Post-mastectomy radiotherapy (PMRT) has been shown to improve disease-free survival and overall survival for locally advanced breast cancer. However, long term survivors may develop life threatening acute and chronic treatment-related toxicities after radiotherapy, like cardiac toxicity and second cancers. The more advanced techniques like volumetric arc therapy (VMAT), and proton therapy have the potential to improve treatment outcome by constraining doses to radiosensitive organs, but evidence from outcome study will not be available until years or decades later. Furthermore, the literature is largely incomplete regarding systematic comparison of potential benefits of advanced technologies for PMRT. The purpose of this study was to compare proton therapy, both passively scattered (PSPT) and intensity modulated (IMPT), to VMAT and develop an evidence-based rationale for selecting a treatment modality for left sided post-mastectomy radiotherapy (PMRT) patients. Eight left-sided PMRT patients previously treated with VMAT were included in this study. Planning target volumes (PTV) included the chest wall and regional lymph nodes. PSPT and IMPT plans were created using a commercial proton treatment planning system. The resulting plans were compared to the corresponding VMAT on the basis of dosimetric and radiobiological endpoints. The uncertainties in risk from proton range, set-up errors, and dose-response models were also evaluated. All modalities produced clinically acceptable treatment plans with nearly 100% tumor control probability. Both proton techniques provided significantly lower normal tissue complication probability values for the heart (p < 0.02) and lung (p < 0.001). Patient-averaged second cancer risk for the contralateral breast and lungs were also significantly lower (p < 0.001) with protons compared to VMAT. The findings of this study were upheld by the uncertainty analysis. All three techniques provided acceptable PMRT treatment plans. Proton therapy showed significant advantages in terms of predicted normal tissue sparing compared to VMAT, taking into account possible uncertainties.

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Purpose: To evaluate two dose optimization strategies for maintaining target volume coverage of inversely‐planned post mastectomy radiotherapy (PMRT) plans during patient motion. Methods: Five patients previously treated with VMAT for PMRT at our clinical were randomly selected for this study. For each patient, two plan optimization strategies were compared. Plan 1 was optimized to a volume that included the physician's planning target volume (PTV) plus an expansion up to 0.3 cm from the bolus surface. Plan 2 was optimized to the PTV plus an expansion up to 0.3 cm from the patient surface (i.e., not extending into the bolus). VMAT plans were optimized to deliver 95% of the prescription to 95% of the PTV while sparing organs at risk based on clinical dose limits. PTV coverage was then evaluated following the simulation of patient shifts by 1.0 cm in the anterior and posterior directions using the treatment planning system. Results: Posterior patient shifts produced a difference in D95% of around 11% in both planning approaches from the non‐shifted dose distributions. Coverage of the medial and lateral borders of the evaluation volume was reduced in both the posteriorly shifted plans (Plan 1 and Plan 2). Anterior patient shifts affected Plan 2 more than Plan 1 with a difference in D95% of 1% for Plan 1 versus 6% for Plan 2 from the non‐shifted dose distributions. The least variation in PTV dose homogeneity for both shifts was obtained with Plan 1. However, all posteriorly shifted plans failed to deliver 95% of the prescription to 95% of the PTV. Whereas, only a few anteriorly shifted plans failed this criteria. Conclusion: The results of this study suggest both planning volume methods are sensitive to patient motion, but that a PTV extended into a bolus volume is slightly more robust for anterior patient shifts.

Purpose: The delivery of post‐mastectomy radiotherapy (PMRT) can be challenging for patients with left‐sided breast cancer due to the PTV size and proximity to critical organs. This study investigates the use of protons for PMRT in a clinically‐representative cohort of patients, and quantitatively compares volumetric modulated arc therapy (VMAT) to proton therapy to have an evidence‐based rationale for selecting a treatment modality for these patients. Methods: Eight left‐sided PMRT patients previously treated at our clinic with VMAT were identified for the study. PTVs included the chest wall and regional lymph nodes. Passively scattered (PS) and intensity modulated proton therapy (IMPT) plans were constructed using the Eclipse proton planning system. The resulting plans were compared to the original VMAT plan on the basis of PTV coverage; dose homogeneity index (DHI) and conformity index (CI); dose to organs at risk (OAR); tumor control probability (TCP), normal tissue complication probability (NTCP) and secondary cancer complication probability (SCCP). Differences were tested for significance using the paired Student's t‐test (p<0.01). Results: All modalities produced clinically acceptable PMRT plans. The comparison demonstrated proton treatment plans provide significantly lower NTCP values for the heart and the lung while maintaining significantly better CI and DHI. At a prescribed dose of 50.4 Gy (RBE) in the PTV, the calculated mean NTCP value for the patients decreased from 1.3% to 0.05% for the whole heart (cardiac mortality) and from 3.8% to 1.1% for the lungs (radiation pneumonitis) for both proton therapy plans from VMAT plans. Both proton modalities showed a significantly lower SCCP for the contralateral breast compared to VMAT. Conclusion: All three plans (VMAT, PS, and IMPT) provide acceptable treatment plans for PMRT. However, proton therapy shows a significant advantage over VMAT with regards to sparing OARs and may be more advantageous for patients with unfavorable anatomy.

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