To our knowledge, this is the first study to address patient preferences for shorter versus longer courses of RT for postoperative breast cancer. Furthermore, the study demonstrated patients’ enthusiasm for UHF-WBI after BCS, despite knowledge of the potential deterioration in breast cosmesis.
From a healthcare provider’s standpoint, the shorter the treatment, the less burdensome it becomes for the patients in terms of physical, emotional, and financial perspectives. Fewer treatment visits would decrease the chance of acquiring unwanted infections such as COVID-19. A shorter treatment period may also improve the cost-effectiveness of RT centers by reducing the number of patients on waiting lists, thus benefitting other patients [14]. The value of treatment duration in medical care should also be validated from the patients’ perspectives. This study confirmed that most patients preferred UHF RT following BCS, with very few patients expressing a preference for an even longer treatment course.
Time toxicity is typically discussed in the context of limited life expectancy. There is an emerging recognition that time toxicity should be considered in the earlier phase of cancer treatment [15]. Patients with breast cancer undergoing BCS and postoperative RT generally expect a healthy life for more than a decade thereafter. Patients tend to have various social roles within their families and communities, including workplaces. The time toxicity faced by this patient population directly affects their financial standing. Approximately one-quarter of the patients in this study experienced decreased wages due to RT, and this impact could have been minimized by a shorter treatment period. Further, 39% of the patients in the current study experienced more financial stress than expected prior to RT.
A quality-of-life (QOL) assessment comparing patients receiving CF- and HF-WBI was performed by Arsenault et al. HF-WBI resulted in improved overall QOL and that related to skin, breast, and attractiveness [16]. The FAST-Forward sub-study examining the acute skin toxicity of the HF versus UHF regimen revealed a lower incidence of grade 2 or 3 skin toxicities [17]. Although the study was not designed to show the statistical significance between the regimens, the overall QOL would be reasonably improved with the UHF regimen.
The late effects of RT may vary among different ethnicities, particularly when a higher dose/fractionation is used. The UK FAST hypofractionation trial revealed that larger breasts are more likely to change in breast size and shape 2 years after a breast RT regimen of 28.5–30 Gy in five once-weekly fractions [18]. Given the generally smaller breasts in the Asian population than those in the Caucasian population, the UHF regimen may be favorably applied to Asians for long-term breast cosmesis. Nevertheless, some researchers are concerned about pronounced toxicity to the breast and skin when applying the HF regimen to Japanese patients [13, 19]. The FAST-Forward trial demonstrated a trend toward the deterioration of breast cosmesis at the cost of treatment duration. Longitudinal analysis of moderate or marked clinician-assessed normal tissue effects at 5 years revealed an increased incidence of breast induration outside the tumor bed and breast/chest wall edema in the UHF arm compared with the MHF arm, without statistical significance. Breast induration and cosmesis deterioration were meaningful sequelae for nearly 70% of the patients in the current study. However, the priority level was lower than that given to the other effects of postoperative breast RT.
A systematic review and meta-analysis conducted by Liu et al. examined 28,267 patients with locally advanced non-small cell lung cancer receiving definitive RT and demonstrated that Asian patients were prone to developing radiation pneumonitis of any grade despite favorable lung DVH parameters compared to non-Asian patients[20]. They concluded that Asians appear to have poor tolerance to radiation to the lungs. The ethnic composition of the FAST-Forward population has not yet been published. Based on census data from the UK[21], most patients would have been Caucasian. Data from the JCOG 0906, a prospective single-arm confirmatory trial validating MHF-WBI in Japanese patients, showed that symptomatic radiation pneumonitis occurred in 2.3% of the patients[19]. The incidence appears to be reasonably low; however, it is slightly higher than that reported in the START-A and START-B trials, where the rates of symptomatic radiation pneumonitis/lung fibrosis were 0.8% and 1.4%, respectively[8, 9]. Given these differences in late toxicities between ethnicities, it may be reasonable to conduct a validation study of UHF-WBI in Asian populations.
This study had several limitations. Although the data were collected from multiple institutions in geographically scattered locations, the study was performed in Japan, meaning the majority of the respondents were Japanese. The value of UHF RT in relation to the potentially increased risk of long-term side effects might differ in other populations with different cultures or traditions. The current study mainly included patients aged 40 years or older. Although the age distribution in this study represents the general breast cancer population, the results may disregard the perspectives of younger patients, who might be more concerned about long-term breast cosmesis.
In conclusion, the patients’ enthusiasm for UHF-WBI was demonstrated in this study. We believe that our results will motivate clinicians and researchers to reevaluate the long-term effects of this new regimen, particularly breast cosmesis, in ethnic populations different from that included in the FAST-Forward. It will allow us to safely implement the regimen in daily practice and ultimately standardize globally.