Extended Survival in Patients With Non-Small-Cell Lung Cancer-Associated Brain Metastases in the Modern Era
Berger, Assaf; Mullen, Reed; Bernstein, Kenneth; Alzate, Juan Diego; Silverman, Joshua S; Sulman, Erik P; Donahue, Bernadine R; Chachoua, Abraham; Shum, Elaine; Velcheti, Vamsidhar; Sabari, Joshua; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:Brain metastases (BM) have long been considered a terminal diagnosis with management mainly aimed at palliation and little hope for extended survival. Use of brain stereotactic radiosurgery (SRS) and/or resection, in addition to novel systemic therapies, has enabled improvements in overall and progression-free (PFS) survival. OBJECTIVE:To explore the possibility of extended survival in patients with non-small-cell lung cancer (NSCLC) BM in the current era. METHODS:During the years 2008 to 2020, 606 patients with NSCLC underwent their first Gamma Knife SRS for BM at our institution with point-of-care data collection. We reviewed clinical, molecular, imaging, and treatment parameters to explore the relationship of such factors with survival. RESULTS:The median overall survival was 17 months (95% CI, 13-40). Predictors of increased survival in a multivariable analysis included age <65 years (P < .001), KPS ≥80 (P < .001), absence of extracranial metastases (P < .001), fewer BM at first SRS (≤3, P = .003), and targeted therapy (P = .005), whereas chemotherapy alone was associated with shorter survival (P = .04). In a subgroup of patients managed before 2016 (n = 264), 38 (14%) were long-term survivors (≥5 years), of which 16% required no active cancer treatment (systemic or brain) for ≥3 years by the end of their follow-up. CONCLUSION/CONCLUSIONS:Long-term survival in patients with brain metastases from NSCLC is feasible in the current era of SRS when combined with the use of effective targeted therapeutics. Of those living ≥5 years, the chance for living with stable disease without the need for active treatment for ≥3 years was 16%.
The Cost Effectiveness of Implementation of a Postoperative Endocrinopathy Management Protocol after Resection of Pituitary Adenomas
Benjamin, Carolina G; Dastagirzada, Yosef; Bevilacqua, Julia; Kurland, David B; Fujita, Kevin; Sen, Chandra; Golfinos, John G; Placantonakis, Dimitris G; Jafar, Jafar J; Lieberman, Seth; Lebowitz, Richard; Lewis, Ariane; Agrawal, Nidhi; Pacione, Donato
The Value of Intraoperative Magnetic Resonance Imaging in Endoscopic Endonasal Resection of Pituitary Adenoma
Patel, Aneek; Dastagirzada, Yosef; Benjamin, Carolina; Lieberman, Seth; Lebowitz, Richard; Golfinos, John G; Pacione, Donato
Surgical cytoreduction of deep-seated high-grade glioma through tubular retractor
Hajtovic, Sabastian; Sun, James; Multani, Jasjit S; Herrmann, Linda L; Britton, Hannah; Gautreaux, Jose; Tortolero, Lea; Harrison, Gillian; Golfinos, John G; Shepherd, Timothy M; Tanweer, Omar; Placantonakis, Dimitris G
OBJECTIVE:Maximal safe resection is the goal of surgical treatment for high-grade glioma (HGG). Deep-seated hemispheric gliomas present a surgical challenge due to safety concerns and previously were often considered inoperable. The authors hypothesized that use of tubular retractors would allow resection of deep-seated gliomas with an acceptable safety profile. The purpose of this study was to describe surgical outcomes and survival data after resection of deep-seated HGG with stereotactically placed tubular retractors, as well as to discuss the technical advances that enable such procedures. METHODS:This is a retrospective review of 20 consecutive patients who underwent 22 resections of deep-seated hemispheric HGG with the Viewsite Brain Access System by a single surgeon. Patient demographics, survival, tumor characteristics, extent of resection (EOR), and neurological outcomes were recorded. Cannulation trajectories and planned resection volumes depended on the relative location of white matter tracts extracted from diffusion tractography. The surgical plans were designed on the Brainlab system and preoperatively visualized on the Surgical Theater virtual reality SNAP platform. Volumetric assessment of EOR was obtained on the Brainlab platform and confirmed by a board-certified neuroradiologist. RESULTS:Twenty adult patients (18 with IDH-wild-type glioblastomas and 2 with IDH-mutant grade IV astrocytomas) and 22 surgeries were included in the study. The cohort included both newly diagnosed (n = 17; 77%) and recurrent (n = 5; 23%) tumors. Most tumors (64%) abutted the ventricular system. The average preoperative and postoperative tumor volumes measured 33.1 Â± 5.3 cm3 and 15.2 Â± 5.1 cm3, respectively. The median EOR was 93%. Surgical complications included 2 patients (10%) who developed entrapment of the temporal horn, necessitating placement of a ventriculoperitoneal shunt; 1 patient (5%) who suffered a wound infection and pulmonary embolus; and 1 patient (5%) who developed pneumonia. In 2 cases (9%) patients developed new permanent visual field deficits, and in 5 cases (23%) patients experienced worsening of preoperative deficits. Preoperative neurological or cognitive deficits remained the same in 9 cases (41%) and improved in 7 (32%). The median overall survival was 14.4 months in all patients (n = 20) and in the newly diagnosed IDH-wild-type glioblastoma group (n = 16). CONCLUSIONS:Deep-seated HGGs, which are surgically challenging and frequently considered inoperable, are amenable to resection through tubular retractors, with an acceptable safety profile. Such cytoreductive surgery may allow these patients to experience an overall survival comparable to those with more superficial tumors.
Comparing Rates of Postoperative Meningitis After Endoscopic Endonasal Procedures Based on Methicillin-Resistant Staphylococcus aureus/Methicillin-Sensitive Staphylococcus aureus Colonization and Antibiotic Prophylaxis
Orillac, Cordelia; Patel, Aneek; Dastagirzada, Yosef; Benjamin, Carolina; Lieberman, Seth; Lebowitz, Richard; Golfinos, John G; Pacione, Donato
BACKGROUND:Endoscopic endonasal approach (EEA) procedures are inherently contaminated due to direct access through the nasopharyngeal mucosa. The reported rate of postoperative meningitis in EEA procedures is 0.7%-3%. A variety of methods exist to minimize the risk of meningitis with antibiotic prophylaxis, although their value is not completely understood. This study investigated whether there is a difference in rates of postoperative meningitis based on Staphylococcus aureus colonization and use of preoperative antibiotic prophylaxis. METHODS:All adult patients who underwent EEA resection at our institution from 2013 to 2021 were retrospectively reviewed. Patients with preoperative cerebrospinal fluid infections were excluded. Data including recent preoperative infections, preoperative colonization status, antibiotic administration, and postoperative outcomes were recorded for each patient. RESULTS:Of 483 patients identified (mean age, 51 years; range, 18-90 years; 274 [56.7%] female), 80 (16.6%) had a positive preoperative methicillin-resistant Staphylococcus aureus (MRSA)/methicillin-sensitive Staphylococcus aureus (MSSA) screening swab. Twenty-one (26.3%) colonized patients were treated with preoperative decolonizing antibiotics. Within 30 days of surgery, 13 (2.7%) patients developed culture-positive meningitis. There was no significant difference in meningitis rates based on MRSA/MSSA colonization status. Among colonized patients, there was no significant difference in rates of MRSA/MSSA meningitis based on preoperative antibiotic decolonization. CONCLUSIONS:Postoperative rates of meningitis after EEA surgery were not significantly changed based on MRSA/MSSA colonization status of the patient or preoperative decolonization. The utility of preoperative testing of MRSA/MSSA status and antibiotics for decolonization to prevent postoperative meningitis should be further investigated.
Modern Hearing Preservation Outcomes After Vestibular Schwannoma Stereotactic Radiosurgery
Berger, Assaf; Alzate, Juan Diego; Bernstein, Kenneth; Mullen, Reed; McMenomey, Sean; Jethanemest, Daniel; Friedmann, David R; Smouha, Eric; Sulman, Erik P; Silverman, Joshua S; Roland, J Thomas; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:For patients with vestibular schwannoma (VS), stereotactic radiosurgery (SRS) has proven effective in controlling tumor growth while hearing preservation remains a key goal. OBJECTIVE:To evaluate hearing outcomes in the modern era of cochlear dose restriction. METHODS:During the years 2013 to 2018, 353 patients underwent Gamma knife surgery for VS at our institution. We followed 175 patients with pre-SRS serviceable hearing (Gardner-Robertson Score, GR 1 and 2). Volumetric and dosimetry data were collected, including biological effective dose, integral doses of total and intracanalicular tumor components, and hearing outcomes. RESULTS:The mean age was 56 years, 74 patients (42%) had a baseline GR of 2, and the mean cochlear dose was 3.5 Gy. The time to serviceable hearing loss (GR 3-4) was 38 months (95% CI 26-46), with 77% and 62% hearing preservation in the first and second years, respectively. Patients optimal for best hearing outcomes were younger than 58 years with a baseline GR of 1, free canal space â‰¥0.041 cc (diameter of 4.5 mm), and mean cochlear dose <3.1 Gy. For such patients, hearing preservation rates were 92% by 12 months and 81% by 2 years, staying stable for >5 years post-SRS, significantly higher than the rest of the population. CONCLUSION/CONCLUSIONS:Hearing preservation after SRS for patients with VS with serviceable hearing is correlated to the specific baseline GR score (1 or 2), age, cochlear dose, and biological effective dose. Increased tumor-free canal space correlates with better outcomes. The most durable hearing preservation correlates with factors commonly associated with smaller tumors away from the cochlea.
Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas
Marinelli, John P; Killeen, Daniel E; Schnurman, Zane; Nassiri, Ashley M; Hunter, Jacob B; Lees, Katherine A; Lohse, Christine M; Roland, Thomas J; Golfinos, John G; Kondziolka, Douglas; Link, Michael J; Carlson, Matthew L
OBJECTIVE:Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements. STUDY DESIGN/METHODS:Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements. SETTING/METHODS:Three tertiary referral centers. PATIENTS/METHODS:Patients with sporadic vestibular schwannoma. INTERVENTIONS/METHODS:Wait-and-scan. MAIN OUTCOME MEASURES/METHODS:Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume. RESULTS:Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6-2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92-95%; 662), 86% (83-89%; 275), and 78% (73-82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8-2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92-97%; 260), 84% (79-89%; 99), and 75% (67-83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up. CONCLUSION/CONCLUSIONS:Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.
Matched Comparison of Hearing Outcomes in Patients With Vestibular Schwannoma Treated With Stereotactic Radiosurgery or Observation
Schnurman, Zane; Gurewitz, Jason; Smouha, Eric; McMenomey, Sean O; Roland, J Thomas; Golfinos, John G; Kondziolka, Douglas
BACKGROUND:Previous studies comparing hearing outcomes in patients managed with stereotactic radiosurgery (SRS) and a watch-and-wait strategy were limited by small sample sizes that prevented controlling for potential confounders, including initial hearing status, tumor size, and age. OBJECTIVE:To compare hearing outcomes for patients with vestibular schwannomas (VS) managed with observation and SRS while controlling for confounders with propensity score matching. METHODS:Propensity score matching was used to compare 198 patients with unilateral VS with initial serviceable hearing (99 treated with SRS and 99 managed with observation alone) and 116 with initial class A hearing (58 managed with SRS and 58 with observation), matched by initial hearing status, tumor volume, age, and sex. Kaplan-Meier survival methods were used to compare risk of losing class A and serviceable hearing. RESULTS:Between patients with VS managed with SRS or observation alone, there was no significant difference in loss of class A hearing (median time 27.2 months, 95% CI 16.8-43.4, and 29.2 months, 95% CI 20.4-62.5, P = .88) or serviceable hearing (median time 37.7 months, 95% CI 25.7-58.4, and 48.8 months, 95% CI 38.4-86.3, P = .18). For SRS patients, increasing mean cochlear dose was not related to loss of class A hearing (hazard ratio 1.3, P = .17) but was associated with increasing risk of serviceable hearing loss (hazard ratio of 1.5 per increase in Gy, P = .017). CONCLUSION/CONCLUSIONS:When controlling for potential confounders, there was no significant difference in loss of class A or serviceable hearing between patients managed with SRS or with observation alone.
Long-term Natural History and Patterns of Sporadic Vestibular Schwannoma Growth: A Multi-institutional Volumetric Analysis of 952 Patients
Marinelli, John P; Schnurman, Zane; Killeen, Daniel E; Nassiri, Ashley M; Hunter, Jacob B; Lees, Katherine A; Lohse, Christine M; Roland, J Thomas; Golfinos, John G; Kondziolka, Douglas; Link, Michael J; Carlson, Matthew L
BACKGROUND:The current study aims to characterize the natural history of sporadic vestibular schwannoma volumetric tumor growth, including long-term growth patterns following initial detection of growth. METHODS:Volumetric tumor measurements from 3,505 serial MRI studies were analyzed from unselected consecutive patients undergoing wait-and-scan management at three tertiary referral centers between 1998 and 2018. Volumetric tumor growth was defined as a change in volume â‰¥20%. RESULTS:Among 952 patients undergoing observation, 622 experienced tumor growth with initial growth-free survival rates (95% CI) at 1, 3, and 5 years following diagnosis of 66% (63-69), 30% (27-34), and 20% (17-24). Among 405 patients who continued to be observed despite demonstrating initial growth, 210 experienced subsequent tumor growth with subsequent growth-free survival rates at 1, 3, and 5 years following initial growth of 77% (72-81), 37% (31-43), and 24% (18-31). Larger tumor volume at initial growth (HR 1.13, p=0.02) and increasing tumor growth rate (HR 1.31; p<0.001) were significantly associated with an increased likelihood of subsequent growth, whereas a longer duration of time between diagnosis and detection of initial growth was protective (HR 0.69; p<0.001). CONCLUSIONS:While most vestibular schwannomas exhibit an overall propensity for volumetric growth following diagnosis, prior tumor growth does not perfectly predict future growth. Tumors can subsequently grow faster, slower, or demonstrate quiescence and stability. Larger tumor size and increasing tumor growth rate portend a higher likelihood of continued growth. These findings can inform timing of intervention: whether upfront at initial diagnosis, after detection of initial growth, or only after continued growth is observed.
Pial brainstem artery arteriovenous malformation with flow-related intracanalicular aneurysm masquerading as vestibular schwannoma: illustrative case [Case Report]
Liu, David D; Kurland, David B; Ali, Aryan; Golfinos, John G; Nossek, Erez; Riina, Howard A
BACKGROUND:Lesions of the internal auditory canal presenting with partial hearing loss are almost always vestibular schwannomas (VSs). Intracanalicular anterior inferior cerebellar artery (AICA) aneurysms are extremely rare but can mimic VS based on symptoms and imaging. The authors report the case of a flow-related intracanalicular AICA aneurysm from a pial brainstem arteriovenous malformation (AVM) masquerading as VS. OBSERVATIONS/METHODS:A 57-year-old male with partial left-sided hearing loss and an intracanalicular enhancing lesion was initially diagnosed with VS and managed conservatively at an outside institution with surveillance imaging over 3 years. When he was referred for VS follow-up, new imaging raised radiological suspicion for vascular pathology. Cerebral angiography revealed a small pial AVM located at the trigeminal root entry zone with an associated flow-related intracanalicular AICA aneurysm. The AVM was obliterated with open surgery, during which intraoperative angiography confirmed no AVM filling, preservation of the AICA, and no further aneurysm filling. LESSONS/CONCLUSIONS:Intracanalicular AICA aneurysms and other lesions, including cavernous malformations, can mimic radiographic features of VS and present with hearing loss or facial weakness. Modern vascular neurosurgical techniques such as endovascular intervention and open surgery in a hybrid operating room allowed definitive management of both lesions without untoward morbidity.