Friday, March 9, 2018

CONCURRENT radiation and immunotherapy for brain mets is BEST!!!! (yes, AGAIN!!!)

"I know, I know!!!!"   I keep ranting about this.  And I will continue until it seeps into the pores of all melanoma (as well as NSCLC and renal cell carcinoma) patients and docs!!! Here are just a few zillions rants, posts, and data:  Yes, you SHOULD COMBINE radiation and immunotherapy!!!!
Now, there's this ~

Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. Chen, Douglass, Kleinberg, et al.  Int J Radiat Oncol Biol Phys. 2018 Mar 15. 

To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs).

We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs.

A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of greater than/= to 3 new BMs after SRS-SRT. Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone and compared with nonconcurrent SRS-SRT and ICI on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI or after ICI.  
Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.

Here folks looked at patients suffering from brain mets due to NSCLC, melanoma, and renal cell carcinoma.  Between 2010 and 2016, these peeps were treated with SRS-SRT and given either ipi, nivo or pembro.  CONCURRENT immunotherapy was defined as the meds having been given within 2 weeks of the radiation.  There were three groups:  1) those treated with radiation alone, 2) those treated with radiation and NON-concurrent immunotherapy, 3) and those treated with radiation and CONCURRENT immunotherapy.  260 patients were given radiation to 623 brain mets.  181 had radiation alone.  70 patients got radiation and immunotherapy with 35% of those attaining radiation concurrent with immunotherapy.  Overall survival for radiation alone = 12.9 months.  OS for radiation and NON-concurrent immunotherapy = 14.5 months.  OS for radiation with CONCURRENT immunotherapy = 24.7 months.  This was true no matter if the radiation was given before or after the immunotherapy....AND....wait for it....CONCURRENT administration of immunotherapy and radiation did NOT cause increased immune side effects NOR an increased rate of neurologic problems!!!!!!!!!!!!!!!!!!!  However, CONCURRENT immunotherapy and radiation DID decrease development of additional brain mets later!!!!

Come on folks!!!  This matters.  This is important.  This changes SAVES lives!!!  Do NOT settle for less.  If you have brain mets, demand CONCURRENT immunotherapy and SRS!!!!  There is more than enough proof.  It makes a positive difference!!! - c

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