bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-04. SEQUENCING OF CHECKPOINT INHIBITORS AND RADIOTHERAPY IN MELANOMA BRAIN METASTASES: A META-ANALYSIS OF COMPARATIVE STUDIES
Authors: Haddad Philip , Kantamani Deepti , Gupta Ankita 
Published: November 2024

Abstract

OBJECTIVE
Melanoma brain metastases significantly worsen prognosis, with incidence rates as high as 50%. While both immunotherapy and radiotherapy improve survival, the optimal sequencing remains undetermined. This meta-analysis aims to define the most effective treatment sequence for improving progression-free survival (PFS) and overall survival (OS).

METHODS
A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of melanoma brain metastases, comparative studies of immune checkpoint inhibitors given before or after radiotherapy, and those that reported overall (OS) and progression-free (PFS) survival. Studies that reported mixed data that included concurrent immune checkpoint inhibitors with radiotherapy were excluded. A meta-analysis using the fixed effects and random effects models was conducted.

RESULTS
Our analysis included six retrospective studies encompassing 213 patients, with a median age of 62 years and follow-up of 22 months. The results indicate a clear disadvantage in PFS when immunotherapy precedes radiotherapy (HR=1.77; 95% CI 1.21-2.60; p=0.003; I2=13.5%). Similarly, initiating treatment with immune checkpoint inhibitors followed by radiotherapy showed a trend towards poorer OS compared to the reverse sequence, although this finding was of borderline significance (HR=1.39; 95%CI 0.97-1.99; p=0.07; I2=0%).

CONCLUSIONS
This meta-analysis, the first and largest to date, provides compelling evidence that initiating treatment with radiotherapy followed by immune checkpoint inhibitors significantly improves PFS with a trend for a better OS in patients with melanoma brain metastases. These findings suggest that radiotherapy should precede immunotherapy to optimize clinical outcomes in this patient population. Further research, particularly prospective studies, is necessary to confirm these results.
RADT-10. CEREBELLAR RE-IRRADIATION AFTER WHOLE BRAIN RADIOTHERAPY SIGNIFICANT SYMPTOM RELIEF WITH MINIMAL TOXICITY IN METASTATIC BRAIN PATIENTS
Authors: Haisraely Ory , Lawerence Yaccov , Taliansky Alicia 
Published: November 2024

Abstract

INTRODUCTION
Whole-brain irradiation (WBRT) remains a standard treatment for patients with extensive brain metastases, providing symptom relief and prolonging survival. However, patients often experience recurrent metastases, necessitating re-irradiation. This study evaluates the efficacy and safety of cerebellar-only re-irradiation for improving symptoms and reducing toxicity in patients with recurrent cerebellar metastases following WBRT.

METHODS
A retrospective review was conducted on patients who underwent cerebellar re-irradiation between 2017 and 2023 after prior WBRT for symptomatic cerebellar metastases. Clinical, dosimetric, and outcome data were collected. Symptom improvement was assessed based on patient, caregiver, and physician reports three months post-treatment.

RESULTS
The study included 56 patients with a median age of 53 years. Symptom domains included gait dysfunction, nausea/vomiting, dysarthria, movement disorder, dizziness, and headache. Breast cancer was the most common histology. The median interval from WBRT to cerebellar re-irradiation was 15 months. Symptomatic improvement was observed in 75% of patients, with notable improvements in nausea/vomiting (84.6%) and headache (80%). Age, dose deliver and time from WBRT were significant for clinical improvement. Dexamethasone use decreased in 76.3% of patients post-treatment. Radiological responses correlated with clinical improvements in 90% of cases. Only one patient developed symptomatic radiation necrosis. Six-month overall survival and progression-free survival were 50% and 39.2%, respectively.

CONCLUSION
Cerebellar-only re-irradiation is an effective and safe option for managing recurrent cerebellar metastases, significantly improving symptoms with minimal toxicity. This approach also allows for subsequent systemic therapy or radiosurgery for supratentorial lesions, potentially reducing the need for additional WBRT. Further studies are required to validate these findings in larger cohorts.
RADT-16. ADJUVANT CHEMO-RADIATION THERAPY AS A RISK FACTOR FOR POSTOPERATIVE HYDROCEPHALUS FOLLOWING RESECTION OF HIGH-GRADE GLIOMA: A PROPENSITY-MATCHED CASE SERIES
Authors: Das Nikita , Dhamija Ravi , Sridharan Preety , Swetz Joseph , Harper Elleson , Perez Jaime , Newton Herbert , Vempati Prashant , Hodges Tiffany 
Published: November 2024

Abstract
The discovery of the neural glymphatic network in the past decade has significant implications for clinical investigations on hydrocephalus. With emerging understanding of how meningeal lymphatics and perivascular pathways impact cerebrospinal fluid dynamics, it is conceivable that inflammatory and fibrotic changes induced by radiation and chemotherapy may contribute to the pathogenesis of postoperative hydrocephalus, a well-documented sequela of resective neurosurgery. This study investigates differences in adjuvant chemo-radiation therapy patterns between patients who develop hydrocephalus following high-grade glioma resection and those who do not experience this postoperative complication. A retrospective chart review identified 328 adult patients who underwent tumor resection at our institution between 2010-2020, of which 257 had high-grade gliomas. Demographic and clinical data were collected, including resection history and adjuvant chemotherapy and radiation history. Propensity Score Matching generated comparative cohorts (n=27) using covariates sex, age at first surgery, surgery type, tumor location, extent of first resection, tumor-associated seizures, ventricular opening, number of additional resective surgeries, and pre-surgical Karnofsky Performance Scale score. Independent t-tests assessed differences in adjunctive chemo-radiation trends between patients who developed hydrocephalus within 3 years postoperatively and those who did not. 27 of 257 patients (10.5%) who underwent resection for high-grade glioma developed hydrocephalus within 3 years of their first surgery. Patients who developed hydrocephalus were more likely to have initiated the Stupp protocol(P=0.004), completed the Stupp protocol(P=0.02), and undertaken multiple cycles of the Stupp protocol(P=0.0004). Additionally, these patients had a smaller time window between surgery and adjuvant chemo-radiotherapy initiation than patients who did not develop hydrocephalus (P=0.02). Importantly, engagement in other clinical trial regimens with chemotherapy or radiation therapy did not differ significantly between groups(P=0.08, P=0.49, respectively). Shortened time to initiation of chemo-radiation therapy postoperatively and increased number of chemo-radiation cycles may increase a patient’s susceptibility to develop postoperative hydrocephalus following resection of high-grade glioma.
RADT-19. PILOT STUDY OF VELOCITY-SELECTIVE ARTERIAL SPIN LABEL MRI (VSASL-MRI) DERIVED RELATIVE CEREBRAL BLOOD FLOW TO DISTINGUISH IMAGING CHANGES AFTER RADIOSURGERY (SRS) FROM PROGRESSIVE BRAIN METASTASIS (BM)
Authors: Zhu Dan , Xu Feng , Liu Dapeng , Katulis Lisa , Lin Doris , Kleinberg Lawrence 
Published: November 2024

Abstract
Management of imaging progression on standard contrast enhanced MRI (cMRI) after SRS for brain metastasis is challenging as treatment effect/necrosis appears similar to progressive tumor. VSASL-MRI uses water labeled based on velocity, rather than spatial location, as an endogenous contrast agent and is therefore insensitive to transit delay impacting other ASL-MRI techniques. Other advantages include no IV contrast, limited susceptibility artifact, and absence of confounding leakage of gadolinium contrast into tissues. VSASL-MRI was performed (median 15 (4-123) months after SRS) to evaluate SRS treated solid tumor BM with clinician determined imaging progression on cMRI to evaluate the hypothesis that VSASL-MRI may distinguish biologic tumor (hyperperfused compared with normal brain) from treatment effect/necrosis (hypoperfused). 17 patients (19 progressing lesions) were enrolled. 13/19 index lesions had hypoperfusion. Of these, 3/13 had resection with no tumor present, 8/13 were conservatively managed and appeared to be treatment effect/necrosis as they stabilized or improved on follow-up cMRI without further BM directed intervention, and 2/13 had resection for further progression with active tumor present. For 6 index lesions that were hyperperfused: 3/6 had pathology were confirmed to be tumor, whereas the other 3/6 continued to progress (one got additional RT, two expired with progression). In addition, two pts had concurrent identification of new non-index previously untreated lesions on cMRI that were hyperperfused on VSASL-MRI and were treated. One of these patients had subsequent VSASL-MRI demonstrating post-SRS resolution of perfusion 2 months after treatment. This pilot data supports the hypothesis that VSASL-MRI may be useful in distinguishing tumor progression from radiation related imaging changes and/or be an early biomarker of radiosurgery response. We are initiating further study (1R01CA282928-01, PI; Qin) to refine the technique and prospectively assess the value of this approach in a larger number of patients.
RADT-26. RADIATION FRACTIONATION IN THE MANAGEMENT OF ELDERLY PATIENTS WITH GLIOBLASTOMA BY AGE
Authors: Afzal Rimsha , Kim Michelle , Wahl Daniel , Lawrence Theodore , Takayesu Jamie 
Published: November 2024

Abstract
Multiple studies have investigated hypofractionated radiation (HFX) for elderly patients with glioblastoma (GBM), using varying age cut-offs. This leads to uncertainty about who benefits most from a hypofractionated course. This study examines the use of and outcomes with HFX, between two commonly used cut offs to define elderly GBM: 65 versus 70 years old. In this retrospective review, 309 patients diagnosed with GBM who were treated with radiation at a single academic institution were included. The Kaplan-Meier method was used to analyze overall survival. A Chi-square test was conducted to compare the use of SFX and HFX and the median survival between those 65-69 versus 70-74 years old. Patients aged 70-74 were more likely to receive HFX radiation compared to those aged 65-69 (80.00% vs. 42.65%, p=0.0002). Median survival for the entire cohort was 12 months. Among those 65-69 years old, SFX was associated with a significantly higher median survival compared to HFX (14 months vs. 7 months, HR 2.00, 95% CI 1.16 – 3.46, p=0.03). This was also true for those 70-74 years old, (18 months vs. 4 months, HR 4.50, 95% CI 1.84 – 11.01, p=0.03). We demonstrate a decrease in the use of SFX in patients 65 years or older, and that that standard fractionation is associated with longer survival in older patients with GBM. This suggests that in a well selected population, SFX should be considered even among elderly patients. Additional work is needed to determine whether these findings are causal or due to patient selection. Performance status and MGMT methylations status, for instance, should guide clinical decision making. Such results highlight the importance of further studies to fine tune radiation dose and fractionation elderly patients with GBM.
RADT-31. EMBRACING HYPOFRACTIONATED RADIOTHERAPY FOR GLIOBLASTOMA IN A RESOURCE CONSTRAINED SETTING
Authors: Menon Durgapoorna , G Kiron , Panikar Dilip , Warrier Arun , Sasi Sandra 
Published: November 2024

Abstract

BACKGROUND
Various hypofractionated schedules of radiation have been tried in glioblastoma with limited success. Though the shorter fractionation is appealing and there is evidence (since 2017) to use the 40Gy in 15 fractions regime in the elderly, the fear of toxicity limits its use, especially in the developing nations. We have tried this regime in younger patients (not eligible for supportive care alone) who had a poor Performance status or if only a biopsy had been performed.

METHODS
25 patients treated for glioblastoma from 2017 to 2023 using 4000cGy delivered in 15 fractions were included in the study. The patient details were obtained retrospectively from the medical records and the Eclipse Treatment Planning system.

RESULTS
There were 16 males and 9 females. Median age was 62 years (range 52 to 77 years). 56% of the patients had an ECOG performance score of 3; and the rest 2. 12 lesions were on the Right side, 9 in the left and the rest extended across the midline. Surgery was limited to biopsy alone in 8; almost as many (n=7) had a Near Total Resection; the rest underwent decompression. Surprisingly, almost half the patients were MGMT unmethylated. 16 patients were on steroids either during or after radiation. All 25 maintained their Performance Status and completed radiation as planned. The mean GTV Volume - 53.48 cc (Range 6-201). Dmax was never above 103%; Brainstem and Optic Apparatus Dmax were also kept below 100%. In the majority, 3 beams of mixed energy were used. 19 patients received both Concurrent and adjuvant temozolomide; only adjuvant was given to 6. The median overall survival was 7.7 months (range 2-60.6 months) and the Disease free survival was 7.5 months (Range 1-60.5 months).

CONCLUSIONS
Hypofractionated radiotherapy of 4000 cGy in 15 fractions seems to be a kinder treatment in glioblastoma patients with a poor performance status.
RADT-32. FREQUENT MULTIFOCAL INTRATUMORAL HEMORRHAGE IN MULTIPLE BRAIN METASTASES FROM HEPATOCELLULAR CARCINOMA
Authors: Ishi Yukitomo , Nishioka Kentaro , Yamaguchi Shigeru , Okamoto Michinari , Motegi Hiroaki , Oki Sogo , Mori Takashi , Aoyama Hidefumi , Fujimura Miki 
Published: November 2024

Abstract

OBJECTIVE
Brain metastasis (BM) rarely occurs in hepatocellular carcinoma (HCC); however, it frequently causes intratumoral hemorrhage (ITH). We investigated the clinical manifestations of ITH in patients with multiple BMs from HCC (HCC-BM).

METHODS
Patients who underwent treatment for multiple BMs with more than two metastatic sites were retrospectively reviewed and those diagnosed with HCC-BM were further analyzed. The multifocality of hemorrhage was classified into two groups, spatial and temporal multifocality, according to the radiological findings. The characteristics of multifocal hemorrhage in HCC were compared with those of BMs from other cancer types.

RESULTS
Fifteen out of 636 (2.36%) cases of multiple BMs were due to HCC metastasis. Out of 15 HCC-BM cases, 13 (86.7%) presented multifocal hemorrhage and 1 presented unifocal hemorrhage during the follow-up period. Spatial and temporal multifocality were observed in 9 and 5 cases, respectively, among 13 cases of multifocal hemorrhage. Among 636 cases of multiple BMs, HCC cases showed the highest frequency of multifocal hemorrhage, and HCC was significantly associated with multifocal hemorrhage compared with other primary-site cancer types (30/621 cases, 4.8%). Out of 15 patients with multiple HCC-BMs, 12 underwent whole-brain irradiation (WBI), and their median overall survival was 147 days. In one patient (8.3%), although treatment was stopped due to neurological deterioration by ITH, local BM control was favorable after the completion of WBI, and the only cause of death in six patients who completed WBI and were radiologically followed up until death was the progression of extracranial lesions.

CONCLUSIONS
Multiple HCC-BMs frequently present with multifocal ITH compared with BMs from other cancer types. Despite poor treatment outcome, WBI may show favorable local control considering the potential hemorrhagic event by tiny metastases that would not be detected radiologically. Immediate commencement of treatment before hemorrhage progression will be required for the treatment of multiple HCC-BMs.
RADT-37. PROTON THERAPY REIRRADIATION FOR RECURRENT MALIGNANT GLIOMA: PROSPECTIVE ANALYSIS FROM THE PROTON COLLABORATIVE GROUP
Authors: Gal Omer , Mihalcik Stephen , Zeng Jing , Chang John H , Rosen Lane , Choi Isabelle , Simone Charles B , Vargas Carlos E , Tsai Henry K , Press Robert H 
Published: November 2024

Abstract

BACKGROUND
Standard of care treatment for recurrent malignant glioma after prior radiotherapy (RT) is not well established. Proton therapy (PT) is increasingly used for reirradiation (ReRT) at the time of recurrence; however, treatment outcomes, toxicity, and prognostic factors for patients treated with PT-ReRT remain poorly defined.

METHODS
The prospective, multi-institutional Proton Collaborative Group (PCG) registry was queried for patients with malignant glioma who previously received RT and underwent PT-ReRT between 7/2011-12/2023. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method, and Cox proportional hazards regression was used for uni- and multivariate analysis (UVA and MVA). Dose was calculated using equivalent dose in 2-Gy fractions (EQD2).

RESULTS
143 consecutive patients were identified. Median follow-up was 11.2 months and median time interval (TI) from prior RT (median 58.5 Gy) to PT-ReRT (median 44.6 Gy) was 42.4 months. Primary histology was glioblastoma (n=74), astrocytoma (n=35), and oligodendroglioma (n=34). Median PFS and OS were 8.1 and 11.2 months, respectively. On UVA, improved OS was associated with oligodendroglioma (HR 0.37) and astrocytoma histology (HR 0.53) compared to glioblastoma, TI &gt;60 months (HR 0.2), CNS WHO Grade 2 compared to 4 (HR 0.42), and ECOG performance status 0 (HR 0.47). On MVA, improved OS remained associated only with oligodendroglioma (HR 0.42) and TI &gt;60 months (HR 0.49). Acute and Late Grade 3 toxicity occurred in 7% and 4% of patients. Acute Grade 3 toxicity was associated with poor performance status (HR 16.15).

CONCLUSIONS
In the largest series of glioma PT-ReRT reported to date, retreatment appears well tolerated with variable outcomes based on clinical prognostic factors. Toxicity rates were acceptable compared to historical photon-based literature despite a high median prescription dose.
RADT-41. RADIOSURGERY FOR GLOMUS TUMORS: IMPACT OF MRI-PET FUSION ON TREATMENT PLANNING AND OUTCOMES
Authors: Sreenivasan Sanjeev , Jung Jessica , Calugaru Emel , Schulder Michael , Goenka Anuj 
Published: November 2024

Abstract
Paragangliomas present a challenge for stereotactic radiosurgery (SRS) treatment planning, particularly regarding the delineation of tumor boundaries. We propose that integrating 68Ga-DOTATATE PET scans alongside MRI in SRS planning will facilitate superior target identification and tumor coverage compared to reliance on MRI alone. A retrospective analysis of 9 patients diagnosed with paraganglioma who underwent MRI and 68Ga-DOTATATE PET imaging over a 20-month period was conducted. Images were imported into GammaPlan treatment planning software, partitioned into separate sessions: one with MRI and another with MRI-PET fusion. A single evaluator contoured paragangliomas as gross tumor volume (GTV) initially using MRI alone and subsequently with PET/MRI fusion. The pre- and post-PET fusion GTV volumes were compared. The standard deviation of the percentage increases in volume was calculated to assess variability across the sample. Of included 9 patients, 7 were females and median age was 58.3 years. Four patients had prior surgery. Seven patients were treated with Gamma Knife, while 2 with LINAC. Two patients were treated with single fraction SRS while 7 with hypofractionated SRS. Across all treated patients (n=9), GTV volumes significantly increased with PET fusion, with an average volume increase of 26.02% (n=8). One patient reported dryness of throat after SRS. Significant PET avidity over structures like temporal bone, internal jugular vein, petrous internal carotid artery and sigmoid sinus-IJV junction were included in PET/MRI fusion GTVs, which were missed on isolated MRI contours. At median 6-month follow up, all patients had a stable radiological response. Integration of 68Ga-DOTATATE PET scans with MRI enhances the visualization of paragangliomas in patients undergoing SRS. Further extensive studies are warranted to validate this observation and to better understand the variability in treatment response observed across the patient population. Our practice has initiated routine utilization of DOTATATE-PET imaging in paraganglioma patients undergoing SRS planning.
RADT-44. EARLY CLINICAL EXPERIENCE WITH PROTON CRANIOSPINAL IRRADIATION FOR THE TREATMENT OF LEPTOMENINGEAL DISEASE
Authors: Marciscano Ariel E , Ehret Felix , Yuan Ammy M , Zieminski Stephen , Leland Peggy A , Khandekar Melin J , Oh Kevin S , Shih Helen A 
Published: November 2024

Abstract

BACKGROUND
Leptomeningeal disease (LMD) is a uniformly terminal event of advanced cancer with limited therapeutic options, with survival ranging from weeks to a few months. Recently, proton craniospinal irradiation (pCSI) has been demonstrated to confer a progression-free and overall survival benefit in select patients with LMD as compared to more limited site radiotherapy. Early results from an institutional experience of pCSI for patients with LMD from solid tumor malignancies are reviewed.

METHODS
All patients with LMD and treated with pCSI at our institution were reviewed, specifically with regards to baseline patient characteristics, radiation dosimetry parameters and clinical outcomes.

RESULTS
Between February 2023-April 2024, nine patients were treated with pCSI for a range of primary tumor histologies, including two with triple-negative breast cancer and one each with ER+/PR+/HER2- breast cancer, non-small cell lung cancer, small cell lung cancer, gastric cancer, esophageal cancer, pancreatic cancer and ovarian cancer. All patients received 30Gy(RBE) in 10 fractions to the craniospinal axis, with one patient receiving an intracranial boost (6Gy(RBE)). Median age and performance status was 58 years and KPS 80, respectively. Five (56%) patients underwent CSF diversion prior to pCSI, 22% of patients had undergone prior CNS-directed radiotherapy, and all patients received at least one line of systemic therapy in the metastatic setting prior to pCSI. Median survival from the first day of pCSI was 4.3 months (range 1.3-10.7mo). Median survival among patients undergoing CSF diversion prior to pCSI (n=5) was 5.3 months (vs. 2.9mo with no CSF diversion). Median survival among patients who received systemic treatment after pCSI (n=5) was 9.1 months (vs. 2.9mo for patients who did not).

CONCLUSIONS
Careful patient selection is imperative to identify those who will best benefit from pCSI with suggestion of patients undergoing pre-pCSI CSF diversion and receiving post-pCSI systemic therapy achieving superior survival.