Abstract

Although whole-brain radiation therapy (WBRT) is the mainstay of treatment for brain metastases (BMs), the concept of saving eloquent cortical lesions has been promoted. If BMs from lung cancer are spatially biased to certain regions, this approach can be justified more. We evaluated whether BMs from lung cancer show a preference for certain brain regions and if their distribution pattern differs according to the histologic subtype of the primary lung cancer. In this retrospective study, 562 BMs in 80 patients were analyzed (107 BMs from small cell carcinoma, 432 from adenocarcinoma, and 23 from squamous cell carcinoma). Kernel density estimation was performed to investigate whether BM spatial patterns differed among lung cancer subtypes. Further, we explored more detailed subregions where BMs from adenocarcinomas occur frequently using one-way analysis of variance. Finally, we divided our cohort into those with fewer (≤10) and more (>10) BMs and evaluated whether this biased pattern was maintained across limited and extensive stages. For small cell carcinoma, BMs were biased to the cerebellum, but this did not reach statistical significance. For adenocarcinoma, BMs were found more frequently near the distal middle cerebral artery (MCA) territory and cerebellum than in other arterial territories (p < 0.01). The precentral and postcentral gyri were the most significant subregions within the distal anterior cerebral artery (ACA) and MCA territories (p < 0.01). Crus I and Lobule VI were significant regions within the cerebellum (p < 0.01). Regardless of the number of BMs, the affinity to the distal MCA territory and cerebellum was maintained. The present data confirm that BMs from lung adenocarcinoma may preferentially involve the distal MCA territory and cerebellum.

Highlights

  • Brain metastases (BMs) are the most common intracranial neoplasms, outnumbering primary malignant brain tumors by more than 10-fold [1, 2]

  • A total of 80 patients with 562 metastases were included in this study: 13 cases of small cell carcinoma with 107 BMs, 58 cases of adenocarcinoma with 432 BMs, and 9 cases of squamous cell carcinoma with 23 BMs

  • Probabilistic density functions showed different spatial distribution of BMs according to histologic subtypes of primary lung cancer (Figure 2)

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Summary

Introduction

Brain metastases (BMs) are the most common intracranial neoplasms, outnumbering primary malignant brain tumors by more than 10-fold [1, 2]. Advanced therapies have improved the survival rates of lung cancer patients, BMs remain an important cause of morbidities associated with progressive neurologic deficits [5]. Whole-brain radiation therapy (WBRT) is currently the treatment of choice for patients with multiple BMs not amenable to surgery or radiosurgery. Hippocampal-sparing WBRT has been recently introduced to prevent radiationinduced cognitive deficits, which reduces the radiation dose to the hippocampus while applying the usual higher dose to other brain regions [10]. Stereotactic radiosurgery (SRS) has been explored and is increasingly utilized for patients with limited BMs, as multiple Phase III randomized trials have demonstrated comparable overall survival and superior cognitive preservation and quality of life with SRS alone compared to SRS with WBRT [11,12,13]. The application of SRS has been expanded to patients with up to 10 BMs [14]

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