With low a/b, breast cancer is one of few malignancies for which a high dose per fraction provides a benefit in killing cancer cells. Hypofractionation is the current standard in adjuvant radiotherapy and has been increasingly used in many centers. A new ultrahypofractionation regimen has recently been introduced and has demonstrated noninferiority in terms of acute skin toxicity and oncological outcomes when compared to standard hypofractionation . Brunt et al.  published results of the FAST-Forward trial and concluded that ultrahypofractionation, 26 Gy in 5 fractions for 1 week, did not show a significant difference in terms of patient-assessed normal tissue effects, clinician-assessed normal tissue effects, photographic changes in breast appearance, and oncological outcomes compared with 40 Gy in 15 fractions. With this short radiotherapy treatment course, this dose-fractionation regimen could be an option during the COVID-19 pandemic. Piras et al.  reported a dosimetric study of the FAST-Forward protocol of post-conservative surgery left breast cancer using the VMAT technique compared with the 3D-CRT technique, while our study compared VMAT with IMPT in postmastectomy plans. Piras’s results showed an ipsilateral lung V30 of 8.33 Gy, while our study revealed V20 approximately 6.4-7.6 Gy in VMAT plans. Our center aims to introduce ultrahypofractionation using proton beams; thus, dosimetric comparison of the target volume and OARs with VMAT is necessary. Although the DVH of most OARs except the ipsilateral lung in IMPT is clearly superior compared with those of VMAT in our study, we cannot assert that proton therapy will become the standard treatment in breast cancer in the near future. Further clinical studies are needed to assess whether the dosimetric advantage will translate into a clinical benefit. In addition, cost effectiveness should be considered. The cost of radiotherapy sessions and the cost of treatment for related toxicities must be weighed. However, we believe that in some special cases in which cardiac sparing is needed, proton therapy could be an appropriate alternative treatment .
Regarding toxicities, chest wall irradiation carries the risk of radiation pneumonitis, cardiac mortality, and secondary cancers [14, 21–22]. Our study evaluated the dosimetric parameters of VMAT and IMPT for ultrahypofractionation postmastectomy in breast cancer. The PTV coverage was equivalent for IMPT versus VMAT plans. These results corresponded well with Ares’s study  which showed IMPT reduced the bath of low dose distribution for OARs. Our study demonstrated that the V5 and Dmean of the ipsilateral lung in IMPT were less than those in VMAT in 3 out of 4 scenarios. In lung cancer patients, the large volumes of lung that receive low-dose irradiation (5 Gy or 10 Gy) increase the rate of pneumonitis . The volume of lung tissue receiving radiation could be associated with the risk of late toxicity, including second malignancy, particularly in young women. Our study confirmed that both high-dose and low-dose exposure to normal tissues were less common in the IMPT plan, which corresponded with MacDonald’s report .
Heart dose is well known to be correlated with cardiac morbidity . Our study supported that IMPT can reduce the potential risk to the cardiac structure. MacDonald’s study  reported that proton therapy allows for the treatment of deep-seated lymph nodes, such as the internal mammary lymph node (IMN), with minimal cardiopulmonary doses. Our results also support that V5, V10 and the mean heart dose were much lower in IMPT than in VMAT. With this dosimetric advantage, lower long-term morbidity from heart disease could be expected from proton beam therapy.
One concern with IMPT to the chest wall from this study is the increased dose to the skin because of the lack of a skin-sparing effect with protons. However, the total dose of our regimen was only 26 Gy, and the actual differences in doses between IMPT and VMAT are negligible. Therefore, acute skin toxicity, which typically relates to the total radiation dose, should not be greatly affected. We predict that this dose level is feasible and will be well-tolerated by patients. However, cosmesis is also an important outcome. Data collection in clinical studies is in progress and is reported in the near future.
Only 3 mm and 3.5% robust CTV optimization was sufficient and applied in this study because breathing motion management was concerned with access in clinical use. In addition, chest wall volumes are usually superficial in depth, ranging from 3 cm or less, and there was very little uncertainty about intrafraction motion for postmastectomy patients [20, 23]. Depauw et al.  reported that the patient’s chest wall movement along the AP/longitudinal direction was approximately 3 mm when motion management was performed during treatment. In addition, the beam path in proton plans is parallel to the target movement direction, which results in a minimal change in the position of the target; thus, the overall dosimetric impact is below 1% [5, 26].
Even though our study provided insights into proton and photon therapy in ultrahypofractionated postmastectomy irradiation, there are some limitations. First, only ten plans were evaluated for each scenario, and a large sample would provide more reliable data. Second, this is a dosimetric study, and the clinical outcomes of the proton interventions are needed. Nonetheless, the dose constraints to PTV and OARs of this study have been applied in our clinical practice, and we plan to report the clinical outcomes in the future.