Introduction: Recent trials in radiotherapy have associated heart dose and survival, inadequately explained by the existing literature for radiation-related late cardiac effects. Authors aimed to review the recent literature on cardiac dosimetry and survival/cardiac endpoints. Areas covered: A systematic review of the literature in the past 10 years (2008-2017) was performed to identify manuscripts reporting both cardiac dosimetry and survival/cardiac endpoints. Authors identified 64 manuscripts for inclusion, covering pediatrics, breast cancer, lung cancer, gastrointestinal diseases (primarily esophageal cancer), and adult lymphoma. Expert commentary: In the first years after radiotherapy, high doses (>40 Gy) to small volumes of the heart are associated with decreased survival from an unknown cause. In the long-term, mean heart dose is associated with a small increased absolute risk of cardiac death. For coronary disease, relative risk increases roughly 10% per Gy mean heart dose, augmented by age and cardiac risk factors. For valvular disease and heart failure, doses >15 Gy substantially increase risk, augmented by anthracyclines. Arrhythmias after radiotherapy are poorly described but may account for the association between upper heart dose and survival. Symptomatic pericardial effusion typically occurs with doses >40 Gy. Close follow-up and mitigation of cardiovascular risk factors is necessary after thoracic radiotherapy.

This interim analysis evaluated changes in quality of life (QOL), American Urological Association Symptom Index (AUA), or adverse events (AEs) among prostate cancer patients treated with hypofractionation. Results for hypofractionated prostate cancer with photon therapy are encouraging. No prior trial addresses the role of proton therapy in this clinical setting. Forty-nine patients with low-risk prostate cancer received 38-Gy relative biologic effectiveness in 5 treatments. They received proton therapy at 2 fields a day, magnetic resonance imaging registration, rectal balloon, and fiducial markers for guidance pre-beam. We evaluated AEs, Expanded Prostate Index Composite (EPIC) domains, and AUA at pretreatment and at 3, 6, 12, 18, and 24 months. An AUA change >5 points and QOL change of half a standard deviation (SD) defined clinical significance. Median follow-up was 18 months; 17 patients reached follow-up of ≥24 months. For urinary function, statistically and clinically significant change was not seen (maximum change, 3). EPIC urinary QOL scores did not show statistically and clinically significant change at any end point (maximum, 0.45 SD). EPIC bowel QOL scores showed small but statistically and clinically significant change at 6, 12, 18, and 24 months (SD range, 0.52-0.62). EPIC sexual scores showed small but statistically and clinically significant change at 24 months (SD, 0.52). No AE grade ≥3 was seen. Patients treated with hypofractionated proton therapy tolerated treatment well, with excellent QOL scores, persistently low AUA, and no AE grade ≥3.

Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Randomized evidence for extreme hypofractionation in prostate cancer is lacking. We aimed to identify differences in toxicity and quality-of-life outcomes between standard fractionation and extreme hypofractionated radiation in a phase 3 randomized trial. We analyzed the results of the first 75 patients in our phase 3 trial, comparing 38 Gy relative biologic effectiveness (RBE) in 5 fractions (n = 46) versus 79.2 Gy RBE in 44 fractions (n = 29). Patients received proton radiation using fiducials and daily image guidance. We evaluated American Urological Association Symptom Index (AUASI), adverse events (AEs), and Expanded Prostate Index Composite (EPIC) domains. The primary endpoint of this interim analysis was the cumulative incidence of grade 2 (G2) or higher AEs. The randomized patient allocation scheme was a 2:1 ratio favoring the 38 Gy RBE arm. The median follow-up was 36 months; 30% of patients reached 48-month follow-up. AUASI scores differed <5 points (4.4 vs 8.6; P = .002) at 1 year, favoring the 79.2 Gy arm. Differences in AUASI were not significant at ≥18 months. EPIC urinary symptoms favored the 79.2 Gy arm at 1 year (92.3 vs 84.5; P = .009) and 18 months (92.3 vs 85.3; P = .03); bother scores were not significant at other time points. Cumulative ≥G2 genitourinary toxicity was similar between the 79.2 Gy and 38 Gy arms (34.5% vs 30.4%; P = .80). We found no differences in the EPIC domains of bowel symptoms, sexual symptoms, or bowel ≥G2 toxicities. Bladder V80 (79.2 Gy arm; P = .04) and V39 (38 Gy arm; P = .05) were predictive for cumulative G2 genitourinary AEs. Low AE rates were seen in both study arms. Early temporary differences in genitourinary scores disappeared over time. Bladder constraints were associated with genitourinary AEs.