Melanoma
Conditions
Keywords
Choroid Melanoma
Brief summary
Ocular melanomas have been treated for a long time by enucleation, with an unfavorable major impact on the patient's quality of life, social life, self-image, how they feel about others and about living with this disability. As a matter of fact, classical radiation therapy by photons is not accurate enough to deliver a sufficiently high dose to eradicate a melanoma without causing irreversible ocular brain complications since these tumors are " relatively radio resistant ". The possibility of delivering high doses due to the precision of protons ("Bragg peak") has allowed to overcome this limitation. The conservative uveal melanoma treatment has become a standard after the Collaborative Ocular Melanoma Study (COMS) indicating an equivalent rate of metastases and a non-impaired survival rate with a conservative treatment when compared to immediate enucleation. The quality of life benefits due to a conservative treatment has been demonstrated. Protontherapy dose has been defined in an empirical manner, it is probably excessive even if it applies to radio-resistant tumors. In France, radiotherapy by protons for choroidal melanomas delivers a dose of 60 Gy cobalt equivalent (that is 52 measured Gy, or " Physical dose") in 4 fractions and 4 days. Referential treatment of ocular melanomas (other than conjunctiva) indicates proton-therapy for T1, T2, T3 \< 40% of ocular volume, and T4 only if extra scleral extension ≤ 2mm. However, there is an enucleation indication for T3 \> 40% of ocular volume and T4. Our purpose is to override this relative contraindication, choroidal melanoma volume ≥ 40% of ocular volume. As a matter of fact, the investigators observe an increasing demand from ophthalmologists and patients for not performing primary enucleation. Also, during the last five years treatment of complications have improved and a less " hard " hypo fractionation (6.5 Gy per fraction) has equivalent local control results as for " hard " fractionation (13 Gy per fraction).
Detailed description
A more fractioned proton-therapy treatment, with doses per fraction of 6.5 Gy rather than 13 Gy, can limit the rate and the severity of complications degrading the quality of life by complications (pain, diminished visual acuity) and treatments (intra-ocular injections...). In this study, patients will receive a total dose of 52 Gy in four 13 Gy sessions for the standard arm and in eight 6.5 Gy sessions for the experimental arm. The investigators expect an identical local control rate within 2 year's time with a decrease in rate and severity of severe complications due to adapted fractionation (eight sessions with lower doses instead of four fractions with very high doses as it is usually recommended in the guidelines for small to medium melanomas).
Interventions
RADIATIONProtontherapy
Proton-therapy consists in four consecutive sessions. The experimental arm consists in eight sessions. Irradiation is administered over two weeks, delivering a total dose of 60 Cobalt Gris Equivalent (CGE is the physical Gray dose multiplied by a biological factor of relative efficiency of 1.1 for protons compared to photons).
Sponsors
Centre Antoine Lacassagne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
Study with 2 differents dosages of proton therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient diagnosed with choroidal melanoma by an ophthalmologist and proton-therapy treatment proposed by the multi-disciplinary board meeting * Patient over 18 years old, male or female * Performance status ≤ 2 * Size and/or thickness greater than those proposed on proton-therapy appendix indications (tumor volume/ocular globe \> 40% and/or thickness ≥ 12 mm and/or diameter ≥ 18 mm or thickness ≥ 10 mm and diameter ≥ 15 mm). Possible ophthalmological follow-up examinations at 6 months, one year, 18 months and two years. * No contraindication for adjuvant chemotherapy * Authorized technique to preserve the optic nerve * Patient having undergone the required medical procedures: * Ophthalmological examination * Clip positioning * Proton-therapy treatment (localization CT, first simulation, second simulation, final simulation) * Patient reads information note and signs consent form
Exclusion criteria
* Exclusive iris damage * Exclusive conjunctival damage * First melanoma surgery * Enucleation planned post-proton-therapy * Exentration indication * Life expectancy \< 2 years * Scleral exteriorisation \> 2 mm * Absolute radiotherapy contraindication (ataxia-telangiectasia) * Cancer history, except for complete remission cancers of over 5 years, basocellular skin carcinomas completely resected, in-situ carcinomas or treated in situ cervical epithelioma * Presence of metastases other than hepatic (endoresection authorized)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| local control rate without severe complications 2 years after. | up to 60 months |
Secondary
| Measure | Time frame |
|---|---|
| Enucleation rate | up to 60 months |
| Tumoral transretinien endoresection by unplanned vitrectomy in inclusion (emergency procedure) | up to 60 months |
| Number of months without metastases evaluation | up to 60 months |
| Number of months of Specific global survival evaluation | up to 60 months |
| Complications and toxicity evaluation (number of subjects with adverse events related to treatment) | up to 60 months |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORJuliette THARIAT, md
Centre Antoine Lacassagne
Outcome results
None listed