Study identifies potential strategy to reduce breast reconstruction complications after proton therapy

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by Jessica Saenz, Mayo Clinic

edited by Sadie Harley, reviewed by Andrew Zinin

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Radiation therapy is sometimes needed after mastectomy and breast reconstruction for breast cancer. However, patients with implant-based reconstruction who receive radiation therapy have a higher risk of capsular contracture, a complication in which scar tissue tightens around the implant. In more severe cases, it can cause breast pain, firmness or distortion and may require additional surgery.

A Mayo Clinic study published in the International Journal of Radiation Oncology*Biology*Physics found that areas around the implant receiving both higher proton beam radiation doses and elevated linear energy transfer (LET) were associated with capsular contracture.

LET measures how densely protons deposit energy as they travel through tissue. If validated in larger studies, the findings could help clinicians refine proton therapy plans to reduce the risk of this complication.

"Pencil beam scanning proton therapy can deliver precise doses of radiation for breast cancer while sparing healthy tissue and organs in the chest," says Wei Liu, Ph.D., research director of medical physics at Mayo Clinic in Arizona and co-senior author of the study. "These findings give us a possible direction for making an already precise treatment even safer."

The retrospective study reviewed data from 145 patients at Mayo Clinic who received pencil beam scanning proton therapy for breast cancer. Eight patients developed clinically significant capsular contracture. Researchers compared their treatment plans with those of 16 carefully matched patients who did not develop the complication.

"We found that patients who developed capsular contracture tended to have more small areas where moderate or high radiation doses overlapped with elevated LET," says Liu. "Our findings suggest that it may not be enough to evaluate radiation dose or LET separately during radiation therapy planning, but rather the combination and overlap should be considered."

The research is part of the Mayo Clinic Comprehensive Cancer Center's Novel Therapeutics and Therapeutic Modalities Research Program, which includes research on proton therapy and strategies to reduce treatment toxicity. Liu is a member of the program. Robert Mutter, M.D., a breast radiation oncologist at Mayo Clinic in Rochester, Minnesota, and co-senior author of the study, co-leads the program.

"Proton therapy gives us extraordinary control over where radiation dose is deposited, but dose alone may not tell the whole story," says Mutter. "At Mayo Clinic, we routinely consider linear energy transfer when designing proton treatment plans, particularly where beams stop near sensitive normal tissues. These findings reinforce the importance of considering dose and LET together and may help us refine how we optimize proton therapy moving forward."

Next, the research team plans to validate the findings in larger groups of patients across multiple institutions and further evaluate the dose-LET relationships identified in this study. The team also will investigate whether incorporating LET into proton treatment planning can reduce normal tissue exposure to unfavorable combinations of dose and LET while preserving treatment effectiveness and sparing nearby organs.

Publication details

Jingyuan Chen et al., Dose-Linear Energy Transfer Interactions Predict Capsular Contracture After Proton Postmastectomy Radiation Therapy, International Journal of Radiation Oncology*Biology*Physics (2026). DOI: 10.1016/j.ijrobp.2026.07.059

Journal information: International Journal of Radiation Oncology*Biology*Physics

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