Citations

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly used as a primary treatment modality for intracranial meningiomas. We aim to describe clinical outcomes after single-fraction SRS for sporadic intracranial meningiomas. METHODS: A prospectively maintained database was reviewed for patients with sporadic meningiomas who underwent SRS (Gamma Knife) as primary treatment modality from April 1997 to February 2022. Primary outcomes included progression-free survival (PFS) and treatment-related complications. RESULTS: Six hundred sixteen patients (653 tumors) underwent SRS with median follow-up of 6.3 years (interquartile range [IQR] 3.1-10.5 years). The median tumor volume was 4.5 cm 3 (IQR 2.0-8.0 cm 3 ). The median margin dose was 15.0 Gy (IQR 14.0-16.0). In-field progression was noted in 7 tumors (1.1%) and marginal progression in 2 tumors (0.3%) for a raw failure rate of 1.4%. PFS estimates at 5, 10, and 15 years were 99.8%, 99.0%, and 93.2%, respectively. Factors associated with reduced PFS on univariable analysis included older age (hazards ratio [HR] 1.14, 95% CI, 1.05-1.22, P < .001), male sex (HR 5.44, 95% CI, 1.45-20.4, P = .010), increasing tumor volume (HR 1.06, 95% CI, 0.99-1.13, P = .028), and lower tumor margin dose (HR 0.65, 95% CI, 0.43-0.97, P = .006). Treatment-related complications were noted in 56 patients (9.1%), of which 45 (7.3%) were temporary, 5 (0.8%) were minor, and 6 (1.0%) were permanent and/or required intervention. Radiosurgical parameters associated with treatment-related complications included increased number of isocenters (odds ratio [OR] 1.09, 95% CI, 1.04-1.14, P < .001), higher 12-Gy volume (OR 1.06, 95% CI, 1.03-1.09, P < .001), larger tumor volume (OR 1.06, 95% CI, 1.02-1.10, P < .001), and lower maximal dose (OR 0.90, 95% CI, 0.82-0.98, P = .11). CONCLUSION: SRS is effective as a primary treatment modality for sporadic, small-volume to medium-volume intracranial meningiomas. Pre-emptive SRS should be discussed as a safe management strategy compared with observation alone for incidentally discovered meningiomas.

TPS2092 Background: Glioblastoma (GBM) is the most common primary brain malignancy in adults. GBM is universally recurrent and associated with dismal outcomes. Re-irradiation (reRT) is ideal for evaluating combination therapy for recurrent GBM (rGBM) due to its multifactorial mechanism of action, including downstream immunomodulatory activity. RT (especially multi-fraction) increases immunogenicity in preclinical models by promoting immune activation, immune migration, and antigen uptake. Additionally, a recent study demonstrated enhanced PD-L1 expression in the glioma tumor microenvironment (TME) following RT, and combining stereotactic RT with a PD-1 inhibitor improved survival in murine models. Retifanlimab is a humanized monoclonal anti-PD1 IgG4 antibody that received FDA approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma. Bevacizumab, an anti-VEGF antibody, is a treatment for radiation necrosis/cerebral edema with less immune suppression than corticosteroids. In a previous Phase 2 study, hypofractionated RT (HFRT), retifanlimab, and bevacizumab was associated with a 9-month overall survival (OS) rate of 71.4%. To demonstrate the efficacy of this regimen compared to HFRT and bevacizumab, we have designed a new randomized controlled Phase 2 trial. We hypothesize that combination reRT with retifanlimab will produce a more robust anti-tumor immune response and improve OS compared to reRT without retifanlimab. Methods: This is a multicenter, open-label, randomized, controlled Phase 2 study of retifanlimab, bevacizumab, and HFRT for adult patients with rGBM. Patients are randomized 1:1 to the experimental (bevacizumab + retifanlimab + HFRT) or control cohort (bevacizumab + HFRT). Key eligibility criteria include age ≥ 18 years, Karnofsky performance status ≥ 60, ≥ 4 months since administration of any prior bevacizumab, and dexamethasone dose ≤ 4 mg at the time of randomization. The primary endpoint is 9-month OS. Secondary endpoints include OS, progression-free survival, objective response rate, neurologic assessment by NANO criteria, and adverse events profile. Protocol treatment will continue up to two years, or until progression or intolerable toxicity. Survival follow up will continue every two months, up to four years. Seven of the planned 94 patients have been enrolled as of submission on 1/28/25. Clinical trial #: NCT06160206. Funding provided by Incyte. Clinical trial information: NCT06160206 .

ABSTRACT In 2005, the Paediatric Radiation Oncology Society (PROS), a multi‐professional association to promote radiotherapy for children and young people, was created. Its mission has been to educate those involved in this field, and to improve the standards of radiation oncology care for children, adolescents, and young adults across the globe, not least in less privileged settings where the majority of the world's children, and most with cancer, live. Through regular congresses, and joint meetings with the International Society of Paediatric Oncology (SIOP), PROS has facilitated a focus on this treatment modality, and advocated on behalf of those who might benefit from it.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Central Nervous System Cancers provide multidisciplinary diagnostic workup, staging, and treatment recommendations for diffuse high-grade gliomas and medulloblastomas in children and adolescents. This article summarizes the studies and panel discussion that serve as the rationale for comprehensive care recommendations included in the NCCN Guidelines for Pediatric Central Nervous System Cancers.

Abstract To propose a novel entity of possible intraosseous pseudoprogression in clival chordoma following proton radiation therapy (PRT). A total of 38 consecutive patients who underwent surgical resection followed by PRT for clival chordoma between January 2015 and December 2023 were analyzed retrospectively. Follow-up magnetic resonance imaging (MRI) suggesting recurrence or progression was evaluated for validity. Apparent diffusion coefficient (ADC) and tumor-to-brainstem signal intensity ratio on contrast-enhanced T1-weighted imaging (Rce) were assessed. Pseudoprogression was defined as (1) MRI signs of recurrence or progression with no pathological confirmation despite obtaining a specimen, or (2) MRI signs of recurrence or regression with spontaneous resolution/regression. Of the 11 patients with MRI findings suggestive of recurrence or progression, 3 were diagnosed with recurrence, 5 with progression, and 3 with pseudoprogression. Patients with pseudoprogression were significantly younger than those with progression (p = 0.04), and all were female. The median time to recurrence, progression, and pseudoprogression was 31, 29, and 21 months, respectively. The three pseudoprogression cases were managed with gross-total resection followed by stereotactic radiosurgery, extensive biopsy, and observation, respectively. Although statistical significance was not reached, ADC (p = 0.33) and Rce (p = 0.13) tended to be higher in pseudoprogression cases. After PRT for clival chordoma, intraosseous pseudoprogression should be considered in the differential diagnosis, particularly in relatively young female patients, although the role of ADC and Rce on MRI remains inconclusive. Multidisciplinary teams managing chordomas should take this into account when determining the aggressiveness of treatment in such cases.

Objective: Pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) undergo aggressive multimodality treatment. This single institutional analysis of outcomes in this group explored factors associated with local control and survival. Methods: Patients ≤18 years old diagnosed with NRSTS between 10/1990-11/2021 who received radiotherapy (RT) were retrospectively identified. Overall Survival (OS) and disease-free survival (DFS) analyses were performed using Kaplan Meier methods. Cumulative incidence of local and distant failure were estimated. Univariate analysis was performed. Results: Fifty-one pediatric patients with NRSTS were included. Extremity tumors were most common (33/51, 65%), with 80% T1 or T2 (AJCC 8 th ) and 90% non-metastatic. Surgery in 49/51 (96%) resulted in 32 (65%) R0 resections. All received RT (median EQD2 50 Gy, range 42.4-76.9), with brachytherapy or intraoperative (IORT) boosts in 21 cases (41%) (mean EQD2 24.5 Gy). Thirty-four (66.7%) received chemotherapy. With 5.7 years median follow up, 5-year OS and DFS were 70.7% and 67.9%, respectively. Positive margins were significantly associated with worse OS on univariate analysis. Two-year local failure incidence for EBRT was 18.1% and 5.3% for EBRT+boost (HR 3.67, p=0.24). Among 6 observed local failures, 5 occurred after EBRT alone, 3 of which had positive margins. Among the EBRT+boost group, 2 had positive margins, neither with local recurrence. Conclusion: Multimodality treatment of pediatric NRSTS results in 5-year OS and DFS around 70%. R0 resection is essential to optimize outcomes in this population. Although incidence of R1 resections has declined in the modern era, IORT/brachytherapy boost may have a role in selected patients at high-risk for local recurrence.

Abstract BACKGROUND Pineocytoma is a rare pineal parenchymal WHO grade 1 tumor, typically well-managed with surgical resection alone. With gross total resection (GTR), 91% 1-year and 84% 5-year survival rates have been reported. Recurrent pineocytoma is rare and optimal management in that setting is unknown, in part owing to the rarity of the condition. METHODS We report an atypical course of pineocytoma in a 58-year-old male involving metastatic disease. RESULTS A pineal mass was identified upon MRI of the brain obtained for vision changes. Patient underwent GTR, pathology was consistent with pineocytoma, WHO grade 1. Ki-67 labeling index was low at 1-2%. Despite low-grade pathology, two years later, surveillance imaging demonstrated recurrence in the pineal region and a second lesion in the right thalamus. The patient underwent gamma knife surgery (GKRS) to both lesions. Three years later, he developed three new lesions in the right cerebellum and again underwent GKRS. Subsequent surveillance imaging identified new lesions in the right cerebellum and along ventricular walls, treated with further GKRS. Nine years after initial diagnosis, focal nodular leptomeningeal metastases were discovered, along with progression at the primary tumor site. Patient was treated with GKRS to the nodular deposits followed by pembrolizumab. Further disease progression as noted despite immunotherapy. Patient was treated with 6 cycles of temozolomide chemotherapy and at further progression 3 cycles of lomustine. Upon additional progression, further radiation therapy was administered with bevacizumab to reduce risk of radiation necrosis. Patient remains on surveillance 13 years after initial diagnosis with visual changes and mild headache representing only clinical issues. CONCLUSIONS Although exceedingly rare, pineocytoma is capable of metastasizing to brain parenchyma and the leptomeninges, as demonstrated in our patient. However, our case demonstrates prolonged survival is possible even in the setting of relentlessly progressive metastatic disease with utilization of multimodality treatment.

Abstract INTRODUCTION Lymphopenia attributed to postoperative chemoradiotherapy (CRT) can accelerate tumor recurrence and contribute to poor prognosis in GBM. We hypothesize that short course (1-2 weeks) CRT can mitigate lymphopenia compared to standard course and may provide immune benefits for future combination therapy. METHODS GBM patients were randomized on a multi-site phase II study comparing short course (35Gy/5Fx or 40Gy/10Fx depending on target volume) (Arm A) versus standard dose fractionation (60Gy/30Fx or 40Gy/15Fx, Arm B). All patients received concurrent and adjuvant temozolomide (TMZ). This unplanned interim analysis evaluates changes of absolute lymphocyte count (ALC), CD4 and CD8 prospectively at 3-timepoints: baseline (prior to CRT), end of CRT, and 1-month post-CRT. RESULTS To date, 72 patients enrolled (34 Arm A, 38 Arm B). Median age 66 (35-86), ECOG 0-2. Patients characteristics as followed in Arm A vs. Arm B, respectively: female 47% vs. 42%, MGMT promotor methylated 31% vs. 34%, steroid use 46% vs. 45%, ALC 1310 cells/mm3 (330 –9730) vs. 1480 (750 –7750), CD4 531 cells/mm3 (86 –1368) vs. 662 (318 –1671), and CD8 151 cells/mm3 (56 –940) vs. 272 (68 –875). Lymphocytes data were collected in 49 patients (21 Arm A, 28 Arm B). There were signficantly fewer reductions of ALC, CD4 and CD8 in Arm A. Median ALC changes were 95% and 99% of baseline (Arm A) vs 52% and 61% of baseline (Arm B) at the end of CRT and 1-month post-CRT, respectively (p&lt;0.01). Median CD4 changes 93% and 96% of baseline (Arm A) vs 51% and 49% (Arm B), and median CD8 changes 97% and 98% of baseline (Arm A) vs 57% and 71% (Arm B) at the end of CRT and 1-month post-CRT, respectively (p&lt;0.05). CONCLUSIONS This interim analysis suggests that short course RT could reduce treatment-related lymphopenia and immune suppression compared to standard RT, thus could be potentially beneficial to combine with immunotherapy.

Abstract BACKGROUND Fatigue is among the most common symptoms managed by patients with cancer. Hypothalamic pituitary axis dysfunction has an established role in a subset of patients with fatigue. Our primary aim was to longitudinally assess the impact of hypothalamic radiation exposure to patient self-reported fatigue. METHODS We included a sample of patients who received radiation therapy treated at a single institution from 2014-2024. The PROMIS-10 questionnaire (“How would you rate your fatigue on average,” scale 1-5) was used in standard clinical practice, with measures from 6 time points over 2 years. We performed descriptive statistics. Linear mixed models were used to assess the impact of hypothalamic radiation dose on fatigue scores. Mixed models were controlled for gender, age, time, tumor category (CNS vs. non-CNS), and modality (photon vs. proton). Models were fit with random intercepts for each Patient ID. RESULTS 1092 patients (43% female) with a median age of 54 years (range: 18-92) were included. Most patients were treated for CNS cancer (76%), with about 50% each photon and proton. Median hypothalamus radiation dose was 1306 cGy (range: 0.01-6138). Mean baseline fatigue (2.4) increased after treatment (2.7) remaining elevated at 3- and 6-months post-treatment (2.6, 2.5), returning near baseline at 1- and 2-years post-treatment (2.4, 2.3). Higher radiation dose (Estimate (SE): 0.014 (0.006), p=0.0266) and CNS cancer treatment (0.11 (0.051), p=0.0319) were significant predictors of higher fatigue in the mixed model. Male patients (-0.16 (0.042), p=0.0001) and time (-0.003 (0.0016), p=0.0398) were associated with lower fatigue. Age and treatment modality were not significant predictors of fatigue. CONCLUSIONS We found that higher hypothalamic radiation dose was related to more self-reported fatigue, which peaked by 6 months. This effect was seen more prominently in female patients and those treated for CNS disease. Treatment modality and age did not influence fatigue scores.