation field (except if completely resolved prior to the initiation of radiotherapy).
10. Uncontrolled intercurrent comorbidities that may impair wound healing including Diabetes Mellitus (HbA1c > 8.5% or evidence of active diabetic ulceration), Chronic Venous Insufficiency with active venous ulcers, or severe (Grade 3+) oedema in the treatment field.