Monday, June 13, 2016

Brain mets in melanoma: Don't wait to add anti-PD1 to SRS!!! And....TILs correlates with extent of brain edema and survival time in patients with brain mets

When used alone, radiation does little to help folks with melanoma.  But we've learned that when combined with other can make a world of difference!  This post looks at data re: radiation with immunotherapy, intralesional therapy and associated abscopal response:   Radiation and melanoma...a review...    

Here researchers addressed the combination of nivo (Opdivo) and radiation specifically for brain mets:  Nivo/opdivo with radiation better for melanoma patients with brain mets

And now this....reaffirming that both immunotherapy and radiation can be given TOGETHER!!!  Do NOT put off one, to do the other!!!  And...anti-PD1 did better than ipi....

Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery.  Qia, Yu, Kluger, Chiang.  Cancer. 2016 Jun 10.  

Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. This study was performed to determine the effect of the relative timing and type of immune checkpoint therapy on the response of melanoma brain metastases (BrMets) to treatment with stereotactic radiosurgery (SRS).  Seventy-five melanoma patients with 566 BrMets were treated with both SRS and immune checkpoint therapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment of any single lesion were considered concurrent if SRS was administered within 4 weeks of immunotherapy. [After statistical analysis...]  Concurrent use of immunotherapy and SRS resulted in a significantly greater median percent reduction in the lesion volume at 1.5, 3, and 6 months in comparison with nonconcurrent therapy. The median percent reduction in the lesion volume was also significantly greater for anti-programmed cell death protein 1 (anti-PD-1) than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) at 1.5, 3, and 6 months.  The administration of immunotherapy within 4 weeks of SRS results in an improved lesional response of melanoma BrMets in comparison with treatment separated by longer than 4 weeks. Anti-PD-1 therapy also results in a greater lesional response than anti-CTLA-4 after SRS.

And while this is a bit does describe the phenomenon that both causes edema in brain mets as well as survival....

Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases.  Berghoff, Fuchs, Ricken, et al.  Oncoimmunology. 2015 Jun 9.  

The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density. TIL density was not associated with corticosteroid administration. A significant difference in infiltration density according to TIL subtype was present; high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8+ TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging. The density of CD3+ (15 vs. 6 mo), CD8+ (15 vs. 11 mo) and CD45RO+ TILs (18 vs. 8 mo) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings.

Brain mets suck great big, green, hairy, wizard balls!!!  But...there's hope.  Hang in there!  - c

1 comment:

  1. I want the Anti PD-1 perhaps I should get the patient advocate at MD Anderson involved

    We are leaving Seattle for Texas tomorrow 10/22's been ugly getting out of here