Timing of cranial radiotherapy in HER2-positive breast Cancer brain metastases treated with Pyrotinib: a multicentre real-world cohort study.
- 1Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming 650118, China.
- 2Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
- 3Yunnan Key Laboratory of Breast Cancer Precision Medicine, The Department of Breast Surgery, Breast Cancer Center of the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming 650118, China.
Abstract
Background and purpose
Cranial radiotherapy (RT) and pyrotinib both demonstrate efficacy in HER2-positive breast cancer brain metastases (BCBM); however, the optimal sequencing of these modalities remains to be established. We evaluated survival across treatment sequences within a real-world cohort.Materials and methods
This retrospective, two-centre study included 101 patients with HER2-positive BCBM treated with cranial RT plus pyrotinib (June 2018-July 2025). Based on treatment sequence, patients were categorized into: concurrent RT and pyrotinib (Group A, n = 41); RT after intracranial progression on pyrotinib (Group B, n = 38); and pyrotinib upon progression following RT (Group C, n = 22). The primary endpoint was CNS-PFS. Survival outcomes were assessed via Kaplan-Meier estimation and Cox proportional hazards models.Results
At a median follow-up of 43.3 months, 63 patients (62.4%) had died and 70 (69.3%) experienced CNS-PFS events. Median CNS-PFS was 14.8 months (95% CI 10.68-19.92) overall, and 14.3, 15.0, and 21.4 months in groups A, B, and C, respectively (P = 0.252); median OS was 36.0 months (95% CI 28.0-39.7) overall, and 33.0, 35.4, and 42.0 months in groups A, B, and C, respectively (P = 0.281). Focal cranial RT was independently associated with longer OS (HR 0.56, 95% CI 0.34-0.94; P = 0.028). Any-grade adverse events occurred in 100 of 101 patients (99.0%); grade ≥ 3 events occurred in 2.4%, 7.9%, and 4.5% of groups A, B, and C, respectively (all P > 0.05), and radiation necrosis occurred in 7 patients (6.9%). An exploratory threshold of RT initiated >3.9 months before pyrotinib (OS 49.9 vs 29.8 months; HR 0.31, 95% CI 0.11-0.91; P = 0.025) did not withstand internal validation.Conclusions
Treatment sequence did not significantly affect OS or CNS-PFS. Focal cranial RT was independently associated with longer survival, and toxicity was manageable. The proposed timing threshold is hypothesis-generating and warrants prospective validation.
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BibTeX
@article{chen2026timing,
title = {{Timing of cranial radiotherapy in HER2-positive breast Cancer brain metastases treated with Pyrotinib: a multicentre real-world cohort study.}},
author = {Zhengting Chen and Hao Jing and Sheng Huang and Miao Wang and Dan Mao and Lan Li and Shuang Lu and Xinyan Zhou and Dongyu Bi and Ye Zhang and Xuesong Chen and Yuchao Ma and Yaoxiong Xia and Junlin Yi and Yu Hou},
journal = {Clinical and translational radiation oncology},
year = {2026},
month = oct,
doi = {10.1016/j.ctro.2026.101310},
url = {https://europepmc.org/article/MED/42927325},
note = {CC BY},
}
RIS
TY - JOUR
TI - Timing of cranial radiotherapy in HER2-positive breast Cancer brain metastases treated with Pyrotinib: a multicentre real-world cohort study.
AU - Zhengting Chen
AU - Hao Jing
AU - Sheng Huang
AU - Miao Wang
AU - Dan Mao
AU - Lan Li
AU - Shuang Lu
AU - Xinyan Zhou
AU - Dongyu Bi
AU - Ye Zhang
AU - Xuesong Chen
AU - Yuchao Ma
AU - Yaoxiong Xia
AU - Junlin Yi
AU - Yu Hou
PY - 2026
DA - 2026/10/07
JO - Clinical and translational radiation oncology
DO - 10.1016/j.ctro.2026.101310
UR - https://europepmc.org/article/MED/42927325
AB - Background and purpose Cranial radiotherapy (RT) and pyrotinib both demonstrate efficacy in HER2-positive breast cancer brain metastases (BCBM); however, the optimal sequencing of these modalities remains to be established. We evaluated survival across treatment sequences within a real-world cohort.Materials and methods This retrospective, two-centre study included 101 patients with HER2-positive BCBM treated with cranial RT plus pyrotinib (June 2018-July 2025). Based on treatment sequence, patients were categorized into: concurrent RT and pyrotinib (Group A, n = 41); RT after intracranial progression on pyrotinib (Group B, n = 38); and pyrotinib upon progression following RT (Group C, n = 22). The primary endpoint was CNS-PFS. Survival outcomes were assessed via Kaplan-Meier estimation and Cox proportional hazards models.Results At a median follow-up of 43.3 months, 63 patients (62.4%) had died and 70 (69.3%) experienced CNS-PFS events. Median CNS-PFS was 14.8 months (95% CI 10.68-19.92) overall, and 14.3, 15.0, and 21.4 months in groups A, B, and C, respectively (P = 0.252); median OS was 36.0 months (95% CI 28.0-39.7) overall, and 33.0, 35.4, and 42.0 months in groups A, B, and C, respectively (P = 0.281). Focal cranial RT was independently associated with longer OS (HR 0.56, 95% CI 0.34-0.94; P = 0.028). Any-grade adverse events occurred in 100 of 101 patients (99.0%); grade ≥ 3 events occurred in 2.4%, 7.9%, and 4.5% of groups A, B, and C, respectively (all P > 0.05), and radiation necrosis occurred in 7 patients (6.9%). An exploratory threshold of RT initiated >3.9 months before pyrotinib (OS 49.9 vs 29.8 months; HR 0.31, 95% CI 0.11-0.91; P = 0.025) did not withstand internal validation.Conclusions Treatment sequence did not significantly affect OS or CNS-PFS. Focal cranial RT was independently associated with longer survival, and toxicity was manageable. The proposed timing threshold is hypothesis-generating and warrants prospective validation.
SN - 2405-6308
ER -