{
  "abstract": "Background and purpose\n\nCranial 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\n\nThis 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\n\nAt 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\n\nTreatment 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming 650118, China.",
    "Department 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.",
    "Yunnan 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."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhengting Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Hao Jing"
    },
    {
      "affs": [
        2
      ],
      "name": "Sheng Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Miao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Mao"
    },
    {
      "affs": [
        0
      ],
      "name": "Lan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuang Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyan Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongyu Bi"
    },
    {
      "affs": [
        1
      ],
      "name": "Ye Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xuesong Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuchao Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaoxiong Xia"
    },
    {
      "affs": [
        1
      ],
      "name": "Junlin Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Hou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bpfcy6kwq1z3m.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ctro.2026.101310",
  "fulltext_url": "https://europepmc.org/articles/PMC13695302",
  "id": "bpfcy6kwq1z3m",
  "issns": [
    "2405-6308"
  ],
  "landing_url": "https://europepmc.org/article/MED/42927325",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Brain Metastases and Treatment"
    ]
  ],
  "openalex": "W7220935635",
  "pdf_url": "https://europepmc.org/articles/PMC13695302?pdf=render",
  "pmcid": "PMC13695302",
  "pmid": "42927325",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bpfcy6kwq1z3m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927325",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927325"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Brain Metastases and Treatment",
      "subfield": "general"
    }
  ],
  "title": "Timing of cranial radiotherapy in HER2-positive breast Cancer brain metastases treated with Pyrotinib: a multicentre real-world cohort study.",
  "title_text": "Timing of cranial radiotherapy in HER2-positive breast Cancer brain metastases treated with Pyrotinib: a multicentre real-world cohort study.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/bpfcy6kwq1z3m",
  "venue": "Clinical and translational radiation oncology",
  "versions": []
}