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Dose-LET Interactions Predict Capsular Contracture After Proton Postmastectomy Radiation Therapy
Jingyuan Chen1, Zeliang Ma2, Meiyun Cao1
1Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ 85054, USA.
International Journal of Radiation Oncology, Biology, Physics
|August 13, 2026
Summary
Capsular contracture after proton postmastectomy radiation therapy (PMRT) is linked to both radiation dose and linear energy transfer (LET) in breast tissue. New dose-LET volume constraints (DLVCs) show promise for predicting and preventing this complication.
Area of Science:
- Radiation Oncology
- Medical Physics
- Breast Cancer Treatment
Background:
- Pencil beam scanning (PBS) proton therapy offers precise dose delivery for postmastectomy radiation therapy (PMRT), reducing cardiopulmonary toxicity.
- Implant-based reconstruction (IBR) following PMRT is associated with capsular contracture, a known complication.
- The role of elevated linear energy transfer (LET) from PBS in capsular contracture after PMRT is not well understood.
Purpose of the Study:
- To investigate the combined impact of radiation dose and dose-averaged linear energy transfer (LETd) on capsular contracture in patients undergoing proton PMRT with IBR.
- To derive preliminary, exploratory dose-LET volume constraints (DLVCs) for peri-implant tissues.
Main Methods:
- A retrospective case-control study matched patients with and without Baker grade III-IV capsular contracture.
- Dose-LET volume histograms (DLVHs) were calculated for a 5-mm shell around the breast implant.
- Generalized linear mixed-effects regression (GLMER) identified significant DLVH indices, and receiver operating characteristic (ROC) analysis derived DLVCs.
Main Results:
- Three DLVH indices (V(55.8 Gy[RBE=1.1], 2.2 keV/μm), V(50.3 Gy[RBE=1.1], 5.4 keV/μm), and V(32.8 Gy[RBE=1.1], 0.9 keV/μm)) were significantly associated with capsular contracture (q_BH=0.052).
- Derived DLVCs included V(55.8 Gy[RBE=1.1], 2.2 keV/μm) < 0.0017%, V(50.3 Gy[RBE=1.1], 5.4 keV/μm) < 0.0033%, and V(32.8 Gy[RBE=1.1], 0.9 keV/μm) > 96.98%.
- A support vector machine (SVM)-based normal tissue complication probability (NTCP) model demonstrated high predictive performance (AUROC=0.867).
Conclusions:
- Capsular contracture following proton PMRT is significantly influenced by the interplay of dose and LETd in the peri-implant tissues.
- The identified DLVCs are promising as potential dosimetric constraints for mitigating capsular contracture.
- Further prospective validation of these DLVCs is warranted for patients undergoing proton PMRT with IBR.