Uptake of ultra-hypofractionated radiation therapy following breast conserving surgery among patients with early-stage breast cancer: A multi-institutional questionnaire survey

Uptake of ultra-hypofractionated radiation therapy following breast conserving surgery among patients with early-stage breast cancer: A multi-institutional questionnaire survey | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Uptake of ultra-hypofractionated radiation therapy following breast conserving surgery among patients with early-stage breast cancer: A multi-institutional questionnaire survey Haruka Uezono, Tsuyoshi Onoe, Naoto Shikama, Yuka Onoe, Hidenari Hirata, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4359787/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 24 Jul, 2024 Read the published version in Breast Cancer → Version 1 posted 5 You are reading this latest preprint version Abstract Background In patients with early-stage breast cancer following breast surgery, ultra-hypofractionated (UHF) breast/chest wall radiation therapy (RT) has been shown to be non-inferior to a moderate-hypofractionated (MHF) regimen, with a minimal risk of breast induration, in the FAST-Forward trial, and UHF is now becoming the standard regimen in Europe. Herein, we aimed to investigate Japanese patients’ attitudes toward the UHF regimen. Methods A questionnaire-based survey was conducted at 13 RT centers in nine prefectures across Japan. All patients underwent breast-conserving surgery, followed by either conventional fractionation (2 Gy/fr) or MHF (2.66 Gy/fr) whole-breast irradiation (WBI) with or without a tumor bed boost. The questionnaire consisted of 12 questions mainly addressing quality of life during RT. Key questions included an 11-point scale (0–10) for rating the patients’ enthusiasm for the UHF regimen and prioritization of the following treatment-related effects: treatment efficacy, acute/late adverse effects, physical/emotional/financial burden, and breast cosmesis. The patient and treatment characteristics were assessed by a physician. Results In total, 247 questionnaires were administered between November 2022 and June 2023. The age distribution was as follows: <50:50s:60s:≥70 = 59 (24%):76 (30%):63 (26%):49 (20%). Sixty-nine percent of patients rated their enthusiasm for the UHF regimen at ≥ 6 out of 10 points (45% rated 10/10). Treatment efficacy was the highest priority for most patients (89%), whereas breast cosmesis the lowest priority (53%). Conclusions Patients’ enthusiasm for UHF-WBI was observed across the cohort. These results could motivate researchers and clinicians to introduce UHF regimens in clinical practice. ultra-hypofractionated whole breast irradiation patients’ preference breast-conserving therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Adjuvant radiation therapy (RT) is an essential component of breast-conserving therapy for early-stage breast cancer. It has been shown to reduce breast cancer mortality and local recurrence in a meta-analysis [ 1 ] and multiple prospective phase III trials. Whole breast irradiation (WBI) using 1.8–2 Gy/fr daily treatment over 4–6 weeks, the so-called conventional fractionation (CF), was initially employed for post-lumpectomy RT [ 2 ]. In recent decades, more options following breast-conserving surgery (BCS) have been developed depending on patient and tumor characteristics. RT can be safely omitted in selected elderly populations with favorable tumor biology without compromising overall survival [ 3 , 4 ]. Accelerated partial breast irradiation (APBI) is another option for patients with favorable tumor characteristics [ 5 – 7 ], requiring fewer treatment visits and a larger dose/fractionation. Although few patients are eligible for these relatively new options, WBI is indicated for most patients. The dose/fractionation regimen for WBI has been revolutionized. Multiple phase III trials have demonstrated the non-inferiority of moderate-hypofractionated (MHF) WBI over the CF regimen [ 8 – 10 ]. The MHF regimen is currently recommended in many guidelines [ 6 , 7 , 11 ] and is considered the standard treatment. Furthermore, the FAST-Forward trial conducted in the UK showed the non-inferiority of ultra-hypofractionated (UHF) WBI/chest wall RT compared to the MHF regimen, with a minimally increased risk of deterioration in breast cosmesis [ 12 ], and the UHF regimen is on the way to becoming the standard treatment for postoperative early-stage breast cancer in Europe [ 6 ]. There is some concern about adapting the UHF regimen to clinical practice among Japanese radiation oncologists, as the difference in ethnicity from the UK might result in a higher incidence of adverse events (AEs) [ 13 ]. The Japan Clinical Oncology Group (JCOG) Unit of Radiation Oncology Investigators with Youngers (JOURNEY) proposed retesting this regimen in a multi-institutional clinical trial in Japan following the publication of FAST-Forward. Expert breast radiation oncologists raised concerns regarding long-term AEs, specifically breast cosmesis; therefore, the trial should be awaited until longer follow-up data from the FAST-Forward come out. However, the benefits of shorter RT periods in patients with breast cancer are not negligible. The value of this innovative treatment should be assessed from the perspective of not only researchers and clinicians but also patients. To this end, we conducted a questionnaire-based study to evaluate the patients’ attitudes toward UHF regimens, given the potential long-term AEs. Patients and Methods We planned to distribute 250 questionnaires and obtain 200 valid responses between November 2022 and June 2023. Eligible patients underwent either CF (45–50 Gy/ 25–28 fr) or MHF (40–43 Gy/15–16 fractions) WBI after BCS. The patients were excluded if they were receiving one of the following: a UHF regimen (i.e., 26–28.5 Gy/5 fr), APBI, or regional nodal irradiation, in addition to WBI. The questionnaire contained the following questions: 1) age; 2) date of survey; 3) travel time/mode of transportation for a treatment visit; 4) number of household, number of those for need support or care at home; 5) employment status; 6) discrepancies between patient’s experience during RT and prior expectation in terms of physical/socioeconomical aspects; 7) magnitude of RT impact on daily living using an 11-point (0–10) scale; 8) impact of RT on family or work environment; 9) enthusiasm for UHF regimen using an 11-point scale; 10) reluctance of long-term cosmetic deterioration of the treated breast using an 11-point scale; 11) enthusiasm for shortening RT period with UHF regimen vs reluctance for developing breast induration using an 11-point scale; and 12) prioritization of the following treatment-related effects: treatment efficacy, acute AEs, late AEs, physical/emotional burden during treatment, financial burden of the treatment, and long-term breast cosmesis. The following data were collected by the local research staff: 1) location of the facility, 2) start/completion date of RT, 3) RT regimen including WBI and tumor bed boost, 4) decision process of the RT regimen, either conventional or moderate hypofractionation, and 5) use of endocrine/chemo-/targeted therapy. Written informed consent was obtained from all patients before enrollment in the study. The questionnaire was to be completed within 5 days before or after completion of RT and then typically reviewed by the research staff to minimize unintentional errors before sending the sheet to the research administration office. The patients were asked to send the questionnaire directly to the research administration office if they did not want their response sheets to be reviewed by the local research staff. The study protocol was approved by the institutional review board of Hyogo Cancer Center. The study was conducted at 13 radiation oncology centers affiliated with the JOURNEY in nine prefectures across Japan. A minimum and maximum of 10 and 25 cases, respectively, were assigned to the participating centers, depending on their capacity. This study was registered in the UMIN Clinical Trials Registry (UMIN000049536). Results In total, 247 questionnaires were collected from the research administration office. Valid answers were obtained from more than 240 (97%) patients for most questions, except for Question 12, which evaluated the prioritization of various treatment-related effects. The median number of valid answers for priorities 1 through 6 in Question 12 was 231 (93.5%; range, 229–240; 92.7–97.2%). The patient and treatment characteristics are listed in Table 1 . Among the 247 patients, 80 (32%) were treated at one of the four institutions in the Tokyo or Yokohama metropolitan area, which is the most densely populated area in Japan. These locations were regarded as urban, whereas the six prefectures where the other nine institutions were located were considered suburban. The adoption of the dose/fractionation regimen was dependent on the institution; all 20 patients from institution X were treated with the SF regimen, whereas 223 of the 227 (98%) patients from other institutions were treated with the MHF regimen. Table 1 A. Patient and treatment characteristics variable N = 247 Age (years) < 40 7 (3%) 40–49 52 (21%) 50–59 76 (30%) 60–69 63 (26%) ≥ 70 49 (20%) Date of survey November 2022 – March 2023 124 (50%) April – June 2023 123 (50%) Location of the institution Urban* 80 (32%) Suburban 167 (68%) Fractionation of WBI 16 223 (90%) 25 24 (10%) Fractionation of TB boost no boost 150 (61%) 4 84 (34%) 5 4 (2%) 6 9 (4%) Decision process of RT regimen Physician recommendation 141 (57%) Patient desire 28 (11%) Both of the above 72 (29%) Unknown 6 (2%) Endocrine therapy use Current 96 (39%) Planned after RT 73 (30%) Chemotherapy use Neoadjuvant 21 (9%) Adjuvant before RT 23 (9%) Planned after RT 12 (5%) Targeted therapy use Neoadjuvant 5 (2%) Adjuvant before RT 11 (4%) Planned after RT 7 (3%) Abbreviations: RT, radiation therapy; WBI, whole breast irradiation; TB, tumor bed *Urban indicates Tokyo and Yokohama metropolitan area; suburban indicates all others. Table 1 B. Patients’ background lifestyle Variable N = 247 Travel time for a treatment visit (hours, one way) 2 4 (2%) Inpatient care/rent an accommodation 4 (2%) Mode of transportation* Car drive 85 (34%) Car ride (driven by a family) 37 (15%) Public transportation 119 (48%) Walk/bike 31 (13%) Number of households 1 41 (17%) 2 103 (42%) 3 57 (23%) 4+ 46 (19%) Number of households requiring care/observation One child aged < 15 59 (24%) Two children aged < 15 41 (17%) Three or more children aged < 15 9 (4%) Anyone aged ≥ 15 26 (11%) Employment status Housewife 59 (24%) Full-time work 81 (33%) Part-time work 45 (18%) Leave from work 17 (7%) Self-employed 15 (6%) Inoccupation 30 (12%) *29 patients used multiple modes of transportation. The travel time (one-way) for a treatment visit was less than an hour for 82% of the patients. The most common modes of travel were public transport (39%) and driving (30%). Four (2%) patients received inpatient care or rented a nearby apartment due to inconveniences related to travel for daily treatment. The majority of the patients continued to fulfill their roles in the family or at work throughout the RT period, while 17 (7%) patients were on leave from work for treatment. Details of the patients’ background and circumstances are shown in Table 2. The patients’ experiences during RT were compared with their prior expectations in terms of physical and socioeconomic aspects. Approximately half of the patients stated that RT was “easier” than they had anticipated (Fig. 1 a). Mixed responses were noted regarding treatment duration, with 17% and 23% of the cohort perceiving the treatment duration as being short and long, respectively. Of note, more than 70% of the patients considered weekday treatment for 3 to 5 weeks to be more burdensome than they had expected (Fig. 1 b). A few patients commented that longer treatment periods would have been comfortable, as they had a healthy lifestyle throughout the RT course. In other comments regarding longer treatment, the patients stated that they felt like the tumor cells were being killed at each treatment session. The impact of RT on patients’ families and work environments is shown in Fig. 2 . Approximately one-quarter of the patients experienced decreased income during RT. The magnitude of the impact of RT on the patients’ daily living was evaluated using an 11-point scale (0–10), and the results are shown in Fig. 3 A. More than half of the patients felt that RT had a moderate-to-significant (5–10) impact on their daily lives. Patients’ enthusiasm for the UHF regimen was evaluated on an 11-point scale. Nearly 70% of the patients rated it 6 points or more out of 10 (Fig. 3 b). Forty-five percent rated it 10, whereas only 4% rated it 4 points or less. The magnitude of the patient’s reluctance to undergo posttreatment breast induration was evaluated using an 11-point scale (Fig. 3 c). Approximately two-thirds of the patients rated their reluctance at 5 points or more out of 10 (moderate-to-significant reluctance). Figure 3 shows box plots representing the scale score of (a) the impact of RT on patients’ daily living, (b) enthusiasm for the UHF regimen, and (c) reluctance to breast cosmesis deterioration, each stratified by various background factors. Patients who were young, employed full- or part-time, and those treated in urban centers were likely to experience a greater impact of treatment than their older, unemployed/self-employed, and elsewhere treated counterparts (Fig. 3 a). Patients from urban areas, those who received the MHF regimen, and those who received chemotherapy were more likely to prefer the UHF regimen (Fig. 3 b). Patients aged < 60 years and those from urban areas were more likely to be concerned about the development of breast induration (Fig. 3 c). Patients’ enthusiasm for UHF RT versus the risk of breast cosmesis deterioration was assessed using an 11-point scale, with 0 indicating the highest priority for breast cosmesis rather than for a short treatment period and 10 indicating the opposite. Overall, 55% of the patients rated their enthusiasm at 6 points or more (i.e., a shorter treatment period was preferred to post-treatment cosmesis deterioration). The final question was used to assess patient prioritization of the six RT-related effects, which included, in ascending order, acute AEs, late AEs, physical/emotional burden during RT, financial burden during RT, and long-term breast cosmesis (Fig. 5 ). Nearly 90% of the patients rated treatment efficacy as the first priority, while more than half of the patients rated breast cosmesis as the lowest priority. Discussion 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. Declarations Author contributions All authors contributed to the study conception and design, as well as material preparation. Data collection and analysis were performed by H.U. and T.O. The first draft of the manuscript was written by H.U., T.O., and N.S., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements This research was supported by the National Cancer Center Research and Development Fund (2023-J-03). Conflicts of interest : N.S. reports research grant from Elekta. The other authors declare no conflicts of interest. Statement of human rights All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. References Early Breast Cancer Trialists' Collaborative Group, Darby S, McGale P, Correa C, Taylor C, Arriagada R, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–16. Early Breast Cancer Trialists’ Collaborative Group. 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Cite Share Download PDF Status: Published Journal Publication published 24 Jul, 2024 Read the published version in Breast Cancer → Version 1 posted Editorial decision: Minor Revision 20 Jun, 2024 Reviewers agreed at journal 12 May, 2024 Reviewers invited by journal 05 May, 2024 Editor assigned by journal 04 May, 2024 First submitted to journal 02 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4359787","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":298977083,"identity":"a3a3988b-3a9f-473d-ac52-ad8774b4fb58","order_by":0,"name":"Haruka Uezono","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIie2RwWoCMRCGE1JmL7FeJxS3+AYLAUXch9m9pK+RU06VvkEfQzymzNXi1dKTCHsr1IvQg8VULO2lcb0JzQcDQ+Bj/pkwlkhcIEUosfvEHITwjNvjM55QmIRSX2dQnaWY+rErix8lxjB7bhAl1U7ILX7Mypxl5Nlo9rcyur8bYIGknehM1WRuNJOmYmoeCeYNYFVQ70vBjqPaYkioXERZNIC+Ih6CNWrXSlkaUNabflDgpt2UZSPG3JYaBOhxzxkNYRcf3WVh+Cu3mN8+0OrlzZV5N6OntYpc7DdXhw+EUKRsO0W8f3d801JJJBKJf8EeTW5H8DUPkPEAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-5736-5655","institution":"Hyogo Cancer Center: Hyogo Kenritsu Gan Center","correspondingAuthor":true,"prefix":"","firstName":"Haruka","middleName":"","lastName":"Uezono","suffix":""},{"id":298977084,"identity":"ab8a4f14-64ce-4cef-bd11-5f24dcd395da","order_by":1,"name":"Tsuyoshi Onoe","email":"","orcid":"","institution":"Shizuoka Cancer Center: Shizuoka Kenritsu Shizuoka Gan Center","correspondingAuthor":false,"prefix":"","firstName":"Tsuyoshi","middleName":"","lastName":"Onoe","suffix":""},{"id":298977085,"identity":"62173cd0-6526-47e7-a26d-dedd6f08eef2","order_by":2,"name":"Naoto Shikama","email":"","orcid":"","institution":"Juntendo Daigaku - Hongo Campus: Juntendo Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Naoto","middleName":"","lastName":"Shikama","suffix":""},{"id":298977086,"identity":"9d7112ef-4938-4b1e-bd99-fd947b8618ee","order_by":3,"name":"Yuka Onoe","email":"","orcid":"","institution":"Kyoto University Graduate School of Medicine Faculty of Medicine: Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu","correspondingAuthor":false,"prefix":"","firstName":"Yuka","middleName":"","lastName":"Onoe","suffix":""},{"id":298977087,"identity":"d8c15d11-c25b-49ba-8516-bc443f728bb2","order_by":4,"name":"Hidenari Hirata","email":"","orcid":"","institution":"National Cancer Center-Hospital East: Kokuritsu Gan Center Higashi Byoin","correspondingAuthor":false,"prefix":"","firstName":"Hidenari","middleName":"","lastName":"Hirata","suffix":""},{"id":298977088,"identity":"2427539c-0a31-4e7e-b937-ef8e5a3843a4","order_by":5,"name":"Yoshinori Ito","email":"","orcid":"","institution":"Showa University Graduate School of Medicine School of Medicine: Showa Daigaku Daigakuin Igaku Kenkyuka Igakubu","correspondingAuthor":false,"prefix":"","firstName":"Yoshinori","middleName":"","lastName":"Ito","suffix":""},{"id":298977089,"identity":"4f549326-be60-4c74-9e66-26019790110c","order_by":6,"name":"Koichi Yasuda","email":"","orcid":"","institution":"Hokkaido University Graduate School of Medicine School of Medicine: Hokkaido Daigaku Daigakuin Igaku Kenkyuin","correspondingAuthor":false,"prefix":"","firstName":"Koichi","middleName":"","lastName":"Yasuda","suffix":""},{"id":298977090,"identity":"ba2d60e4-c8cf-4450-913e-3e0ccbea7168","order_by":7,"name":"Nobuki Imano","email":"","orcid":"","institution":"Hiroshima University Hospital: Hiroshima Daigaku Byoin","correspondingAuthor":false,"prefix":"","firstName":"Nobuki","middleName":"","lastName":"Imano","suffix":""},{"id":298977091,"identity":"162f97ae-3462-492a-9cef-460d4611d150","order_by":8,"name":"Koyo Kikuchi","email":"","orcid":"","institution":"Iwate Medical University: Iwate Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Koyo","middleName":"","lastName":"Kikuchi","suffix":""},{"id":298977092,"identity":"c0329030-a633-41e9-9712-63189ca95be3","order_by":9,"name":"Tairo Kashihara","email":"","orcid":"","institution":"National Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Tairo","middleName":"","lastName":"Kashihara","suffix":""},{"id":298977093,"identity":"f32bbe51-ed99-49da-b753-4fee0e25afbb","order_by":10,"name":"Terufumi Kawamoto","email":"","orcid":"","institution":"Juntendo University - Hongo Campus: Juntendo Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Terufumi","middleName":"","lastName":"Kawamoto","suffix":""},{"id":298977094,"identity":"4f095a4e-ff98-45fe-a635-6a4ec155b7ad","order_by":11,"name":"Naoki Nakamura","email":"","orcid":"","institution":"St Marianna University School of Medicine: Sei Marianna Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Nakamura","suffix":""}],"badges":[],"createdAt":"2024-05-02 14:41:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4359787/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4359787/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12282-024-01621-2","type":"published","date":"2024-07-24T16:15:55+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":56398534,"identity":"229b5ed2-03ad-41ac-a92e-68b518673792","added_by":"auto","created_at":"2024-05-13 15:56:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":931488,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Patients’ experience during radiation therapy compared to expectations\u003c/p\u003e\n\u003cp\u003eBlack bar indicates “yes” and gray bar indicates “no” answers to each question.\u003c/p\u003e\n\u003cp\u003e(b) Patients’ experience during radiation therapy compared to prior expectation in terms of financial/emotional burden\u003c/p\u003e\n\u003cp\u003eBlack bar indicates “yes” and gray bar indicates “no” answers to each question.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/c3f4a8be1ad30528f6c82a8c.png"},{"id":56398535,"identity":"c17a7c1b-0796-4476-9dd0-0480b37da0e3","added_by":"auto","created_at":"2024-05-13 15:56:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10715393,"visible":true,"origin":"","legend":"\u003cp\u003eImpact of radiation therapy on patients' family relationships and work environment\u003c/p\u003e\n\u003cp\u003eDark gray bar indicates “yes” and light gray bar indicates “no” answers to each question.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/0f5af2f6afdffcb34637fa45.png"},{"id":56398539,"identity":"436a0eda-c135-45df-b96f-b309d7189766","added_by":"auto","created_at":"2024-05-13 15:56:56","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":316933,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Distribution of RT impact on patient’s daily living using 11-point scale (0–10)\u003c/p\u003e\n\u003cp\u003e“0” and “10” indicate “no impact at all” and “significant impact,” respectively. The top and bottom number in each box indicates score and per cent who rated the score, respectively.\u003c/p\u003e\n\u003cp\u003e(b) Distribution of patient’s enthusiasm scores for ultra-hypofractionated (UHF) regimen using 11-point scale (0–10)\u003c/p\u003e\n\u003cp\u003e“0” and “10” indicate, respectively, “reluctant to receive UHF RT” and “desire to receive UHF RT.” The top and bottom numbers in each box indicate score and percent of the patients who selected the score, respectively.\u003c/p\u003e\n\u003cp\u003e(c) Distribution of patient’s reluctance scores for breast cosmesis deterioration using 11-point scale (0–10)\u003c/p\u003e\n\u003cp\u003e“0” and “10” indicate “don’t care at all” and “much concerned about cosmesis deterioration,” respectively.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/3c2723c0e4c738e2a3e27895.jpg"},{"id":56398538,"identity":"0209a3ad-f78f-4394-93d0-34aa3b071c61","added_by":"auto","created_at":"2024-05-13 15:56:56","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":810934,"visible":true,"origin":"","legend":"\u003cp\u003eBox plots representing the scale score of (a) magnitude of radiation therapy (RT) impact on patients’ daily living, (b) enthusiasm for UHF regimen, and (c) reluctance to breast cosmesis deterioration following RT\u003c/p\u003e","description":"","filename":"Fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/88fd0e40b785bba61d8e5226.jpg"},{"id":56398537,"identity":"dfba4881-7f81-4796-9fa5-34a6a82873a4","added_by":"auto","created_at":"2024-05-13 15:56:56","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":662460,"visible":true,"origin":"","legend":"\u003cp\u003ePatients’ prioritization of six treatment-related effects\u003c/p\u003e\n\u003cp\u003eNearly 90% of the patients rated treatment efficacy as the top priority, while more than half rated breast cosmesis as the lowest priority among the six treatment effects.\u003c/p\u003e","description":"","filename":"Fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/a244ac78c4b973d98fe7eb75.jpg"},{"id":61596288,"identity":"3a326a5e-a9f8-41a9-90c2-b8ba24312d46","added_by":"auto","created_at":"2024-08-01 17:26:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":14694968,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4359787/v1/a607ffbf-0669-41b9-8967-276e6eb6e843.pdf"}],"financialInterests":"","formattedTitle":"Uptake of ultra-hypofractionated radiation therapy following breast conserving surgery among patients with early-stage breast cancer: A multi-institutional questionnaire survey","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAdjuvant radiation therapy (RT) is an essential component of breast-conserving therapy for early-stage breast cancer. It has been shown to reduce breast cancer mortality and local recurrence in a meta-analysis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and multiple prospective phase III trials. Whole breast irradiation (WBI) using 1.8\u0026ndash;2 Gy/fr daily treatment over 4\u0026ndash;6 weeks, the so-called conventional fractionation (CF), was initially employed for post-lumpectomy RT [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In recent decades, more options following breast-conserving surgery (BCS) have been developed depending on patient and tumor characteristics. RT can be safely omitted in selected elderly populations with favorable tumor biology without compromising overall survival [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Accelerated partial breast irradiation (APBI) is another option for patients with favorable tumor characteristics [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], requiring fewer treatment visits and a larger dose/fractionation. Although few patients are eligible for these relatively new options, WBI is indicated for most patients.\u003c/p\u003e \u003cp\u003eThe dose/fractionation regimen for WBI has been revolutionized. Multiple phase III trials have demonstrated the non-inferiority of moderate-hypofractionated (MHF) WBI over the CF regimen [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The MHF regimen is currently recommended in many guidelines [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and is considered the standard treatment. Furthermore, the FAST-Forward trial conducted in the UK showed the non-inferiority of ultra-hypofractionated (UHF) WBI/chest wall RT compared to the MHF regimen, with a minimally increased risk of deterioration in breast cosmesis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and the UHF regimen is on the way to becoming the standard treatment for postoperative early-stage breast cancer in Europe [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. There is some concern about adapting the UHF regimen to clinical practice among Japanese radiation oncologists, as the difference in ethnicity from the UK might result in a higher incidence of adverse events (AEs) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The Japan Clinical Oncology Group (JCOG) Unit of Radiation Oncology Investigators with Youngers (JOURNEY) proposed retesting this regimen in a multi-institutional clinical trial in Japan following the publication of FAST-Forward. Expert breast radiation oncologists raised concerns regarding long-term AEs, specifically breast cosmesis; therefore, the trial should be awaited until longer follow-up data from the FAST-Forward come out. However, the benefits of shorter RT periods in patients with breast cancer are not negligible. The value of this innovative treatment should be assessed from the perspective of not only researchers and clinicians but also patients. To this end, we conducted a questionnaire-based study to evaluate the patients\u0026rsquo; attitudes toward UHF regimens, given the potential long-term AEs.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003eWe planned to distribute 250 questionnaires and obtain 200 valid responses between November 2022 and June 2023. Eligible patients underwent either CF (45\u0026ndash;50 Gy/ 25\u0026ndash;28 fr) or MHF (40\u0026ndash;43 Gy/15\u0026ndash;16 fractions) WBI after BCS. The patients were excluded if they were receiving one of the following: a UHF regimen (i.e., 26\u0026ndash;28.5 Gy/5 fr), APBI, or regional nodal irradiation, in addition to WBI. The questionnaire contained the following questions: 1) age; 2) date of survey; 3) travel time/mode of transportation for a treatment visit; 4) number of household, number of those for need support or care at home; 5) employment status; 6) discrepancies between patient\u0026rsquo;s experience during RT and prior expectation in terms of physical/socioeconomical aspects; 7) magnitude of RT impact on daily living using an 11-point (0\u0026ndash;10) scale; 8) impact of RT on family or work environment; 9) enthusiasm for UHF regimen using an 11-point scale; 10) reluctance of long-term cosmetic deterioration of the treated breast using an 11-point scale; 11) enthusiasm for shortening RT period with UHF regimen vs reluctance for developing breast induration using an 11-point scale; and 12) prioritization of the following treatment-related effects: treatment efficacy, acute AEs, late AEs, physical/emotional burden during treatment, financial burden of the treatment, and long-term breast cosmesis. The following data were collected by the local research staff: 1) location of the facility, 2) start/completion date of RT, 3) RT regimen including WBI and tumor bed boost, 4) decision process of the RT regimen, either conventional or moderate hypofractionation, and 5) use of endocrine/chemo-/targeted therapy.\u003c/p\u003e \u003cp\u003e Written informed consent was obtained from all patients before enrollment in the study. The questionnaire was to be completed within 5 days before or after completion of RT and then typically reviewed by the research staff to minimize unintentional errors before sending the sheet to the research administration office. The patients were asked to send the questionnaire directly to the research administration office if they did not want their response sheets to be reviewed by the local research staff.\u003c/p\u003e \u003cp\u003e The study protocol was approved by the institutional review board of Hyogo Cancer Center. The study was conducted at 13 radiation oncology centers affiliated with the JOURNEY in nine prefectures across Japan. A minimum and maximum of 10 and 25 cases, respectively, were assigned to the participating centers, depending on their capacity. This study was registered in the UMIN Clinical Trials Registry (UMIN000049536).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, 247 questionnaires were collected from the research administration office. Valid answers were obtained from more than 240 (97%) patients for most questions, except for Question 12, which evaluated the prioritization of various treatment-related effects. The median number of valid answers for priorities 1 through 6 in Question 12 was 231 (93.5%; range, 229\u0026ndash;240; 92.7\u0026ndash;97.2%).\u003c/p\u003e \u003cp\u003eThe patient and treatment characteristics are listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Among the 247 patients, 80 (32%) were treated at one of the four institutions in the Tokyo or Yokohama metropolitan area, which is the most densely populated area in Japan. These locations were regarded as urban, whereas the six prefectures where the other nine institutions were located were considered suburban. The adoption of the dose/fractionation regimen was dependent on the institution; all 20 patients from institution X were treated with the SF regimen, whereas 223 of the 227 (98%) patients from other institutions were treated with the MHF regimen.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eA. Patient and treatment characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003evariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;247\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u0026ndash;49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (21%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u0026ndash;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63 (26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDate of survey\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNovember 2022 \u0026ndash; March 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e124 (50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApril \u0026ndash; June 2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123 (50%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLocation of the institution\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrban*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSuburban\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e167 (68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFractionation of WBI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e223 (90%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (10%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFractionation of TB boost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eno boost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e150 (61%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (34%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDecision process of RT regimen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePhysician recommendation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e141 (57%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient desire\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBoth of the above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (29%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEndocrine therapy use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCurrent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e96 (39%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlanned after RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (30%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eChemotherapy use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjuvant before RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlanned after RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTargeted therapy use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNeoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjuvant before RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePlanned after RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: RT, radiation therapy; WBI, whole breast irradiation; TB, tumor bed\u003c/p\u003e \u003cp\u003e*Urban indicates Tokyo and Yokohama metropolitan area; suburban indicates all others.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eB. Patients\u0026rsquo; background lifestyle\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;247\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTravel time for a treatment visit (hours, one way)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95 (38%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.5\u0026ndash;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109 (44%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (14%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInpatient care/rent an accommodation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMode of transportation*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCar drive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (34%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCar ride (driven by a family)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (15%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePublic transportation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119 (48%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWalk/bike\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (13%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of households\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (42%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (23%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (19%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNumber of households requiring care/observation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOne child aged\u0026thinsp;\u0026lt;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTwo children aged\u0026thinsp;\u0026lt;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThree or more children aged\u0026thinsp;\u0026lt;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnyone aged\u0026thinsp;\u0026ge;\u0026thinsp;15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEmployment status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHousewife\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59 (24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFull-time work\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81 (33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePart-time work\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeave from work\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSelf-employed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInoccupation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e*29 patients used multiple modes of transportation.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe travel time (one-way) for a treatment visit was less than an hour for 82% of the patients. The most common modes of travel were public transport (39%) and driving (30%). Four (2%) patients received inpatient care or rented a nearby apartment due to inconveniences related to travel for daily treatment. The majority of the patients continued to fulfill their roles in the family or at work throughout the RT period, while 17 (7%) patients were on leave from work for treatment. Details of the patients\u0026rsquo; background and circumstances are shown in Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eThe patients\u0026rsquo; experiences during RT were compared with their prior expectations in terms of physical and socioeconomic aspects. Approximately half of the patients stated that RT was \u0026ldquo;easier\u0026rdquo; than they had anticipated (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003ea). Mixed responses were noted regarding treatment duration, with 17% and 23% of the cohort perceiving the treatment duration as being short and long, respectively. Of note, more than 70% of the patients considered weekday treatment for 3 to 5 weeks to be more burdensome than they had expected (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eb). A few patients commented that longer treatment periods would have been comfortable, as they had a healthy lifestyle throughout the RT course. In other comments regarding longer treatment, the patients stated that they felt like the tumor cells were being killed at each treatment session.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe impact of RT on patients\u0026rsquo; families and work environments is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Approximately one-quarter of the patients experienced decreased income during RT. The magnitude of the impact of RT on the patients\u0026rsquo; daily living was evaluated using an 11-point scale (0\u0026ndash;10), and the results are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eA. More than half of the patients felt that RT had a moderate-to-significant (5\u0026ndash;10) impact on their daily lives. Patients\u0026rsquo; enthusiasm for the UHF regimen was evaluated on an 11-point scale. Nearly 70% of the patients rated it 6 points or more out of 10 (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). Forty-five percent rated it 10, whereas only 4% rated it 4 points or less. The magnitude of the patient\u0026rsquo;s reluctance to undergo posttreatment breast induration was evaluated using an 11-point scale (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ec). Approximately two-thirds of the patients rated their reluctance at 5 points or more out of 10 (moderate-to-significant reluctance). Figure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows box plots representing the scale score of (a) the impact of RT on patients\u0026rsquo; daily living, (b) enthusiasm for the UHF regimen, and (c) reluctance to breast cosmesis deterioration, each stratified by various background factors. Patients who were young, employed full- or part-time, and those treated in urban centers were likely to experience a greater impact of treatment than their older, unemployed/self-employed, and elsewhere treated counterparts (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ea). Patients from urban areas, those who received the MHF regimen, and those who received chemotherapy were more likely to prefer the UHF regimen (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003eb). Patients aged\u0026thinsp;\u0026lt;\u0026thinsp;60 years and those from urban areas were more likely to be concerned about the development of breast induration (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003ec).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatients\u0026rsquo; enthusiasm for UHF RT versus the risk of breast cosmesis deterioration was assessed using an 11-point scale, with 0 indicating the highest priority for breast cosmesis rather than for a short treatment period and 10 indicating the opposite. Overall, 55% of the patients rated their enthusiasm at 6 points or more (i.e., a shorter treatment period was preferred to post-treatment cosmesis deterioration).\u003c/p\u003e \u003cp\u003eThe final question was used to assess patient prioritization of the six RT-related effects, which included, in ascending order, acute AEs, late AEs, physical/emotional burden during RT, financial burden during RT, and long-term breast cosmesis (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Nearly 90% of the patients rated treatment efficacy as the first priority, while more than half of the patients rated breast cosmesis as the lowest priority.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo 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\u0026rsquo; enthusiasm for UHF-WBI after BCS, despite knowledge of the potential deterioration in breast cosmesis.\u003c/p\u003e \u003cp\u003eFrom a healthcare provider\u0026rsquo;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 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The value of treatment duration in medical care should also be validated from the patients\u0026rsquo; 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.\u003c/p\u003e \u003cp\u003eTime 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 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eA 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 [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eThe 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\u0026ndash;30 Gy in five once-weekly fractions [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. 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 [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. 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.\u003c/p\u003e \u003cp\u003eA 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[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. 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[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], 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[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. 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[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Given these differences in late toxicities between ethnicities, it may be reasonable to conduct a validation study of UHF-WBI in Asian populations.\u003c/p\u003e \u003cp\u003eThis 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.\u003c/p\u003e \u003cp\u003eIn conclusion, the patients\u0026rsquo; 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.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design, as well as material preparation. Data collection and analysis were performed by H.U. and T.O. The first draft of the manuscript was written by H.U., T.O., and N.S., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the National Cancer Center Research and Development Fund (2023-J-03).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eN.S. reports research grant from Elekta. The other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatement of human rights\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEarly Breast Cancer Trialists' Collaborative Group, Darby S, McGale P, Correa C, Taylor C, Arriagada R, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEarly Breast Cancer Trialists\u0026rsquo; Collaborative Group. Effects of radiotherapy and surgery in early breast cancer: an overview of the randomized trials. N Engl J Med. 1995;333:1444\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKunkler IH, Williams LJ, Lack WJL, Cameron DA, Dixon JM. Breast-conserving surgery with or without irradiation in early breast cancer. N Engl J Med. 2023;388:585\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhelan TJ, Smith S, Parpia S, Fyles AQ, Bane A, Liu FF, et al. Omitting radiotherapy after breast-conserving surgery in luminal a breast cancer. N Engl J Med. 2023;389:612\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShaitelman SF, Anderson BM, Arthur DW, Bazan JG, Bellon JR, Bradfield L, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: An ASTRO Clinical Practice Guideline. 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The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008;9:331\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362:513\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurstein HJ, Curigliano G, Thurlimann B, Weber WP, Poortmans P, Regan MM, et al. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021;32:1216\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrunt MA, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al. 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Int J Surg. 2016;33(Suppl 1):S92\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBanerjee R, George M, Gupta A. Maximizing home time for persons with cancer. JCO Oncol Pract. 2021;17:513\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArsenault J, Parpia S, Goldberg M, Rakovitch E, Reiter H, Doherty M, et al. Acute toxicity and quality of life of hypofractionated radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 2020;107:943\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrunt AM, Wheatley D, Yarnold J, Somaiah N, Kelly S, Harnett A, et al. Acute skin toxicity associated with a 1-week schedule of whole breast radiotherapy compared with a standard 3-week regimen delivered in the UK FAST-Forward Trial. Radiother Oncol. 2016;120:114\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldsmith C, Haviland J, Tsang Y, Sydenham M, Yarnolg J, FAST Trialists\u0026rsquo; Group. Large breast size as a risk factor for late adverse effects of breast radiotherapy: is residual dose inhomogeneity, despite 3D treatment planning and delivery, the main explanation? Radiother Oncol. 2011;100:236\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNozaki M, Kagami Y, Shibata T, Nakamura K, Ito Y, Nishimura Y, et al. A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906. Jpn J Clin Oncol. 2019;49:57\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu T, Li S, Ding S, Qiu J, Ren C, Chen J, et al. Comparison of post-chemoradiotherapy pneumonitis between Asian and non-Asian patients with locally advanced non-small cell lung cancer: a systematic review and meta-analysis. EClinicalMedicine. 2023;64:102246.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGathani T, Reeves G, Brioggio J, Barnes I. Ethnicity and the tumour characteristics of invasive breast cancer in over 116,500 women in England. Br J Cancer. 2021;125:611\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"ultra-hypofractionated whole breast irradiation, patients’ preference, breast-conserving therapy","lastPublishedDoi":"10.21203/rs.3.rs-4359787/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4359787/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn patients with early-stage breast cancer following breast surgery, ultra-hypofractionated (UHF) breast/chest wall radiation therapy (RT) has been shown to be non-inferior to a moderate-hypofractionated (MHF) regimen, with a minimal risk of breast induration, in the FAST-Forward trial, and UHF is now becoming the standard regimen in Europe. Herein, we aimed to investigate Japanese patients\u0026rsquo; attitudes toward the UHF regimen.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA questionnaire-based survey was conducted at 13 RT centers in nine prefectures across Japan. All patients underwent breast-conserving surgery, followed by either conventional fractionation (2 Gy/fr) or MHF (2.66 Gy/fr) whole-breast irradiation (WBI) with or without a tumor bed boost. The questionnaire consisted of 12 questions mainly addressing quality of life during RT. Key questions included an 11-point scale (0\u0026ndash;10) for rating the patients\u0026rsquo; enthusiasm for the UHF regimen and prioritization of the following treatment-related effects: treatment efficacy, acute/late adverse effects, physical/emotional/financial burden, and breast cosmesis. The patient and treatment characteristics were assessed by a physician.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn total, 247 questionnaires were administered between November 2022 and June 2023. The age distribution was as follows: \u0026lt;50:50s:60s:\u0026ge;70\u0026thinsp;=\u0026thinsp;59 (24%):76 (30%):63 (26%):49 (20%). Sixty-nine percent of patients rated their enthusiasm for the UHF regimen at \u0026ge;\u0026thinsp;6 out of 10 points (45% rated 10/10). Treatment efficacy was the highest priority for most patients (89%), whereas breast cosmesis the lowest priority (53%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePatients\u0026rsquo; enthusiasm for UHF-WBI was observed across the cohort. These results could motivate researchers and clinicians to introduce UHF regimens in clinical practice.\u003c/p\u003e","manuscriptTitle":"Uptake of ultra-hypofractionated radiation therapy following breast conserving surgery among patients with early-stage breast cancer: A multi-institutional questionnaire survey","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-13 15:56:50","doi":"10.21203/rs.3.rs-4359787/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor Revision","date":"2024-06-20T06:18:03+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-05-12T21:34:23+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-05T23:10:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-04T05:12:55+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer","date":"2024-05-02T10:40:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brca","sideBox":"Learn more about [Breast Cancer](http://link.springer.com/journal/12282)","snPcode":"12282","submissionUrl":"https://www.editorialmanager.com/brca/default2.aspx","title":"Breast Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"91413ba0-0ea4-4c08-9450-53bd8e54bf43","owner":[],"postedDate":"May 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-01T17:07:54+00:00","versionOfRecord":{"articleIdentity":"rs-4359787","link":"https://doi.org/10.1007/s12282-024-01621-2","journal":{"identity":"breast-cancer","isVorOnly":false,"title":"Breast Cancer"},"publishedOn":"2024-07-24 16:15:55","publishedOnDateReadable":"July 24th, 2024"},"versionCreatedAt":"2024-05-13 15:56:50","video":"","vorDoi":"10.1007/s12282-024-01621-2","vorDoiUrl":"https://doi.org/10.1007/s12282-024-01621-2","workflowStages":[]},"version":"v1","identity":"rs-4359787","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4359787","identity":"rs-4359787","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}