In our clinic, patients who received adjuvant radiotherapy with TOMO or IMRT after surgery for early stage breast cancer in the Oncology Department of the First Affiliated Hospital, Army Medical University were evaluated retrospectively. Patient characteristics, treatment details, and acute adverse event data were obtained from the electronic medical records system, patient interview notes, and patient follow-up records. Acute adverse events in patients were evaluated by medical oncologists, radiation oncologists, and surgeons.

This study was designed as a single- center retrospective cohort analysis. All patients with early stage breast cancer who underwent lumpectomy or mastectomy between September 2021 and February 2024 were included in the primary analyses. According to the inclusion criteria, the patients were divided into two groups, the IMRT and TOMO groups, based on the radiotherapy regimens they received. After screening with the exclusion criteria, patients who met the above two criteria were included in the final analyses.

The eligibility criteria were as follows: age >18 years, invasive cancer, American Joint Committee on Cancer AJCC Stage I to II, lumpectomy or mastectomy, and TOMO or IMRT radiotherapy. The main exclusion criteria were extensive intraductal carcinoma, multiple foci of cancer, final surgical margins < 5 mm, lack of clinical data, vital organ failure, and failure to complete radiotherapy.

Radiation therapy was systematically prescribed following our institutional policy. Radiotherapy treatment was started 30 days and within 60 days from the surgery; if adjuvant chemotherapy was performed, radiotherapy was postponed until 4 weeks after the last chemotherapy cycle. Patients in different groups received radiation of the whole breast and/or surgical bed using two different devices, TOMO or IMRT. The treatment procedure followed institutional rules, which have been described in detail elsewhere (17, 18).

Treatment planning for TOMO was performed using the Accuray^® Planning Station System (TomoHDTM version 2.1.9, Inc., Sunnyvale, CA, USA). The Monte Carlo algorithm is used for dose calculation, treatment planning, and quality assurance. The grid size is 3 mm. In line with the internal irradiation regimes, the dose prescribed to the planning target volume (PTV) varied from 40 Gy to 60 Gy, with a median dose of 50 Gy for the PTV. Before radiation treatment, the patient’s positioning in each automatic registration was executed by experienced staff members (see Supplementary File 1 , detailed protocols of treatment planning).

As a newly introduced therapy equipment, TOMO is more expensive than that of IMRT. TOMO was chosen for some patients mainly based on their economic conditions and fully complied with the patient’s voluntary choice.

We utilized the Eclipse version 16.1 (Varian Medical Systems Inc., Palo Alto, USA) to create IMRT treatment plans. Patients undergoing IMRT were administered a cumulative dose of 50 Gy in 25 fractions. Subsequently, a radiation therapy boost of 10 Gy was administered in five weekly fractions to the surgical bed. The dose was delivered through wedged photon tangential fields, and the boost was treated using an electron direct field. The organs at risk (OARs) were contoured according to internal guidelines. The constraints specified that 5% of the heart and 20% of the lung should receive a dose of less than 20 Gy (see Supplementary File 1 , detailed protocols for treatment planning).

The follow-up period was 3 months. After completion of TOMO or IMRT radiotherapy, according to the research plan, the follow-up schedule was as follows: we followed up all patients weekly for 3 months. The start date of follow-up for each patient was the radiation therapy start date, and the end date was 3 months after the last radiation therapy date. Follow-up mainly depended on the outpatient department, and telephone contact was reserved as an auxiliary method. Clinical examinations were performed by clinicians at each follow-up visit, and other examinations, such as hematologic or endoscopic examinations, were performed depending on the patients’ suspected symptoms. Adverse events were diagnosed by clinicians according to objective clinical and physical examinations after radiotherapy during treatment and follow-up. This study was completed in February 2024.

The clinical endpoint of this study was acute adverse events immediately following the completion of radiation therapy. Patients’ acute adverse events were prospectively recorded for a period of 3 months and were evaluated by medical oncologists, radiation oncologists and clinicians in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) (Version 5.0) (19). In this study, acute adverse events were defined as those first observed and diagnosed within 90 days of the latest radiotherapy session. We recorded acute skin toxicity (erythema, epilation, desquamation, decreased sweating, edema, ulceration, hemorrhage, and necrosis), localized edema, sore throat, tracheal mucositis, nausea, oral mucositis, esophagitis, and pneumonitis. Adverse events were recorded weekly during TOMO or IMRT treatment and then repeated until 3 months after the last radiotherapy. Particularly, before the implementation of treatment, clinicians assessed the skin condition to ensure that the skin was clear, normal, and with out lesions. Patients were also excluded from the study if they had any risk factors (such as comorbidities or concurrent medications) for vulnerable skin.

This study was designed to compare the toxicity rates of IMRT and TOMO in patients with early stage breast cancer after lumpectomy or mastectomy. Statistical analyses were performed using the SPSS Statistics software (version 26; SPSS Statistics, IBM Corporation, Armonk, NY, USA). Independent t-tests, chi-square tests, and Fisher’s exact tests were used to compare the statistical differences between the two groups. Econometric data that conformed to normal distribution with homogeneous variances were expressed as mean ± standard deviation () and subjected to t-tests. Count data were expressed as the number of cases (percentage) N (%), and intergroup comparisons were performed using the X²-test or Fisher’s exact test. All 2-sided P values <0.05 were considered significant.

The median age of the patients in this retrospective cohort was 47 years (range, 20–74 years). Table 2 summarizes the clinical characteristics of the 315 patients, divided by planning method into IMRT and TOMO. The length of follow-up was 3 months. 185 patients (59%) received IMRT and 130 patients (41%) underwent TOMO. Negative HER-2 overexpression was found in 38% and 51% of the TOMO and IMRT groups, respectively (RR 0.63; 95% CI 0.40 –0.99; P = 0.053).With regard to the degree of tumor differentiation, poor-moderate differentiation was 69% in the TOMO group and 81% in the IMRT group (RR 0.53; 95% CI 0.31 –0.89; P = 0.052). There were 66% and 55% of TOMO and IMRT groups, respectively, receiving hormone therapy (RR 1.59; 95% CI 1.00 –2.53; P = 0.5). However, there were no statistical differences in the demographic and tumor characteristics between the TOMO and IMRT groups.

The baseline clinical characteristics were well-balanced between the TOMO and IMRT groups ( Table 1 ), and no significant differences were observed in terms of age, menopausal status, laterality, pathology, estrogen receptor status, progesterone receptor status, triple negative, clinical T stage, clinical N stage, or surgical methods.

The clinical results of adverse responses and comparisons between TOMO and IMRT are summarized in Table 3. There was no significant relationship between observed localized edema (RR 1.02; 95% CI 1.00 –1.04; P = 0.092); sore throat (RR 0.95; 95% CI 0.33 –2.73; P = 0.918); tracheal mucositis (RR 2.88; 95% CI 0.26 –32.04; P = 0.369); nausea (RR 1.02; 95% CI 1.00 –1.04; P = 0.145); Oral mucositis (RR 0.28; 95% CI 0.03 –2.42; P = 0.216); esophagitis (RR 4.35; 95% CI 0.45 –42.26; P = 0.168). Compared to the IMRT group, the TOMO group had a higher proportion of grade 3–4 grade skin toxicity [16.2% (TOMO) versus 7.6% (IMRT), (RR 2.13; 95% CI 1.04 –4.37; P = 0.017)]. Pneumonitis was lower in the TOMO group than in the IMRT group [0.0% (TOMO) vs. 4.3% (IMRT), (RR 1.05; 95% CI 1.01 –1.08; P = 0.016]]. No fair or poor judgments were recorded in the 315 patients during the follow-up period. No other adverse events or toxicities were observed during the follow-up period. The clinical results are summarized in Table 1 .

On comparing adverse events, we found a statistically significant difference between the TOMO and IMRT groups in the presence of acute skin toxicity (P = 0.017) and pneumonitis (P = 0.016). Compared with the IMRT group, the TOMO group seemed to have a lower incidence rate of pneumonitis. However, the incidence of acute skin toxicity was higher in the TOMO group was higher than that in the IMRT group, especially for grade 3–4 skin toxicity. The results suggest that TOMO could decrease the incidence rate of pneumonitis but increase the risk of acute skin toxicity.

We are aware of the limitations of our study. The retrospective, single-center design of this analysis might affect the interpretation of the data, and the persuasiveness of our conclusions was weaker than that of multicenter prospective studies. Moreover, although we enrolled patients strictly in accordance with the inclusion and exclusion criteria, the absence of randomization in group assignment might have led to potential selection bias.

In the present study, we focused only on eight types of adverse events, with a relatively small number of clinical indicators observed during radiotherapy. Furthermore, the primary goal of this data release is to retain as much clinical data as possible for reference and discussion among physician peers. Based on the above considerations, we did not apply strict multiple test correction methods, such as the Bonferroni correction, to adjust the p-values. Instead, we only performed limited statistical methods, such as t-test and chi-square analysis, which might increase the risk of false positives in the statistical results.

Due to the lack of experience in our work, we failed to precisely match the occurrence of adverse events with the corresponding follow -up periods while implementing the research plan. We only summarized the outcomes after the three-month follow-up was completed, which hindered our understanding of how time influenced the development of adverse events during or after radiotherapy. In other words, we were unable to leverage weekly follow-up data using longitudinal models to evaluate toxicity trajectories over time.

It is worth mentioning that a 3-month follow-up might be too short to capture the late effects of radiation therapy. Because we only focused on short-term complications at the initial stage of the study, a relatively short follow-up period was designed accordingly. Consequently, only acute toxicity complications were reported in our study, while long-term prognosis, including late effects and survival analysis results, were lacking due to the short follow-up duration.

Lastly, the relatively simplistic and limited statistical methods, such as the T-test and Chi-square analysis, employed in the study may compromise the persuasiveness of the results and weaken the robustness of the conclusions.

Future perspectives call for continued efforts to conduct more extensive studies with longer follow -up periods. In the next phase of our study, we will extend the follow-up period to 3 years and shift our focus to late adverse events and survival analysis to gain a better understanding of survival and long -term toxicity outcomes and provide valuable clinical research data and experience for radiotherapy treatment after breast cancer surgery.