Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases.

INTRODUCTION: Brain metastases are common in metastatic melanoma and radiosurgery is often utilized for local control. Immune checkpoint inhibitors (CPIs) play a central role in contemporary melanoma management; however, there is limited data exploring outcomes and potential toxicities for patients treated with CPIs and radiosurgery. METHODS: We retrospectively identified all consecutive cases of newly diagnosed melanoma brain metastases (MBM) treated with Gamma Knife radiosurgery at a single institution between 2012 and 2017, and included only patients that initiated CPIs within 8 weeks before or after radiosurgery. RESULTS: Thirty-eight patients were included with a median follow-up of 31.6 months. Two-year local control was 92%. Median time to out-of-field CNS and extra-CNS progression were 8.4 and 7.9 months, respectively. Median progression-free survival (PFS) was 3.4 months and median overall survival (OS) was not reached (NR). Twenty-five patients (66%) received anti-CTLA4 and 13 patients (34%) received anti-PD-1+/-anti-CTLA4. Compared with anti-CTLA4, patients that received anti-PD-1+/-anti-CTLA4 had significant improvements in time to out-of-field CNS progression (p = 0.049), extra-CNS progression (p = 0.015), and PFS (p = 0.043), with median time to out-of-field CNS progression of NR vs. 3.1 months, median time to extra-CNS progression of NR vs. 4.4 months, and median PFS of 20.3 vs. 2.4 months. Six patients (16%) developed grade ≥ 2 CNS toxicities (grade 2: 3, grade 3: 3, grade 4/5: 0). CONCLUSIONS: Excellent outcomes were observed in patients that initiated CPIs within 8 weeks of undergoing radiosurgery for newly diagnosed MBM. There appears to be an advantage to anti-PD-1 or combination therapy compared to anti-CTLA4.

Four-year Survival (and Counting) after Stereotactic Radiosurgery to Nearly 100 Brain Metastases: A Case Report.

Brain metastases are a relatively common consequence of Stage IV melanoma. Historically, patients with brain metastases fare poorly, with median survival of only weeks to months. Patients with multiple metastases in the brain have often been overlooked in the literature, with the focus being placed more on patients with only a small number of metastases. The authors present a case of a 42-year-old man with a total of 98 brain metastases treated over several Gamma Knife sessions. He is nearly five years out from his initial treatment. This case highlights the fact that there is a large amount of variability in survival after diagnosis with brain metastases. Selection for treatment should be based on the clinical picture and clinicians should take care to avoid selection bias in this population.

A transient rise in tropical sea surface temperature during the Paleocene-Eocene thermal maximum.

The Paleocene-Eocene Thermal Maximum (PETM) has been attributed to a rapid rise in greenhouse gas levels. If so, warming should have occurred at all latitudes, although amplified toward the poles. Existing records reveal an increase in high-latitude sea surface temperatures (SSTs) (8 degrees to 10 degrees C) and in bottom water temperatures (4 degrees to 5 degrees C). To date, however, the character of the tropical SST response during this event remains unconstrained. Here we address this deficiency by using paired oxygen isotope and minor element (magnesium/calcium) ratios of planktonic foraminifera from a tropical Pacific core to estimate changes in SST. Using mixed-layer foraminifera, we found that the combined proxies imply a 4 degrees to 5 degrees C rise in Pacific SST during the PETM. These results would necessitate a rise in atmospheric pCO2 to levels three to four times as high as those estimated for the late Paleocene.