No Association Between Radiation Dose and Clinical Outcomes in Merkel Cell Carcinoma in the Veteran Population

Merkelcell.org Summary

Merkel cell carcinoma (MCC) is a rare skin cancer that is often treated with surgery and/or radiation therapy, which is a type of treatment that uses high-energy rays to kill cancer cells and shrink the tumors. MCC is especially sensitive to radiation; so many patients receive this treatment as part of their care.

Conventional radiation treatment usually means giving small doses of radiation (2Gy) over 5 to 6 weeks. The total dose is often about 50 to 60 Gy “Gy” stands for gray, which is a unit used to measure the amount of radiation energy delivered to the tissue. However, MCC is very sensitive to radiation therapy. Because of this, shorter radiation treatments may also be used. For example, some patients may receive a single higher dose of radiation, such as 8 Gy given in one treatment.

This study included 324 patients, all of whom were U.S. Veterans. The researchers found that giving one or several higher doses of radiation, also called hypofractionated radiation, worked about as well as conventional radiation treatment for controlling MCC. Overall, 94% of patients did not have the cancer come back in the area that was treated with radiation. These findings support the important role of radiation therapy in treating MCC. They also suggest that shorter courses of radiation treatments may work just as well as conventional radiation courses in helping prevent MCC from coming back to the treated area.

Abstract

Purpose: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Treatment often includes high-dose radiation therapy (RT); however, studies suggest that even 8 Gy in 1 fraction can provide local control.

Methods and materials: In this retrospective, IRB-approved study, we mined the national Veterans Affairs Corporate Data Warehouse for MCC patients treated with RT. Using a combination of manual chart review and semiautomated data extraction from free-text notes, we collected information on diagnosis, tumor site and size, treatment technique, and radiation dose/fractionation. We assessed local and distant tumor control and overall survival as a function of radiation dose.

Results: We identified 324 patients with 618 treated sites that were evaluable. Of these, 386 sites were treated for microscopic disease and 232 for gross disease. Among the gross disease sites, 64 were treated with curative intent, 164 with palliative intent, and 4 with neoadjuvant intent. The 5-year local progression-free probability (LPFP) was 94.0% across the entire cohort, with 1-, 3-, and 5-year LPFP of 92%, 89%, and 86%, respectively, for patients with gross disease. Local tumor control was excellent across the entire spectrum of delivered radiation doses, ranging from 7.5 to 122.4 Gy (biologically effective dose, α/β = 10), both for sites with gross disease and those treated for microscopic disease risk. Local tumor control was 90% to 95% in both the highest and lowest RT dose groups. Univariate and multivariate Cox proportional hazard assessment of radiation dose showed no significant association with LPFP (hazard ratio, 0.99; 95% confidence intervals [CIs], 0.97-1.01; P = .22 and hazard ratio, 1.00; 95% CI, 0.97-1.02; P = .67, respectively). Distant progression-free probability was also independent of radiation dose.

Conclusions: MCC is generally sensitive to RT, with traditionally palliative doses demonstrating similar local and distant disease control compared with higher dose regimens. Acknowledging several caveats to this work, these data support considering dose de-escalation as a treatment option for MCC.