Malignant melanoma brain metastases: Treatment results and prognostic factors - a single-center retrospective study

Abstract

Abstract. The brain is one of the most frequent locations of metastasis in malignant melanoma. We aimed to identify prognostic factors for overall survival (OS) and local tumor control (LC) in patients with malignant melanoma metastasized to the brain treated by multimodal therapy. All patients diagnosed with malignant melanoma brain metastases between 1992 and 2011 at a single center were registered (n=100, 65% male, 35% female). OS and LC of individual brain metastases were retrospectively analyzed. Subgroup analyses was performed in patients with multiple brain metastasis (n=35) and LC per lesion (n=72) was evaluated in 37 patients. Median age was 57 (27-81) years. Fifty-three percent of patients had 1-2 brain metastases, 47% had >2 and 71% presented with additional extracranial metastases. Primary treatment included systemic therapy alone (temozolomide/fotemustine, 14%), local therapy (surgery and/or stereotactic radiotherapy, 25%), whole-brain radiotherapy (WBRT, 10%), combined WBRT and systemic therapy (18%), local therapy plus WBRT (5%) and combination of local and systemic therapy (8%). Three percent received a tri-modal therapy (WBRT, local and systemic therapy) and 17% refused treatment. Median follow-up in surviving patients was 32 (4-222) months, median OS in all patients 3.9 months (1-year survival 21.4%). Local therapy (p<0.001), systemic therapy (p=0.002), number of brain metastases and primary therapy including a local therapy (p<0.001) were significantly associated with OS. In the subgroup with multiple brain metastases (n=35), a trend (p=0.058) for improved OS after initial treatment with WBRT plus systemic therapy was noted (median OS 3.8 months) and use of these two modalities over the course of the disease was significantly associated with OS (p=0.007). The best LC per single lesion (n=37) could be achieved by combination of local with systemic therapy (p=0.011). Number of brain metastases, extracranial metastases and use of local therapy are independent prognostic factors in melanoma metastatic to the brain. LC and OS can be improved by combining local with systemic treatment. In patients with multiple brain metastases, WBRT plus systemic therapy provides superior OS.

Risk factors for development of melanoma brain metastasis and disease progression: a single-center retrospective analysis

“…Although other studies [8,25] found that NM histologic type was associated with BM development, we did not see this when corrected for tumor depth. Our patients with BM were predominantly male, as seen in other studies [8,12,17,26], although our stage-matched control group was similarly male-predominant. A review of multiple studies concluded that male patients with BM have a poorer prognosis [18], although we did not address that issue here.…”

“…In fact, we were able to confirm development of stage IV disease in only 10/237 (8.4%) of our control patients and lack of distant metastasis in only 79/237 (33.3%); for the remainder of our control patients (100/237, 42.2%), we did not have recent follow-up to ascertain this information. In reviewing the literature, we note that of nine studies examining melanoma BM, four had no control group [4,12,26,29], four had a control group similarly constructed as ours [5,6,8,9], and only one had a control group with non-brain distant metastasis [10]. …”

<p>Whole-brain helical tomotherapy with integrated boost for brain metastases in patients with malignant melanoma – final results of the BRAIN-RT trial</p>

“…However, this is in line with previously published data. In the cohort of Ostheimer et al, the reported median OS times for patients with multiple BM from MM were around 2.5 months despite systemic and local treatment and as short as 1.5 months with best supportive care only 29. In a recent analysis by Frinton et al, OS was 4.8 months from the diagnosis of BM and 2.2 months in patients receiving WBRT only 30.…”

Brain metastasis in a patient with melanoma receiving Pembrolizumab therapy

“…Many drugs (e.g., fotemustine and temozolomide) are not effective for the treatment of melanoma with brain metastasis due to the blood–brain barrier. [ 7 ] With emerging studies of immune checkpoint inhibitors (anti-CTLA-4/anti-PD1), immunotherapy has brought hope to MBM patients. Clinical trials have proven the efficacy of ipilimumab (the CTLA-4 inhibitor), with reported central nervous system control rates of 16–65% and median OS times of 2.5 to 29.3 months, grade 3 to 4 toxicity was 6 to 44.7% (Table 2 ).…”