Does Pencil Beam Scanning Proton Therapy Impart a Higher Risk of Capsular Contracture when Compared with Intensity Modulated Photon Radiotherapy in the Post-Mastectomy Reconstruction Setting?

[BACKGROUND] Post-mastectomy radiotherapy (PMRT) may cause adverse events in the reconstruction setting. Proton-based PMRT is increasingly utilized and has been shown to improve cardiac and pulmonary dosimetry. Data reporting the risk of capsular contracture (CC) with proton compared to photon PMRT remain scarce. We compared the CC rate of the largest cohort of pencil beam scanning (PBS) proton PMRT reconstructed patients reported to date with an intensity modulated (IMRT) photon cohort hypothesizing that the proton cohort would have a higher rate of CC.

[METHODS] An IRB approved retrospective study was conducted on breast cancer patients who underwent subpectoral two stage tissue expander/implant (TE/I) or direct-to-implant (DTI) breast reconstruction and received either PBS proton or IMRT photon PMRT between January 2017 and December 2023 at two centers within a single institution. All TE/I patients had the TE irradiated. CC rates were estimated using the Kaplan-Meier method. Cox proportional hazards analysis, denoted as hazard ratios (HRs) with 95% confidence intervals (CI), was used to assess variables potentially associated with outcome, and a binary logistic regression model was used to verify the results.

[RESULTS] The study cohort comprised 175 patients (89 proton; 86 photon). The median age was 49 years (range 24-78), 63% were Hispanic. Patient demographics were well balanced between the groups, except in tumor laterality (p<0.001) and reconstruction type (TE/I vs. DTI, p<0.001). Median follow up was 42 and 47 months for the proton and photon groups, respectively. In a multivariable analysis, DTI patients had a significantly higher risk of CC compared to TE/I patients (HR 3.0, 95% CI 1.7-5.5, p<0.001). Proton patients had a higher risk of developing CC compared to the photon group in univariate analysis (HR 2.3, 95% CI 1.26-4.30, p=0.007)), though this effect did not reach statistical significance in the multivariable model (HR 1.76, 95% CI 0.93-3.32, p=0.083). The 2-year CC rate for patients treated with protons and DTI (n=36), photons and DTI (n=15), protons and TE/I (n=53), and photons and TE/I (n=71) was 50%, 35%, 23%, 12%, respectively (p<0.001). No other factors were significantly associated with CC development.

[CONCLUSION] In this contemporary large proton versus photon PMRT cohort, proton patients trended towards increased risk of CC. DTI patients treated with protons had the highest risk of CC (50%). Careful consideration of reconstruction and radiotherapy modalities, assessing CC risk and also involving patient input, is important for treatment selection.