Editor's Note: The 48th San Antonio Breast Cancer Symposium (SABCS 2025) was held from December 9–12 in San Antonio, Texas, USA. As one of the world’s most influential academic meetings in breast cancer research, SABCS continues to drive advances in both clinical practice and scientific discovery. At this year’s meeting, the highly anticipated RadComp study presented results comparing cardiac dose–volume parameters and heart-specific health-related quality of life (HRQOL) between proton and photon radiotherapy in breast cancer patients (Abstract RF6-04). The findings highlighted the significant advantage of proton therapy in reducing cardiac radiation exposure, while also evaluating its short-term impact on cardiac HRQOL. Cancer Outlook invited Professor Jiayi Chen from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, to provide expert commentary on this study.Study Overview
RadComp (NCT02603341) is a multicenter, prospective, randomized phase III trial designed to determine whether the reduction in cardiac radiation dose achieved with proton therapy, compared with photon therapy, translates into fewer radiation-related cardiac events and improved survival outcomes. The study also aims to identify patient subgroups most likely to benefit from proton therapy.
This prespecified analysis compared radiation dose differences to cardiac substructures between proton and photon therapy, evaluated changes in cardiac-specific HRQOL within six months after radiotherapy, and explored correlations between dose–volume parameters and HRQOL outcomes.
Eligible patients included those with locally advanced breast cancer who completed protocol-defined radiotherapy, had complete cardiac substructure dosimetric data, and completed at least one cardiac-specific HRQOL assessment before treatment and within six months after radiotherapy. HRQOL instruments included the PROMIS Fatigue scale and PRO-CTCAE assessments for dyspnea, chest pain, chest tightness, and angina. Dosimetric analyses covered the whole heart, left and right ventricles, left and right atria, and the left anterior descending (LAD) coronary artery.
Key Results
Among 1,160 patients in the RadComp trial, significant differences in cardiac radiation exposure were observed between proton and photon therapy, influenced by tumor laterality. Median mean heart dose was markedly lower with proton therapy than with photon therapy (0.9 Gy vs 2.83 Gy, p<0.001). Right-sided breast cancer was associated with lower mean heart dose compared with left-sided or bilateral disease.
Proton therapy significantly reduced mean doses to the LAD artery, left atrium, left ventricle, and right atrium. However, for the whole heart, right atrium, and right ventricle, small-volume maximum doses (e.g., 0.03 cc) were higher with proton therapy.
Overall HRQOL scores remained favorable across all time points, with low rates of grade ≥3 toxicity (≤5.5%). PROMIS fatigue scores increased during radiotherapy but returned to baseline levels by six months post-treatment. Dyspnea severity and interference with daily activities did not change significantly over time. Chest pain frequency, severity, and daily-life interference showed mild worsening compared with baseline. Importantly, no significant association was observed between any cardiac dose–volume parameter and cardiac-specific HRQOL outcomes, even after stratification by tumor laterality.
Study Conclusions
Compared with photon therapy, proton therapy significantly reduced radiation doses to the whole heart and multiple cardiac substructures. Cardiac-related HRQOL outcomes were generally favorable: fatigue resolved by six months, dyspnea remained stable, and chest pain increased only slightly. Within six months after radiotherapy, reduced cardiac dose did not translate into measurable differences in cardiac-specific HRQOL. Future analyses will focus on other organs-at-risk, longer follow-up, and major cardiac events.
Expert Commentary by Prof. Jiayi Chen
Radiation-induced cardiac toxicity has long been a key concern in breast cancer radiotherapy, particularly because clinically significant cardiac events often emerge years or even decades after treatment. While the Bragg peak property of proton therapy theoretically allows substantial cardiac dose reduction, whether this dosimetric advantage leads to meaningful clinical benefit remains a critical question.
This RadComp analysis confirms that proton therapy provides superior cardiac dose sparing compared with photon therapy, including substantial reductions in mean dose to the whole heart, left ventricle, left atrium, and LAD artery. However, these advantages did not translate into improved cardiac-specific HRQOL within six months after radiotherapy. Given the long latency of radiation-induced heart disease—often 5–15 years—this absence of short-term HRQOL differences does not negate the potential for long-term benefit.
Comparisons with other ongoing studies are informative. The Danish DBCG trial focuses on patients at high cardiac risk based on photon treatment plans, with final results expected in 2037. The UK PARABLE trial compares proton therapy with advanced photon techniques such as VMAT combined with deep inspiration breath hold (DIBH) in patients predicted to have ≥2% late cardiac toxicity. Together with RadComp, these studies form a complementary evidence framework for defining the true clinical value of proton therapy.
In summary, while proton therapy’s dosimetric superiority is clear, confirmation of long-term clinical benefit requires extended follow-up and careful patient selection. The key unanswered question remains: which patients are most likely to benefit from proton therapy, and how can this resource-intensive modality be applied in a precise and rational manner? The oncology community now awaits long-term cardiac event and survival data from RadComp and related trials to guide evidence-based decision-making.
Prof. Jiayi Chen
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Yang Jing
Resident Physician, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
