Association of Brain Metastases With Survival in Patients With Limited or Stable Extracranial Disease

Abstract

ImportanceIntracranial metastatic disease (IMD) is a severe complication of cancer with profound prognostic implications. Patients with IMD in the setting of limited or stable extracranial disease (IMD-SE) may represent a unique and understudied subset of patients with IMD with superior prognosis.ObjectiveTo evaluate overall survival (OS), progression-free survival (PFS), and intracranial PFS (iPFS) in patients with IMD-SE secondary to any primary cancer.Data SourcesRecords were identified from MEDLINE, EMBASE, CENTRAL, and gray literature sources from inception to June 21, 2021.Study SelectionStudies in English reporting OS, PFS, or iPFS in patients with IMD-SE (defined as IMD and ≤2 extracranial metastatic sites) and no prior second-line chemotherapy or brain-directed therapy were selected.Data Extraction and SynthesisAuthor, year of publication, type of study, type of primary cancer, and outcome measures were extracted. Random-effects meta-analyses were performed to estimate effect sizes, and subgroup meta-analysis and metaregression were conducted to measure between-study differences in February 2022.Main Outcomes and MeasuresThe primary end point was OS described as hazard ratios (HRs) and medians for comparative and single-group studies, respectively. Secondary end points were PFS and iPFS.ResultsOverall, 68 studies (5325 patients) were included. IMD-SE was associated with longer OS (HR, 0.52; 95% CI, 0.39-0.70) and iPFS (HR, 0.63; 95% CI, 0.52-0.76) compared with IMD in the setting of progressive extracranial disease. The weighted median OS estimate for patients with IMD-SE was 17.9 months (95% CI, 16.4-22.0 months), and for patients with IMD-PE it was 8.0 months (95% CI, 7.2-12.8 months). Pooled median OS for all patients with IMD-SE was 20.9 months (95% CI, 16.35-25.98 months); for the subgroup with breast cancer it was 20.2 months (95% CI, 10.43-38.20 months), and for non–small cell lung cancer it was 27.5 months (95% CI, 18.27-49.66 months). Between-study heterogeneity for OS and iPFS were moderate (I2 = 56.5%) and low (I2 = 0%), respectively.Conclusions and RelevanceIn this systematic review and meta-analysis of patients with IMD-SE, limited systemic disease was associated with improved OS and iPFS. Future prospective trials should aim to collect granular information on the extent of extracranial disease to identify drivers of mortality and optimal treatment strategies in patients with brain metastases.

Morphological Features as Prognostic Indicators in Brain Metastases

“…Besides, the use of overall survival to evaluate BMs may be inappropriate because metastatic patients may die from a variety of causes, including systemic disease, intracranial progression, or a combination of both. It has been proved that, in the context of BM patients, overall survival is in uenced not only by intracranial control 23 , but also strongly in uenced by the status of extracranial disease 24,25 .…”

Heterogeneity in intracranial relapses after complete resection of lung adenocarcinoma: Distinct features of brain‐only relapse versus synchronous extracranial relapse

“…It has been recognized that the prognosis of cancer patients with brain metastases is affected by the status and the number of synchronous extracranial metastases(ECM), 28 , 29 and even the status of lymph node metastases. 30 However, which group of patients might develop brain oligometastases remained a problem.…”

Prevention of Brain Metastases: A New Frontier

“…Although early diagnosis and treatment has improved the prognosis in the last few decades, patients with brain metastases continue to have a short survival, even in cases of limited or stable extracranial disease [ 1 ]. One of the main reasons is that the brain is a sanctuary site for metastases due to the poor penetration through the normal blood–brain barrier (BBB) of most cytotoxic and targeted compounds, which leads to difficulty in targeting micrometastases [ 2 ].…”