RESUMO
Background: Lymphopenia is a known significant factor for treatment outcome in cancer patients, with underlying risk factor poorly understood in breast cancer. We hypothesize that the effective dose to the circulating immune cells (EDIC) which was related with lymphopenia in lung cancer will also have significant effect for radiation induced lymphopenia (RIL) in patients with breast cancer. Material and Methods: Patients treated with adjuvant radiotherapy (RT) and with complete blood tests within one week from RT end/start (post/preRT) were eligible in this study. Radiation dosimetric factors were collected retrospectively, and EDIC for each patient was calculated based on the doses to lung, heart and total body according to the model description, as previously reported. RIL was defined by the CTCAE5.0 based on postRT peripheral lymphocyte count (PLC). Linear regression was first used to test the correlation between EDIC with post/preRT PLC ratio and postRT PLC, using all these as continuous variables. Normal tissue complication probability (NTCP) was used to develop models that predict the CTCAE graded RIL from EDIC. Results: A total of 735 patients were eligible. The mean post/preRT PLC ratio was 0.66 (95% CI: 0.64-0.68) and mean EDIC of breast cancer was 1.70Gy (95% CI: 1.64-1.75). Both post/preRT PLC ratio and postRT PLC were significantly correlated with EDIC (P<0.001), with R2 of 0.246. For patients with normal preRT PLC, the post/preRT PLC ratio was better associated with EDIC, and postRT PLC was expressed as PLC preRT × (0.89 - 0.16 × EDIC). For patients with preRT lymphopenia, postRT PLC was better associated with EDIC and it was 1.1 - 0.17 × EDIC. Using binned EDIC as the dose variable, the bootstrap validated NTCPs fit the data nicely with R2 of 0.93, 0.96, and 0.94 for grade-1, grade-2, and grade-3 RIL, respectively. The corresponding EDIC to induce 50% of grade-1, grade-2 and grade-3 RIL was 1.2, 2.1 and 3.7 Gy, respectively. Conclusion: EDIC is a significant factor for RIL in patients with breast cancer, and may be used to compute the risk of lymphopenia in each individual patient with the use of the conventional NTCP modeling. External validation is needed before the EDIC can be used to guide RT plan.
RESUMO
PURPOSE: Application of hypofractionated radiotherapy (HFRT) is growing in patients with breast cancer (BC). This study aimed to explore a real-world practice of HFRT in early and locally advanced BC. METHODS: Patients with invasive BC between 2015 and 2019 were retrospectively reviewed. Radiotherapy (RT) was delivered by HFRT and conventionally fractionated radiotherapy (CFRT). Locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) were calculated by Kaplan-Meier curve and compared by Log-rank test. The effect of treatment modality on DFS was estimated by univariate and multivariable analyses. RESULTS: A total of 1,010 patients were included in this study, and 903 (89.4%) were treated with HFRT. At a median follow-up of 49.5 months, there was no significant difference in a 4-year cumulative incidence of LRRFS in HFRT group (1.5%) and in CFRT group (3.8%) (p = 0.23), neither in different nodal stages nor in N2-3 patients with different molecular subtypes. The 4-year DFS was 93.5% in HFRT group compared with 89.9% in CFRT group with no significant difference either (p = 0.17). Univariate and multivariable analyses also showed no significant difference in DFS between HFRT and CFRT group. However, DFS of HFRT group tended to be lower in N2-3 patients with triple negative BC compared with that of CFRT group (76.2% versus 100%). CONCLUSION: HFRT can achieve similar cumulative incidence of LRRFS and DFS in patients with BC after lumpectomy or mastectomy, and also in different nodal stage, and in locally advanced stage with different molecular subtypes.