bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-03. A CASE OF PARTIAL HIPPOCAMPAL-AVOIDANCE WHOLE BRAIN RADIOTHERAPY IN A PATIENT WITH METASTATIC INFILTRATION OF THE LEFT HIPPOCAMPUS
Authors: Leskinen Sandra , Shah Harshal , Vojnic Morana , Yaffe Beril , Schneider Shonna , D'Amico Randy , Wernicke A Gabriella 
Published: November 2023

Abstract
In addition to surgical resection and systemic therapy, whole brain radiotherapy (WBRT) is a crucial modality in the treatment of cancers that have metastasized to the brain. It has been shown to improve intracranial disease control and overall survival. However, WBRT also increases the risk of radiation-associated damage to sensitive structures like the hippocampus, often resulting in neurocognitive dysfunction and decline. Hippocampal avoidance WBRT (HAWBRT) has been shown to reduce neurocognitive sequalae without worsening survival outcomes or increasing the risk of metastasis to the spared region compared to conventional WBRT. In cases where both hippocampi cannot be completely spared, the effectiveness of partial hippocampal avoidance on neurocognitive function and tumor control have been poorly described. We present the case of a patient diagnosed with triple negative invasive ductal carcinoma of the breast and disease metastatic to the brain, lung, bones, adrenal glands, and liver. Brain imaging revealed multiple brain metastases, two of which were noted near the left hippocampus. The patient underwent partial HAWBRT with complete avoidance of the right hippocampus and partial avoidance of the left. At 1-year follow-up, there was no evidence of metastasis in or near the partially spared left hippocampus. The patient’s neurocognitive functional status remained consistent with the findings of prospective randomized trials in which total bilateral hippocampal sparing was performed. To our knowledge, no such case has been presented in the literature. Further studies assessing the role of partial hippocampal avoidance in WBRT are needed.
RADT-05. SINGLE VERSUS MULTI-FRACTION STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: RATES OF LOCAL PROGRESSION AND NECROSIS
Authors: Frechette Kelsey , Sara Leier , William Harmsen , Laack Nadia , Mahajan Anita , Yan Elizabeth , Routman David , Kenneth Merrell , Lucido John , Grams Michael , Brooks Jay , Parney Ian , Pollock Bruce , Burns Terry , Sener Ugur , Brown Paul , Breen William 
Published: November 2023

Abstract

PURPOSE
For large brain metastases, it is unknown whether single fraction stereotactic radiosurgery (sSRS) or multi-fraction stereotactic radiosurgery (fSRS) is optimal. We aimed to compare rates of local progression and necrosis between sSRS and fSRS for large brain metastases.

METHODS
Patients with intact or resected brain metastases with a target volume ≥ 4.2 cc (corresponding to a diameter ≥ 2 cm) treated with Gamma Knife (GK) or linear accelerator-based SRS from 2014-2022 were included in this retrospective review.

RESULTS
A total of 343 large brain metastases in 276 patients were included; 171 lesions were treated with sSRS (96% with GK) and 172 lesions with fSRS (100% with linear accelerator). Median lesion volume was 19.8 cc and 8.4 cc for fSRS and sSRS, respectively. Resection was performed prior to SRS in 228 (66%), with the remaining 115 metastases treated intact. There was no difference in rate of local progression between sSRS versus fSRS, or between resected versus intact targets (p &gt;0.8 for both). Cumulative incidence of local progression (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 24% and 30%, respectively, compared to 22% and 34% for fSRS. FSRS was associated with significantly higher rates of necrosis than sSRS (HR 5.58, 2.38-13.08, p &lt; 0.001). This association remained significant after controlling for target volume. Cumulative incidence of necrosis (with death as a competing risk) at 1 and 3 years for patients receiving sSRS was 1% and 3%, respectively, compared to 10% and 18% for fSRS. Necrosis rates were significantly higher with fSRS for both intact and resected targets (P &lt; 0.02 for both).

CONCLUSION
While local control for large resected or intact brain metastases appears similar after sSRS or fSRS, this retrospective study shows higher rates of necrosis after fSRS. Prospective validation is needed.
RADT-09. CLINICAL OUTCOMES OF FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR INTACT AND POSTOPERATIVE RADIORESISTANT RENAL CELL CARCINOMA AND MELANOMA BRAIN METASTASES
Authors: Cruz-Chamorro Ruben , Bryant John , Liveringhouse Casey , Nakashima Justyn , Graham Jasmine , Jiang Shirley , Oliver Daniel , Ahmed Kamran , Vogelbaum Michael A , Etame Arnold , Liu James , Beer-Furlan Andre , Tran Nam , Yu Hsiang-Hsuan Michael 
Published: November 2023

Abstract

PURPOSE
Fractionated Stereotactic Radiotherapy (FSRT) may be an optimal strategy for radioresistant renal cell carcinoma (RCC) and melanoma brain metastases (BM). We reviewed our institutional experience of FSRT to intact BM and postoperative cavities for patients with melanoma and RCC.

METHODS
We retrospectively identified consecutive patients with melanoma and renal cell carcinoma with unresected or resected BM treated with FSRT at our institution from 1/2018 to 1/2021. Time to event outcomes were estimated using the Kaplan-Meier method with log-rank tests and multivariable Cox regression analyses.

RESULTS
We identified 44 patients with a total of 64 BM: 31 intact (48.4%) and 33 resected BMs (51.6%). Thirty-six (81.8%) were melanoma and eight (18.2%) were RCC. The majority of intact BM (n = 22/31; 71%) and cavities (n = 21/33; 64%) were treated to 30 Gy (24-30) in 5 fractions and 25 Gy (24-35), respectively. Median PTV volume for intact BM was 5.04 cc (1.2-19.8) and for resected BM was 16.7 cc (4.8-89.1). Median interval from planning MRI to FSRT was 10 days (3-28). Median time from surgery to FSRT was 37 days (9-90). At 18.6 months median follow-up, local and intracranial distant failures were observed in 4 and 20 patients, respectively. Our cohort had a local recurrence-free survival (LRFS) of 83% and overall survival (OS) of 57% at 12 months; no difference between primary FSRT versus surgery followed by FSRT (p = 0.93 and p = 0.52, respectively). On MVA, higher FSRT dose was associated with better local control (p = 0.01). Radiation Necrosis (RN) was observed in eight treatment areas (12.5%). Neither resection status (p = 0.99) nor PTV volume (p = 0.61) were associated with RN.

CONCLUSION
FSRT is associated with low rates of toxicity and clinically significant disease control for both intact and resected melanoma and RCC BM, with higher FSRT dose being correlated with improved control.
RADT-11. THE HEMORRHAGIC RISK OF MELANOMA BRAIN METASTASES AFTER STEREOTACTIC RADIOSURGERY
Authors: Hong Sukwoo , Bouchal Samantha , Bauman Megan , Riviere-Cazaux Cecile , Pumford Andrew , Brown Paul , Yan Elizabeth , Stafford Scott , Markovic Svetomir , Link Michael , Burns Terry , Jusue-Torres Ignacio , Pollock Bruce , Parney Ian 
Published: November 2023

Abstract

OBJECTIVE
This study aimed to analyze the hemorrhagic risk of melanoma brain metastases following SRS.

METHODS
A retrospective analysis was conducted using a prospective institutional database between 1990 and 2021. Lesional hemorrhage was categorized as definite or possible, and hemorrhage severity was graded using CTCAE.

RESULTS
The study identified 291 patients with 1083 lesions. The mean age of patients was 60 ± 15 years, with 61% being male. Median follow-up was 11 months, corresponding to 581 patient-years. Among the patients, 82 (28%) experienced 135 lesional hemorrhages (13%). Of these, 88 lesions in 61 patients were grade 1-2 hemorrhages, 42 lesions in 25 patients were grade 3, and five lesions in five patients progressed from grade 1 to 3. Surgical intervention was required for 17 lesions (2%) in 16 patients (5%). Lesional hemorrhage was associated with radiosurgery performed between 2015 and 2021 (OR, 0.373; 95% CI, 0.231-0.60; p &lt; 0.001), increasing marginal dose (OR, 0.89; 95% CI, 0.82-0.98; p = 0.017), antiplatelet use (OR, 0.192; 95% CI, 0.082-0.45; p &lt; 0.001), and WBRT (OR, 0.51; 95% CI, 0.330-0.77; p = 0.0017). The cumulative lesional hemorrhage risk reached 17–20% at 36 months following radiosurgery, with 95-96% of hemorrhages occurring within the initial year. Median OS was 11 months (95% CI, 9-13 months). Patients who received radiosurgery between 2015 and 2021 exhibited a median OS of 17 months (95% CI, 10-24 months; p &lt; 0.001), while those without hemorrhage had a median OS of 12 months (95% CI, 10-14 months; p = 0.054).

CONCLUSIONS
Definitive hemorrhage risk was 17% for melanoma brain metastases after SRS within the first three years, with 95% of lesional hemorrhages occurring within the initial year. Surgical intervention was necessary in 5% of patients. Hemorrhage risk and overall survival improved after 2015.
RADT-15. INTRACRANIAL OUTCOMES OF DUAL IMMUNE-CHECKPOINT INHIBITION AND SRS COMBINATION IN PATIENTS WITH MELANOMA AND NSCLC BRAIN METASTASES
Authors: Vaios Eugene , Shenker Rachel , Hendrickson Peter , Wan Zihan , Niedzwiecki Donna , Winter Sebastian F , Dietrich Jorg , Salama April , Clarke Jeffrey , Allen Karen , Mullikin Trey , Floyd Scott , Kirkpatrick John , Reitman Zachary 
Published: November 2023

Abstract

INTRODUCTION
The intracranial benefit of offering dual immune checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to melanoma and non-small cell lung cancer (NSCLC) patients receiving SRS for brain metastases is unknown. We hypothesized that D-ICPI improves local control compared to SRS alone.

METHODS
Melanoma and NSCLC patients treated with SRS between 2016-2022 were evaluated. Patients were stratified by treatment with D-ICPI, single ICPI (S-ICPI), or SRS alone. Local recurrence (LR), intracranial progression (IP), and overall survival (OS) were estimated using competing risk and Kaplan-Meier analyses. IP included both local and distant intracranial recurrence.

RESULTS
288 patients (44% melanoma, 56% NSCLC) with 1,704 brain metastases were included. 53% of patients had symptomatic metastases. Median follow up was 58.8 months. Patients were treated with D-ICPI (28%), S-ICPI (45%), or SRS alone (27%). 12-month local control rates with D-ICPI, S-ICPI, and SRS alone were 94.73% (95%CI:91.11-96.90%), 91.72% (89.29-93.64%), and 88.22% (84.06-91.41%). Only D-ICPI was significantly associated with reduced LR (p = 0.0032). 173 patients (60%) developed IP. The 12-month cumulative incidence of IP was 41.27% (95%CI:30.27-51.92%), 51.86% (42.78-60.19%), and 57.15% (44.98-67.59%) following D-ICPI, S-ICPI, and SRS alone. On competing risk analysis, only D-ICPI was significantly associated with reduced IP (p = 0.0408). On multivariate Cox regression, D-ICPI (HR:0.595,95%CI:0.373-0.951,p = 0.0300) and presentation with &gt;10 BMs (2.492,1.68-3.725,p &lt; .0001) remained significantly correlated with IP. Median OS following D-ICPI, S-ICPI, and SRS alone was 26.1 (95%CI:15.5-40.7), 21.5 (16.5-29.6) and 17.5 (11.3-23.8) months. Only D-ICPI trended toward improved OS (p = 0.0772). S-ICPI, fractionation, and timing of immunotherapy were not predictive of clinical outcomes.

CONCLUSIONS
The addition of D-ICPI for melanoma and NSCLC patients undergoing SRS is associated with improved local and intracranial control. This appears to be an effective strategy, including for symptomatic brain metastasis patients, regardless of fractionation or immunotherapy timing. Toxicity with this combination should be evaluated and balanced against clinical benefits.
RADT-16. A RETROSPECTIVE COMPARISON OF OUTCOMES AFTER WHOLE BRAIN RADIOTHERAPY AND RAPID SIMPLE (RAPPLE) TARGETED THERAPY FOR BRAIN METASTASES IN MATCHED COHORTS OF PATIENTS WITH POOR PROGNOSIS
Authors: Nichol Alan , Parmar Gurjit , Kong Tim , Hamm Jeremy , Liu Mitchell , Lefresne Shilo , Carolan Hannah , Berthelet Eric , Chan Jessica 
Published: November 2023

Abstract

BACKGROUND
For patients whose poor prognosis does not warrant stereotactic radiosurgery, we use the RAPPLE radiotherapy technique to treat multiple brain metastases. RAPPLE uses single-isocenter, coplanar volumetric modulated arc therapy and a non-stereotactic head-shell with IntegraBite™. Brain metastasis are contoured in a single gross tumour volume and expanded by 3 mm to create a planning target volume, covered by 95-110% of 20 Gy in 5 fractions. Our study compares clinical outcomes after RAPPLE and whole brain radiotherapy (WBRT).

METHODS
From January 2017 to December 2021, we identified patients receiving a first course of RAPPLE and matched patients receiving a first course of WBRT. Cox regression was used to analyze overall survival and Fine-Gray analysis was used to analyze intracranial progression. For each cohort, we compared patient-reported fatigue before and 2-6 weeks after radiotherapy.

RESULTS
Each cohort had 137 patients whose median Karnofsky Performance Score was 70. The diagnoses were lung cancer (72%) and other cancers (28%). The median survival was 4.1 months for RAPPLE and 4.2 months for WBRT (log-rank p = 0.8). On multivariable analysis of survival, the radiotherapy technique was not predictive (HR = 0.96, 95%CI: 0.73-1.25, p = 0.7). On multivariable analysis, intracranial progression was more likely after RAPPLE (HR = 1.6, 95%CI: 1.1 – 2.3, p = 0.02). The 18-month risk of intracranial progression was 0.49 for RAPPLE and 0.37 for WBRT (p = 0.04). After RAPPLE, 17% of patients required more focal RT and 4% required salvage WBRT, while after WBRT, 3% required focal RT and 4% required repeat WBRT. After RAPPLE, mean patient-reported fatigue remained stable from baseline to first follow-up (2.18 vs. 2.27, p = 0.9), but after WBRT it worsened (1.95 vs. 2.63, p = 0.002).

CONCLUSIONS
Ninety-six percent of patients treated with RAPPLE avoided WBRT. Patients reported worse fatigue after WBRT.
RADT-19. FACTORS PREDICTIVE OF OUTCOME IN GAMMA KNIFE STEREOTACTIC RADIOSURGERY FOR CEREBRAL METASTASES
Authors: Crispi Vassili , Reveendran Dharsshini , Hatfield Paul , Mathew Ryan 
Published: November 2023

Abstract

BACKGROUND
Stereotactic radiosurgery (SRS) in brain metastases is associated with prolonged quality of life, locoregional control, and stabilisation of neurological symptoms. Optimal patient selection is pivotal to achieving improved overall survival (OS). This study aimed to evaluate patient and disease factors associated with optimal outcomes.

METHODS
This retrospective study analysed 3,940 intracranial metastases in 1,113 patients treated with SRS at the Leeds Gamma Knife Centre between 2010 and 2020. Data on primary tumour, Karnofsky performance status (KPS), intracranial disease burden, steroid therapy, and treatment toxicity were recorded. Follow-up MRI imaging was performed at 6 months. OS curves were compared using the Log-Rank test (p &lt; 0.05).

RESULTS
Multivariate analysis revealed primary diagnosis (p &lt; 0.001), KPS (p &lt; 0.001), number of lesions (p = 0.005) and total tumour volume (p = 0.012) as significant predictors of median OS. Breast carried the highest median OS (18 months) compared to gastrointestinal tumours (7 months) and metastases of unknown origin (5 months). Higher functional performance at baseline was associated with greater median OS: from KPS 100 (18 months) to KPS 70 (6 months). Lower intracranial disease burden conferred greater median OS: patients with 1-3 treated lesions survived significantly longer (11 months) than those with 4 or more (9 months)(p = 0.001). Median OS reduced with an increasing total volume of treated metastases: 13 months if &lt;5000mm3, compared to 4 months if &gt;30000mm3. Following SRS, 375(33.7%) patients had new brain metastases with a median time of 6 months. 13.3% of these were local recurrence, and median time to recurrence ranged from 1.5 months in renal primary to 14.3 and 17.7 months in breast and gastrointestinal tumours, respectively. 195(17.5%) patients underwent further SRS with a median time of 7 months.

CONCLUSION
Primary diagnosis, KPS, and intracranial disease burden are significant pre-treatment predictors of OS for SRS in brain metastases.
RADT-28. DISRUPTION OF BIOENERGETICS ENHANCES RADIO-SENSITIVITY OF PATIENT-DERIVED GLIOBLASTOMA TUMORSPHERES
Authors: Yoon HongGyu , Park Junseong , Kim Seo Jin , Shim Jin-kyoung , Lee Eunhee , Choi Ran Joo , Moon Ju Hyung , Kim Eui-Hyun , Kang Seok-Gu 
Published: November 2023

Abstract

INTRODUCTION
Glioblastoma (GBM), the most common primary brain tumor, has been associated with poor prognosis despite various treatment modalities, the surgical resection accompanied by chemotherapy and radiotherapy. Although the importance of radiotherapy is well known, its combination with bioenergetics regulators has not been established in clinical practice. Here, we hypothesized that bioenergetics regulators improve the radio-sensitivity of GBM-tumorspheres (TS).

METHODS
Gene expression profiles of GBM patient-derived TSs were obtained from microarray. In vitro efficacies of the treatment were evaluated using clonogenic assay, 3D invasion assay, neurosphere-formation assay, and apoptosis-analysis. Protein expression was evaluated by western blot, and immunofluorescence was performed for detection of γH2AX foci. In vivo efficacies were confirmed using a mouse orthotopic-xenograft model.

RESULTS
GBM TSs with high-radioresistant or low-radioresistant were selected according to expression levels of radiation response associated genes. In order to select the bioenergetics regulators that significantly increased the radiotherapy effect of GBM-TSs, five bioenergetics regulators were combined which are oxidative-phosphorylation (OxPhos) inhibitor (IM156A), aldehyde-dehydrogenase inhibitor (gossypol) + OxPhos inhibitor (phenformin), fatty acid oxidation inhibitor (etomoxir), pentose-phosphate pathway inhibitor (dehydroepiandrosterone; DHEA) and glycolysis inhibitor (2-deoxy-D-glucose; 2DG). Amongst of these five bioenergetics regulators, DHEA and 2DG significantly augmented the therapeutic efficacies of ionizing radiation (IR) by reducing the survival fraction, stemness, and invasiveness in both high-radioresistant and low-radioresistant GBM TSs. IR combined with bioenergetics regulators (DHEA or 2DG) induced DNA damage response and apoptosis in low-radioresistant GBM TSs. In vivo experiments using a mouse orthotopic-xenograft model confirmed the tendency to prolong survival period and reduced the size in tumor after the combined treatment of 2DG with IR in low-radioresistant GBM TS.

CONCLUSION
These data proposes that the combination of bioenergetics regulators and radiotherapy is more effective than IR monotherapy itself. We expect that this combination regimen can strategically establish as a future treatment practice of GBM.
RADT-32. USING NEUROANATOMICAL SUBSITE TO PREDICT PATTERNS OF GLIOBLASTOMA INFILTRATION: POTENTIAL FOR INDIVIDUALISING RADIATION THERAPY TARGET VOLUME DELINEATION OF THE PARIETAL AND POSTERIOR FRONTAL REGIONS
Authors: Back Michael , Horsley Patrick , Yim Jackie , Drummond James 
Published: November 2023

Abstract

BACKGROUND
Radiation therapy(IMRT) protocols for glioblastoma utilize isotropic margin expansion around neurosurgical cavities/residual contrast enhancing(T1gd) disease. However pathways of infiltration may be associated with white matter tract(WMT) involvement varying between neuroanatomical subsites. Posterior frontoparietal tumours involving posterior cingulate region (PostCing) may have extensive infiltration centrally. This study aims to quantify the PostCing infiltration pathway/relapse sites.

METHODS
Consecutive patients managed for GBMwt with IMRT between 1/2016-6/2022 were classified into 15 neuroanatomical subsites. Tumour segmentation on T1-gadolinium-enhanced(T1gd) and T2-weighted(T2) sequences was performed at diagnosis/relapse. Subsites of Frontal Lobe (Posterior) and Parietal Lobe (Superior/Posterior/Lateral) were identified. On both sequences involvement of adjacent/distant regions (cingulate gyrus, cingulum, splenium, ventricular trigone, parahippocampal-hippocampal gyrus) were identified; as were major WMT: cingulum-parahippocampal formation(CING-PHG), and arcuate fasciculus–inferior longitudinal fasciculus(AF-ILF). Survival was analysed in relation to pattern of infiltration and site of relapse.

RESULTS
Of 348 patients with glioblastoma, fifty-five(16%) involved PostCing region. Pre-IMRT features included near-total resection in 25%; impaired ECOG 2-3 in 47%; and 58% MGMT-methylated. Parietal lobe tumours(67%) were predominantly posterior(42%) with only 7% lateral parietal. WMT involvement was evident in 94% with T1gd(62%), and T2 alone(33%) abnormality. Infiltration to distal sites of cingulum/splenium/PHG was frequent and predictable; correlating to cingulum pathway involvement in 70% of patients. Median RFS and OS was 13.2 months(95%CI: 11.8-14.8) and 16.6 months(95%CI:14.8-18.5) respectively. Distant relapse was evident in 53% of relapses. In the forty-four Stupp60Gy patients, distant relapse occurred later and was associated with improved overall survival(p = 0.02). No difference in RFS(p = 0.82) or OS(p = 0.31) was noted if tract involvement was either T1gd or T2 alone abnormality.

CONCLUSION
For glioblastoma in posterior cingulate region, the infiltration and relapse pathways followed white matter tracts in a predictable distribution with high rate of distant disease at diagnosis and relapse. IMRT potentially may be individualised for neuroanatomical subsite and non-isotropic target volume expansion.
RADT-35. STEREOTACTIC RADIOSURGERY FOR RESIDUAL, RECURRENT, AND METASTATIC HEMANGIOPERICYTOMAS: A SINGLE INSTITUTION EXPERIENCE
Authors: Yoo Kelly , Park David , Veeravagu Anand , Lee Marco , Marianayagam Neelan , Zamarud Aroosa , Gu Xuejun , Pollom Erqi , Soltys Scott , Chang Steven , Meola Antonio 
Published: November 2023

Abstract

INTRODUCTION
Hemangiopericytomas are infrequent vascular tumors originating from Zimmermann pericytes. The conventional treatment approach involves gross total resection (GTR), followed by adjuvant radiotherapy. Nevertheless, due to their tendency to infiltrate dural sinuses, high degree of vascularity, and anatomic inaccessibility, radical resection may be challenging with substantial risk of recurrence. To address this challenge, stereotactic radiosurgery (SRS) has been proposed as a promising adjuvant therapy. Objectives Our study aims to evaluate the effectiveness and safety of SRS as a potential treatment modality in patients with residual, recurrent, and metastatic hemangiopericytomas.

METHODS
From 1998 to 2023, 27 patients with 101 tumors underwent CyberKnife SRS at Stanford University Medical Center. The median age was 51 years at the time of treatment. The median follow-up period from SRS was 103 months (range: 6-250). All patients underwent upfront surgical resection. The median tumor volume was 1.5 cc. The median single-fraction equivalent dose (SFED) was 19 Gy. The SRS was administered at the 76% of the median isodose line (range: 64-89).

RESULTS
Of the 101 treated tumors, 24 (23.8%) progressed with a median time to recurrence of 30 months. At 10 years, the rates of local tumor control (LTC), overall survival (OS), and progression-free survival (PFS) were 74.3%, 80.8%, and 67%, respectively. In patients with residual lesions, the LTC rates were significantly greater when compared to those with residual or metastatic tumors. There was no significant difference between patients with residual, recurrent, and metastatic hemangiopericytomas in OS and PFS. Notably, no cases of radiation-induced adverse events were detected.

CONCLUSION
Our study provides the largest single-institutional retrospective series with hemangiopericytomas treated with SRS. SRS leads to excellent LTC, PFS, and OS at 10 years with negligible risk for adverse events. Therefore, it is an effective and safe management modality for patients with residual, recurrent, and metastatic hemangiopericytomas.