Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis

Abstract

Purpose: To investigate the effect of chemotherapy and radiotherapy timing after breast conserving surgery (BCS) on recurrence and survival of women with early-stage breast cancer. Patients and Methods: We retrospectively analyzed 900 patients who underwent BCS followed by both adjuvant chemotherapy and radiotherapy. Of these, 488 women received chemotherapy first (CT-first group) while the other 412 received radiotherapy first (RT-first group). Locoregional recurrence (LRR), distant metastasis (DM), diseasefree survival (DFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and further confirmed with propensity-score matching (PSM) and the Cox proportional hazards model. The optimal cutoff value of interval time from surgery to the start of chemotherapy was calculated by Maxstat. Results: The median follow-up was 7.1 years. In pre-match analysis, the CT-first group had a significantly higher 8-year DFS than the RT-first group (90.4% vs. 83.1%, P = 0.005). PSM analysis of 528 patients indicated that the 8-year DFS (91.0% vs. 83.3%, P = 0.005) and DM (8.6% vs. 14.6%, P = 0.017) were significantly better in the CT-first group, but that the OS (P = 0.096) and LRR (P = 0.434) were similar. We found the optimal cutoff value of interval from surgery to chemotherapy was 12 weeks. Patients starting chemotherapy later than 12 weeks after surgery had significantly inferior survival outcomes. Conclusion: For women with breast cancer who require both chemotherapy and radiotherapy after BCS, adjuvant chemotherapy should be started within 12 weeks. Delaying the initiation of radiotherapy, for administration of long-course chemotherapy, does not compromise outcomes.

Learning interpretable causal networks from very large datasets, application to 400,000 medical records of breast cancer patients

“…This short term causal effect between vital status and radiotherapy is consistent with the rapid decline of the survival delay distribution for the first 3–6 months in absence of radiotherapy, Figure 4 C, which corresponds to the typical range of delays for radiotherapy after diagnosis, depending on whether it is performed as second treatment after surgery or as third treatment after both surgery and chemotherapy. 34 All in all, this short term causal effect of vital status on radiotherapy outweighs the causally reversed, beneficial effect of radiotherapy on the long term survival of patients. This suggests a strong “immortal time bias” 32 in the apparent benefit of radiotherapy, Figure 4 D, which would need to be corrected with the “landmark method” 32 , 35 excluding patients dying within a specified period after surgery, or by emulating a target trial from observational data.…”

Flourish of Proton and Carbon Ion Radiotherapy in China

“…Only one clinical trial to evaluate the efficacy of CIRT with concurrent cisplatin for LR-NPC at the SPHIC was registered (NCT02801487). In addition, radiotherapy fractionation for different tumor sites and sequential treatment of chemotherapy and radiotherapy is also important for the treatment outcome ( 138 , 139 ). The same is true in China, where more clinical trials are needed to determine the optimal fractional dose and treatment sequence.…”

Prognostic Value and Possible Mechanism of m6A Methyltransferase METTL3 in Prostate Cancer

“…The "survival" R package [18] was used for Kaplan-Meier curve and uni-variate Cox regression analysis. The "maxstat" R package [19] was used to determine the optimal cutoff value of METTL3 for Kaplan-Meier curve. Log Rank (Mantel-Cox) test was used to evaluate long-term PFS, and Breslow (Generalized Wilcoxon) test was used to evaluate short-term PFS.…”