Association of Neurosurgical Resection With Development of Pachymeningeal Seeding in Patients With Brain Metastases

Abstract

Importance: Neurosurgical resection represents an important management strategy for patients with large, symptomatic brain metastases and increasingly is followed by stereotactic radiation as opposed to whole-brain radiation. Whether neurosurgical resection is associated with tumor spread beyond the resection site and adjuvant stereotactic radiation field remains unknown.

Objective: To characterize the association and incidence of pachymeningeal seeding with neurosurgical resection in patients with brain metastases treated with adjuvant stereotactic radiation.

Design, setting, and participants: Retrospective cohort study of a consecutive sample of patients with newly diagnosed brain metastases managed with neurosurgical resection and stereotactic radiation (n = 318) vs radiation alone (n = 870) between 2001 and 2015.

Main outcomes and measures: Incidence of pachymeningeal seeding (dural and/or outer arachnoid) and leptomeningeal disease in patients treated with neurosurgical resection and stereotactic radiation vs radiation alone and the risk factors and outcomes associated with pachymeningeal seeding in patients treated with neurosurgical resection followed by stereotactic radiation.

Results: In 1188 patients with newly diagnosed brain metastases, 133 men and 185 women (mean [SD] age, 58.9 [11.5] years) underwent neurosurgical resection. Resection was found to be associated with pachymeningeal seeding (36 of 318 patients vs 0 of 870 patients; P < .001) but not leptomeningeal disease (hazard ratio [HR], 1.14; 95% CI, 0.73-1.77; P = .56). In total, 36 (8.4%) of 428 operations were complicated by pachymeningeal seeding, with a higher incidence noted with resection of previously irradiated vs unirradiated metastases (HR, 2.39; 95% CI, 1.25-4.57; P = .008). Patients with pachymeningeal seeding had relatively low rates of subsequent development of new brain metastases and leptomeningeal disease (8 [16%] of 51 and 6 [13%] of 48, respectively). Among patients with pachymeningeal seeding, neurologic death primarily owing to progressive pachymeningeal disease accounted for 26 (72%) of 36 deaths, but when treated with salvage radiation, 49.1% of patients survived 1 year or longer.

Conclusions and relevance: In the era of omission of adjuvant whole-brain radiation after neurosurgical resection, pachymeningeal seeding beyond the stereotactic radiation field represents a notable oncologic event that often proves difficult to salvage. However, in some patients, disease control can be achieved with radiotherapeutic approaches.

Figure 1.. Axial T1-Weighted Postcontrast Magnetic Resonance Images of Leptomeningeal Disease and Pachymeningeal Seeding

Figures show enhancement (arrowheads) along the cerebellar folia (A) and the cerebellar folia and supratentorial sulci (B) in the setting of leptomeningeal disease. In the setting of pachymeningeal seeding, nodular enhancement (arrowheads) of the right tentorium and dural surface of right temporal lobe (C) and of the dural surface of left occipital and temporal lobe (D) is visible.

Figure 2.. Kaplan-Meier Curves With Associated Log-Rank Test for Freedom From Leptomeningeal Disease and Pachymeningeal Seeding

Patients treated with neurosurgical resection (red) vs without neurosurgical resection (blue).

Figure 3.. Kaplan-Meier Curve for Freedom From Neurologic Death in Patients Who Developed Pachymeningeal Seeding

Time zero refers to the date of diagnosis of pachymeningeal seeding.