Descriptive statistics
85 patients were included. 54 (60%) were female and 31 (40%) were male, with a mean age of 60.5 (9.84) years at time of BM diagnosis. 61 (72%) patients were diagnosed with supratentorial metastasis, while 24 (28%) patients were diagnosed with infratentorial lesions. Supratentorial metastases were most often located in the frontal (n = 25, 41%), parietal (n = 13, 21%) or occipital lobe (n = 9, 15%). Of those with an infratentorial location, 23 (96%) metastases were found in the cerebellum and 1 (4%) was found at the cerebellopontine angle. The most commonly identified primaries were lung (n = 46), breast (n = 7) and colorectal (n = 6). The most common comorbidity was hypertension (n = 18, 21%) and 31 (36%) patients were either current or former smokers. 19 (22%) patients had no recorded comorbidities. For patients with necessary data available (n = 73, 86%), the median time from the BM diagnosing scan to surgery was 28 days (range = 0-893). 99% (n = 83/84) of patients survived longer than 30 days, 90% (n = 76/84) survived longer than 90 days and 77% (n = 65/84) survived longer than 120 days. No patients were censored prior to 120 days following surgery. Table I provides an overview of the patient data analysed in the present study.
Exploratory analyses
A chi-square test showed a significant relationship between sex and brain metastasis location, X2 (1, N = 85) = 4.68, p = 0.03, with infratentorial tumours presenting more commonly than expected in males. There was no significant association between surgical approach (gross total versus subtotal resection) and brain metastasis location, X2 (1, N = 85) = 0.578, p = 0.45. Adjuvant therapy use (none, SRT, or WBRT) was not related to region of brain metastasis, as evidenced by Fisher’s exact test (p = 0.88).
Infratentorial location and OS
Necessary data for survival analysis was available for 99% (n = 84/85) of patients. By the end of the follow up period, 19/84 (23%) of patients were still alive and therefore censored. This censorship level was comparable between supratentorial (23%) and infratentorial (22%) patients. Supratentorial patients had mean OS of 575 days (95% CI 403-747), compared to 561 days (95% CI 270-853) for infratentorial metastases. The median OS was 323 days (95% CI 235-411) for supratentorial metastases and 277 days (95% CI 195-359) for infratentorial metastases. In univariate analysis, posterior fossa location was not associated with a significant change in overall survival (log rank test = 0.276, p = 0.60). A log rank test was used despite the crossing of the Kaplan-Meier survival curves. This is because any deviations from proportional hazards are believed to be a coincidence of random sampling, rather than evidence that patients in one group were more likely to die early and patients in the other group were more likely to die late. This approach has been validated elsewhere [8]. The comparison of survival between supra- and infratentorial patients is shown in figure I.
Infratentorial location and post-operative complications
The most common neurological post-operative complication was a speech deficit (n = 3, 4%). Wound infection was the most common non-neurological post-operative complication (n = 4, 5%). A significant association between infratentorial location and post-operative deficits was found using Fisher’s exact test (p = 0.002). Patients undergoing resection for supratentorial metastases experienced neurological deficits in 13% (n = 8/61) of cases and non-neurological complications 2% of the time (n = 1/61). This was in comparison to posterior fossa lesions, where neurological complications occurred in 21% (n = 5/24) of cases and non-neurological events occurred in 25% (n = 6/24). Supratentorial patients more frequently experienced no post-operative complications (82% v 54%).
Infratentorial location and KPS
KPS was assessed at time of BM diagnosis in 64 patients and post-operatively in 63 patients. At diagnosis, mean KPS was 87.8 (11.8) amongst supratentorial patients and 90.0 (8.45) for patients with infratentorial metastases. Following resection, supratentorial patients had a mean KPS of 86.1 (13.0), compared to infratentorial patients with 89.3 (16.4). Using two-tailed independent samples t-tests, posterior fossa location was not associated with a significant difference in KPS at diagnosis, t(62) = 0.685, p = 0.50, or after resection, t(61) = 0.755, p = 0.45. Among all 63 patients with a KPS assessment both at diagnosis and post-operatively, resection was not associated with a significant change in functional status, as per a two-tailed paired t-test (mean = -1.59, standard deviation = 8.65), t(62) = -1.456, p = 0.15. The decline was comparable between supra- and infratentorial patients, t(61) = 0.077, p = 0.94.
Infratentorial location, extracranial disease, and OS
No significant association was found between BM location and timing of presentation (synchronous or metachronous), as shown in a chi-square test, X2 (1, N = 85) = 0.30, p = 0.58. Further, there was no significant difference in the presence of extracranial disease activity between the two patient groups, X2 (1, N = 84) = 0.27, p = 0.61. Analysis of the survival distributions of patients with and without active extracranial disease (figure II) suggested there was no significant relationship between the two variables (log rank test = 1.221, p = 0.27). The log rank test was used despite the crossing of Kaplan-Meier survival curves for the reasons stated previously. Patients with and without extracranial disease varied with respect to size and censorship. 17/83 (20.5%) patients did not have any extracranial disease present, and of these, 11.8% were censored. In comparison, 17/66 (25.8%) patients with systemic disease were censored.
Multivariate analysis of survival
Multivariate analysis was conducted using a Cox proportional hazards model incorporating sex, age, extracranial disease activity (present or absent), adjuvant therapy use (none, SRT or WBRT), post-operative complications (none, neurological, non-neurological or both) and BM region (supratentorial or infratentorial). Pre- and post-operative Karnofsky Performance Scales were not included in the model due to a high level of missingness from our dataset (~25%). All included variables satisfied the proportional hazards assumption, as evaluated by the addition of time-dependent covariates to the model. Age was found to be independently prognostic of survival, HR 1.037 per year (95% CI 1.007-1.067, p = 0.02). Brain metastasis location was not found to be associated with survival, HR 1.51 (95% CI 0.780-2.92) for infratentorial lesions (p = 0.22). Similarly, extracranial disease activity did not have a significant prognostic effect on survival, HR 0.619 (95% CI 0.315-1.22) for those with extracranial disease activity present (p = 0.17).