EFLASH for Skin Lesions of Malignant Melanomas

Inclusion criteria

1. Signed study Informed Consent Form.

2. Males and females, age ≥ 18 years, no upper age limit.

3. Patients with metastatic melanoma and ≥ 1 skin/subcutaneous metastases (clearlydefinable in clinical examination: largest dimension of ≥ 5mm and ≤ 55 mm; ≤ 2.8 cmthickness (caliper-based measurement); volume ≤ 100ccm) with an indication forpalliative radiotherapy of ≥ 1 skin/subcutaneous metastases according to themultidisciplinary tumorboard.

4. The treated lesions must be at least 5 cm apart from each other, if applicable.

5. Lesions located on the scalp can be treated.

6. ECOG 0-2. Note: Patients may receive concurrent standard of care systemic treatment.

Exclusion criteria:

1. Previous radiotherapy of the target lesions.

2. Ulcerated lesions may not be treated within the study. Patients may have ulceratedtumor lesions besides those selected for treatment within the trial.

3. Lesions, for which a homogeneous dose distribution inside the tumor D95%> 95% - D2% <107% for the PTV (acceptable deviation D90%> 80% - D2% <115%) in the treatmentplanning system cannot be achieved.

4. Lesions should not be located on the face. Lesions on the forehead located craniallyfrom a line situated 1 cm above the eyebrows can be treated (=cranial of sinusfrontalis).

5. Lesions should not be located directly on genitals.

6. Lesions with close proximity to air-filled cavities or air-filled, luminal organs (e.g. bowel). Close proximity is defined by intersection of the respective part ofthe organ at risk with the 80% isodose line of the lesion planned for radiotherapy.

7. Women who are pregnant or breast feeding.

8. Lack of safe contraception during the study, defined as: Female participants ofchildbearing potential and male participants with partner of childbearing potential,not using and not willing to continue using a medically reliable method ofcontraception for the entire study duration, such as oral, injectable, orimplantable contraceptives, or intrauterine contraceptive devices, or who are notusing any other method considered sufficiently reliable by the investigator inindividual cases.

9. Known or suspected non-compliance, drug or alcohol abuse, inability to follow theprocedures of the study, e.g. due to language problems, psychological disorders,dementia, etc. of the participant, previous enrollment into the current study.

10. Enrollment of the investigator, his/her family members, employees and otherdependent persons.

11. Active infection including tuberculosis (clinical evaluation that includes clinicalhistory, physical examination and radiographic findings, and TB testing in line withlocal practice), hepatitis B (known positive HBV surface antigen (HBsAg) result),hepatitis C. Patients with a past or resolved HBV infection (defined as the presenceof hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patientspositive for hepatitis C (HCV) antibody are eligible only if polymerase chainreaction is negative for HCV RNA. Not adequately controlled HIV disease (HIV-viralload detectable).

12. Other severe comorbidities or psychiatric disorders (e.g. myocardial infractionwithin 6 months prior to registration, permanent cardiac arrhythmia, COPD Gold IV,schizophrenia, ongoing alcohol abuse) that would, according to the evaluation of theinvestigator, limit compliance with study requirement, substantially increase therisk of incurring adverse events or compromise the ability of the patient to givewritten informed consent.

13. History of sun hypersensitivity or photosensitive dermatoses including porphyria,systemic lupus erythematosus, Sjögren's syndrome, xeroderma pigmentosum,polymorphous light eruptions.

14. Concomitant auto-immune disease with skin lesions.

15. Concomitant use of radio-sensitizer drug.

16. Current, recent (within 10 days prior to start of study treatment), or plannedparticipation in an experimental drug study (before end of treatment (EOT) visit).

17. Concomitant use of systemic oncological treatment for another cancer than themetastatic melanoma.