bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIRL-04 BRAIN METASTASES DISTRIBUTION WIDTH (BMDW): A NOVEL METRIC TO PREDICT DISTANT BRAIN FAILURE FOLLOWING STEREOTACTIC RADIOSURGERY IN PATIENTS WITH MULTIPLE BRAIN METASTASES
Authors: Gal Omer , Yarlagadda Sreenija , Hall Matthew D , Press Robert H , Wieczorek D Jay , Lee Yongsook C , Bejarano Tatiana , Tolakanahalli Ranjini , Gutierrez Alonso N , McDermott Michael W , Mehta Minesh P , Kotecha Rupesh 
Published: August 2024

Abstract

INTRODUCTION
We introduce a method of predicting clinical outcomes in newly diagnosed brain metastases (BM) patients after upfront stereotactic radiosurgery (SRS), based on a novel metric - brain metastases distribution width (BMDW) – which measures the amount of variation in BM volume.

METHODS
BMDW was defined as the coefficient of variation of mean BM volume (mBMV) per patient and was calculated by dividing the standard deviation of the mBMV (SD-mBMV) by the mBMV and multiplying by 100, to yield a percentage value representing BM volume heterogeneity. Patients were classified by BMDW into low (≤100) and high (&gt;100) risk groups and the distant brain failure (DBF)-free and overall survival (OS) outcomes were summarized using the Kaplan-Meier method and compared between the two risk groups using the log-rank test.

RESULTS
The study cohort included 99 patients, the median age was 67 years (Range: 18-88) and 51% were female. The high- and low-risk groups included 63 (64%) and 36 (36%) patients, respectively. At a median follow-up of 20 months, a low BMDW predicted for a statistically significant prolonged DBF-free survival with a median of 21.4 months (95% confidence interval [CI]: 8.7-34.1 months) versus 4.9 months (95% CI: 3.3-6.5 months) for the high-risk group (p=0.023). OS was not significantly different between the groups (p=0.159). Multivariate analysis showed that BMDW was a dominant predictor of DBF, with a hazard ratio (HR) of 2.45 for the high-risk group (95% CI: 1.26-4.77, p=0.008), in addition to performance status (HR=2.16, 95% CI: 1.29-3.62, p=0.003) and presence of &gt;10 lesions at diagnosis (HR=1.95, 95% CI: 1.01-3.77, p=0.046).

CONCLUSIONS
BMDW is a novel predictor of DBF in this cohort of newly diagnosed lung cancer patients with multiple brain metastases. It may be considered as a metric for patient selection between SRS and alternative options, such as hippocampal-avoidance whole brain radiotherapy.
NIRL-06 IS THE PRESENCE OF NEOPLASTIC MENINGITIS ASSOCIATED WITH A WORSE PROGNOSIS IN REAL-WORLD PATIENTS WITH BREAST CANCER AND BRAIN METASTASES?
Authors: Cacho-Díaz Bernardo , Cabrera Paula , Arrieta Oscar 
Published: August 2024

Abstract

BACKGROUND
Central nervous system (CNS) metastases are a severe and frequent scenario in patients with breast cancer; CNS metastases can be divided into parenchymal metastases (brain metastases) or neoplastic meningitis (leptomeningeal disease). The occurrence of both in the same patient is a common picture but scantly reported.

OBJECTIVE
To measure the association of brain metastases with or without meningeal involvement in patients with breast cancer and brain metastases.

METHODS
A prospectively acquired database from patients with breast cancer and central nervous system metastases was retrospectively analyzed.

RESULTS
In 659 patients, 292 (44%) had brain metastases (BM), 169 (26%) had neoplastic meningitis (NM), and 198 (30%) had both (BM+NM). The median overall survival (MOS) in the whole cohort was 9.59 months (95%CI 8.0 – 11.2); in those with BM, the MOS was 12.2 months (95%CI 10 – 14.5); in the NM group, the MOS was 5.8 months (95%CI 4.3 – 7.2 months); and for those on the group with both BM and NM (BM+NM) the MOS was 10.3 months (95%CI 8.0 – 26.7), P &lt;0.001. After statistical adjustment, the difference in survival between BM and BM+NM persisted.

CONCLUSION
The presence of meningeal involvement in patients with breast cancer and brain metastases is associated with a worse prognosis.
NIRL-12 UNDERSTANDING LESION RESPONSE ON MRI AFTER LASER INTERSTITIAL THERMAL THERAPY (LITT) IN METASTATIC BRAIN TUMOR PATIENTS
Authors: Robert Stephanie , Sirota Madison , Sotoudeh Mahdi Salimi , Kaur Manpreet , Merkaj Sara , Aboian Mariam , Chiang Veronica 
Published: August 2024

Abstract
Laser-interstitial thermal therapy (LITT) at the time of radiographic regrowth after stereotactic radiosurgery (SRS) of brain metastases allows lesions to be biopsied and treated simultaneously. While excellent post-LITT responses have been reported, indications for use remain unclear. This study describes the variability seen in post-LITT imaging changes, especially FLAIR, reflecting perilesional edema, and examines clinical and treatment variables that may affect post-LITT response. Using a novel 3D-segmentation tool created at our institution, we analyzed volumetric changes in both FLAIR and contrast-enhancing lesions before and for 12-months post-LITT across 23 patients. Over half (57%, 13/23) of patients demonstrated an initial increase in FLAIR volume at 2 weeks post-LITT and 43% demonstrated stable or decreased FLAIR. For those with an initial decrease, their percentage volume change from 0 to 0.5 months ranged from 21% to 67%, while those with an initial increase, percentage volume change varied from 2.6% to 254%. Of the 13 patients with an initial increase in FLAIR, 6 had FLAIR resolution over the subsequent 6-12 weeks. Four patients did not show FLAIR resolution until 12 months. Of the 10 patients with initial decrease, 6 had resolution of FLAIR signal abnormality by 3 months and 9 by 6 months. At 12 months, in those patients with an initial FLAIR increase, only 54% showed a decrease in enhancing lesion volume compared to 70% of patients with an initial decrease in FLAIR. No clinical or treatment factors were statistically associated with any pattern of lesional change although trends were seen with pre-LITT size and immunotherapy use. Survival was found to be associated with biopsy pathology. This study demonstrates FLAIR changes after LITT can be even more variable than for contrast enhancing lesion volumes. A larger study is needed to determine clinical and treatment factors that contribute to early favorable responses to LITT.
NVTG-05 LONGITUDINAL OBSERVATION OF THE TREATMENT RESPONSE TO INTRATHECAL CHEMOTHERAPY WITH PEMETREXED VIA CIRCULATING TUMOR DNA FROM CEREBROSPINAL FLUID OF NON-SMALL CELL LUNG CANCER LEPTOMENINGEAL METASTASES
Authors: Hong Weiping , Yang Yanying , Wang Hui , Liu Qiongyao , Zhen Junjie , Lai Mingyao , Cai Linbo 
Published: August 2024

Abstract
Approximately 5% of patients with advanced non-small cell lung cancer may develop leptomeningeal metastasis (LM). 1,2 Patients with LM may have a poor prognosis; the median overall survival (OS) of LM NSCLC patients was only 3.6 to 11 months2,3. Although targeting therapies, particularly tyrosine-kinase inhibitors (TKI), are effective against primary tumors, the blood-brain barrier may limit their intracranial performance, resulting in variable patient survival outcomes. 4 LM patients have been shown to benefit from a variety of treatments, including surgery, radiation, systematic chemotherapy, targeted chemotherapy, immunotherapy, and intrathecal injection, but there is still a lack of conventional treatment paradigms for LM patients’ care. In patients with NSCLC, intrathecal administration, which delivers medications directly into the subarachnoid space via cerebrospinal fluid (CSF), was reported to be highly effective in controlling LM. 5,6 However, evaluating the efficacy of treatment for LM remains difficult and lacks standardization. Due to the diffusion of LM lesions, it is challenging to quantify tumor size using imaging techniques. Karnofsky performance score (KPS) is a commonly used assessment tool for functional impairment of LM 7, but it cannot disclose the tumor change in a quantifiable manner. Response Assessment in Neuro-Oncology (RANO) is a generally accepted response criterion that evaluates treatment response by incorporating a novel radiographic scorecard, CSF cytology or flow cytology, and neurological examination, while it was limited on measuring lesions for response assessment. 8,9 Recent research has demonstrated that circulating tumor DNA released by tumor apoptosis can be used as a biomarker to track treatment responses and tumor evolution. 10 Ct-DNA from cerebrospinal fluid (CSF) has also demonstrated superior intracranial response prediction performance compared to plasma. 11 In this study, patients with leptomeningeal metastasis (LM) who had undergone multiple courses of therapy received intrathecal pemetrexed (IP). Then, we monitored the dynamic changes in CSF-ctDNA to assess their response.
NVTG-11 EFFICACY OF TRASTUZUMAB DERUXTECAN IN HER2-POSITIVE AND HER2-LOW BREAST CANCER WITH ACTIVE BRAIN METASTASES
Authors: Burnside Georgiana , Gu Bo , Carlson-Clarke Brandon , Lalwani Kriti , Hayden-Gephart Melanie 
Published: August 2024

Abstract
Trastuzumab deruxtecan (T-DXd) has demonstrated strong CNS penetrance for HER2+ breast cancer with brain involvement, but further evidence is needed to support the use of T-DXd in HER2-low patients. This institutional retrospective review investigates the efficacy of T-DXd between HER2+ and HER2-low breast cancers with active brain metastases (BM). Using the Stanford Research Repository from 2020-2023, we identified 36 patients with breast cancer and active BM treated with T-DXd. Out of the 36, 7 had HER2+ breast cancer and 29 had HER2-low breast cancer. Of the 7 HER2+ patients, 6 are still living with 5 still continuing on treatment while median survival of the 29 HER2-low patients was 18 months (95%LCL 7 with indeterminate UCL based on available data) with 12 still living and 2 continuing on treatment. Using RANO-BM criteria we measured intracranial objective response rate (ORR-IC) on MRI for those with available target lesion measurements at initiation and end of treatment (EOT) windows (n=33). Of the HER2+ patients (n=7), 1/7 (14%) showed complete response, 2/7 (29%) had partial response, 3/7 (43%) had stable disease, and 1/7 (14%) had progressive disease with a notable 73.7% reduction in size of target lesions but numerous new enhancing lesions at EOT. In contrast, of the HER2-low cohort (n=26), 6/26 (23%) demonstrated partial response, 8/26 (31%) had stable disease, and 12/26 (46%) had progressive disease. Of the 12 HER2-low patients with progressive disease, 2/12 had &gt;30% reduction in size of target lesions but numerous new lesions at EOT. Despite some intracranial responses in HER2-low patients, their median survival and high progression rates indicate limited benefits, highlighting the need for more robust prospective studies to further investigate T-DXd’s efficacy in this subgroup.
OCTS-07 TRIAL IN PROGRESS: PHASE II STUDY OF RADIATION THERAPY FOLLOWED BY INTRATHECAL TRASTUZUMAB/PERTUZUMAB IN THE MANAGEMENT OF HER2+ BREAST LEPTOMENINGEAL DISEASE
Authors: Ahmed Kamran , Kumthekar Priya , Kim Youngchul , DeJesus Michelle , Pina Yolanda , Oliver Daniel , Evernden Brittany , Arrington John , Vogelbaum Michael , Rosa Marilin , Soliman Hatem , Yu Michael , Han Hyo , Forsyth Peter 
Published: August 2024

Abstract

BACKGROUND
HER2+ leptomeningeal disease (LMD) has a poor prognosis with a high unmet clinical need. A previous phase I/II study revealed intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2+ breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the systemic management of HER2+ breast cancer. The phase I portion of the current study used a modified toxicity probability interval-2 (mTPI-2) design to determine 80 mg IT pertuzumab as the recommended phase II dose with a fixed dose of 80 mg IT trastuzumab.

METHODS
The study is designed as a prospective, single-arm, nonrandomized, open-label, phase II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. HER2+ LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥18, with a life expectancy &gt; 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. The primary objective of the phase II portion is to evaluate OS following IT trastuzumab/pertuzumab. Secondary objectives involve evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal). A single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled with plans to enroll an additional 10 patients if criteria are met. This study is open with 14 patients enrolled at the time of submission. Clinical trial information: NCT04588545.
RADT-01 A COMPREHENSIVE REVIEW OF THE UTILITY OF BRACHYTHERAPY IN THE MANAGEMENT OF BRAIN METASTASIS
Authors: Leskinen Sandra , Ben-Shalom Netanel , Ellis Jason , Langer David , Boockvar John A , D’Amico Randy S , Wernicke A Gabriella 
Published: August 2024

Abstract

PURPOSE
This literature review investigates the current applications of brachytherapy in treating brain metastases (BMs), focusing on its advantages, limitations, and clinical outcomes.

METHODS
A comprehensive literature search was conducted using PubMed, Embase, and ClinicalTrials.gov, focusing on studies related to brachytherapy in BM treatment and adhering to PRISMA guidelines. We included studies if they reported brachytherapy techniques, isotopes, and patient outcomes.

RESULTS
Our initial search yielded 1,813 articles, of which 42 studies met inclusion criteria reporting on brachytherapy techniques, the isotopes utilized, and patient outcomes. Specifically, we identified 19 total studies assessing the use of Iodine-125 (I-125) brachytherapy, including two prospective studies, 16 retrospective studies, and one case report. There were 23 total studies assessing the use of Cesium-131 (Cs-131) brachytherapy, including five clinical trials, four prospective studies, 11 retrospective studies, and three case reports. Two retrospective studies used both Cs-131 and I-125 seeds. We identified three registered national clinical trials examining the use of Cs-131 brachytherapy for BM treatment. Although I-125 brachytherapy was found to be effective in BM treatment with local control rates and median overall survival paralleling stereotactic radiosurgery and whole brain radiotherapy, the rates of radiation necrosis were as high as 23% in one study. Conversely, Cs-131 studies described high rates of locoregional tumor control with minimal rates of radiation necrosis. One clinical trial found a statistically significant improvement in cognitive functioning and quality of life at four- and six-months following Cs-131 seed implantation.

CONCLUSION
Brachytherapy, with a particular focus on I-125 and Cs-131 isotopes, has shown promise in treating brain metastases, offering targeted radiation with minimal effects on surrounding healthy tissue. Future research, including randomized controlled trials and long-term follow-up studies, is necessary to optimize the role of brachytherapy in the treatment of brain metastases.
RADT-07 IMPACT OF KEAP1/NFE2L2 VARIANTS ON LOCAL CONTROL IN NSCLC BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Chen Mark , Carpenter David , Leng Jim , Qazi Jamiluddin , Wan Zihan , Niedzwiecki Donna , Alder Laura , Clarke Jeffrey , Kirkpatrick John , Floyd Scott , Reitman Zachary , Mullikin Trey 
Published: August 2024

Abstract
The Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-like 2 (NFE2L2) reactive oxygen species processing pathway may be a useful biomarker of clinical radioresistance in localized non-small cell lung cancer (NSCLC). It is unknown whether KEAP1/NFE2L2 variants impact the response of brain metastases from NSCLC to radiotherapy. Here, we tested whether KEAP1/NFE2L2 variants associate with rates of local control in patients with NSCLC brain metastases undergoing stereotactic radiosurgery (SRS). We hypothesize KEAP1/NFE2L2 pathogenic variants (PV) are associated with decreased local control (LC) and increased time to intracranial progression (ICP). 541 patients undergoing SRS for NSCLC brain metastases at a single institution were retrospectively identified; n=269 underwent clinical next generation sequencing. Kaplan-Meier analyses were calculated for LC and ICP; results across variant status were compared using the log-rank test. Comparisons were performed for variant versus no mutation, and by variant type (PV and variant of unknown significance (VUS)). At 12 months, LC was 90.8% (95% CI, 79.2-96.1%) among patients with variants, compared to 90.6% (84.4-94.4%) in patients without. There was no significant difference in median time to ICP between patients with variants (5.1 months; 95% CI, 3.3-9.5 months) compared to those without (7.2 months; 95% CI, 5.7-9.5 months). 12-month LC was 92.15±5.33% in PV, 89.43±5.89% in VUS, and 90.6±2.46% in patients without mutations. LC and ICP displayed a non-significant trend for differences when KEAP1/NFE2L2 PV and VUS were compared. Overall, KEAP1/NFE2L2 variant status did not demonstrate a statistically significant difference in LC or ICP after SRS for brain metastases in this cohort. On the basis of these data, KEAP1/NFE2L2 variant status should not impact clinical management of NSCLC brain metastasis patients. Larger cohorts are needed to examine KEAP1/NFE2L2 status association with outcomes among NSCLC brain metastasis patients. Thus, the impact of KEAP1/NFE2L2 mutations may differ in the localized versus metastatic setting.
RADT-12 HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIOTHERAPY WITH REDUCED WHOLE BRAIN DOSE ENABLES IMPROVED SPARING OF HIPPOCAMPI WITHOUT INCREASED RISK OF DISTANT BRAIN FAILURE IN NON-SMALL CELL LUNG CANCER
Authors: Khandekar Melin , Keane Florence , Soto Dan , Tansky Joanna , Oh Kevin , Willers Henning , Shih Helen 
Published: August 2024

Abstract
Hippocampal avoidance whole brain radiation (HA-WBRT) results in improved neurocognitive function (NCF) compared to standard WBRT, but &gt; 50% of patients still experience NCF failure. We examined whether lower biologically effective dose (BED) of HA-WBRT enables better hippocampal sparing without impacting intracranial disease control in patients with non-small cell lung cancer (NSCLC). We conducted an IRB approved, retrospective study of patients with NSCLC receiving HA-WBRT between 2014-2022. Endpoints were distant brain failure free survival (DBFFS), local brain failure free survival (LBFFS), left and right hippocampal mean BED2 and BED21%. Kaplan-Meier survival analysis and Welch’s t-test were performed. Sixty-nine patients treated with HA-WBRT were included, with median follow up of 51.2 weeks. Thirty-six patients received standard HA-WBRT (SD) with median dose of 30 Gy in 10 fractions. Thirty-three patients received reduced BED HA-WBRT (RD), with median dose of 30 Gy in 15 fractions. All patients in the RD group had simultaneous integrated boost (SIB) to gross disease (median 37.5 Gy) while 18/36 in the SD group had an SIB (median 35 Gy). There were no significant differences between SD and RD cohorts in age, systemic therapy use, or targetable mutations. There was no difference in median DBFFS of the SD (23.1 weeks) and RD groups (40 weeks) (p=0.27). There was no difference in LBFFS of the SD (median 26.4 weeks) and RD groups (median 40 weeks), p=0.84). For the left and right hippocampi, both mean BED2 and D1% were significantly lower in the RD group (p&lt;0.001). In this cohort, lower BED HA-WBRT improved hippocampal sparing without compromising intracranial control in patients with NSCLC. Further optimization of HA-WBRT dose and schedule may improve both intracranial control and neurocognitive outcomes. This study is limited by its retrospective nature and potential selection bias. A phase II prospective study to test these concepts is ongoing.
RADT-15 STEREOTACTIC RADIOSURGERY FOR ADENOID CYSTIC CARCINOMA BRAIN METASTASES: A SINGLE INSTITUTION RETROSPECTIVE STUDY
Authors: Kattaa Ahed , Hori Yusuke , Akhavan-Sigari Amirhossein , Persad Amit , Tayag Armine , Ustrzynski Louisa , Emrich Sara , Park David , Chang Steven 
Published: August 2024

Abstract

BACKGROUND
Adenoid cystic carcinoma (ACC) is a malignant neoplasm arising from the minor and major salivary glands that tends to spread by perivascular and perineural routes. Brain metastases (BM) secondary to ACC are very rare, and the standard management strategy has not been well reported due to the rarity. Especially, only a few case reports described the use of stereotactic radiosurgery (SRS) for BM from ACC.

METHODS
We retrospectively reviewed cases of BM from ACC treated with SRS at our institute between 1998 and 2023. A total of 40 lesions from 5 patients were included, and the patient and lesion background variables were collected. Tumor control was defined based on radiological response to SRS as a complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) per RECIST guidelines.

RESULTS
The median overall survival was 12.0 months (interquartile range (IQR): 6.5–33.5 months). The mean age at treatment was 51.2 years (standard deviation (SD): 7.8 years) and 60% were male patients. The mean maximum diameter of the lesions was 11.1 mm (SD: 10.9 mm). The median dose delivered was 24 Gy (IQR: 22– 24Gy). The MRIs at 3 and 6 months demonstrated reductions in mean maximum diameters at 5.5 mm and 3.3 mm, respectively. The treatment responses at the first follow-up were; CR/PR/SD/PD: 10/19/11/0. At the last follow-up, 5 lesions had local progression, with one lesion at 39 months, and 4 lesions at 11 months after CK SRS, while 16 lesions remained CR. The cumulative 3-months, 6-months, and 12-months local control rates were 100%, 100%, and 87.5%, respectively.

CONCLUSION
To date, this is the largest study examining the efficacy of SRS for ACC BM. Our results showed the sufficient local control following the treatment. Further studies are required to confirm our results.