Median Karnofsky Performance Status Research Articles

Efficacy and Safety of Erzhu Jiedu Decoction Granules in Treating Mid-advanced Hepatitis B Virus-Associated Primary Liver Cancer Patients with Pi (Spleen)-Deficiency and Dampness-Heat Syndrome.

To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8+ levels were decreased, while CD3+ and CD4+ levels, as well as CD4+/CD8+ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).

QLTI-18. TREATMENT AND OUTCOMES OF FRAIL PATIENTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMAS: SHOULD WE CONSIDER CHANGING OUR TREATMENT APPROACH?

Abstract BACKGROUND Patients with newly diagnosed high-grade glioma (HGG) and low Karnofsky Performance Status (KPS) often face challenges in receiving cancer-directed therapy. They are excluded from prospective trials, limiting the chance of developing novel therapeutic approaches. METHODS We retrospectively reviewed charts of patients with functional debility and newly diagnosed HGG who received radiotherapy (RT) while admitted to the inpatient service at Memorial Sloan Kettering between 2013 and 2023. Multivariable analyses were performed which associated patient demographics, KPS, histology, genetic and molecular pathology, RT duration and dose, chemotherapy, palliative/supportive care consultation, and advanced care planning documentation with overall survival (OS) and discharge location, separately. RESULTS Fifty-four patients were identified; median age was 68 years (range:21-86) and 28 (52%) were women. Median KPS was 50 (range:30-70). Per WHO 2021 criteria, 47 (87%) were glioblastoma, IDH wild-type and 7 (13%) were HGG not otherwise specified, diagnosed by biopsy in 30 (56%), subtotal resection in 23 (43%), and gross total resection in one. MGMT promoter methylation was performed in 39/54 and was hypermethylated in 15 (38%). All patients received RT and 52 (96%) with concurrent temozolomide; 47/54 (87%) completed planned RT, with the median dose of 4,005 cGy in 15 fractions. 13 (24%) received bevacizumab. The median length of stay (LOS) was 29 days (range:20-65). Only 17 (31%) had palliative care consultation prior to discharge. The median OS (mOS) from the last radiation treatment was 4.21 months (95% CI: 2.73, 6.63). In multivariable Cox and logistic regression, respectively, lower KPS remained the sole factor significantly associated with increased risk of death (p=0.004) and decreased chance of return home (p=0.040). CONCLUSION In our patient cohort, treatment was associated with prolonged LOS and poor outcomes. A clinical trial should be considered to evaluate shorter RT courses and early palliative care consultation in this patient population.

SURG-06. IMPACT OF LASER INTERSTITIAL THERMAL THERAPY VERSUS RESECTION FOR METASTASES ASSOCIATED WITH THE MOTOR CORTEX

Abstract BACKGROUND For brain metastases (BM), resection remains a mainstay for the upfront management of large, symptomatic lesions, while laser interstitial thermal therapy (LITT) has become a key treatment for radiographically progressive BM following stereotactic radiosurgery (SRS). Compared to LITT, resection-associated morbidity may delay systemic therapies. We evaluated functional outcomes for resection versus LITT to primary motor cortex (PMC)-associated metastases. METHODS Patients receiving resection or LITT for BM radiographically associated with the PMC from 2015-2023 were retrospectively reviewed. Demographic and survival data were collected, with patient Karnofsky Performance Status (KPS) or modified Rankin Scale (mRS) scores assessed out to 1-year by independent raters. RESULTS Forty-one patients underwent resection and 30 underwent LITT to a PMC-associated lesion. Median age was 67 (range 38 – 80) vs 65 (44 – 80) for resection vs LITT; median pre-operative KPS (70 vs 80, P = 0.1) or mRS (2 vs 2, P = 0.66) did not differ between groups. Lung was the most common primary (56.1% resections vs 56.7% LITTs). Resected lesions were of larger median diameter than LITT, 2.8 vs 1.9 cm, P = 0.0001. For resections, length of stay was longer, median 2 vs 1 day, P = 0.0002, and ICU use more frequent (75.6% versus 20.0%, P &amp;lt; 0.0001). At 1-month post-op, 66.7% of resection patients and 51.7% of LITT patients had stable or improved symptoms from pre-op, P = 0.21, with parity at 3-months (65.7% vs 62.9%) and therafter. Further, there was no significant decrement in KPS or mRS score out to a year for either intervention. CONCLUSIONS While there is a short-term increased risk of post-operative neurologic worsening due to LITT-associated edema, our data shows that, relative to resection, this is a transient and clinically limited phenomenon. With careful patient selection, LITT to lesions involving the PMC is feasible.

Factors Influencing the Outcome of Patients with Surgically Managed Intracranial Meningioma

Background: Intracranial Meningiomas are the most common primary brain tumor in adult which are predominantly non-malignant. Surgical intervention is the goldstandard treatment option for intracranial meningiomas but the surgical outcomes are influenced by various epidemiological risk factors. Understanding these factors is essential for a precise decision-making process, application of effective therapeutic intervention and prognostication. Aims: This study aimed to identify the possible predictive factors influencing surgical outcome in patients with intracranial meningioma. Materials and Methods: This Prospective Observational Study included 34 patients of intracranial Meningioma who had surgery in the Department of Neurosurgery, Chittagong Medical College Hospital between February 2022 to August 2023. Outcome measures were the Glasgow Outcome Scale (GOS) and Karnofsky Performance Status (KPS) score at the immediate postoperative period, “0” postoperative day, at the time of discharge, 1 month, 3 months, and 6 months post-surgery. GOS score 1-3 was considered as poor outcome. Results: The mean age of the patients was 46.8±12.6 years and 70.6% were female. Most of the patients were in either ASA class I (35.3%) or Class II (55.9%), and the median KPS score was 80% before surgery. Twenty-eight (82.4%) patients survived at least six months following surgery and the 6-months mortality rate was 17.6%. Twenty-seven (79.4%) patients had a good outcome and 7 (20.6%) patients had a poor outcome. Preoperative KPS score (p=0.024), tumor location (p=0.019), and tumor volume (p=0.003) were found to have a significant association with outcome in univariate analysis. However, none of these factors retained a significant association in multivariate analysis. Conclusions: In conclusion, specific influencing factors for postoperative poor outcomes revealed in univariate analysis in the present study were low preoperative KPS score, skull base meningioma, and large-size tumor Bang. J Neurosurgery 2024; 13(2): 121-129

The surgical management of third ventricle region tumors

ObjectivesThe goal of this study was to characterize the largest known cohort of patients presenting with different tumor pathologies in the third ventricle region to better understand outcomes of surgical management. MethodsAll patients undergoing surgical intervention on tumors in or encroaching upon the third ventricle at Loyola University Medical Center between the years 1986–2021 were reviewed. Information recorded included presenting symptoms, pre- and post-operative interventions, tumor pathology, operative technique, extent of resection (EOR), and approach of operation. The primary clinical outcome was Karnofsky Performance Status (KPS) score. ResultsNinety-seven patients underwent 123 operations. Forty-six (47.4 %) patients were female, and the median age at operation was 39 years. Eighty-seven (70.7 %) operations were open, and 36 (29.3 %) were endoscopic. Gross total resection (GTR) was achieved in 34.4 % of operations, near-total resection (NTR) in 31.5 %, subtotal resection in 25.0 %, and biopsy alone in 9.3 %. Median KPS increased pre- to postoperatively, regardless of surgical technique. Adjusting for preoperative KPS, age, and operation number, regression analysis demonstrated a trend that lesser EOR is associated with lower KPS at most recent follow-up (p=0.031 for NTR vs GTR, p=0.022 for biopsy vs GTR). There was no statistically significant association between the most recent KPS and either open or endoscopic surgical technique, with or without adjusting for the previously stated factors (p=0.26). There was no association between postoperative complication rates or age with either surgical technique. ConclusionsHere, we characterize a large cohort of patients presenting for neurosurgical evaluation of tumors in the region of the third ventricle. Our results demonstrate a trend that a more aggressive resection may yield better KPS outcomes. Additionally, both open and endoscopic techniques lead to a similar improvement in clinical outcome and rates of complication. While ultimate surgical approach and technique is determined by individual tumor characteristics, patient health status, and surgeon expertise, ability to resect the tumor in its entirety should be taken into consideration.

Epilepsy in Patients With Primary CNS Lymphoma: Prevalence, Risk Factors, and Prognostic Significance.

Epilepsy is a common comorbidity of brain tumors; however, little is known about the prevalence, onset time, semiology, and risk factors of seizures in primary CNS lymphoma (PCNSL). Our objectives were to determine the prevalence of epilepsy in PCNSL, to identify factors associated with epilepsy, and to investigate the prognostic significance of seizures in PCNSL. We performed an observational, retrospective single-center study at a tertiary neuro-oncology center (2011-2023) including immunocompetent patients with PCNSL and no history of seizures. We collected clinical, imaging, and treatment data; seizure status over the course of PCNSL; and oncological and seizure outcome. The primary outcome was to determine the prevalence of epilepsy. Furthermore, we aimed to identify clinical, radiologic, and treatment-related factors associated with epilepsy. Univariate analyses were conducted using the χ2 test for categorical variables and unpaired t test for continuous variables. Predictors identified in the unadjusted analysis were included in backward stepwise logistic regression models. We included 330 patients, 157 (47.6%) were male, median age at diagnosis was 68 years, and the median Karnofsky Performance Status score was 60. Eighty-three (25.2%) patients had at least 1 seizure from initial diagnosis to the last follow-up, 40 (12.1%) as the onset symptom, 16 (4.8%) during first line of treatment, 27 (8.2%) at tumor progression and 6 (1.8%) while in remission. Focal aware seizures were the most frequent seizure type, occurring in 43 (51.8%) patients. Seizure freedom under antiseizure medication was observed in 97.6% patients. Cortical contact (odds ratio [OR] 8.6, 95% CI 4.2-15.5, p < 0.001) and a higher proliferation index (OR 5.7, 95% CI 1.3-26.2, p = 0.02) were identified as independent risk factors of epilepsy. Patients with PCNSL and epilepsy had a significantly shorter progression-free survival (median progression-free survival 9.6 vs 14.1 months, adjusted hazard ratio 1.4, 95% CI 1.0-1.9, p = 0.03), but not a significantly shorter overall survival (17 vs 44.1 months, log-rank test, p = 0.09). Epilepsy affects a quarter of patients with PCNSL, with half experiencing it at the time of initial presentation and potentially serving as a marker of disease progression. Further research is necessary to assess the broader applicability of these findings because they are subject to the constraints of a retrospective design and tertiary center setting.

Lisavanbulin (BAL101553), a novel microtubule inhibitor, plus radiation in patients with newly diagnosed, MGMT promoter unmethylated glioblastoma.

Lisavanbulin (BAL101553) is a small, lipophilic, oral microtubule destabilizer with promising antitumoral activity observed in preclinical glioblastoma (GBM) models. This multicenter phase 1 study sought to determine the MTD of oral Lisavanbulin in combination with standard RT (60 Gy/30 fractions) but without temozolomide in patients with newly diagnosed MGMT promoter unmethylated GBM (uGBM). Dose escalation followed a modified 3 + 3 design. Secondary objectives included estimation of OS and PFS and pharmacokinetic analysis. Twenty-six patients with uGBM (median age, 63 years, 42.3% male, 61.5% with gross total resection, median Karnofsky performance status 80) were enrolled; 2 tumors had an IDH1 mutation. Predefined dose levels of Lisavanbulin, administered daily concomitantly with RT, were: 4mg (5 pts), 6mg (5 pts), 8mg (7 pts), 12mg (5 pts), and 15mg (4 pts). The initial starting dose was 8mg. Due to grade 4 aseptic meningoencephalitis in the first patient, the dose was decreased to 4mg. Dose escalation resumed and continued to 15mg with dose-limiting toxicities of grade 2 confusion and memory impairment observed at 12mg. Avanbulin exposures increased in a relatively dose-proportional manner with increasing oral dose of Lisavanbulin from 4 to 15mg. Lisavanbulin in combination with RT was considered safe up to the highest predefined oral dose level of 15mg daily.

Abstract CT019: Biological mechanisms underlying objective responses in recurrent GBM patients treated with sequential bortezomib and temozolomide: An interim analysis of NCT03643549 Phase IB/II trial

Abstract Background: Glioblastoma (GBM) has dismal prognosis, where median survival is approximately 12 months for patients harboring unmethylated O6−methylguanine DNA methyltransferase (MGMT) promoter (uMGMT) due to temozolomide (TMZ) chemotherapy resistance. In preclinical studies, we showed that sequential administration of bortezomib (BTZ) prior to TMZ depleted MGMT protein, abrogated autophagic flux and sensitized uMGMT GBM cells to TMZ. Thus, a phase I/II was launched to investigate clinical benefit. An interim analysis based on Simon´s MinMax design (where at least 2 patients should show clinical benefit amongst the first 15 evaluable patients) would allow the study to continue to full recruitment. Clinical benefit, was defined by progression free survival and or objective radiological complete (CR), partial (PR) responses or stable disease (SD) based on RANO criteria at 6 months and 1-year follow-up. This study aimed to identify the biological mechanisms underlying the objective responses in the initial 15 recurrent GBM patients treated in this trial. Methods: Adult recurrent GBM patients with uMGMT promoter, progressing ≥12 weeks after radiotherapy, Karnofsky performance status (KPS) ≥70 and with measurable lesions were enrolled. They received BTZ 1.3mg/m2 IV on days 1,4,7, during each 4-week cycle starting on day 3 with per oral TMZ at 200mg/m2 5 days/week. The sample size was powered for n=63 patients. Quantitative LC-MS/MS was used to identify novel biomarkers that correlate with objective treatment responses by determining proteomic changes in plasma collected on days 1,4,7,11,15 and 22 during first cycle of treatment. Targeted sequencing of 360 cancer genes and whole exome sequencing (WES) of tumor DNA were conducted to identify associated molecular genetic changes. Results: The 15 patients had median age 52 yrs (range 25-62 yrs), 10 male and 5 female treated at Haukeland University Hospital in Norway. Median KPS was 90 (70-100) and median NANO score was 1 (0-7). 27% (n=4/15) of patients obtained objective radiological responses, where 2/4 (50%) obtained PR and 2/4 (50%) had SD. LC-MS/MS revealed significantly increased (p&amp;lt;0.05) levels of proteins important for regulation of cell death and apoptosis (ADAMTS13, HPR, HBD, CLU and APOE) in objective responders compared to the rest of the patients. Sequential BTZ+ TMZ therapy was safe, tolerated and platelet nadirs consistently normalized by day 22 of each cycle. Proteins associated with platelet activation, aggregation and degranulation (ACTN1, ITGB3, PLEK, PPBP, THBS1, TF, TAGLN2, TLN1, PFN1, VCL and FERMT3) were significantly upregulated (1.6-4.8 fold, p&amp;lt;0.05) on day 15 and 22 compared to baseline in patient plasma. Preliminary analysis of sequencing data identified EGFR gain-of-function mutation in 3 of the 4 responder patients; potentially distinguishing this as a molecular biomarker for the objective treatment responders. Conclusion: Sequential BTZ+TMZ therapy is safe and effective as indicated by objective radiological response. Activation of tumor cell death and apoptosis pathways was observed specifically in objective responders. The interim criteria were fulfilled as 4 amongst the first 15 patients showed clinical benefit. The study is currently recruiting. Citation Format: Mohummad Aminur Rahman, Dorota Goplen, Andreas Waha, Leif Oltedal, Judit Haasz, Surendra Kumar, Even Birkeland, Hrvoje Miletic, Frode Selheim, Martha Chekenya. Biological mechanisms underlying objective responses in recurrent GBM patients treated with sequential bortezomib and temozolomide: An interim analysis of NCT03643549 Phase IB/II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT019.

Treatment Outcomes after Dose-Escalated Moderately Hypofractionated Radiotherapy for Frail Patients with High-Grade Glioma.

For high-grade glioma (HGG) patients with old age or poor performance status, hypofractionated radiotherapy (hypoRT) in 10-15 fractions is recommended. Also, limited data exist on the impact of salvage treatment after progression in frail patients. We retrospectively analyzed the outcomes of dose-escalated hypoRT in 40 frail HGG patients who were treated with hypoRT between 2013 and 2021. With a median biologically effective dose of 71.7 Gy, a total dose of 56 Gy in 20 fractions was the most frequently used regimen (53.7%). The median age and Karnofsky Performance Status of patients were 74 years and 70, respectively. Most patients (n = 31, 77.5%) were diagnosed with glioblastoma, IDH-wildtype, CNS WHO grade 4. Only 10 (25.0%) patients underwent surgical resection, and 28 (70.0%) patients received concurrent temozolomide during hypoRT. With a median follow-up of 9.7 months, the median overall survival (OS) was 12.2 months. Of the 30 (75.0%) patients with disease progression, only 12 patients received salvage treatment. The OS after progression differed significantly depending on salvage treatment (median OS, 9.6 vs. 4.6 months, p = 0.032). Dose-escalated hypoRT in 20 fractions produced survival outcomes outperforming historical data for frail patients.

CNS Radiotherapy As Bridging Prior to CAR T-Cell Therapy for Non-Hodgkin B-Cell Lymphoma

Introduction: Up to 80% of patients who receive CAR T-cell therapy (CAR T) for central nervous system lymphoma (CNSL) require bridging therapy, yet optimal regimens remain undefined. Radiotherapy is an established strategy for extracranial lymphoma that provides beneficial cytoreduction. However, CNS bridging radiotherapy (CNS-BRT) prior to CAR T is controversial due to concerns of potential enhanced neurotoxicity. We explored the safety and response profiles in patients treated with CNS-BRT prior to CAR T. Methods: We identified patients with non-hodgkin B-cell lymphoma who received CNS-BRT at our institution prior to commercial CAR T infusion. CNS-BRT was defined as treatment delivered between apheresis and CAR T infusion or within 30 days prior to apheresis, targeting the CNS parenchyma, leptomeninges, or epidural spine. Patients with epidural spine disease were included since the adjacent spinal cord is part of the treatment field. Safety was evaluated by rate of cytokine release syndrome (CRS) and immune effector associated neurotoxicity syndrome (ICANS) after CAR T. Best CNS response post CAR T was evaluated using the International Primary CNS Lymphoma Collaborative Group (IPCG) or Response Assessment in Neuro-Oncology (RANO) for parenchymal or leptomeningeal lesions, respectively. Cytoreduction from CNS-BRT was estimated by calculating the change in lesion size (sum of product diameter) from before and after CNS-BRT, but before CAR T infusion. Risk of any CNS relapse after CAR T was estimated using the Gray's method with death as a competing risk. Patients with epidural spine disease were not evaluate for CNS response or relapse. Results: 12 patients received CNS-BRT with median follow up of 8.5 months (range: 3.2 - 30.2), median age of 60 (30-76), median Karnofsky Performance Status (KPS) of 80 (range: 50 - 90). Histologies included diffuse large B cell (DLBCL) (n = 9), mantle cell (n = 2), and Burkitt lymphoma (n = 1), with disease localizing to the brain parenchyma (n = 6), leptomeninges (n = 4), and epidural spine (n = 2). 9 patients had secondary CNSL and 1 patient had primary CNSL. Prior to CNS-BRT, 11/12 patients had progressive disease. 5/12 patients had disease outside of the CNS. 5/12 patients received prior autologous hematopoietic stem cell transplantation. 9/12 patients received prior high dose methotrexate with median 46-day interval to CNS-BRT (range: 0 - 393). RT targets included whole brain (n = 3), involved site (partial) brain (n = 4), involved site spine (n = 4), and orbits (n = 1) with median dose 24 Gy (range: 15 - 33). CAR T products included Tisagenlecleucel (n = 4), Lisocabtagene maraleucel (n = 7), and Axicabtagene ciloleucel (n = 1). Among 10 patients with available toxicity grading, 6/10 experienced CRS (n = 1 grade (G) 1, n = 4 G2, and n = 1 G3), and 3/10 experienced ICANS (n = 1 G1, n = 1 G3, n = 1 G4). 6/10 patients required tocilizumab and/or steroids. CNS-BRT achieved a 74.4% (95% CI, 62.9 - 85.9) mean reduction in lesion size prior to CAR T infusion. Best CNS response after CAR T infusion included 3 complete responses (CR), 6 partial responses (PR), and 1 progressive disease (PD). The patients who achieved PR remained in PR at last follow up. The 12-month estimated risk of CNS progression after CNS-BRT and CAR T infusion was 20.0% (95% CI, 3- 49). CNS progression was not observed in patients who received involved site brain RT. Conclusion: Preliminary data suggest CNS-BRT achieves rapid cytoreduction prior to CAR T therapy and is associated with a favorable CNS response profile. While overall numbers are limited to date, the rate of severe CRS and ICANS is similar to that of historical series of CNSL patients treated with CAR T. However, a larger cohort will be required to determine the safety of CNS-BRT. These data support further study of RT, and exploration of involved site brain RT, as an effective bridging modality for CAR T-cell therapy in CNSL.

Germinal Center B-Cell-like (GCB) Phenotype Predicts Improved Outcomes in Central Nervous System Diffuse Large B-Cell Lymphoma Patients Receiving Stereotactic Radiosurgery (SRS)

Background: Diffuse large B cell lymphoma (DLBCL) constitutes most cases of both primary and secondary central nervous system lymphoma (CNSL). They represent a highly aggressive subset of non-Hodgkin lymphoma and prognosis varies depending on the cell of origin. Immunohistochemistry using antibodies for CD10, BCL-6, and MUM-1, also known as the Hans algorithm, is the most common method for determining the cell of origin and predicting outcomes in DLBCL. The study by Hans et al. found that the germinal center B-cell-like (GCB) group had a much better prognosis compared to the non-GCB group, with 5-year overall survival (OS) of 76% and 34% respectively. Despite chemotherapy, recurrence is common in these patients, and up to 40-50% do not achieve durable remission. It is important to identify who may benefit from more aggressive or experimental therapy at diagnosis. Stereotactic radiosurgery (SRS) is the administration of a localized, high dose of ionizing radiation and limited studies exist exploring SRS as a treatment modality in relapsed/refractory (r/r) CNSL or prognostic implications of the Hans algorithm in these patients. Aim/Objective: To perform a retrospective analysis of outcomes of patients with CNSL, phenotypes determined by the Hans algorithm, treated with SRS at a single comprehensive cancer center. Methods: We studied the demographic, clinical, pathological, and treatment characteristics of r/r CNSL patients (N=27), age ≥ 18 years, who received SRS at Roswell Park Comprehensive Cancer Center between 01/2000 and 01/2023. The Hans algorithm was used to group the patients into non-GCB (N=17) and GCB (N=10) cohorts. Overall survival (OS) and progression-free survival (PFS) were calculated and reported using Kaplan-Meier analyses and log-rank tests. Cox regression models were used to describe cross-cohort comparisons of survival. Results: The median Karnofsky performance status at diagnosis was 70 for both groups. The overall response rate (ORR) to SRS in GCB-type was 80% (7 complete response and 1 partial response; CR, PR). The ORR in non-GCB type was 58% (6 CR and 4 PR). Post-SRS, stem cell transplant (SCT) was avoided in 100% of the patients in the GCB group, while 17% of the patients in the non-GCB group received SCT. The 6-month overall survival (OS) rate was 100% and 46% for the GCB-type and non-GCB type respectively (p=0.096, Figure 1A). The 6-month progression-free survival (PFS) rate was 80% for the GCB-type and 33% for the non-GCB type (p=0.024, Figure 1B). In the GCB group, the median OS was 18.0 months while the median PFS was 13.8 months. In the non-GCB group, the median OS was 4.9 months while the median PFS was 3.6 months. The median time from chemotherapy completion to SRS administration was 8.0 months in the GCB-type and 2.0 months in the non-GCB type. Conclusion: Our data support that the GCB-type predicts a more favorable outcome in CNSL, with improved OS and PFS rates compared to the non-GCB type. In addition, the non-GCB type patients required earlier SRS administration and had a lower ORR to SRS. Classifying CNSL into GCB and non-GCB phenotypes using the Hans algorithm might help characterize patients into groups with different prognoses.

Radiotherapy As an Effective Bridge for Relapsed/Refractory Secondary CNS Lymphoma

Introduction: Secondary CNS lymphoma (SCNSL) is observed in 2-5% of patients with diffuse large B cell lymphoma (DLBCL). Progression of SCNSL after first line CNS-directed systemic therapy is particularly challenging to treat, without a clear standard of care. Brain radiotherapy (RT) is used for progressive SCNSL in either the chemo-refractory or palliative setting. Historically, the RT field included the whole brain due to concerns about diffuse intracranial involvement. However, treatment fields limited to just involved site(s) (partial brain RT) may provide a favorable balance of disease control and reduced treatment toxicity, particularly in an era of improved CNS-directed systemic therapies. We hypothesized that RT would confer a high rate of intracranial response among patients with chemo-refractory SCNSL. Methods: We identified DLBCL patients with SCNSL who received brain RT at our institution for radiographic or clinical progression after at least 1 line of SCNSL-directed therapy. SCNSL-directed therapy was defined as systemic therapy for active SCNSL (as opposed to prophylaxis). Overall survival (OS) was determined from RT start to death from any cause using the Kaplan-Meier method. OS comparing subsequent therapy was landmarked 2 months post RT to minimize immortal time bias. RT response was evaluated with contrast MRI or CT using International Primary CNS Lymphoma Collaborative Group (IPCG) or Response Assessment in Neuro-oncology (RANO) radiographic criteria for parenchymal or leptomeningeal disease (LMD), respectively. LMD was assessed by cytology and/or imaging. Results: Between 1999-2023, 55 patients received brain RT for progressive SCNSL with median follow up of 3.2 months. At the time of RT, median age was 64 (interquartile range (IQR) 49 - 71), median Karnofsky Performance Status was 70 (IQR, 60 - 80), and 85% had neurologic symptoms. Patients had received a median of 2 lines of SCNSL-directed therapy prior to RT (IQR, 1 - 3), 91% received a methotrexate-based regimen with median interval of 21 days (IQR, 10 - 67) between methotrexate and RT. Median RT dose was 30 Gy in 10 fractions delivered to whole brain (n = 44), partial brain (n = 9), or craniospinal axis (n = 2). 38 patients were evaluable for response; the remainder were lost to follow up/hospice (n = 8), lacked suitable imaging (n = 4), died with progressive neurologic symptoms (n = 4) or other cause (n = 1). The overall response rate was 79%, including a 24% complete response rate. Median time to best response was 60 days (IQR, 30 - 145). 32/55 patients (58%) were successfully bridged to subsequent systemic therapy (n = 22), hematopoietic stem cell transplantation (autologous n = 4, allogeneic n = 1), or CAR T (n = 5), after a median of 34 days from RT (IQR, 20 - 57). Median OS for the entire cohort was 3.5 months, and was improved for those who were bridged to subsequent therapy (no subsequent therapy 0.7 months, subsequent systemic therapy 4.0 months, subsequent cell therapy 8.9 months, p = 0.006). Among patients who received partial brain RT, 7/7 evaluable patients had at least a partial response and 7/9 patients were successfully bridged to subsequent therapy. Conclusion: Patients referred to RT for progressive SCNSL represent a high-risk cohort characterized by rapidly progressive, symptomatic, treatment-resistant disease. RT confers a high response rate in this chemo-resistant population, and can facilitate bridging to subsequent therapy. Preliminary data suggest that partial brain radiotherapy may be an effective bridging strategy among select patients, however a larger sample size will be required to determine this.

British Columbia Experience in Allogeneic Stem Cell Transplantation for Myelofibrosis with or without Pre-Transplant Ruxolitinib

Introduction Allogeneic stem cell transplantation (AlloHSCT) remains the only potentially curative treatment for myelofibrosis (MF). It confronts many challenges stemming from the older age of the typical patients and their age-related comorbidities, as well as disease-specific factors such as splenomegaly and hostile marrow microenvironment, which raise concerns for delayed engraftment and graft failure. Methods We performed a retrospective review of the 58 adult patients who received AlloHSCT for MF in British Columbia, Canada, in the 20-year period between January 2001 and December 2020. Data pertaining to patient demographics, disease characteristics, treatment/transplant details and clinical outcomes were gathered from the available paper and electronic records. Relapse-free survival (RFS) was defined as the time between the day of the transplant and the day of disease relapse or death from any cause. Overall survival (OS) was defined as the time between the day of the transplant and death from any cause. Patients who did not have an event during follow up were censored at the time of the last known follow up. Survival analysis was performed by Kaplan-Meier survival estimator and log-rank test, using Stata version 16.1 (Texas, USA). Results The median age of the cohort was 56 years (range 26-68), with 36% being 60 years old or older. The male to female ratio was 1.6:1. The median Karnofsky Performance Status index was 80 (range 70-100) and the median age-adjusted HCT-specific Comorbidity Index was 2 (range 0-5). The pre-transplant DIPPS plus risk category was: high in 13 patients (22%); intermediate-2 in 29 (50%); intermediate-1 in 15 (26%); and low in 1 (2%). 19/58 (33%) had a peripheral blast percentage greater than 2%. 51/58 (88%) had grade 3 fibrosis seen on the pre-AlloHSCT bone marrow biopsy. 27/57 (47%) patients were transfusion-dependent for pRBC and/or platelets. 28/54 (52%) evaluable patients had a normal karyotype and 6/54 (11%) a complex karyotype. Sixteen patients (28%) had a myeloid gene panel performed by PCR; the most commonly seen variants were ASXL1 (10 patients) and TET2 (5 patients). The median number of variants seen in a single patient was 3 (range 0-5). 42/58 (72%) patients received myeloablative conditioning before AlloHSCT. The donor type was: a volunteer unrelated donor in 54%; a matched sibling in 42%; and an alternative source (double cord or haploidentical donor) in 4%. Peripheral blood stem cells were used in 93% of the AlloHSCT. 24/58 (41%) patients received ruxolitinib pre-AlloHSCT (starting in June 2012) for a median duration of 10 months (range 1-44); 17/24 (71%) of the recipients had a clinical response to ruxolitinib but 3 had lost the response before their AlloHSCT. One patient had stopped ruxolitinib due to cytopenia. During a median follow up period of 41.7 months (range 0.5-260.7), 24/58 (41%) experienced acute graft-versus-host disease (GVHD) and 33/49 (67%) evaluable patients developed chronic GVHD. Graft failure was seen in 2 patients - one primary and the other secondary. MF relapse was seen in 13/58 (22%) after a median time of 1.1 years post-AlloHSCT (IQR 0.7-2.4). The transplant-related mortality (TRM) was 25% at 1 year and 28% at 3 years post-AlloHSCT. The most common causes of death were infection (7 patients), disease relapse (6 patients), and multiorgan failure (5 patients). Transfusion independence was achieved in 45/58 (78%) patients by day +100 and in 40/44 (90%) by 1-year post-AlloHSCT. 17/48 (35%) evaluable patients had persistent grade 3 fibrosis on their day+100 bone marrow biopsy. The estimated 1-year, 5-year and 10-year RFS rates were 66% (95% CI 52-76), 55% (95% CI 41-67) and 47% (95% CI 42-61) respectively. The estimated 1-year, 5-year and 10-year OS rates were 72% (95% CI 59-82), 63% (95% CI 49-74) and 54% (95% CI 37-68) respectively. There were no differences in RFS (p=0.40) and OS (p=0.23) between those who received ruxolitinib pre-transplant vs. those who did not. Conclusion In our cohort, approximately half the AlloHSCT recipients achieved long-term survival, many in remission (10-year OS 54%; 10-year RFS 47%). TRM was seen in 25% within the first year after AlloHSCT, with patients most commonly succumbing to infections. The graft failure rate was low at 3%. An increasing number of patients received pre-AlloHSCT ruxolitinib in the recent years but we were unable to demonstrate improved transplant outcomes with its use in this single centre cohort.

Peripheral Blood Haploidentical Allogeneic Stem Cell Transplantation in Older Adults with Acute Myeloid Leukemia and Myelodysplastic Syndromes Demonstrates Long Term Survival, Results from Australia and New Zealand Transplant and Cellular Therapies

There is a limited body of evidence for haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in older patients. Previous studies have used a high proportion of bone marrow–derived grafts and a variety of conditioning regimens. In Australia and New Zealand, haplo-HCST is predominantly performed using peripheral blood (PB) with universal use of post-transplantation cyclophosphamide (PTCy). To characterize the outcomes of older recipients undergoing haplo-HSCT for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Data were collected through the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) for patients aged 65 or older receiving a PB haplo-HSCT for AML/MDS between January 2010 and July 2020. A total of 44 patients were included in the analysis. The median follow-up time was 377 days. The median age was 68 (range 65-74) with a median Karnofsky performance status of 90. Thirty patients (68.2%) had AML, whereas 14 (31.8%) had MDS. The median donor age was 40. The most common conditioning regimen was nonmyeloablative fludarabine, cyclophosphamide, and total body irradiation (75%); the remainder of the patients received either melphalan- or busulfan-based regimens, and the majority were reduced intensity, with only 2 patients undergoing myeloablative conditioning. All patients received post-transplantation cyclophosphamide and mycophenolate mofetil, with the majority also receiving tacrolimus (90.5%) and the remainder receiving cyclosporine (9.5%). No patients received anti-thymocyte globulin. Neutrophil engraftment was achieved in 97.6% of patients at a median of 18 days, whereas platelet engraftment was achieved in 92.7% of patients at a median of 28 days. The cumulative incidences of cytomegalovirus (CMV) reactivation and CMV disease were 52.5% and 5.1% at 1 year. The incidence of grade 2-4 acute Graft Versus Host Disease (GVHD) was 18.2%. The incidence of chronic GVHD at 2 years was 40.7%, with extensive chronic GVHD occurring in 17.7% of patients. The incidences of relapse and non-relapse mortality (NRM) at 2 years were 8.8% and 20.7% respectively. The leading causes of death were infection (64.7%) followed by relapse (14.2%). The 2-year overall survival was 74%. Relapse free survival and GVHD free, relapse free survival at 2 years was 70% and 48%. Haplo-HSCT using a peripheral blood graft and PTCy GVHD prophylaxis demonstrates long-term disease control with acceptable rates of NRM for older patients with AML/MDS.

SURG-32. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR BIOPSY-PROVEN RADIATION NECROSIS IN RADIOGRAPHICALLY RECURRENT BRAIN METASTASES

Abstract BACKGROUND Evidence is growing for the efficacy of laser interstitial thermal therapy (LITT) for radiation necrosis (RN) following stereotactic radiosurgery (SRS) for patients with brain metastases. Questions remain regarding local control, symptom control, and concurrent use of therapies. METHODS Demographics, intraprocedural data, safety, Karnofsky performance status (KPS) and survival data were prospectively collected from the LAANTERN multi-center registry (NCT02392078) then analyzed on patients consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 U.S. centers. Data was monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan Meier estimated survival. RESULTS Ninety patients met inclusion criteria. Median hospitalization time was 32.5hrs. Median time to corticosteroid cessation after LITT was 13 days (range 0 - 1229) and cumulative incidence of lesional progression was 19% at 1-year. Median post-procedure overall-survival was 2.6 years [1.7, NR] and 77% at one year as estimated by Kaplan Meier. Median KPS remained 80 through 2-year follow-up. Seizure prevalence improved from 34.4% pre-procedure to 12% 1-month post-LITT and 7.9% at 3-months. There was no significant difference in risk of radiographic progression in total and near-total ablations (91% or greater ablative coverage) versus sub-total ablations (&amp;lt; 90%). Lesion size was not a significant predictor of future radiographic progression. CONCLUSIONS LITT is an effective, minimally invasive, safe treatment for RN, in terms of both local control and symptom management. LITT is effective in the management of lesion-related seizures in addition to averting expected neurological death. LITT facilitates ongoing systemic therapy (particularly immunotherapy) by enabling the rapid cessation of corticosteroids. Effective management options for RN could facilitate the more aggressive use of combined systemic and radiotherapeutic treatment options for brain metastases patients in order to avoid failure due to tumor recurrence and extend survival.

Post-Hoc Analysis of the Final, Three-Year Follow-up Results of a Phase I/II Study on Tirabrutinib (ONO-4059) in Patients with Relapsed or Refractory Primary Central Nervous System Lymphoma

[Background] Tirabrutinib (TIR; ONO-4059) is a second-generation inhibitor of Bruton's tyrosine kinase with high kinase selectivity. Based on the results of study ONO-4059-02 in patients with relapsed or refractory (r/r) primary central nervous system lymphoma (PCNSL) (Phase I/II study, jRCT: 2080223590), TIR was approved in Japan, Korea, and Taiwan. We have reported the results of 3-year follow-up (median follow-up: 37.1 months) of study ONO-4059-02, in which the overall response rate (ORR), the primary endpoint, was 63.6% and median duration of response was 9.2 months. The 3-year PFS and OS rates were 13.9% and 56.7%, respectively (Asai et al. ASCO 2023, Abstract 7548). Several clinical questions still remained to be addressed, including the proportion of patients who received subsequent treatment after discontinuation of TIR, and their treatment types; the characteristics of patients with higher efficacy of TIR; and the impact of long-term TIR treatment on Karnofsky Performance Status (KPS) and the Quality of Life (QoL). Here, we report the results of post-hoc analyses of the 37-month follow-up data of study ONO-4059-02. [Methods] In study ONO-4059-02, 44 patients with r/r PCNSL, age ≥20, and KPS≥70 were treated with TIR once daily at doses of 320 mg (n=20), 480 mg (n=7), or 480 mg (n=17) under a fasted condition. TIR was administered in 28-day cycles, and treatment was continued until disease progression or clinically unacceptable toxicity was observed. We assessed the number of patients who received subsequent treatment after discontinuation of TIR and their treatment types. ORR was assessed in patient subgroups according to their characteristics. In addition, patient characteristics associated with 12-month PFS rates were identified using univariate/multivariate logistic regression analysis. The time course of KPS and QoL during the TIR treatment was also assessed. QoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-BN20, and EuroQol 5 dimensions. [Results] Of the 44 patients, 6 patients were treated for 3 years. At the time of last visit, 2 patients (4.5%) continued the TIR treatment, 10 (22.7%) discontinued the TIR treatment but had not received subsequent treatment, and 32 (72.7%) received subsequent treatment after discontinuation of TIR. The subsequent treatments included systemic therapy, radiotherapy, hematopoietic stem cell transplantation, and surgery. Major subsequent treatments were MTX-based therapy (n=18) and radiotherapy (n=10) with the 3-year OS rate of 61.1% and 40.0%, respectively. The subgroup analyses of ORR by patient characteristics showed that response to TIR was observed in all patient subgroups; ORR was low in those refractory to the treatment just before TIR (33.3%), those receiving ≥ 4 previous treatments (33.3%), those receiving hematopoietic stem cell transplantation (28.6%), those with high tumor burden (42.9%), and those having mutations in CD79B and MYD88 (40.0%). The univariate/multivariate analyses for the 12-month PFS rate identified that baseline KPS 90-100 was significantly associated with long-term response (odds ratio 5.99, P=0.0289). The median baseline KPS was 80.0 (range: 70~100) and was maintained during the TIR treatment (max: 49 cycles). QoL scores were generally maintained. [Conclusion] The majority of patients were able to receive subsequent treatment, including MTX, after TIR. TIR responses were observed in all patient subpopulations, and the baseline KPS was suggested to be associated with long-term response. KPS and QoL were generally maintained during the long-term observation period.

Rapid Passive Gamma Mapping as an Adjunct to Electrical Stimulation Mapping for Functional Localization in Resection of Primary Brain Neoplasms

We examined the utility of passive high gamma mapping (HGM) as an adjunct to conventional awake brain mapping during glioma resection. We compared functional and survival outcomes before and after implementing intraoperative HGM. This was a retrospective cohort study of 75 patients who underwent a first-time, awake craniotomy for glioma resection. Patients were stratified by whether their operation occurred before or after the implementation of a U.S. Food and Drug Administration-approved high-gamma mapping tool in July2017. The preimplementation and postimplementation cohorts included 28 and 47 patients, respectively. Median intraoperative time (261 vs. 261 minutes, P= 0.250) and extent of resection (97.14% vs. 98.19%, P= 0.481) were comparable between cohorts. Median Karnofsky performance status at initial follow-up was similar between cohorts (P= 0.650). Multivariable Cox regression models demonstrated an adjusted hazard ratio for overall survival of 0.10 (95% confidence interval: 0.02-0.43, P= 0.002) for the postimplementation cohort relative to the preimplementation cohort. Progression-free survival adjusted for insular involvement showed an adjusted hazard ratio of 1.00 (95% confidence interval: 0.49-2.06, P= 0.999) following HGM implementation. Falling short of statistical significance, prevalence of intraoperative seizures and/or afterdischarges decreased after HGM implementation as well (12.7% vs. 25%, P=0.150). Our results tentatively indicate that passive HGM is a safe and potentially useful adjunct to electrical stimulation mapping for awake cortical mapping, conferring at least comparable functional and survival outcomes with a nonsignificant lower rate of intraoperative epileptiform events. Considering the limitations of our study design and patient cohort, further investigation is needed to better identify optimal use cases for HGM.

Clinical Outcomes of Patients with Brain Metastases from Colorectal Cancer Treated with Stereotactic Radiosurgery

Prior studies have demonstrated that brain metastases from gastrointestinal (GI) primary cancers have a poorer response to stereotactic radiosurgery (SRS) when compared to patients with other primary sites, with reported local control of 62-74%. We report our institutional outcomes for patients with colorectal primary cancer who were treated with SRS for brain metastases. Patients with colorectal primary cancer who underwent SRS for brain metastases between 1989 and 2021 were retrospectively reviewed from a single institutional IRB-approved database. The primary endpoint was local failure (LF) and secondary endpoint was overall survival (OS). LF was estimated using the Cumulative Incidence Function with death as a competing risk. Survival analysis was performed using the Kaplan-Meier Method. Predictors of cumulative incidence of LF were assessed using competing risk regression. The study population comprised of 109 patients with primary colorectal adenocarcinoma with 207 brain metastases. The median follow-up was 5.2 months (range: 0.4-124 months) and median OS was 5.8 months (range: 0.5-71.2 months). Fifty-two patients (48%) were male and median Karnofsky Performance Status at the time of treatment was 80 (range: 40-100). The median tumor diameter was 1.55 cm (range: 0.17-5.48 cm). The median prescription dose and number of fractions were 24 Gy (range: 11-36 Gy) and 1 fraction (range: 1-3 fractions), respectively. The cumulative incidence of LF at 3, 6, and 12 months was 9.7% (95% CI: 6.1-14%), 22% (95% CI: 16-28%), and 25% (95% CI: 20-31%), respectively. Overall survival at 3, 6, and 12 months was 81% (95% CI: 76-87%), 49% (95% CI: 42-56%) and 24% (95% CI: 18-31%), respectively. On univariate analysis, age was a significant predictor (HR = 0.96, 95% CI: 0.94-0.98), p < 0.001) of LF. Tumor size (HR = 0.80, p = 0.13) and prescription dose (HR = 1.02, p = 0.54) did not predict for LF. To our knowledge, this is the largest series of patients with brain metastases from colorectal primary cancer treated with SRS. Compared to historical data, LF and OS in our cohort of patients was favorable. Our data confirms relatively higher rates of LF when compared to brain metastases from other primary disease sites. Further studies are warranted to identify factors that predict for LF following SRS and to develop models that predict which patients with colorectal brain metastases may be at higher risk of failure.

Immune Checkpoint Inhibition and Single Fraction Stereotactic Radiosurgery in Non-Small Cell Lung Cancer Brain Metastases: An International Multicenter Study of 395 Patients

Brain metastases most commonly arise from non-small cell lung cancer (NSCLC). In recent years, immune checkpoint inhibitors (ICI) have demonstrated improvements in overall survival (OS) in NSCLC. However, concerns remain about the risk of radiation necrosis (RN) when ICI are administered with stereotactic radiosurgery (SRS). Logistic regression was used to evaluate prognostic factors associated with the development of any grade RN and symptomatic RN. Cumulative incidence of RN was evaluated using competing risks analysis and the Fine and Gray model, where the null hypothesis was rejected for p < 0.05. There were 395 patients with 2,513 brain metastases treated across 11 international institutions included in the analysis. The median follow-up was 14.2 months. Median patient age was 67 years (Interquartile Range [IQR]: 61-73), 53.4% were male, the median Karnofsky Performance Status was 80 (IQR: 80-90), and 88.6% has active extracranial disease at the time of SRS. The median margin dose was 19 Gy (IQR: 18-20), 97.5% of patients were treated on the Gamma Knife ®, 3.8% underwent prior whole brain radiation therapy (WBRT). The median V12 Gy was 5.2 cm3 and 36.5% of patients had a V12 Gy ≥ 10 cm3, anti-PD-1 agents were administered in 91.6% of patients. A V12 Gy ³ 10 cm3 was associated with an increased risk of developing any grade RN; odds ratio (OR): 2.12, p = 0.04 and OR: 2.18; p = 0.03 on univariable and multivariable analysis, respectively. Similarly, a V12 Gy ≥ 10 cm3 was associated with an increased risk of developing symptomatic RN; OR: 3.80, p = 0.003 and OR: 3.95; p = 0.003 on univariable and multivariable analysis, respectively. Receipt of concurrent ICI and prior WBRT were not statistically significant. At 1-year, the cumulative incidence of any grade and symptomatic RN was 4.8% and 3.8%, respectively. The cumulative incidence of any grade RN was 3.8% vs. 5.3% for the concurrent and non-concurrent groups at 1-year, respectively (p = 0.35). The cumulative incidence of symptomatic RN was 3.8% vs. 3.6% for the concurrent and non-concurrent groups at 1-year, respectively (p = 0.95). The risk of any grade and symptomatic RN following SRS and ICI administration for NSCLC brain metastases increases as the V12 Gy exceeds 10 cm3. Concurrent ICI and SRS does not appear to increase this risk. Radiosurgical planning techniques should aim to minimize the V12 Gy.

Long-Term Outcomes of Non-Vestibular Cranial Nerve Schwannomas Treated with Fractionated Stereotactic Radiotherapy and Stereotactic Radiosurgery

Non-vestibular cranial nerve schwannomas (NVCNS) are rare tumors that account for approximately 10% of cranial nerve schwannomas. They are commonly treated with radiation therapy (XRT) due to their location often precluding safe resection. We examined the long-term outcomes of NVCNS treated with XRT as primary management and for post-operative salvage. We conducted a retrospective review of patients with NVCNS treated with fractionated stereotactic radiation therapy (FSRT) or Gamma Knife Stereotactic Radiosurgery (GK-SRS) from 1996 to 2018 at our institution. We examined patient demographics, cranial nerve (CN) involvement, CN function pre-/post-XRT, treatment volume (TV), toxicity, surgery pre-XRT, and local control. Kaplan-Meier analysis was performed for evaluation of local control. We identified 66 patients (38 female, 28 male) with NVCNS, a portion of whom had tumors involving more than one cranial nerve. Forty-six (69.7%) were treated with FSRT (median dose 50.4 Gy in 1.8 Gy/fraction; range 45-54 Gy), and 20 (30.3%) with GK-SRS (median dose 12 Gy; range 12-15 Gy). Median follow-up time was 92.5 months (5-306). Median Karnofsky Performance Status was 90 (70-100). Median age at start of XRT was 45 years old (15-92). Prior to XRT, 34.8% (23) of patients had surgical resection, with median time from surgery to XRT of 4.25 months (0.5-130 months). Median treatment volume was 4.72 cc (0.26-29). The cranial nerve most commonly involved was CN V (48.4%), followed by CN X (15.2%), CN VII (13.6%), CN VI (6.1%), CN XII (6.1%), CN III (6.1%), and CN IX (3%). Twenty-nine (43.9%) patients experienced grade 1 acute toxicity during treatment. Six (9%) patients experienced grade 1 chronic toxicity. No grade 2 or higher acute or chronic toxicity was observed. No significant difference in rates of acute or chronic toxicity was observed between patients treated with GK-SRS vs. FSRT. Post-XRT, 37 patients (56.1%) had improvement in CN function/symptom, 24 patients (36.3%) had stable function/symptoms, and 5 patients (7.6%) had worsening function/symptoms. Local control at one and five years was 100%. In-field recurrence was observed in one patient (1.5%), at 9 years post-XRT. For salvage this patient was treated with a second course of FSRT to the recurrent tumor. Our large institutional series with long term follow up showed excellent local control of NVCNS treated with FSRT or GK-SRS both for primary management and post-operative salvage. Treatment is well tolerated, with high rates of preservation or improvement of CN function, and minimal acute and chronic toxicity.