bluuebunny/crossref_metadata_2025 huggingface dataset:
MMOD-18 THE IMPACT OF CONTRAST CLEARANCE ANALYSIS-GUIDED REPEAT SRS ON SURVIVAL IN PATIENTS WITH BRAIN METASTASES
Authors: Madhugiri Venkatesh , Goulenko Victor , Recker Matthew , Prasad Dheerendra , Plunkett Robert
Published: August 2024

PURPOSE

Adverse radiation effects (ARE) including pseudoprogression are known toxicities associated with radiation for intracranial lesions. ARE are often difficult to differentiate from tumor progression. Delay in identification of tumor progression or misidentification of progression as ARE can lead impact patient survival. In this study, we demonstrate the utility of Contrast Clearance Analysis® (CCA) in differentiating ARE from progression and the impact of CCA-guided decision making on patient survival.

METHODS

Fifty-seven consecutive patients who had been diagnosed with brain metastasis and treated with Gamma Knife Radiosurgery (GKRS) and had presented with suspicious lesion growth on follow-up MRI scans underwent CCA to distinguish between treatment effect and tumor progression. Lesions considered to have recurrence were retreated with repeat GKRS. Survival analyses were carried out to evaluate the impact of early CCA-guided retreatment on survival.

RESULTS

The most common primary disease was non-small cell lung cancer (40%), followed by breast cancer (12%) and melanoma (11%). The use of CCA indicated ARE in 24 lesions and 35 to be pseudoprogression. The total follow-up period was of 72 months. Kaplan-Meir Survival Analyses showed that retreated patients had better survival than the general cohort of patients who did not have CCA-informed retreatments (p< 0.05).

CONCLUSION

CCA is a promising tool to distinguish between tumor progression and ARE in the setting of radiosurgical treatment. Early differentiation allows early retreatment and improvement of the patient survival.
NIRL-05 DIFFERENTIATING RADIATION NECROSIS FROM TUMOR RECURRENCE IN BRAIN METASTASIS USING MRF– A FEASIBILITY STUDY
Authors: Gongala Sree , Zhao Walter , Vempati Prashant , Hodges Tiffany , Newton Herbert , Ma Dan , Badve Chaitra
Published: August 2024

INTRODUCTION

Current imaging modalities are limited in accurately differentiating between tumor recurrence (TR) and radiation necrosis (RN) in brain metastasis (BM) patients. This can affect the ability to treat these patients in an effective and timely manner. Magnetic Resonance Fingerprinting (MRF) is an imaging modality that provides quantitative relaxation times and information about tissue properties. In this study, we explore the ability of MRF to differentiate between TR and RN in BM patients.

METHODS

This is a retrospective IRB approved cross-sectional analysis of 13 BM patients (4 new metastases; NM, 3 TR and 6 RN). MRF and multiparametric MRI images w/wo contrast were acquired for all the patients. Diagnosis was established by histopathology or brain tumor board consensus. Image preprocessing was performed using Cancer Imaging Phenomics Toolkit (CaPTk) and Deepmedic. For MRF, the pre-contrast T1, post-contrast T1, pre-T2, post-T2, ΔT1 and ΔT2 maps were generated. Voxel based analysis was performed across three groups using Kruskal Wallis test.

RESULTS

There are significant differences in median pre-T1 (Median values in ms; NM = 1638.03, RN = 1824, TR = 1282.2), post- T1 (Median values in ms; NM = 1116.7, RN = 577.9, TR = 892.9), pre-T2 (Median values in ms; NM = 74.6, RN = 75.6, TR = 80.6) and post-T2 (Median values in ms; NM = 74.6, RN = 75.6, TR = 80.6) across NM, RN and TR patient groups. Particularly, these differences were larger, and the density plots were visibly different on T1 dependent maps as compared to T2. Consequently, the ΔT1 and ΔT2 values were also significantly different across these three groups.

CONCLUSIONS

In this ongoing study, our preliminary results show the ability of MRF in differentiating RN from TR in BM patients. Larger datasets will be accrued in the future to further test this relationship.
NIRL-08 AUTOMATED LONGITUDINAL TRACKING OF BRAIN METASTASES INTEGRATED IN A USER-ORIENTED SOFTWARE
Authors: Emiliani Ramon D , Chartrand Gabriel , Son Edward , Pawlowski Sophie A , Rajakesari Selvan , Cengarle-Samak Alexandre , Lavoie Jeremi , Ducharme Simon , Roberge David
Published: August 2024

The burden of detection and segmentation of brain metastases (BM) for treatment planning and response assessment has been found to be alleviated by machine learning methods. However, tracking individual lesions over time remains tedious and would benefit from automated assistance for complex cases. We developed a software solution combining an AI-based BM segmentation method with an automated pairing algorithm allowing to track BM across longitudinal scans. The proposed tracking method comprises two steps: identifying lesions in each scan and pairing identified findings across scans. Identification and segmentation of BM is done with our previously published neural network based algorithm. Tracking of BM is achieved by progressively assigning a lesion ID to individual findings. For each series, individual findings are co-registered using image registration to a reference series which defines the initial set of lesions. A matching function then computes a score for each possible finding-lesion pair based on diameter similarity and inter-centroid distance. Findings from highest scoring pairs are sequentially assigned their matched lesion ID, while pairs scoring under a given threshold are assigned a new lesion ID. Series are processed as such until all findings are dispatched. Assignment accuracy was assessed using adjusted rand index (ARI) on a synthetic noisy dataset simulating registration error and misdetections. Findings from 10 to 20 lesions on 5 series of dimension 100 mm per side were randomly generated for 100 synthetic patients each. With a simulated registration error range of 0-2 deg and 0-5mm, the average per patient ARI was 0.94 +/- 0.05, while an error range of 0-4 deg and 0-10mm lowered ARI to 0.87 +/-0.08. Results support the validity of our software solution for automated detection and longitudinal tracking of BM, which can alleviate the burden of follow-ups in the context of stereotactic radiosurgery.
NIRL-10 LEPTOMENINGEAL ENHANCEMENT WITH PARANEOPLASTIC CEREBELLAR DEGENERATION: AUTOIMMUNE OR METASTASES?
Authors: Shah Trusha , Prince Alaina , Venur Vyshak , Graber Jerome
Published: August 2024

Enhancement has been occasionally reported in patients with paraneoplastic cerebellar degeneration but metastases can also occur in these patients and standard imaging and cerebrospinal cytology lack sensitivity and specificity. Among a retrospective case series of 31 patients with paraneoplastic cerebellar degeneration, 4 patients had enhancement at some point of their MRI. We report a series of four patients with paraneoplastic cerebellar degeneration with enhancement and possible concurrent or subsequent leptomeningeal metastases and review the literature. Patient 1 was a 66 year old man with merkel cell carcinoma who had subacute onset of ataxia with nausea. Initial MRI showed non enhancement cerebellar FLAIR changes. Paraneoplastic panel was negative in blood and CSF and seronegative PCD was diagnosed without response to immunosuppression. Eight months later he developed progressive cerebellar symptoms and diffuse leptomeningeal enhancement was found in the cerebellum and spine consistent with leptomeningeal metastates. Patient 2 is a 50 year old woman with HER2+ breast cancer who developed acute cerebellar symptoms with focal cerebellar enhancement and PCA1 antibody was present. Her symptoms stabilized with immune suppression and enhancement resolved, but CSF showed atypical cells suggestive of concurrent leptomeningeal metastases. Patients 3 and 4 both had serous ovarian carcinoma and subacute onset of cerebellar symptoms with cerebellar enhancement and PCA1 antibody with negative CSF cytology. Both stabilized with immune suppression but within months developed more diffuse widespread CNS nodular enhancement considered to be leptomeningeal enhancement. Enhancement is uncommon but not rare in paraneoplastic cerebellar degeneration, occurring in more than 10% of patients in this retrospective series. Others have reported enhancement in paraneoplastic cerebellar degeneration related to autoimmune process alone, but metastases can also occur and may be difficult to distinguish, creating a diagnostic and therapeutic dilemma.
NIRL-11 3D-FSE IMAGING FOR RADIOSURGERY PLANNING IMPROVES BRAIN METASTASIS DETECTION AND REDUCES INTRACRANIAL RELAPSE
Authors: Akdemir Eyub Y , Press Robert H , Hodgson Lydia C , Rubens Muni B , La Rosa Alonso , Kutuk Tugce , Wieczorek D Jay , Lee Cecillia , Bejarano Tatiana , Tolakanahalli Ranjini , Gutierrez Alonso N , McDermott Michael W , Mehta Minesh P , Kotecha Rupesh
Published: August 2024

INTRODUCTION: Stereotactic radiosurgery (SRS) is an effective treatment for brain metastasis (BM), but patients remain at significant risk for distant intracranial failure (DIF) due to undetected lesions at the time of SRS or subsequent seeding. We implemented dedicated treatment planning imaging with novel MR sequences with the goals of enhancing lesion detection and consequentially increasing time to DIF, correspondingly reducing the need for whole-brain radiotherapy (WBRT). METHODS: Patients treated with SRS for BM between 05/2019-01/2024 were evaluated. MPRAGE sequences were performed for all, and 3D-FSE sequences were added starting in 02/2020. Median times to DIF and WBRT for both cohorts were estimated using the Kaplan–Meier method. RESULTS: 194 patients underwent 310 SRS courses for 1326 BM imaged with both MPRAGE and 3D-FSE (primary cohort), compared to the control cohort (88 patients, 116 SRS courses, 373 BM). MPRAGE sequences detected 1456 lesions in all 282 patients (373 in 88 control patients, 1083 in 194 primary cohort patients). In the primary cohort, an additional 204 lesions were identified with 3D-FSE (18% increase). An additional 39 lesions (3.6% increase) were identified on multidisciplinary review of both MR modalities. Although there was no statistically significant difference in median time to DIF between the cohorts (11.3 vs. 6.7 months, p=0.14), there was a trend towards longer DIF in the 1-4 metastases subgroup (14.6 vs. 7.9 months, p=0.052) and a statistically significant difference in those with a single BM (35.9 vs. 11.8 months, p=0.017). WBRT rates at 2-years were similar between the cohorts, 15% vs. 20%, p=0.2, respectively. CONCLUSIONS: A dual sequence approach at the time of SRS with multidisciplinary review improves lesion detection and lengthens time to DIF and, ultimately, next intervention. This is especially useful in confirming true BM number in those with limited intracranial disease.
NIRL-13 HISTOPATHOLOGIC CONFIRMATION OF TUMOR RECURRENCE IDENTIFIED ON CONTRAST CLEARANCE ANALYSIS MAPS - A VALIDATION STUDY
Authors: Madhugiri Venkatesh , Goulenko Victor , Bregdy Amade , Recker Matthew , Lipinski Lindsay , Fabiano Andrew , Fenstermaker Robert , Plunkett Robert , Abad Ajay , Belal Ahmed , Alberico Ronald , Qiu Jingxin , Prasad Dheerendra
Published: August 2024

BACKGROUND

Stereotactic radiosurgery (SRS) has become a standard modality in the treatment of brain metastases. The differentiation between adverse radiation effects (ARE) and tumor recurrence or progression is important in this setting. The advent of immunotherapy and targeted therapy often makes this distinction difficult to achieve. Contrast clearance analysis (CCA) is a useful technique that can inform clinical decisions but has so far only been histologically validated in the context of high-grade gliomas.

METHODS

Between 2018 and 2023, more than 200 patients who had been treated with SRS for various brain pathologies including brain metastasis, atypical meningiomas, and high-grade gliomas underwent CCA studies. Among these patients, clinical scenarios mandated surgery in 7 patients. Targeted biopsies were taken at the time of surgery in all patients. Histopathology findings were compared with the CCA findings in these patients.

RESULTS

All 7 patients had been treated with gamma knife radiosurgery and were being followed up with periodic MR imaging. All patients underwent CCA when the necessity to distinguish tumor recurrence from ARE/ radiation necrosis arose. Targeted biopsies showed 100% concordance of the pre-surgery CCA findings with histological findings. Viable tumor tissue was identified on pathology in all instances where the CA map indicated the presence of viable tumor represented in blue color.

CONCLUSIONS

Based on prior studies on GBM and the surgical findings in our series, delayed contrast extravasation MRI findings correlate well with histopathology. CCA can provide a quick diagnosis and have a direct impact on patient treatment and outcomes.
NVTG-02 CIRCULAR RNAS AS NOVEL TARGETS IN BREAST-TO-BRAIN CANCER METASTASIS
Authors: Szczepaniak Adrian , Bronisz Agnieszka , Godlewski Jakub
Published: August 2024

Breast-to-brain metastatic (BTB met) cancer constitutes a great challenge for modern medicine and science, and thus, a quest for the discovery of novel therapeutic targets is underway. As the research on protein-coding genes has brought only incremental progress in discovering such targets, much attention is currently devoted to understanding the role of non-coding RNAs, including a relatively recently discovered group of circular RNAs. These non-coding RNAs, which arise from linear RNA transcripts, possess a covalently closed structure that renders them resistant to RNA turnover and a specific circularization site sequence that allows their precise suppression while keeping the linear parental transcript intact. These features thus make them promising candidates for biomarkers and therapeutic targets. This project aimed to map the circular RNA landscape in a comprehensive model of BTB met cancer cells, primary breast carcinoma, primary brain tumor cells, and relevant non-malignant breast and brain cell controls. Despite different tissue-of-origin, the analysis of global circRNAomes showed striking similarities between BTB mets and glioblastoma stem-like cells (GSCs) and allowed the selection of reliable candidates for mechanistic studies. Interestingly, the circRNAome of BTB mets clustered particularly closely with mesenchymal GSC, the most aggressive and therapy-resistant subtype of GSCs. Efficient knockdown of candidate circular RNAs in BTB met cells by antisense oligonucleotides resulted in molecular and phenotypic alterations such as diminished viability and clonality, arrested cell cycle concurrent with increased expression of cyclin-dependent kinase inhibitors, and changed expression of epithelial-mesenchymal transition markers. These results thus demonstrated the role of circular RNAs in shaping the oncogenic traits of BTB met cells. Further research focuses on circular RNA-dependent chemotherapy resistance, stemness/differentiation balance, and relevant models of metastatic progression (primary site/pleural effusion/brain). Therefore, circular RNAs can serve as valuable biomarkers and promising novel mechanistic candidates whose modulation may become a paradigm-shifting therapeutic approach.
NVTG-07 SAFETY, TOLERABILITY, AND ANTITUMOR ACTIVITY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH HER2+ METASTATIC BREAST CANCER (MBC) AND ACTIVE BRAIN METASTASES (BMS) IN DESTINY-BREAST07 (DB-07)
Authors: Anders Carey , Loi Sherene , Hamilton Erika , Jhaveri Komal , Schmid Peter , Gökmen Erhan , Im Seock-Ah , Karaçin Cengiz , Barrios Carlos , Park Yeon Hee , Topaloğlu Sernaz , Boston Sarice , Konpa Adam , Mondal Shoubhik , André Fabrice
Published: August 2024

BACKGROUND

DEBBRAH, ROSET-BM, TUXEDO-1, and a pooled DB-01, -02, -03 analysis indicate robust efficacy of T-DXd in patients with stable/active BMs; however, efficacy in active BMs is not yet fully established. DB-07 is a Phase 1b/2, multicenter, open-label study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). Results are from an interim analysis of the dose-expansion phase of T-DXd monotherapy in patients with active BMs.

METHODS

Patients had locally assessed HER2+ mBC with measurable disease. No or one prior line of therapy for mBC was allowed; a ≥12-month disease-free interval from (neo)adjuvant HER2-directed therapy or chemotherapy was required. Patients had untreated BMs not requiring local therapy or progressing BMs after local therapy. Ongoing use of systemic corticosteroids (>2 mg dexamethasone daily or equivalent) for control of BMs symptoms was exclusionary. Patients received T-DXd 5.4 mg/kg intravenously every 3 weeks. Primary objectives were safety and tolerability; additional endpoints included objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1 and Response Assessment in Neuro-Oncology (RANO)-BM.

RESULTS

Thirty-five patients with active BMs were treated. As of August 1, 2023, median follow up was 11.5 months (range 5.3–24.6). The most common any-grade adverse events (AEs) were nausea (74.3%; Grade 3, 5.7%) and vomiting (45.7%; Grade 3, 2.9%); AEs Grade ≥3 occurred in 18 patients (51.4%). By RECIST 1.1, confirmed ORR was 77.1% (80% CI 65.5, 86.2), and 12-month PFS rate was 84.5% (80% CI 74.1, 91.0). By RANO-BM, confirmed ORR was 57.1% (80% CI 44.9, 68.7) and 12-month PFS rate was 74.6% (80% CI 59.4, 84.8).

CONCLUSION

The safety profile is consistent with the known profile for T-DXd, and data confirm promising efficacy in patients with active BMs. Ongoing analyses will provide more mature data.
NVTG-08 PERSONALIZED TREATMENT OF MELANOMA BRAIN METASTASES THROUGH HIGH THROUGHPUT DRUG SCREENING
Authors: Doonan Bently , Spicer Timothy , Rahman Maryam , Scampavia Louis , Vega Virneliz Fernandez , Benslimane Nesrine , Mctiernan Raquel , Von Roemeling Christina , Mitchell Duane
Published: August 2024

Melanoma is an increasing clinical concern, with an expected increase in incidence over the next 20 years. Compounding this problem, as many as 70% of all metastatic patients will develop brain metastases as a manifestation of their disease. Current strategies including immunotherapy, targeted therapy, and local therapies (surgery, SRS, and LITT) have greatly improved patient outcomes yet fail to cure the majority of patients, with intracranial progression a major driver of mortality. Novel treatment strategies are needed to provide immediate options for our patients. To combat this issue, we have developed a pipeline of high throughput drug screening of patient derived tumor microspheres, capable of screening over 100,000 compounds rapidly for potential therapeutic options for patient at time of progression following standard of care. These high throughput results are further paired with tumor derived genomic sequencing to identify potential biomarkers of drug responsiveness. Through this work we will identify potential patient specific therapy options for use in compassionate care trials and through utilization of blood brain barrier permeabilization strategies (LITT or low frequency ultrasound) we plan to expand the pool of available therapies to include those therapies traditionally not capable of reaching drug concentration intracranially. If successful, this strategy has the potential for reshaping both individual patient outcomes, but identifying novel candidate therapies for future clinical trial design.
NVTG-09 TARGETING TRKB IN LUNG-TO-BRAIN METASTATIC PROGRESSION
Authors: Contreras-Zárate Maria J , Koliavas Stella , Heasley Lynn , Pine Sharon , Nemenoff Raphael , Camidge D Ross , Cittelly Diana
Published: August 2024

Brain metastases (BM) are a common site of metastasis for both non-small cell (NSCLC) and small cell lung cancer, affecting 20-56% of advanced lung cancer (LC) patients. In breast cancer models, we have shown that astrocytes secrete brain-derived neurotrophic factor (BDNF), which, in a paracrine manner, activates its receptor tropomyosin-related kinase B (TrkB, also called NTRK2) in a subset of cancer cells, promoting BM. Although NTRK gene rearrangements are known to function as primary oncogenic drivers in a subset of NSCLC, wildtype TrkB has been shown to promote lung adenocarcinoma metastases and TrkB expression was associated with worse survival in multiple LC subtypes. Thus, we

HYPOTHESIZE

that paracrine BDNF/TRKB activation is also a mechanism whereby subsets of non-NTRK rearranged LC cells can colonize the brain. We investigated TrkB expression levels in murine (CMT167) and human (LU65, H358, PC9BR3, H2030BR3) LC cell lines and their ability to form BM in mouse models. TrkB expression varied among cell lines, with brain metastases incidence of 20% (CMT167), 50% (PC9BR3), 64% (H358) and 75% for H2030BR3. While all cells responded to BDNF stimulation activating AKT, ERK and PLCg signaling, H358 and H2030BR3 cells showed faster and stronger TRKB activation. Stimulation with astrocyte-conditioned media (Ast-CM) or coculture with astrocytes, activated TrkB and promoted proliferation and invasion of LC cells. Entrectinib, an FDA-approved drug for NTRK fusion-positive solid tumors, decreased BDNF and Ast-CM-induced TrkB activation and proliferation, particularly in models with increased BDNF-dependency. Importantly, co-culture of a subset of LC cells with astrocytes renders them less sensitive to Entrectinib, suggesting that additional survival mechanisms contribute to LC cell fitness in the brain niche. Ongoing studies interrogate the effectiveness of Entrectinib to decrease early and late brain metastatic progression in LC. These studies suggest that targeting TrkB could impact LC therapy even in tumors lacking NTRK rearrangements
OCTS-04 TRIAL IN PROGRESS: PHASE II STUDY OF PRE-OPERATIVE HYPOFRACTIONATED STEREOTACTIC RADIOSURGERY FOR RESECTABLE BRAIN METASTASES
Authors: Oliver Daniel , Tran Nam , Ahmed Kamran , DeJesus Michelle , Liu James , Furlan Andre Beer , Kim Jongphil , Farinhas Joaquim , Vogelbaum Michael , Booth-Jones Margaret , Etame Arnold , Yu Michael
Published: August 2024

BACKGROUND

The current standard of care for limited resectable brain metastases is surgical resection followed by post-operative single-fraction stereotactic radiosurgery (sfSRS) to the resection cavity. Recent retrospective studies showed that pre-operative SRS improves tumor bed control and nodular leptomeningeal disease, but prospective data are lacking. We hypothesize that hypofractionated stereotactic radiosurgery (hfSRS) delivered pre-operatively to resectable brain metastases will result in improved durable local control.

METHODS

This is a single institution phase II study to assess time to local failure in patients with resectable brain metastases (BM) who elect for hfSRS followed by resection. The intervention is hfSRS delivered to a BM designated for resection. The planned target volume for hfSRS is the enhancing tumor + 1-2 mm margin expansion. The dose prescription is 9 Gy per fraction for a total of 3 consecutive daily fractions, to a total of 27 Gy. Surgical resection is planned within 7 days following completion of hfSRS. Other BMs, if present, are treated concurrently with either sfSRS or hfSRS. Key eligibility criteria include patients with at least 1 BM between 1 cm and 6 cm in maximal dimension not previously treated with SRS, deemed resectable by neurosurgery, and are asymptomatic from BM with or without steroids. The primary endpoint is time to local failure at the resection cavity. Other endpoints include time to leptomeningeal disease, changes in neurocognitive function, changes in quality of life (QoL), intracranial distant control, and overall survival. Time-to event outcomes will be analyzed with Kaplan-Meier curves. Changes in neurocognitive function and QoL metrics will be analyzed using descriptive statistics. This study is currently open with 34 patients enrolled at the time of submission. Clinical trial information: NCT05267587
OCTS-08 MRI SCREENING FOR BRAIN METASTASES AMONG PATIENTS WITH TRIPLE NEGATIVE OR HER2+ STAGE II OR III BREAST CANCER: A MULTI-CENTRE, SINGLE ARM PHASE II CLINICAL TRIAL – THE INSIGHT TRIAL
Authors: Fernandes Italo , Watson Geoffrey , Cescon Dave , Mahler Mary , Brezden-Masley Christine , Soliman Hany , Jerzak Katarzyna
Published: August 2024

BACKGROUND

The incidence of asymptomatic brain metastasis (BrM) among patients with early-stage HER2+ and Triple Negative (TN) breast cancer (BC) is not well understood. Our goal is to determine the proportion of patients with stage II or III HER2+ or TN BC who have asymptomatic BrM identified on a screening contrast-enhanced MRI of the brain in a prospective clinical trial.

METHODS

A phase II, single-arm, multi-centre, conducted in Ontario, Canada (NCT06247449). One hundred patients (50 with HER2+ and 50 with TN disease) are being recruited over 24-months. Key inclusion criteria: i) age ≥18; ii) HER2+ or TN BC (2018 ASCO/CAP guidelines); iii) stage II or III disease. Key exclusion criteria: i) symptoms suggestive of BrM which would otherwise require imaging; ii) known asymptomatic BrM; iii) pregnancy. Patients will undergo a contrast-enhanced MRI of the brain (or contrast-enhanced CT if MRI is not possible), blood collection for ctDNA analysis, and completion of the Testing Morbidities Index (TMI) questionnaire within 4 weeks of recruitment. Interventions must be performed within 12 months of original BC diagnosis and within 6 weeks of starting post-operative adjuvant therapy. Co-primary endpoints: i) the proportion of eligible patients with stage II or III HER2+ BC who have asymptomatic BrM, and ii) the proportion of eligible patients with stage II or III TN BC who have asymptomatic BrM. Secondary endpoints: the proportion of patients who are approached about the study who agree to enroll; patients’ acceptability of the brain imaging as evaluated by the TMI; and the proportion of patients who have subsequent brain MRIs after the initial trial MRI. The association of baseline clinical, tissue-based, and ctDNA based biomarkers with the presence of asymptomatic BrM at initial staging and with future development of BrM at 1-year, 2-year and 3-years (captured by chart review) will also be assessed.
RADT-08 IMPACT OF ELEKTA LIGHTENING OPTIMIZER ON DOSIMETRIC AND CLINICAL OUTCOMES FOR INTACT LUNG AND BREAST METASTASES USING GAMMA KNIFE RADIOSURGERY
Authors: Yeoh Desmond , O’Carroll Kyle , Lima Jason , Calugaru Emel , Sreenivasan Sanjeev , Chitti Bhargava , Schulder Michael , Goenka Anuj
Published: August 2024

In 2022, we incorporated the Lightening optimizer software into our Gamma Knife treatment planning workflow. This allows for the rapid generation of treatment plans based on user selected parameters. We aimed to compare plans used for treatment before and after incorporation of the optimizer on patients with intact breast and lung metastases to identify dosimetric differences (gradient index, selectivity index, and coverage) and clinical outcomes (radionecrosis and local control). We also subdivided lesions by size, defining small as <1cc, medium as 1 to 4 cc, and large as >4 cc. We identified 317 metastases that were treated before Lightening and 284 metastases that were treated after Lightening. Using independent sample t-tests, we found that plans had a higher gradient index (p=<0.001), higher selectivity index (p=0.031), and similar coverage (p=0.082) following incorporation of the Lightening software. ANOVA demonstrated that both tumor size and Lightening influenced the gradient and selectivity indices. After size stratification, we found that only small lesions had different gradient indices and only medium lesions had different selectivity indices between pre- and post-Lightening groups. Before investigating clinical outcomes, we removed lesions that did not have at least a 9 month follow up, reducing pre- and post-Lightening cases to 106 and 90 respectively. Cox regressions showed that there were no significant differences in local failure rates (p=0.871) and radionecrosis (p=0.202) between pre- and post-Lightening plans. Interestingly, there was a marginally insignificant increase in the likelihood of radionecrosis for small lesions planned with Lightening (HR=7.75, p=0.062). Since the gradient index was also increased in small lesions for Lightening plans, this might indicate a clinically valuable correlation. Overall, these results suggest that while there were dosimetric differences between plans, clinical outcomes did not change. However, attention should be placed on small lesions to better understand the impact of gradient index on radionecrosis.
RADT-11 PREDICTING BIOPSY RESULTS OF ENLARGING BRAIN METASTASES FOLLOWING STEREOTACTIC RADIOSURGERY
Authors: Gonzalez Ariel , Haskell-Mendoza Aden , Reason Ellery , Jackson Joshua , Wang Chunhao , Vaios Eugene , Bradbury Claire , Zhao Jingtong , II James Herndon , Fecci Peter
Published: August 2024

Stereotactic radiosurgery (SRS) is the standard of care for initial management of brain metastases (BM) and provides excellent local control with reduced incidence of adverse neurocognitive effects. However, radiographically progressive lesions post-SRS pose a key clinical challenge, as imaging characteristics cannot effectively distinguish between local recurrence (LR) and radiation necrosis (RN). A retrospective analysis was performed on patients receiving SRS treatment for BM between 2011-2022 and who subsequently underwent biopsy alone or in combination with laser interstitial thermal therapy for suspicion of LR vs RN on imaging. Patient demographics, clinicopathologic characteristics, SRS treatment parameters, and biopsy results were collected. The study included 145 patients with 151 progressive lesions biopsied after SRS treatment. The median age at biopsy was 62 (range: 27-92), with lung being the most prevalent primary site (84 cases, 57.9%). Post-SRS biopsy confirmed 92 lesions (61.3%) with RN, 58 (38.7%) with LR, and 1 biopsy result was missing. The median duration from SRS to biopsy was 13 months (range: 3-81), with a median prescribed SRS dose of 20.0 (range: 14.0-30.0) Gy. Of the lesions, 70.3% received unfractionated SRS, while 29.7% received fractionated SRS. Univariate analyses demonstrated that breast primary (vs. lung, P = 0.027, vs. skin, P = 0.012) and receipt of biopsy ≥ 9 months following SRS (P = 0.0062) were associated with lower odds of LR, while fractionation or prescribed SRS dose were not predictive. The association of biopsy timing ≥ 9 months with lower odds of LR remained significant on multivariate analyses (P = 0.0065). The natural history of LR and RN differ such that for patients presenting with an enlarging lesion ≥ 9 months post-SRS, radiation necrosis should be suspected over local tumor recurrence. Multi-disciplinary oncology teams should consider adjusting treatment for lesions progressing prior to this timepoint.
RADT-14 STEREOTACTIC RADIOSURGERY AND SACITUZUMAB-GOVITECAN FOR BREAST CANCER BRAIN METASTASES
Authors: Khatri Vaseem , Doniparthi Ajay , Nakashima Justyn , Zhao Dekuang , Mills Matthew , Oliver Daniel , Yu Hsiang-Hsuan , Soliman Hatem , Han Hyo , Ahmed Kamran
Published: August 2024

BACKGROUND

Sacituzumab-govitecan (SG) is an antibody drug conjugate (ADC) with activity against breast cancer brain metastases (BCBM). Efficacy and safety information of SG with stereotactic radiosurgery (SRS) is limited. Reports suggest SRS with ADCs may increase risk of symptomatic radiation necrosis (SRN).

METHODS

Patients treated with SG from 2020-2023 were reviewed. Patients had BCBM prior to SG and received SRS for active BM within 6 months of SG. Patients with prior leptomeningeal disease (LMD) were excluded. Kaplan-Meier method was used to estimate overall survival (OS), intracranial PFS (CNS-PFS), extracranial PFS (EC-PFS), local control (LC) and distant intracranial control (DIC). RESULTS: Between 2020-2023, 121 lesions were treated over 25 courses in 14 patients. Median follow up was 28.6 months. Median age was 60 (range 30-72). Five (36%) patients had neurologic symptoms, 7 (50%) were HR+. Eleven (9%) lesions received fractionated SRS (fSRS) and 110 (91%) single-fraction. Median dose for single fraction was 24 Gy (range 16-24), and for fSRS was 27 Gy (range 20-30) in median 5 fractions (range 3-5). Seventy-seven (63%) received SRS concurrent with SG. The median gross tumor volume (GTV) was 0.047 cc (range 0.007-17.4) and median planning target volume (PTV) was 0.14 cc (0.032-30). Six (5%) lesions were treated post-operatively. Median OS was 8.4 months (95% CI 4.2-not reached), with 12-month rate of 48%. Median CNS-PFS was 4.2 months (95% CI 1.9-6.3), with 12-month rate of 11%. Median EC-PFS was 4.4 months (95% CI 1.4-8.1), with 12-month rate of 17%. Twelve-month LC from SRS was 91%. Median DIC from SRS was 4.2 months (95% CI 2.1-7.5) with 12-month DIC rate of 12%. Two patients developed LMD. SRN occurred in 1 lesion, which received SRS prior to SG. CONCLUSIONS: SRS and SG demonstrated excellent local control and no increased risk of RN. Prospective investigation is warranted.
RMTD-07 LOST CHANCES: THE SYSTEMATIC EXCLUSION OF PATIENTS WITH BRAIN METASTASIS IN EARLY-PHASE ONCOLOGY TRIALS
Authors: Fernandes Italo , Carmona-Gonzalez Carlos A , Suthaaharan Shonekaa , Sandhu Serena Serena , Menjak Ines , Smoragiewicz Martin , Jerzak Katarzyna
Published: August 2024

RATIONALE

Historically, cancer trials have often excluded patients with brain metastases (BrM). This limits our understanding of CNS-specific drug efficacy. We aimed to determine the proportion of phase I clinical trials for patients with solid tumors that exclude patients with BrM.

METHODS

In March 2023, a systematic search of the clinicaltrials.gov website was performed. Results are described as frequencies and compared using the Pearson’s chi-square or Cochran-Armitage tests.

RESULTS

1,714 phase I trials were identified and 990 met inclusion criteria. Most trials spanned several tumor types (n=659, 66.6%) and were registered between 2000- 2023 (n=884, 89.3%). Trials were mainly conducted in Asia (n=95, 9.6%), Europe (n=112, 11.3%), and North America (n=619, 62.5%). Categories of investigational agents were: targeted therapy (n=496, 50.1%), cytotoxic chemotherapy (n=118, 11.9%), immunotherapy (n=73, 7.37%); the most common combinations included chemotherapy plus targeted therapy (n=265, 26.8%) and chemotherapy plus immunotherapy (n=14, 1.4%). Patients with BrM were included in 25.1% (n=248) trials, included under certain conditions in 53.6% (n= 521), and excluded in the remaining 22.3% (n=221) of trials. Recent trials (2015-2019) were less likely to exclude patients with BrM compared to trials conducted between 2000-2004 (18% vs 38%, p=0.003). Exclusion of patients with BrM was less common in trials focusing on melanoma (16%), breast (15%) and lung (14%) cancer. Trials involving the use of cytotoxic chemotherapy were significantly more likely to exclude patients with BrM (n=58, 49%) than those employing targeted therapy (n= 110, 22%) or immunotherapy (n=15, 21%) (p=0.016). Trial location and stage of disease were not associated with exclusion of patients with BrM.

CONCLUSION

Recent phase I trials, particularly those evaluating the use of targeted therapy and/or immunotherapy, have a low rate of exclusion of patients with BrM compared to previous cytotoxic trials. However, many opportunities to test drugs with potential CNS efficacy are still lost.
SPCM-03 TRENDS IN INTRAOPERATIVE NEUROMONITORING USAGE IN SURGERIES FOR PATIENTS WITH DIAGNOSED PRIMARY MALIGNANT SPINE TUMORS
Authors: Bishop Brandon , Woo Joshua , Rowe Dana , Luo Emily , Ndika Tobechukwu , Charles Antoinette , Arango Alissa , Yoo Seeley , Zachem Tanner , O’Callaghan Ellen , Owolo Edwin , Sperber Jacob , Crowell Kerri-Anne , Rivera Nicole , Nguyen Annee , Hockenberry Harrison , Reitz Kendall , Dalton Tara , Johnson Eli , Erickson Melissa , Goodwin C Rory
Published: August 2024

BACKGROUND

Given the complex nature of surgical resection and the potential for neural injury in spinal tumor surgery, the use of intraoperative neuromonitoring (IONM) could improve clinical outcomes and injury prevention in surgeries for patients diagnosed with primary malignant spine tumors (PMTs). While IONM has been growing in usage, especially during spinal procedures, its utility has been mixed due to undefined guidelines and potentially high costs. In this study, we examined trends in IONM use in surgeries for PMT patients, regional variations in IONM usage, and associations between IONM and clinical outcomes.

METHODS

A retrospective review was performed using the PearlDiver Patient Record Database to identify cases of PMTs that underwent surgery from 2011 to 2021. Rates of IONM usage were compared based on patient age, sex, family income, and region. Complications and 30-day readmissions were also assessed.

RESULTS

4,551 patients undergoing surgery for PMTs were identified, with 1,643 (36.1%) of these utilizing IONM. Significant regional variability was observed in IONM usage (Midwest: 32.6%; Northeast: 28.1%; South: 26.4%; West: 12.5%; p < 0.001) and those using IONM were more likely to be in inpatient settings, compared to outpatient (p < 0.001). Both younger age and mean family income were associated with IONM usage (p < 0.001, p < 0.01, respectively), although, clinically insignificant. 30-day readmission rates and complication rates were significantly higher for patients undergoing PMT surgery with IONM (both p < 0.001).

CONCLUSIONS

This study demonstrates significant differences in IONM usage across geographic regions, sex, and operation settings among PMT patient surgeries. Differences in family income were observed to be significant but not clinically relevant. Notably, IONM was associated with higher 30-day post-operative readmission rates and complication rates. Given the increased adoption of IONM, these trends provide valuable insights in assessing its value and applicability across diverse settings.
SPCM-05 SPINAL EPITHELIOD SOLITARY FIBROUS TUMOR METASTATIC TO THE 4TH VENTRICLE
Authors: Wang Ryan , Pejhan Shervin , Ang Lee-Cyn , Megyesi Joseph
Published: August 2024

Twenty-four years prior to his current presentation, a 76 year old man underwent resection of a solitary fibrous tumor from the lower cervical spinal cord (C5-C7) (called hemangiopericytoma at that time). He had been treated with radiotherapy. His current symptoms included headache and gait ataxia. Neuroimaging revealed a 4th ventricular tumor with mild hydrocephalus. He underwent a suboccipital craniectomy and resection of the 4th ventricular tumor. Pathology showed a hypercellular tumor composed of epitheliod cells with eosinophilic cytoplasm and moderately pleomorphic enlarged oval nuclei containing finely dispersed chromatin and prominent eosinophilic nucleoli in some nuclei. The tumor cells were arranged in nests and sheets separated by thin walled branching to thick walled hyalinized vessels with frequent areas of hemorrhage. Tumor cells showed high mitotic activity (about 8 mitoses/mm squared). The majority of tumor cells were positive for CK7, synaptophysin, E-cadherin, and rarely for CK20 and D2-40. Tumor cells were negative for EMA, transthyretin, myogenin, desmin, progesterone receptor, NeuN, Olig-2, TTF-1, GATA3, PAX8, OCT3/4, SALL4, CD117, S100 and GFAP. Vasculature was highlighted by PAS, reticulin, CD31, ERG, and CD34. INI-1 was intact in the nuclei. Final diagnosis was epitheliod solitary fibrous tumor, at least CNS WHO grade 2. This was consistent with the pathology from 24 years prior. Solitary fibrous tumor is known for recurrence and metastasis a long time after initial diagnosis. However, this case highlights the delayed metastatic spread of a relatively rare subtype of solitary fibrous tumor (epitheliod) to rare location (intraventricular, specifically the 4th ventricle). The literature will be reviewed.
QSPC-03 PATIENT-REPORTED QUALITY OF LIFE AFTER UNDERGOING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES: A PROSPECTIVE ASSESSMENT UTILIZING A U.S. NATIONAL REGISTRY
Authors: Pham BA Duy , Sheehan Darrah , Sheehan Kimball , MBBS Konstantinos Katsos , MD Camilo Fadul , MD Jason Sheehan
Published: August 2024

Patients with brain metastases (BMETS) frequently emphasize the impact on quality of life (QOL) over prolongation of life at the time of making treatment decisions. Thus, it is critical to evaluate patient-reported health utility scores after treatment of BMETS. Stereotactic surgery (SRS) is becoming the most frequent treatment modality. The objective of this study was to determine the changes in the EuroQol- 5 Dimension (EQ-5D) in patients with BMETS treated with SRS. The NPA SRS Registry is a multi-institutional collaboration prospectively collecting information from patients undergoing SRS since 2017. We queried the registry for the results of the baseline and follow-up EQ-5D questionnaire, with a utility index score given based on the patient’s responses for five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The cohort included 522 cases treated with SRS between 2017 and 2023; 264 (47.8%), 197 (35.7%), and 91 (16.5%) had 1, 2-4, and 5-14 metastases, respectively. The mean EQ-5D score at the time of SRS was 0.551 (SD=0.443). At the last follow-up after SRS, 107 (34.0%) patients indicated improvement from their EQ-5D baseline while 51 (16.2%) were stable. The score decreased in 113 patients (35.9%) while 44 (13.9%) showed mixed changes (i.e., domain sub-scores both increased and decreased). For mobility, usual activities, pain/discomfort, and anxiety/depression domains patients experienced similar rates of improvement (21.0%-22.5%). In the self-care domain, 32 (10.2%) patients reported improvement, 232 (73.7%) reported no change and 89 (28.3%) had worsening scores. Our study provided the first longitudinal prospective real-world data using the EQ-5D, a health utility tool, in patients with BMETS treated with SRS. In more than half of the cases, the patients reported improved or stable EQ-5D scores over time after treatment. Factors independent of treatment that may prompt worsening QOL following SRS are being identified and will be presented.
QSPC-04 BRAIN AND SPINE METASTASIS AWARENESS: AN INTERNATIONAL CAMPAIGN TO EDUCATE PATIENTS, PROVIDERS, AND POLITICIANS AND IMPROVE OUTCOMES
Authors: Van Swearingen Amanda , Roha Kiley , Harbers Carol , Painter Brice , Anders Carey , Fecci Peter
Published: August 2024

Almost any cancer can spread, or metastasize, to other locations in the body, including the brain, spine, or lining (leptomeninges) that all comprise the central nervous system (CNS). Each year, an estimated 480,000 new cases of CNS metastasis are diagnosed in the U.S., making them 5-10 times more common than primary brain tumors. The incidence is increasing as improved treatments for cancers result in longer patient survival, and many treatments do not protect the CNS. Despite the growing incidence and clinically unmet need, there is a lack of understanding among the general population and providers about the frequency and effective treatment options for patients with CNS metastases. To help raise awareness of the unique needs of these patients, and to improve their outcomes, the Duke Center for Brain and Spine Metastasis (DCBSM) has initiated a Brain and Spine Metastasis Awareness Initiative. This campaign seeks to educate the general public, patients, caregivers, providers, and politicians on several topics, including that brain and spine metastases can happen with almost any cancer, distinguishing between primary brain cancer and metastatic (secondary) brain tumors, the need for a different and multi-disciplinary treatment approach, and the availability of dedicated centers and clinical trials for these patients. Increasing awareness of brain and spine metastasis will improve the outcomes and quality of life for these patients, and will help these patients feel “seen.” The campaign will involve educational material developed by the DCBSM and shared digitally though social media and a website (brainspinemetastasis.org). It will also include the use of a new awareness ribbon, designed at Duke. In collaboration with Duke Government Relations and partnering international advocacy and research groups, we will push for U.S. Congressional actions towards designated funding on brain and spine metastasis, as well as proclaiming June National Brain and Spine Metastasis Awareness Month.
QSPC-10 DEVELOPMENT OF ISOLATED BRAIN METASTASES UNDERNEATH THE BLOCKED PORTION OF PROPHYLACTIC CRANIAL IRRADIATION FIELD IN A PATIENT WITH SMALL CELL LUNG CANCER, LEADING TO SIGNIFICANT MORBIDITY AND DEATH
Authors: Haldar Nilanjan , Ans Sharif Muhammad , Cappelli Louis , Werner-Wasik Maria
Published: August 2024

INTRODUCTION

The paradigm shift towards forgoing prophylactic cranial irradiation (PCI) in small cell lung carcinoma (SCC) management in favor of a surveillance approach raises concerns regarding metastases-induced patient morbidity. We present here a case exemplifying the morbidity associated with the development of brain metastases in a portion of the radiation field blocked due to concerns of increased toxicity due to re-irradiation.

CASE PRESENTATION

A 69-year-old male presented with a history of T1N0M0 laryngeal cancer treated with small field definitive radiation, followed by adjuvant post-prostatectomy radiation therapy to 68 Gy delivered in 34 fractions with androgen deprivation, and finally a history of pT1N2bM0 oropharyngeal cancer, treated with a comprehensive large-field radiation with concurrent chemotherapy. The oropharyngeal radiation field included a portion of the midbrain and cerebellum. Five years later, the patient developed limited stage SCC, for which he received definitive chemoradiation, followed by PCI. The previously irradiated mid-brain and cerebellum regions were blocked from the whole brain PCI fields due to  concerns for toxicity. Two years post-PCI, the patient developed multiple symptomatic brain metastases, with a dominant lesion located in the mid-brain, responsible for his double-vision, as well as several lesions in the cerebellum causing complete ambulatory dysfunction. Stereotactic radiosurgery (SRS) was administered but the patient succumbed to his illness two weeks later from neurologic death.

DISCUSSION

This case underscores the benefit of PCI in preventing significant neurologic morbidity in patients with SCC. Forgoing PCI and adopting a surveillance approach may increase the risk of introducing increased metastases-induced morbidity in SCC patients.