Objective: Brain metastases are associated with high rates of mortality and morbidity, and therefore new, effective treatment options are consistently in demand. Gamma Knife Radiosurgery (GKRS) has proven effective in previous clinical trials. There is a noticeable reduction in neurocognitive problems and brain toxicity with GKRS as sole management. Moreover, GKRS is continuously preferred as the sole management option over whole-brain radiotherapy (WBRT).  

However, the effects of GKRS on peritumoral edema (PTE) is poorly understood. This is of concern in metastases present in the posterior fossa, as masses and associated edema can compress the brain stem, reduce the size of the fourth ventricle, lead to neurological deterioration and increased risk of mortality. The purpose of the present study, was to evaluate the effect of GKRS as monotherapy on large posterior fossa metastases (LPFM, defined as ≥ 2 cm), associated PTE and mass effect compression on the fourth ventricle.

Methods: The investigators conducted a retrospective chart review to study patients with LPFM who had previously undergone GKRS. Patients were included in the final study if they were at least 18 years old, had ≥ one LPFM and ≥ one clinical + radiological following GKRS. Patients were excluded if they 1) underwent surgical excision of metastases, 2) experienced hemorrhaging within the tumour, 3) were experiencing leptomeningeal disease and 4) if they underwent subsequent or staged GKRS to the lesion. The review found 51 mass lesions in 49 patients spread over eight years (January 1, 2009-December 31, 2017). The study examined patient demographics, presentation in the clinic, lesion diameter (cm), volume (cm³) Karnofsky performance status (KPS) score, the number of metastases in the posterior fossa, dose of GKRS, details of whole brain radiation treatment (WBRT), duration of follow up post-treatment and overall survival.

Results: The median age of the included patients was 61.5 years, with patients ranging between 29-94 years. Of the included patients, 57.1% (28) identified as men. The median KPS score was 90, while the median counts of cerebellar metastases and total brain metastases were one and two respectively. The median mass diameter was 2.6 cm, and the most common source of the metastases was the lung as 22 patients were diagnosed with this. 20 patients had previously received WBRT. Most patients (22) had LPFM in the right cerebellar hemisphere. Most lesions (32) were classified as LPFMs with additional metastases in the posterior fossa and supratentorial region. The median tumour volume identified following the review was 4.96 cm³, which existed in a range of 1.4-21.1cm³. The median volume PTE was 14.98 cm³. The median volume of the fourth ventricle was 1.23 cm³.  At the time of diagnosis, the median volume of the tumour + PTE was 19.61 cm³. Patients have followed up a median of 7.3 months following the procedure.

The researchers found that the combined tumour and PTE volume had decreased in 92.15% of lesions (47) and increased in 7.84% of lesions (4) at the time of first follow-up (median two months). Notably, the investigators found that the median volume decrease in tumors and PTE was 58.66% (range −96.95% to +48.69%, p < 0.001), and 78.10% (range −99.92% to+198.35%, p < 0.001) respectively. Moreover, the treatment was associated with a median increase in fourth ventricle volume of 24.97% (range −37.96% to +545.6%, p < 0.001). The investigators found that GKRS resulted in median overall survival of 8.36 months. The researchers further examined the side effects experienced by patients. The study categorized the side effects into three groups 1. cerebellar, 2. asymptomatic and 3. nonspecific neurological symptoms such as weakness, neuropathy associated with treatment or headaches. Clinical improvement was observed in half of the patients (6/12) who experienced cerebellar symptoms at the first follow-up (6-12 weeks). Five patients did not improve, and one patient experienced worsened symptoms. Of the 19 patients that had experienced nonspecific symptoms, one was observed to be experiencing the new cerebellar symptoms at the time of their first follow-up. Of the 49 total patients in the review, three were experiencing worsening of symptoms at first follow-up. The researchers also examined whether patients had developed radiation necrosis. Three patients studied in the review developed radiation necrosis that was symptomatic. One of these patients was treated with laser interstitial thermal therapy, another with a ventriculoperitoneal shunt and the last was treated with steroids. Two suffered asymptomatic radiation necrosis but no treatment was necessitated. Finally, novel cerebellar metastasis developed in two patients during the follow-up period and were subsequently treated with GKRS.

In conclusion, the retrospective chart review demonstrated that GKRS was able to significantly reduce the volume of the PTE and LPFM and increase the volume of the fourth ventricle in patients with minimal side effects. Therefore, it has potential to be a novel monotherapy for patients living with LPFM. However, there are a few issues with this study.  The inclusion criteria were highly selective. The patients in the study sample, presented with minimal neurological symptoms, no hydrocephalus or intratumor hemorrhage and no compression of the brainstem. Any patient that presented with these issues was excluded.  Moreover, the Karnofsky Performance Status is an important marker of patient outcome in cancer management.  The median KPS score in this group was 90. Twenty-seven of the patients (55.1%) had a KPS of 90. Therefore, the study had a high degree of patient selection. Additionally, the usage of median survival time does not tell the entire story.  Patients below the median survival time (50% of patients) passed away. Among the patients that survived past the median survival time of 8.36 months, there were notable survival times as one patient survived for 57.2 months. Therefore, prospective studies with larger sample sizes are required to confirm the safety, efficacy, and external validity of these results.

Citation:

Baha’eddin, A. M., Joshi, K. C., Lee, B. S., Thapa, B., Borghei-Razavi, H., Jia, X., … & Angelov, L. (2020). The effect of Gamma Knife radiosurgery on large posterior fossa metastases and the associated mass effect from peritumoral edema. Journal of Neurosurgery, 134(2), 466-474.

Recommended articles by Dr. Michael West:

1. Pakkenberg B, Boesen J, Albeck M, Gjerris F: Unbiased and efficient estimation of total ventricular volume of the brain obtained from CT-scans by a stereological method. Neuroradiology 31:413–417, 1989
2. Synek V, Reuben JR: The ventricular-brain ratio using planimetric measurement of EMI scans. Br J Radiol 49:233–237, 1976