Panagiotis Mastorakos, Davis G. Taylor, Ching-Jen Chen, Thomas Buell, Joseph H. Donahue and John A. Jane Jr.
Cavernous sinus invasion (CSI) in Cushing’s disease (CD) negatively affects the probability of complete resection, biochemical cure, and need for adjuvant therapy. However, the prediction of CSI based on MRI findings has been inconsistent and variable. Among macroadenomas, the Knosp classification is the most widely utilized radiographic predictor of CSI, but its accuracy in predicting CSI and the probability of gross-total resection is limited in the setting of microadenomas or Knosp grade 0–2 macroadenomas. The authors noticed that the presence of a triangular shape of adenomas adjacent to the cavernous sinus on coronal MR images is frequently associated with CSI. The authors aimed to determine the correlation of this radiographic finding (“sail sign” [SS]) with CSI.
The authors performed a retrospective review of all patients with a pituitary lesion < 20 mm and a biochemical diagnosis of CD treated with endoscopic or microscopic transsphenoidal resection from November 2007 to May 2017. Overall 185 patients with CD were identified: 27 were excluded for negative preoperative imaging, 32 for lacking tumors adjacent to the sinus, 7 for Knosp grade 3 or higher, and 4 for inadequate intraoperative assessment of the CSI. Following application of inclusion and exclusion criteria, 115 cases were available for statistical analysis. Intraoperative CSI was prospectively evaluated at the time of surgery by one of two neurosurgical attending surgeons, and MRI data were evaluated retrospectively by a neurosurgical resident and attending neuroradiologist blinded to the intraoperative results.
A positive SS was identified in 23 patients (20%). Among patients with positive SS, 91% demonstrated CSI compared to 10% without an SS (p < 0.001). Using the SS as a predictor of CSI provided a sensitivity of 0.7 and a specificity of 0.98, with a positive predictive value (PPV) of 0.91 and a negative predictive value of 0.9. Among patients with positive SS, 30% did not achieve immediate postoperative remission, compared to 3.3% of patients without an SS (p < 0.001).
The presence of a positive SS among Cushing’s adenomas adjacent to the CS provides strong PPV, specificity, and positive likelihood ratio for the prediction of CSI. This can be a useful tool for preoperative planning and for predicting the likelihood of long-term biochemical remission and the need for adjuvant radiosurgery.
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
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.
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.
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).
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.