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  • Author or Editor: Thomas J. Eluvathingal Muttikkal x
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Nasser Mohammed, Yi-Chieh Hung, Thomas J. Eluvathingal Muttikkal, Roy C. Bliley, Zhiyuan Xu and Jason P. Sheehan

OBJECTIVE

The motor root of the trigeminal nerve runs close to the sensory root and receives considerable radiation during Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The object of this study was to evaluate via MRI the changes in the muscles of mastication before and after upfront GKRS in patients with idiopathic TN.

METHODS

In this single-institution retrospective cohort study, all patients with idiopathic unilateral TN treated with primary GKRS at the University of Virginia in the period from 2007 to 2017 were included provided that they had pre- and post-GKRS MRI data. The thicknesses of the temporalis, pterygoid, and masseter muscles were measured on both pre- and post-GKRS MRI in a blinded fashion. Changes in the muscles like fatty infiltration, MRI signal, or atrophy were noted.

RESULTS

Among the 68 patients eligible for inclusion in the study, 136 temporalis muscles, 136 medial pterygoid muscles, 136 lateral pterygoid muscles, and 136 masseter muscles were assessed. A subset of patients was found to have muscle atrophy even prior to GKRS. Pre-GKRS atrophy of the masseter, medial pterygoid, lateral pterygoid, and temporalis muscles was seen in 18 (26%), 16 (24%), 9 (13%), and 16 (24%) patients, respectively. Logistic regression analysis showed that distribution of pain in the V3 territory (p = 0.01, OR 5.43, 95% CI 1.46–20.12) and significant pain on chewing (p = 0.02, OR 5.32, 95% CI 1.25–22.48) were predictive of pre-GKRS atrophy. Reversal of atrophy of these muscles occurred after GKRS in a majority of the patients. The incidence of new-onset permanent post-GKRS muscle atrophy was 1.5%. The median follow-up was 39 months (range 6–108 months).

CONCLUSIONS

A subset of patients with TN with significant pain on chewing have pre-GKRS disuse atrophy of the muscles of mastication. A reversal of the atrophy occurs in a majority of the patients following GKRS. New-onset motor neuropathy post-GKRS was rare.

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Matthew J. Shepard, Zhiyuan Xu, Joseph Donahue, Thomas J. Eluvathingal Muttikkal, Diogo Cordeiro, Leslie Hansen, Nasser Mohammed, Ryan D. Gentzler, James Larner, Camilo E. Fadul and Jason P. Sheehan

OBJECTIVE

Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non–small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS.

METHODS

A retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts.

RESULTS

Seventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39–2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72–6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162).

CONCLUSIONS

The concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.

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Matthew J. Shepard, Zhiyuan Xu, Joseph Donahue, Thomas J. Eluvathingal Muttikkal, Diogo Cordeiro, Leslie Hansen, Nasser Mohammed, Ryan D. Gentzler, James Larner, Camilo E. Fadul and Jason P. Sheehan

OBJECTIVE

Immune checkpoint inhibitors (ICIs) improve survival in patients with advanced non–small cell lung cancer (NSCLC). Clinical trials examining the efficacy of ICIs in patients with NSCLC excluded patients with untreated brain metastases (BMs). As stereotactic radiosurgery (SRS) is commonly employed for NSCLC-BMs, the authors sought to define the safety and radiological and clinical outcomes for patients with NSCLC-BMs treated with concurrent ICI and SRS.

METHODS

A retrospective matched cohort study was performed on patients who had undergone SRS for one or more NSCLC-derived BMs. Two matched cohorts were identified: one that received ICI before or after SRS within a 3-month period (concurrent ICI) and one that did not (ICI naive). Locoregional tumor control, peritumoral edema, and central nervous system (CNS) adverse events were compared between the two cohorts.

RESULTS

Seventeen patients (45 BMs) and 34 patients (92 BMs) composed the concurrent-ICI and ICI-naive cohorts, respectively. There was no statistically significant difference in overall survival (HR 0.99, 95% CI 0.39–2.52, p = 0.99) or CNS progression-free survival (HR 2.18, 95% CI 0.72–6.62, p = 0.11) between the two groups. Similarly, the 12-month local tumor control rate was 84.9% for tumors in the concurrent-ICI cohort versus 76.3% for tumors in the ICI-naive cohort (p = 0.94). Further analysis did reveal that patients receiving concurrent ICI had increased rates of CNS complete response for BMs treated with SRS (8/16 [50%] vs 5/32 [15.6%], p = 0.012) per the Response Assessment in Neuro-Oncology (RANO) criteria. There was also a shorter median time to BM regression in the concurrent-ICI cohort (2.5 vs 3.1 months, p < 0.0001). There was no increased rate of radiation necrosis or intratumoral hemorrhage in the patients receiving concurrent ICI (5.9% vs 2.9% in ICI-naive cohort, p = 0.99). There was no significant difference in the rate of peritumoral edema progression between the two groups (concurrent ICI: 11.1%, ICI naive: 21.7%, p = 0.162).

CONCLUSIONS

The concurrent use of ICI and SRS to treat NSCLC-BM was well tolerated while providing more rapid BM regression. Concurrent ICI did not increase peritumoral edema or rates of radiation necrosis. Further studies are needed to evaluate whether combined ICI and SRS improves progression-free survival and overall survival for patients with metastatic NSCLC.