Oncological Outcomes After Hippocampus-Sparing Whole-Brain Radiotherapy in Cancer Patients With Newly Diagnosed Brain Oligometastases: A Single-Arm Prospective Observational Cohort Study in Taiwan

Shinn-Yn Lin, Din-Li Tsan, Chi-Cheng Chuang, Chi-Cheng Yang, Ping-Ching Pai, Chih-Liang Wang, Yi-Ming Wu, Cheng-Chi Lee, Chia-Hsin Lin, Kuo-Chen Wei, Wen-Chi Chou, Shinn-Yn Lin, Din-Li Tsan, Chi-Cheng Chuang, Chi-Cheng Yang, Ping-Ching Pai, Chih-Liang Wang, Yi-Ming Wu, Cheng-Chi Lee, Chia-Hsin Lin, Kuo-Chen Wei, Wen-Chi Chou

Abstract

Background: Promisingly, the technique of hippocampus sparing during WBRT (HS-WBRT) might preserve NCFs. In this research, we examined oncological outcomes, with emphasis on neurologic/non-neurologic causes of death, CNS progression, and leptomeningeal disease (LMD) recurrence in cancer patients who underwent HS-WBRT.

Methods: One hundred and fourteen cancer patients with newly diagnosed brain oligometastases underwent HS-WBRT were consecutively enrolled. The cumulative incidence of cancer-specific deaths (neurologic or non-neurologic), LMD recurrence, and the composite endpoint of CNS progression (CNS-CE) as the first event were computed with a competing-risks approach to characterize the oncological outcomes after HS-WBRT.

Results: Patients with intact brain metastases had a significantly increased likelihood of dying from non-neurologic causes of death associated with early manifestation of progressive systemic disease (hazard ratio for non-neurologic death, 1.78; 95% CI, 1.08-2.95; p = 0.025; competing-risks Fine-Gray regression), which reciprocally rendered them unlikely to encounter LMD recurrence or any pattern of CNS progression (HR for CNS-CE as the first event, 0.13; 95% CI, 0.02-0.97; p = 0.047; competing-risks Fine-Gray regression). By contrast, patients with resection cavities post-craniotomy had reciprocally increased likelihood of CNS progression which might be associated with neurologic death eventually.

Conclusions: Patterns of oncological endpoints including neurologic/non-neurologic death and cumulative incidence of CNS progression manifesting as LMD recurrence are clearly clarified and contrasted between patients with intact BMs and those with resection cavities, indicating they are clinically distinct subgroups.

Trial registration: ClinicalTrials.gov, Identifier: NCT02504788, NCT03223675.

Keywords: brain oligometastases; competing risks; hippocampus-sparing whole-brain radiotherapy; neurologic death; oncological outcomes.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Lin, Tsan, Chuang, Yang, Pai, Wang, Wu, Lee, Lin, Wei and Chou.

Figures

Figure 1
Figure 1
Survival outcomes in the 114 cancer patients with newly diagnosed brain oligometastases managed with HS-WBRT. (A) Kaplan–Meier estimates of overall survival (OS), stratified into two common clinical contexts (intact BMs versus resection cavities). (B) K-M estimates of OS, stratified by the histopathology of the primary malignancy. (C) K-M estimates of OS, stratified by the status of extracranial involvement. (D) K-M estimates of OS, based on the RTOG RPA classification.
Figure 2
Figure 2
Cumulative incidence curves of neurologic/non-neurologic death, stratified by available clinical characteristics. (A) Overall cumulative incidence curves regarding neurologic and non-neurologic death. (B) Histology of primary malignancy categorized as a binary covariate (primary lung adenocarcinoma versus all others). (C) Histology of primary cancer stratified into four subgroups, with lung adenocarcinoma as the reference group. (D) Status/control of extracranial disease. (E) Cumulative incidence of death depending on whether upfront craniotomy plus tumor resection was performed. (F) The mutual associations between the clinical setting (intact BM versus resection cavity) and the two major cancer-specific causes of death (neurologic or non-neurologic) after controlling for the other meaningful covariates.
Figure 3
Figure 3
Cumulative incidence curves of LMD recurrence and the composite endpoint of CNS progression as the first event. (A) Overall cumulative incidence curves of LMD recurrence and CNS-CE (n = 114). (B) Cumulative incidence curves of CNS-CE as the first event, stratified according to whether upfront craniotomy was performed. (C) Both cumulative incidence curves, stratified based on the status of extracranial involvement. (D) Cumulative incidence rates according to primary lung adenocarcinoma versus all others.

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Source: PubMed

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