Novel risk scores for survival and intracranial failure in patients treated with radiosurgery alone to melanoma brain metastases

Abstract

PurposeStereotactic radiosurgery (SRS) alone is an increasingly common treatment strategy for brain metastases. However, existing prognostic tools for overall survival (OS) were developed using cohorts of patients treated predominantly with approaches other than SRS alone. Therefore, we devised novel risk scores for OS and distant brain failure (DF) for melanoma brain metastases (MBM) treated with SRS alone.Methods and materialsWe retrospectively reviewed 86 patients treated with SRS alone for MBM from 2009-2014. OS and DF were estimated using the Kaplan-Meier method. Cox proportional hazards modeling identified clinical risk factors. Risk scores were created based on weighted regression coefficients. OS scores range from 0-10 (0 representing best OS), and DF risk scores range from 0-5 (0 representing lowest risk of DF). Predictive power was evaluated using c-index statistics. Bootstrapping with 200 resamples tested model stability.ResultsThe median OS was 8.1 months from SRS, and 54 (70.1 %) patients had DF at a median of 3.3 months. Risk scores for OS were predicated on performance status, extracranial disease (ED) status, number of lesions, and gender. Median OS for the low-risk group (0-3 points) was not reached. For the moderate-risk (4-6 points) and high-risk (6.5-10) groups, median OS was 7.6 months and 2.4 months, respectively (p < .0001). Scores for DF were predicated on performance status, ED status, and number of lesions. Median time to DF for the low-risk group (0 points) was not reached. For the moderate-risk (1-2 points) and high-risk (3-5 points) groups, time to DF was 4.8 and 2.0 months, respectively (p < .0001). The novel scores were more predictive (c-index = 0.72) than melanoma-specific graded prognostic assessment or RTOG recursive partitioning analysis tools (c-index = 0.66 and 0.57, respectively).ConclusionsWe devised novel risk scores for MBM treated with SRS alone. These scores have implications for prognosis and treatment strategy selection (SRS versus whole-brain radiotherapy).

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

“…Melanoma patients recommended to receive SRS and initially treated with this modality have a median overall survival of 7.69 months [ 118 ]. This OS for SRS has been corroborated recently (8.1 months) in a report that also devised novel risk scores for OS and intracranial failure [ 151 ]. Chowdhury et al report a model to determine risk scores of OS based on performance status, extracranial disease status, number of lesions, and gender, thereby providing additional predictors for prognosis and treatment strategy [ 151 ].…”

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases – results and lessons learnt

“…Trials of the cytotoxic agents fotemustine and temozolomide, alone or in combination with WBRT, have produced responses in a minority of patients, but again no significant survival benefit (Mornex et al , 2003; Agarwala et al , 2004; Hofmann et al , 2006; Atkins et al , 2008). More recently, in patients with limited tumour burden (generally three or fewer brain lesions), treatment with surgical excision or stereotactic radiosurgery (SRS) has improved survival to 8–9 months (Fife et al , 2004; Davies et al , 2011; Chowdhury et al , 2015). The immunomodulating CTLA-4 inhibitor ipilimumab is effective in some patients with asymptomatic/stable brain metastases (Ajithkumar et al , 2015), whilst the BRAF inhibitors vemurafenib and dabrafenib produce responses in BRAF mutant melanoma patients with symptomatic brain metastases (Long et al , 2012; Dummer et al , 2014).…”

Treatment of melanoma brain metastases

“…Treatment decisions can be guided by prognostic scores such as the melanoma-specific graded prognostic assessment, which divides patients in different prognostic groups based on the Karnofsky performance status (KPS) and the number of brain metastases with a median overall survival ranging from 3.4 months (KPS 70, more than three metastases) to 13.2 months (KPS > 90, single brain metastasis) [14]. However, recent publications suggest that the melanoma-specific graded prognostic assessment needs to be revised because of the advent of novel systemic therapies and should include additional factors such as extracranial disease status and use of targeted agents [14,15]. Current research in radiotherapy for melanoma brain metastases focuses on three topics: reducing the negative effects of whole-brain irradiation on neurocognitive function by hippocampal sparing [16], the replacement of WBRT by SRS in patients with more than three metastases [17] (clinicaltrials.-gov NCT01644591), and on combination of radiotherapy with systemic therapies, particularly with immunotherapy (see below).…”

“…SRS is usually recommended in patients with one to three brain metastases up to 3 cm in size and can achieve high and durable local control rates of 70-80% by delivery of high radiation doses in one or a few fractions [13]. Treatment decisions can be guided by prognostic scores such as the melanoma-specific graded prognostic assessment, which divides patients in different prognostic groups based on the Karnofsky performance status (KPS) and the number of brain metastases with a median overall survival ranging from 3.4 months (KPS 70, more than three metastases) to 13.2 months (KPS > 90, single brain metastasis) [14]. However, recent publications suggest that the melanoma-specific graded prognostic assessment needs to be revised because of the advent of novel systemic therapies and should include additional factors such as extracranial disease status and use of targeted agents [14,15].…”