bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADT-14. EARLY OUTCOMES FROM PROTON CRANIOSPINAL IRRADIATION FOR LEPTOMENINGEAL METASTASIS FROM SOLID TUMORS
Authors: Lam Keng , Nasr Lewis , Andersen Clark , Marqueen Kathryn , Li Jing , Wang Chenyang , Majd Nazanin , Aaroe Ashley , Loghin Monica , McGovern Susan , O’Brien Barbara 
Published: November 2024

Abstract

INTRODUCTION
Treatment options for leptomeningeal metastasis (LM) are limited. A phase II study found that proton craniospinal irradiation (pCSI) was well-tolerated and improved survival. We report our experience with pCSI for solid-tumor LM.

METHODS
This is a retrospective review of patients treated with pCSI for solid-tumor LM from December 2020 to January 2024 at our center. Patient characteristics were summarized using descriptive statistics. Median overall survival (OS) and median central nervous system progression-free survival (CNS-PFS) from the first day of pCSI were estimated using Kaplan-Meier survival curves.

RESULTS
We identified 45 patients who completed pCSI. Median age was 54 years (range, 23-79); 73% were female, and 53% lived more than 100 miles from our center. Breast cancer (53%), lung cancer (20%), and melanoma (9%) were the most common primary cancers; 51% of patients had stable systemic disease at LM diagnosis. All had imaging evidence of LM, and 64% were confirmed by cytologic examination of the cerebrospinal fluid. Eighty percent had symptomatic LM, and the median Karnofsky Performance Scale (KPS) at LM diagnosis was 80. The median time from primary cancer diagnosis to LM diagnosis was 23.1 months (range, 0-221.3). Fifty-three percent of patients had active brain metastasis at LM diagnosis. At the first visit following pCSI, median KPS was 70. Seventy-six percent reported new or worsening nausea, 51% headache, and 31% fatigue. Following pCSI, 18% received LM surveillance, 4% intrathecal chemotherapy, 67% systemic therapy, 9% hospice care, and 2% lost to follow-up. Median OS was 13.7 months (95% confidence interval [CI], 11.2 to infinity), and median CNS-PFS was 6.5 months (95% CI, 4.9 to 12.8).

CONCLUSIONS
The outcomes in our cohort are comparable to those recently reported in a phase II trial. Further study is indicated to determine the optimal candidates for pCSI and sequential therapies.
RADT-18. DEDICATED 3D-FSE SEQUENCE-BASED RADIOSURGERY REDUCES DISTANT INTRACRANIAL RELAPSE RATES IN A HISTOLOGY-AGNOSTIC PATIENT COHORT
Authors: Akdemir Eyub Y , Rubens Muni B , Gurdikyan Selin , Abrams Kevin J , Sidani Charif , Press Robert H , Hall Matthew D , Wieczorek D Jay , Lee Cecillia , Tolakanahalli Ranjini , Gutierrez Alonso N , McDermott Michael W , Mehta Minesh P , Kotecha Rupesh 
Published: November 2024

Abstract

INTRODUCTION
Stereotactic radiosurgery (SRS) is a cornerstone in the treatment of brain metastasis (BM), despite a known risk of distant intracranial failure (DIF). Recent imaging advances, specifically, sensitive 3D-FSE sequences, have started to be incorporated into SRS practice; however, comparisons of outcomes to historical imaging approaches are limited. We evaluated the impact of adding 3D-FSE to MPRAGE in BM detection and prolongation of DIF in a histology-agnostic patient group.

METHODS
Outcomes of patients treated with SRS for BM between 01/2019-01/2024 were evaluated. MPRAGE sequences were obtained for all; 3D-FSE sequences were implemented in 02/2020. Median times to DIF were estimated using the Kaplan-Meier method.

RESULTS
215 patients underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-FSE (primary cohort), compared to the control cohort (92 patients, 135 SRS courses, 462 BM). MPRAGE sequences revealed 1636 lesions in 307 patients (462 in 92 control cohort, 1174 in 215 primary cohort). In the primary cohort, an additional 282 lesions were identified with 3D-FSE (24% increase) by neuroradiologists and multidisciplinary review. There was a statistically significant prolongation in the median time to DIF between the cohorts (11.4 vs. 6.8 months, p=0.029), most pronounced in the 1-4 metastases subgroup (14.7 vs. 8.1 months, p=0.008) and in those with a single BM (36.4 vs. 10.9 months, p=0.001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-FSE (7.2 vs. 5.7 months, p=0.280), those who relapsed on chemotherapy or were off systemic therapy at least four weeks prior to SRS (including synchronous metastases) exhibited a trend towards longer time to DIF with 3D-FSE (14.7 vs. 7.9 months, p=0.057).

CONCLUSIONS
3D-FSE added to MPRAGE lengthens time to DIF via improving BM detection, especially for limited BM, and those relapsing on systemic therapy with limited intracranial penetration or no systemic therapy.
RADT-20. POSTOPERATIVE RADIOTHERAPY PROVIDES ADDITIVE PROGRESSION-FREE SURVIVAL BENEFIT IN ATYPICAL MENINGIOMAS REGARDLESS OF EXTENT OF RESECTION
Authors: Tosi Umberto , Simonetto Marialaura , Giantini-Larsen Alexandra , Ramakrishna Rohan , Stieg Philip , Schwartz Theodore 
Published: November 2024

Abstract
WHO Grade II meningiomas represent a minority of all meningiomas. The creation of treatment algorithms has remained challenging, with the need to add postoperative radiotherapy (RT) following satisfactory gross total resection being oftentimes debated. Thus, the goal of this study was to understand which factors, if any, predispose to recurrence of atypical meningiomas following resection. Therefore, we retrospectively review a 90-patient cohort of WHO grade II meningiomas who underwent surgical resection. Patients were clustered based on tumor location, (convexity or non-convexity) and whether they had received postoperative RT. Following extraction of biographic characteristics, the extent of tumor resection and tumor recurrence were measured. A detailed uni- and multivariate analysis was carried out to determine which factors, if any, predisposed to recurrence. The cohort consisted of 90 patients with a WHO Grade II meningiomas. A gross total resection was achieved in 66.7% of patients. Patients who had a gross total resection and received postoperative RT had longer progression-free survival (p = 0.031) than patients with subtotal resections (STR), regardless of radiation status, and patients with a GTR who did not receive radiation. On uni- and multivariate analysis, receiving postoperative RT was the only factor associated with no recurrence of disease (p = 0.023); no association was found for extent of resection (p = 0.63) or location (p = 0.18). In conclusion, the treatment of WHO grade II meningiomas remains challenging. In this study, we showed how the addition of radiotherapy remains beneficial even in cases of gross total resection, regardless of location. We postulate how microscopic disease not observed on MRI may be responsible for these findings.
RADT-21. EFFICACY AND SAFETY OF DONUT-SHAPED CIRCUMFERENTIAL SPINE CYBERKNIFE STEREOTACTIC BODY RADIOTHERAPY FOR METASTATIC SPINE DISEASE
Authors: Park David , Kattaa Ahed , Chang Steven 
Published: November 2024

Abstract

BACKGROUND
Spinal metastases (SM) with epidural spinal cord compression (ESCC) are challenging to manage due to the risk of radiation-induced injury. Traditional approaches often avoid circumferential stereotactic body radiotherapy (SBRT) because of these risks. The efficacy and safety of donut-shaped circumferential SBRT, which envelops the spinal column while sparing the cord, remains underexplored.

OBJECTIVE
This study evaluates the safety and efficacy of donut-shaped circumferential spine CyberKnife SBRT in treating spinal metastases, focusing on preventing radiation-induced myelopathy and achieving local tumor control.

METHOD
We retrospectively analyzed patients treated with donut-shaped circumferential spine SBRT from 2014 to 2023. We evaluated demographics, grade of ESCC (Bilsky), prior treatments, symptoms, treatment parameters, and outcomes. Key measures included SBRT dosimetric data, radiation exposure to the spinal cord or cauda equina, adherence to dose-volume constraints, occurrence of post-SBRT myelopathy, other radiation-induced complications, and local tumor control.

RESULTS
Forty-eight lesions from 43 patients (median age: 65 years; range: 20-78) were analyzed. Only one patient underwent separation surgery for severe ESCC (Bilsky grade 3). The median clinical target volume (CTV) was 63.77 cc (range: 20.31-270.05), and the median margin dose was 24 Gy (range: 18-30). Over a median follow-up of 8 months (range: 1-91), local tumor control rates were 91.1% at 6 months, 87.1% at 1 year, 82.8% at 3 years, and 62.1% at 5 years. Median overall survival was 17 months. Of 20 lesions exceeding dose constraints, only one patient displayed clinical myelopathy symptoms, correlating with local tumor recurrence. There was no radiographic myelopathy or other radiation-induced complications during follow-up.

CONCLUSION
Donut-shaped circumferential spine CyberKnife SBRT provides effective and safe treatment for spinal metastases with or without epidural involvement. It achieves substantial local tumor control and has a minimal incidence of radiation-induced myelopathy, offering a viable non-surgical option for managing this complex condition.
RADT-28. THE ROLE OF CRANIAL RE-IRRADIATION IN EGFR MUTANT LUNG CANCER PATIENTS WITH BRAIN METASTASES
Authors: Luke Raymond , Ashamalla Hani , Beal Kathryn , Knisely Jonathan , Lee Jonathan , Garcia Christine , Mokhtar Bahaa , Panariti Anthony , Formenti Silvia 
Published: November 2024

Abstract

INTRODUCTION
Re-irradiation with stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT) may be used for treating recurrent brain metastases. Here, we are reporting on the rate of cranial re-irradiation based on our institutional experience in patients with mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (mEGFR-NSCLC).

METHODS
This is a retrospective review of patients from three NYP-WCM hospitals with brain metastases treated with radiotherapy and Tyrosine Kinase Inhibitors (TKIs) from December 2012 to May 2023.

RESULTS
Ninety-eight patients (60.5%) out of 162 with brain metastases from mEGFR-NSCLC were treated with radiation. Twenty-seven patients (27.5%) were treated with WBRT. Among 71 patients treated with SRS, 10 (14.1%) patients underwent surgical resection of the dominant brain lesion followed by fractioned SRS (FSRS) to the surgical bed. Sixty-one (85.9%) patients received SRS for intact brain lesions ranging from single fraction 16-20Gy to FSRT with 24Gy –30Gy in 3-5 fractions based on the size and eloquence of the brain site of the brain metastasis. In the SRS group, fifteen (21.1%) patients required at least one more course of cranial irradiation. The mean duration of local intracranial control between the first and the second course of radiation was 19.6 months [range from 2.0- 56.7 months], while from the start of TKI to the first intracranial failure was 11.3 months [0.8m-45.3 months]. In the WBRT group, two patients (7.4%) were treated with another course of WBRT 20Gy in 5 fractions. These two patients started TKI simultaneously with their first course of WBRT; the mean duration of intracranial local control was 12.8 months [range from 11.6-14.1 months]. Both patients suffered significant cognitive declines.

CONCLUSION
In the Tyrosine Kinase Inhibitor era, patients with brain metastases from mEGFR-NSCLC have protracted progression-free survival. Multiple courses of cranial re-irradiation may be needed. Stereotactic radiotherapy should be preferred for the best results in preserving cognitive functions.
RADT-42. DISSEMINATED TUMORAL AMYLOIDOSIS OF THE CRANIAL NERVES IN THE ABSENCE OF SYSTEMIC DISEASE: CASE REPORT
Authors: Rogers Aubrey , Heller Robert 
Published: November 2024

Abstract
Tumoral amyloidosis, characterized by tumor-like deposits without systemic disease, is rare in the central nervous system. Most often located in the periventricular white matter, tumoral amyloidosis typically consist of immunoglobulin light chains (AL). While prior reports describe cases of tumoral amyloidosis isolated to the trigeminal nerve, we report herein a first known case of diffuse cranial nerve involvement. The patient is a 43-year-old man who presented with left trigeminal dysesthesias, which led to self-excoriation and erosion of the left naris. On exam, he had absent sensation in the V1-V3 distributions, left trochlear nerve palsy, and bilateral abducens nerve palsies. Imaging demonstrated significant thickening of the left trigeminal nerve and diffuse cisternal contrast enhancement of the other cranial nerves, including the oculomotor, abducens, facial, and glossopharyngeal nerves. Work-up began with a lumbar puncture that found elevated protein with otherwise benign results, including flow cytometry. He was therefore recommended to undergo open biopsy of the left trigeminal nerve and cavernous sinus. Pathology from this surgery demonstrated congo red- positive AL amyloid deposits. Following this pathologic diagnosis, he subsequently underwent a full workup for systemic amyloidosis including bone marrow biopsy, abdominal fat pad biopsy, and a PET CT scan. Biopsy of a long nodule was negative for amyloidosis. Systemic amyloid testing did not demonstrate non-CNS sites of amyloid deposition. Medical therapy with daratumumab, cyclophosphamide, bortezomib, and dexamethasone was started but then discontinued due to ineffectiveness. He underwent radiation treatment of 4500 cGy to the left cavernous sinus where the tumoral amyloidosis was most severe. He has had no further progression of his disease. Tumoral amyloidosis of the cranial nerves remains a rare and poorly-understood disease. Prior reports have described the disease isolated to the trigeminal nerve. This report raises attention to this diagnosis in cases of rare multi-nerve involvement and suggests that radiation may be a useful first-line treatment.
RADT-43. RADIOSURGERY FOR BRAIN METASTASES FROM GYNECOLOGICAL PRIMARIES: AN INSTITUTIONAL PERSPECTIVE OF 58 METASTATIC LESIONS
Authors: Sreenivasan Sanjeev , Jung Jessica , Calugaru Emel , Schulder Michael , Goenka Anuj 
Published: November 2024

Abstract
Stereotactic radiosurgery (SRS) is being increasingly employed in the treatment of brain metastases. The evidence of radiological response of metastatic lesions from gynecological primary is lacking in literature. To assess the response rate of metastatic lesions to gamma knife SRS over a longitudinal follow-up period, a single centre prospectively maintained database was analysed retrospectively from 2014 to 2024. Lesion volumes were contoured at each follow up scan using Leksell Gammaplan software. Response assessment in neuro-oncology (RANO) criteria was used to assess radiological tumor response rates. Fifteen patients with 58 lesions were included. Average duration of radiological follow-up available was 16.7 months. The primary gynecological source of brain metastases in patients were cervical(n=4), ovarian(n=7), endometrial(n=3) and vulvar (n=1). Single fraction SRS was used for 49 lesions (range 16-20 Gy) and hypofractionated SRS for 9 lesions (8Gy x 3 to 9Gy x3). Average time to complete response was 9.01 months (range 1-25.7). The average follow-up for lesions with partial response was 12.2 months (range 1 -32) As per RANO criteria, complete response was seen in 33(56.9%) lesions and partial response in 25(43.1%). At 6month follow up, complete response was seen in 58.49% (n=31) of the lesions available(n=53) for assessment and partial response in 41.51%(n=22). At 18-months, complete response was seen in 66.67%(n=22) and partial response in 33.33%(n=11). Within pathological subgroups, endometrial (60%,n=3) primary showed higher rate of complete response at 6months than ovarian (52.7%,n=19), vulvar (50%, n=1) and cervical (40%,n=6) subgroups. Brain metastases from ovarian primary source were most encountered and endometrial metastases showed highest response rates to SRS. Six month and 18-month response rates were better than previously reported literature.
CTIM-04. MODULATION OF THE INTRATUMORAL IMMUNE MICROENVIRONMENT BY LOCAL THERAPY WITH NATURAL KILLER CELLS ENGINEERED WITH A HER2-TARGETED CHIMERIC ANTIGEN RECEPTOR IN COMBINATION WITH SYSTEMIC ANTI-PD-1 CHECKPOINT INHIBITION IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Burger Michael , Ehrend Elisabeth , Straßheimer Florian , Cakmak Pinar , Krenzlin Harald , Elleringmann Philipp , Zeiner Pia , Herkt Stefanie , Poschke Isabel , Macas Jadranka , Weber Katharina , Schupp Jonathan , Lun Jennifer , Opitz Corinna , Roller Bastian , Manns Patricia , Klinsing Svenja , Breuer Stella , Hehlgans Stephanie , Lee Seo-Youn , Mildenberger Iris , Ludmirski Gleb , Hermann Julian , Müller Elvira , Schmitz Marc , Mehlitz Marcus , Senft Christian , Harter Patrick , Rieger Michael , Rödel Franz , Czabanka Marcus , Ratliff Miriam , Platten Michael , Herold-Mende Christel , Ringel Florian , Herrmann Eva , Hattingen Elke , Reiss Yvonne , Bunse Lukas , Bonig Halvard , Plate Karl , Forster Marie-Therese , Tonn Torsten , Wels Winfried , Steinbach Joachim 
Published: November 2024

Abstract
Glioblastoma (GB) is characterized by a marked immunosuppressive tumor microenvironment. In the multicenter CAR2BRAIN phase I first-in-human clinical trial, we investigated the modulation of the tumor microenvironment by repetitive local injection of clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2 alone and in combination with systemic anti-PD-1 checkpoint inhibitor therapy in patients with recurrent HER2-positive GB. 6 patients were treated with repetitive doses of CAR-NK cells as monotherapy and 12 patients received a combination therapy with the anti-PD-1 checkpoint inhibitor ezabenlimab. In three of those, we were able to implement a biopsy-treat-resect-treat strategy. After initial biopsy, combination treatment was initiated before planned tumor resection, enabling analysis of the transformation of the tumor immune microenvironment by highplex multispectral fluorescent analyses and cytokine quantification. None of the patients developed a cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Profound alterations of the immune cell distribution in the cerebrospinal fluid (CSF) and in the tumor were observed. In CSF sampled from the resection cavity, combination immunotherapy induced a local immune response with elevated pro-inflammatory cytokines and cell counts. In post-treatment tissue samples, we observed an increase of CD4+ and CD8+ T cells, and a decrease of regulatory CD4+FoxP3+ T cells. The three patients treated following the biopsy-treat-resect-treat strategy achieved a median progression-free survival (PFS) of 24 weeks, compared to 10 weeks for patients with upfront resection. Local immunotherapy with HER2-targeted CAR-NK cells is feasible and safe both as monotherapy and in combination with the systemic checkpoint inhibitor ezabenlimab and induces local immune reactions in CSF and tumor tissue. Given the signal for possible clinical benefit provided by the increase in PFS in the patients of the biopsy-treat-resect-treat cohort, further trials are warranted.
CTIM-09. INB-200: FULLY ENROLLED PHASE 1 STUDY OF GENE-MODIFIED AUTOLOGOUS GAMMA-DELTA (ΓΔ) T CELLS IN NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME (GBM) PATIENTS RECEIVING MAINTENANCE TEMOZOLOMIDE (TMZ)
Authors: Lobbous Mina , Goswami Trishna , Lamb Larry , Rochlin Kate , Pillay Thiru , ter Haak Mariska , Nabors Louis B 
Published: November 2024

Abstract
IN8bio’s DeltEx drug resistant immunotherapy (DRI), comprising TMZ-resistant γδ T cells engineered to express methylguanine-DNA methyltransferase (MGMT), enables γδ T cells to target upregulated NKG2D ligands on tumor cells in real time during alkylating chemotherapy exposure. Updated results from the fully enrolled Phase 1 trial evaluating DRI in adult newly diagnosed GBM subjects with IDH wild type and mutant tumors, adequate organ function and KPS ≥ 70%. Cohorts (C) 1, 2 and 3 received 1, 3 or 6 doses (1 x 107 DRI cells/dose) into the resection cavity with 150 mg/m2 of IV TMZ on Day 1 of each of 6 Stupp maintenance cycles. The primary endpoint is safety and secondary endpoints include survival; immunologic correlative analyses are included. Dose limiting toxicities (DLTs) are defined as treatment related ≥ grade (G) 3 cardiopulmonary or hepatic toxicity, G4 toxicity exceeding 72 hours or neurologic deterioration that exceeds 2 weeks. A total of 23 subjects were enrolled and 13 dosed (61% male; median age 68 (range: 21-74); 92% IDH-WT, 54% MGMT unmethylated). No DLTs, cytokine release syndrome (CRS), neurotoxicity (ICANS) or treatment related deaths were reported. The most common adverse events were decreased WBC/platelet count, asthenia, fatigue, hydrocephalus, headache, decreased appetite, urinary tract infection, thrombosis and balance disorder with ≥G3 platelet count decreased in 23% and WBC/ neutrophil/ lymphocyte count decreased in 7.7% each. Peripheral TMZ-based lymphodepletion was maintained for up to 1 year evidenced by near or below normal range T, B, and NK subsets. With median follow-up of 10.8 months, 83% of subjects exceeded the median 7 month Progression Free Survival (PFS) of the Stupp regimen alone, had manageable toxicity with a continued encouraging trend in PFS. Subject with IDH mutant tumor remains progression free for &gt; 35 months. Long-term follow-up for durability of PFS and OS continues.
CTIM-10. PHASE 1 TRIAL OF PERSONALIZED NEOANTIGEN VACCINES IN COMBINATION WITH STANDARD CARE TO TREAT GLIOBLASTOMA
Authors: Bozkus Cansu Cimen , Kodysh Julia , Cheng Szu Jung , Cheng Samantha , Rubinsteyn Alex , O’Donnell Tim , Saxena Mansi , Akturk Guray , Meseck Marcia , Yong Raymund , Losic Bojan , Mandeli John , Kim Ryung S , Gnjatic Sacha , Bhardwaj Nina , Hormigo Adilia 
Published: November 2024

Abstract
The tumor microenvironment (TME) of glioblastoma (GBM) is populated by cells that foster immunosuppression. Reversing immunosuppression and promoting tumor surveillance by T cells that recognize the antigens generated by tumor-specific mutations (neoantigens) is critical to eliminating the tumor cells. In a phase 1 clinical trial of newly diagnosed GBM (NCT03223103), patients were treated with personalized neoantigen vaccines (PNV) combined with standard of care (resection, radiotherapy, temozolomide chemotherapy, and TTFields). The neoantigens were identified using the OpenVax computational pipeline. Primary endpoints included safety and feasibility, and the secondary endpoints included PFS, OS, TME analysis, and immunogenicity assays. The study enrolled 12 patients, ages 32-84, between December 2017 - July 2020. With a feasibility endpoint of one successful PNV administration, all patients got at least 6. All developed PNV-related injection site reactions, and flu-like symptoms grade 1-2. Concomitant use with TTFields did not increase toxicity. None of the patients exhibited dose-limiting toxicity within 30 days of receiving the PNV. However, one developed grade 3 SAE, consisting of seizures, neck pain, and progressive neurological deficits, after vaccine 10, culminating in a grade 5 SAE and brain demyelination 10 months later. Assays performed on this subject showed induction of neoantigen-specific responses with PNV. PNV induced CD4+ and CD8+ T cells reactive against multiple vaccine peptide sequences with CD8+ T cell cross-reactivity against one wild-type epitope. Other patients had immunogenicity against the vaccinated peptides. Overall, the 6 months PFS was 100%, with 67% 2-year and 58% 3-year survival. Although the mutation burden is low in GBM, neoantigens were detected in all tumors, and PNV were manufactured for all patients. PNV with synthetic long peptides combined with standard care treatment may help improve outcomes in GBM. Cross-reactivity may potentially be responsible for post-vaccination T-cell demyelination. Further evidence is needed to substantiate a direct effect. Funding: CRI - V Foundation CLIP (#3680)