bluuebunny/crossref_metadata_2025_split huggingface dataset:
MMAP-08 CHEMO-REIRRADIATION (NORMOFRACTIONATED VS. HYPOFRACTIONATED) WITH OR WITHOUT BEVACIZUMAB IN RECURRENT ADULT DIFFUSE HIGH-GRADE GLIOMA (COBRA): PHASE III RANDOMIZED CONTROLLED TRIAL WITH A 2 X 2 FACTORIAL DESIGN
Authors: Baviskar Yamini , Dasgupta Archya , Chatterjee Abhishek , Kanan Sadhana , Epari Sridhar , Sahu Arpita , Puranik Ameya , Patil Vijay , Moiyadi Aliasgar , Gupta Tejpal 
Published: August 2022

Abstract

BACKGROUND
Adult diffuse high-grade gliomas (HGG) predominantly recur locally despite adequate treatment. At recurrence, salvage chemo-reirradiation (CTRT) provides durable local control with significant risk of symptomatic radionecrosis (RN). Reirradiation (reRT) is delivered using either conventional fractionation (CFRT) or hypofractionation based on institutional preferences. Studies have shown that the addition of bevacizumab, a monoclonal antibody inhibiting vascular endothelial growth factor to reRT reduces the risk of RN and potentially improves survival, providing strong scientific rationale for the combination.

OBJECTIVE
Primary endpoint would be a composite endpoint of 1-year event-free survival (EFS) comprising recurrence, symptomatic RN or death as an event. Secondary endpoints include progression-free survival, cumulative incidence of symptomatic RN, and overall survival. Quality-of-life assessment and health-economics would be tertiary endpoints.

METHODS
Target population includes adults with local recurrence (radiology and/or histology) of biopsy-proven diffuse HGG &gt;2-years from primary RT. This is an open-label, phase III randomised control trial using a 2 x 2 factorial design comparing the addition of bevacizumab to chemo-reirradiation (test arm) versus chemo-reirradiation alone (control arm) using a superiority hypothesis. Patients in test arm will receive 6 months of bevacizumab (5mg/kg) 2 weekly, along with standard 6 cycles of temozolomide, starting 1 month following reRT completion. All patients will be further randomized to CFRT (50.4-55.8Gy/28-31/5.5-6 weeks) as control arm versus moderately HFRT (35Gy/10 fractions/2 weeks) as test arm in 1:1 ratio using a non-inferiority hypothesis. The desired sample size is 257 (two-sided alpha 0.05, power 80%, and 10% attrition rate) with a superiority hypothesis of 1-year EFS 45% (bevacizumab with CTRT) vs 30% (CTRT), and non-inferiority hypothesis of 25% (HFRT) vs 37% (CFRT),with delta of 12%.

DISCUSSION
The study will answer critical questions regarding the role of bevacizumab in recurrent HGG along with reRT, along with the differences in outcomes using normofractionated or hypofractionated RT.
NEIM-01 INCIDENCE AND DIAGNOSTIC TECHNIQUES FOR LEPTOMENINGEAL DISEASE IN PATIENTS WITH BRAIN METASTASIS
Authors: Henry Katie , Overholt Brandon , Sinson Grant , Pinheiro Fernando Santos , Bovi Joseph 
Published: August 2022

Abstract

BACKGROUND
Leptomeningeal disease (LMD) is malignant infiltration of the pia mater and cerebrospinal fluid (CSF) space. LMD carries a poor prognosis with median survival of a few months. Annually, 110,000 patients in the United States are diagnosed with LMD. The incidence is rising because of improvements in control of primary cancers and recognizing that LMD is a late sequelae of some malignancies. Definitive diagnosis of LMD is made by CSF cytology and/or spine MRI, although neither tool shows robust sensitivity. The diagnostic challenges for LMD have led to a lack of uniformity in the diagnostic approach.

METHODS
A systematic chart review of brain metastasis patients was conducted at Froedtert Hospital between 2019-2021. Information on primary cancer, LMD suspicion, work up, confirmation, treatment, and survival were collected and analyzed.

RESULTS
Among 151 patients with brain metastasis, 86 were suspected and 29 were confirmed to have LMD. Of the confirmed patients, the most common primary cancers were lung (n=8, 27.6%) and breast (n=8, 27.6%). Most patients (n=24, 82.8%) underwent both LP and MRI. LMD was confirmed by positive cytology in a minority of cases (n=9, 31%), with most patients being confirmed by positive MRI or clinical findings alone (n=20, 69%). All LPs had over 10 mL of CSF sent to analysis. A median of 2 LPs were required before a positive cytology confirmed the diagnosis. Due to small sample size, no statistical analysis was made to correlate positive LP with primary cancer sites.

CONCLUSION
Less than one third of cancer patients with confirmed LMD have positive cytology, despite the majority (&gt;80%) of them undergoing LP. The dissonance between diagnostic strategies and confirmatory results is expected considering the low sensitivity of LPs; however, it highlights the need for more precise diagnostic tools, and development of a data-based strategy for LMD confirmation.
NEIM-02 DEVELOPMENT OF A DEEP LEARNING MODEL FOR DISCRIMINATING TRUE PROGRESSION FROM PSEUDOPROGRESSION IN GLIOBLASTOMA PATIENTS
Authors: Moassefi Mana , Faghani Shahriar , Conte Gian Marco , Rouzrokh Pouria , Kowalchuk Roman O , Trifiletti Daniel , Erickson BradleyJ 
Published: August 2022

Abstract

INTRODUCTION
Glioblastomas (GBMs) are highly aggressive tumors. Despite multimodal treatment, its median overall survival ranges between 16 and 20 months. The standard treatment regimen consists of surgical resection followed by concurrent chemoradiotherapy and adjuvant temozolomide. Despite temozolomide’s effectiveness, it may cause the clinical challenge of treatment-related progression also known as pseudoprogression(PsP). Usually, PSP resolves or stabilizes without further treatment, whereas a true progression (TP) requires more aggressive management. Identifying PSP from TP will affect the patient’s treatment plan. Conventional magnetic resonance imaging (MRI) reading techniques cannot distinguish these entities. This study investigated the feasibility of using deep learning to distinguish PsP from TP.

METHOD
We included GBM patients who met our inclusion criteria. We evaluated all cases to see if they had a new enhancing lesion within the original radiation field or an increase in the size of an existing lesion. The challenging MRIs were collected. Clinical notes regarding tumor and recurrence location, clinical history, and medication were collected. We labeled the ones who stayed stable or improved in the imaging and clinical situation as PSP and those with further imaging and clinical deterioration as TP. We coregistered Contrast-enhanced-T1 MRIs with T2-weighted images for each patient. We performed five-fold cross-validation to generalize the performance. We trained A 3-D Densenet121 model to establish the prediction. We selected the best models with the highest accuracy.

RESULT
After reviewing 1000 patients, we included 124 patients whose imaging showed suspicious progression and their medicational histories were completely retrievable; 63 PsP, and 61 TP. We developed a deep learning model based on the whole dataset. The 5-fold cross-validation revealed that the mean area under the curve (AUC) was 0.81.

CONCLUSION
We report the development of a deep learning model that diagnoses PsP from TP in patients who received temozolomide. Further refinement and external validation are required prior to widespread adoption in clinical practice.
SPCR-01 RAPIDPLAN HIPPOCAMPAL SPARING WHOLE BRAIN MODEL VERSION 2 - HOW FAR CAN WE REDUCE THE DOSE?
Authors: Liu Hefei , Clark Ryan , Magliari Anthony , Foster Robert , Reynoso Francisco , Schmidt Matthew , Gondi Vinai , Abraham Christopher , Curry Heather , Kupelian Patrick , Khuntia Deepak , Beriwal Sushil 
Published: August 2022

Abstract

BACKGROUND
Whole-brain radiotherapy (WBRT) has been the standard palliative treatment for patients with brain metastases due to its effectiveness, availability, and ease of administration. Recent clinical trials have shown that limiting radiation dose to the hippocampus is associated with decreased cognitive toxicity. In this study, we updated an existing Knowledge Based Planning (KBP) model to further reduce dose to the hippocampus and improve other dosimetric plan quality characteristics.

METHODS
42 clinical cases were contoured according to NRG-CC001 guidelines. A new dosimetric scorecard was created as an objective measure for plan quality. The new Hippocampal Sparing Whole Brain Version 2 (HSWBv2) model adopted a complex recursive training process and was validated with five additional cases. HSWBv2 treatment plans were generated on the Varian HalcyonTM and TrueBeamTM systems and compared against plans generated from the existing (HSWBv1) model released in 2016.

RESULTS
On the HalcyonTM platform, 42 cases were re-planned. Hippocampal D100% from HSWBv2 and HSWBv1 models had an average dose of 5.75 Gy and 6.46 Gy, respectively (p&lt;0.001). HSWBv2 model also achieved a hippocampal Dmean of 7.49 Gy, versus 8.10 Gy in HSWBv1 model (p&lt;0.001). Hippocampal D0.03CC from HSWBv2 model was 9.86 Gy, in contrast to 10.57 Gy in HSWBv1 (p&lt;0.001). For PTV_3000, D98% and D2% from HSWBv2 model were 28.27 Gy and 31.81 Gy, respectively, compared to 28.08 Gy (p=0.020) and 32.66 Gy from HSWBv1 (p&lt;0.001). Among several other dosimetric quality improvements, there was a significant reduction in PTV_3000 V105% from 35.35% (HSWBv1) to 6.44% (HSWBv2) (p&lt;0.001). On five additional validation cases, dosimetric improvements were also observed on TrueBeamTM.

CONCLUSION
In comparison to published data in addition to the HSWBv1 model, the HSWBv2 model achieved higher quality HA-WBRT treatment plans through further reductions in hippocampal dose while improving target coverage and dose conformity/homogeneity. HSWBv2 model is shared publicly.
SYST-01 MULTI-INSTITUTIONAL RANDOMIZED TRIAL COMPARING CANCER STEM CELL-TARGETED VS PHYSICIAN-CHOICE TREATMENTS IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS (NCT03632135)
Authors: Sengupta Soma , Ranjan Tulika , Yu Alexander , Howard Candace , Chen Ricky , Chaudahary Rekha , Marko Nicholas , Aregawi Darit , Glantz Michael , Glass Jon , Green Richard , Lu-Hemerson Christine , Mammoser Aaaron , Moulding Hugh , Jubelirer Steven , Schoroeder Jason , Anderson Mark , Chow Frances , Lirette Seth , Denning Krista , Alberico Anthony , Valluri Jagan , Claudio Pier Paolo 
Published: August 2022

Abstract

BACKGROUND
Clinical outcomes in patients with recurrent high-grade glioma (HGG) remain poor. Cancer stem cells (CSCs) have been implicated in metastasis, treatment resistance and recurrence of HHGs. We have shown in several clinical studies that anti-CSC-directed therapy provides benefits in many cancer types; however, this is the first report of a randomized clinical trial evaluating it for recurrent HGGs.

OBJECTIVE
Determine whether CSC-targeted cytotoxic agents selected by ChemoID assay-guided therapy improves survival in patients with recurrent HGG.

DESIGN, SETTING, AND PARTICIPANTS
In this parallel-group, randomized, phase-3 clinical trial, patients at 13 clinical sites in the USA with grade-III/IV recurrent glioma (2016 WHO guidelines) were randomized 1:1 to either ChemoID assay-guided therapy or physician-choice therapy, and then treated and followed until unacceptable toxic effects, hospice, or death.

MAIN OUTCOMES AND MEASURES
The primary endpoint was overall survival (OS).

RESULTS
Combined median follow-up was 9 months. Median OS (mOS) was 12.5 months (95% CI, 10.2-14.7) in the ChemoID assay-guided group vs 9 months (95% CI, 4.2-13.8) in the physician-choice group (log-rank P = .010). Risk of death was significantly lower in the ChemoID assay group (HR = 0.44; 95% CI, 0.24-0.81; P = .008). Median progression free survival (PFS) was 10.1 vs 3.5 months (95% CI, 4.8-15.4 vs 1.9-5.1) (HR, 0.25; 95% CI, 0.14-0.44; P &lt; .001).

CONCLUSIONS AND RELEVANCE
Primary endpoint was met in this randomized clinical trial. The mOS was 3.5 months longer in the ChemoID assay-guided group vs the physician-choice group.
SYST-03 INCIDENCE AND SURVIVAL OF PATIENTS WITH INTRACRANIAL METASTATIC DISEASE AND ERBB2-POSITIVE GASTROINTESTINAL CANCERS: A RETROSPECTIVE COHORT STUDY
Authors: Sherman Madison , Erickson Anders W , Das Sunit 
Published: August 2022

Abstract

BACKGROUND
Intracranial metastatic disease (IMD) is a mortality-driving complication of gastrointestinal (GI) cancers. In breast cancer, ERBB2 positivity is associated with shorter overall survival (OS) and increased risk of IMD, and while ERBB2 status is relevant in primary GI cancer, no study has directly assessed the relationship of ERBB2 status and IMD in these patients.

METHODS
Records for adult patients with GI cancer and IMD, treated with ERBB2-therapy between 2005 and 2018 were retrieved from ICES. Baseline characteristics were compared between subcohorts stratified by IMD and ERBB2 statuses. Kaplan-Meier and Cox regression analyses were performed to estimate survival.

RESULTS
Records for 99,256 patients with GI cancer were collected, and IMD was diagnosed in 2002 patients. The highest IMD incidence rate was among patients with esophageal cancer (5.5%). Among patients with ERBB2+ disease, 306 had gastric (9 IMD), 168 esophageal (15 IMD), and 17 colorectal cancer. Diagnosis of IMD was associated with shorter OS among patients with colorectal (HR 3.0; 95% CI 2.9–3.2), gastric (HR 1.7; 95% CI, 1.5–1.9), and esophageal cancers (HR 1.2; 95% CI, 1.1–1.4). Post-IMD ERBB2-targeted therapy was not associated with OS among patients with ERBB2+ esophageal (HR 0.5; 95% CI, 0.2–1.2; n = 15) or gastric cancer (HR 0; 95% CI 0–Inf; n = 9).

CONCLUSION
Our study assessed patients with ERBB2+ GI cancer and IMD. Diagnosis of IMD was associated with shorter survival in gastric, esophageal, and colorectal cancers. Post-IMD ERBB2 therapy was not associated with OS, and IMD diagnosis was associated with prolonged survival in patients with stage 4 ERBB2+ disease, although interpretation of these results is complicated by small sample size and selection bias. Our results motivate increased reporting and inclusion of patients with ERBB2+ GI cancers in clinical trials.
SYST-05 OPTIMIZING HER2-TARGETED THERAPIES (TT) FOR BREAST CANCER (BC) LEPTOMENINGEAL METASTASES (LM): A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Lazaratos Anna-Maria , Maritan Sarah , Quaiattini Andrea , Bouganim Nathaniel , Dankner Matthew 
Published: August 2022

Abstract

INTRODUCTION
LM is a debilitating condition associated with metastatic cancers, including BC. When oncogenic drivers are identified, TT represents an appealing therapeutic strategy. However, the efficacy of TT for LM is unknown as LM patients are routinely omitted from clinical trials.

METHODS
We conducted a systematic review and meta-analysis of individual patient data to evaluate the effectiveness of HER2-TT in HER2+ BCLM in accordance with PRISMA guidelines. TTs evaluated included trastuzumab (intrathecal (IT) or intravenous (IV)), trastuzumab-emtansine, trastuzumab-deruxtecan, and lapatinib. Primary outcome was overall survival (OS).

RESULTS
Of 7780 abstracts screened, 91 publications and a total of 109 patients were included in the final analysis. Patients receiving chemotherapy (either IT, IV, or as part of an antibody-drug conjugate) concurrently with HER2-TT (N=57) exhibited a median OS (mOS) of 44.0 months, compared to patients treated with targeted anti-HER2 therapies alone (N=52), which exhibited a mOS of 14.5 months (P=0.009, hazard ratio (HR): 0.538, 95% confidence interval (CI): 0.328-0.883). Patients receiving IT trastuzumab (N=83) exhibited a median progression-free survival (mPFS) and mOS of 6.0 and 21.0 months, respectively, while patients receiving IV trastuzumab (N=14) exhibited a mPFS and mOS of 6.5 and 27.0 months, respectively (PFS: P=0.31, HR: 0.712, 95% CI: 0.331-1.531; OS: P=0.68, HR: 1.154, 95% CI: 0.587-2.266). In the subgroup of patients receiving IT trastuzumab (N=58), those who concurrently received IT chemotherapy (N=48) exhibited mPFS and mOS of 5.7 and 14.0 months, respectively, while patients concurrently receiving IV chemotherapy (N=10) exhibited a mPFS and mOS of 6.0 and 27.0 months, respectively (PFS: P=0.45, HR: 1.360, 95% CI: 0.602-3.073; OS P=0.29, HR: 1.821, 95% CI: 0.630-5.260).

CONCLUSIONS
HER2-TT is an effective therapeutic strategy for BCLM. Patients with BCLM receiving concurrent cytotoxic chemotherapy alongside HER2-TT experience prolonged mOS. IV and IT trastuzumab are similarly effective. Univariate and multivariate analyses will be presented.
SYST-06 INTRACRANIAL ACTIVITY OF TEPOTINIB IN PATIENTS WITH MET EXON 14 (METEX14) SKIPPING NSCLC ENROLLED IN VISION
Authors: Leighl Natasha , Bestvina Christine , Patel Jyoti , Le Xiuning , Veillon Remi , Anderson Ian , Demedts Ingel , Garassino Marina Chiara , Mazières Julien , Morise Masahiro , Smit Egbert , Eggleton S Peter , O’Brate Aurora , Otto Gordon , Bruns Rolf , Schumacher Karl Maria , Paik Paul 
Published: August 2022

Abstract

BACKGROUND
Brain metastases (BMs) occur in 20–40% of patients with METex14 skipping NSCLC. Tepotinib, a highly selective MET inhibitor, demonstrated an objective response rate (ORR) of 49.1% and median duration of response (mDOR) of 13.8 months, in METex14 skipping NSCLC patients in the Phase II VISION study (Cohorts A+C; N=275). Here, we report the intracranial activity of tepotinib in VISION.

METHODS
Patients with METex14 skipping NSCLC received oral tepotinib 500 mg QD (450 mg active moiety). Patients with BM (asymptomatic and symptomatic/stable) were eligible. Primary endpoint was systemic ORR (RECIST v1.1); a subgroup analysis in patients with BM was predefined (data cut-off: February 1, 2021). An ad-hoc retrospective analysis of brain lesions was conducted by an IRC using RANO-BM criteria. Responses were determined in patients with ≥1 evaluable post-baseline tumor assessment. For those with only non-target lesions (NTLs) per RANO-BM (enhancing and non-enhancing NTLs), disease control was defined as non-complete response (CR)/nonprogressive disease (PD). Data cut-off: July 1, 2020.

RESULTS
Fifty-one patients had baseline BM (Cohorts A+C). Systemic efficacy was consistent with the overall population (ORR 52.9% [95% CI: 38.5, 67.1], mDOR 9.0 months [95% CI: 5.6, not estimable]). Fifteen patients were evaluable by RANO-BM (Cohort A); 12 received prior radiotherapy for BM (median 6.4 weeks before treatment). Systemic best objective responses (BORs) were partial response (PR, n=9), stable disease (SD, n=3), and PD (n=3). Seven patients had target CNS lesions per RANO-BM (all with prior radiotherapy); intracranial BORs were PR (n=5), SD (n=1), and PD (n=1). For patients with NTL only (n=8), one had PD, and seven achieved intracranial disease control with three patients achieving CR of the enhancing NTL. 13/15 patients achieved intracranial disease control.

CONCLUSIONS
Tepotinib demonstrated robust systemic activity in patients with METex14 skipping NSCLC with BM, complemented by intracranial activity in an ad-hoc analysis using RANO-BM.
SYST-08 SURVIVAL ANALYSIS OF METASTATIC MELANOMA PATIENTS WITH BRAIN METASTASIS USING SURVEILLANCE, EPIDEMIOLOGY, AND END RESULTS (SEER)
Authors: Stahl Caleb , Baroz Angel , Bhanja Debarati , Wilding Hannah , Mansouri Alireza 
Published: August 2022

Abstract
INTRODUCTION: Melanoma brain metastases (BM) are common and are historically associated with poor prognosis. In the early 2010s, the treatment paradigm for malignant metastatic melanoma shifted with the introduction of immunotherapy (IT). Recent studies suggest that IT provides survival benefits for patients with BM from melanoma primary. The goal of this study was to validate these findings in a large population cohort. METHODS: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, version 8.3.4 (22 March 2017). Three cohorts were created based on the FDA approval date of IT: ipilimumab (2011), nivolumab (2014), and nivolumab plus ipilimumab (2015) for use in metastatic melanomas. Respectively, the cohorts are defined as the pre-IT era cohort (2010), early-IT era cohort (2011-2015) and late-IT era cohort (2016-2018). One-year overall survival (OS), 2-year OS, and median OS were assessed using a Kaplan-Meier analysis and log rank tests. RESULTS: 1,893 patients were included in this analysis (190 in the pre-IT era, 1,021 in the early-IT era, and 682 in the late-IT era) that had histologically confirmed melanoma with secondary BM at diagnosis. Median OS was significantly increased across the pre-, early-, and late-IT era cohorts, respectively, with the largest increase occurring between the early-IT and late-IT eras (1-year OS: 20.6% vs. 17.0% vs. 38.2%, 2-year OS: 10.5% vs. 14.2% vs. 27.1%, and median OS: 5 vs. 6 vs. 8 months, p &lt; 0.001 by log-rank test). CONCLUSION: The introduction of IT for malignant melanomas has significantly improved the survival outcomes of melanoma patients with brain metastasis. Novel treatment paradigms involving IT with other adjuvant therapies need to be explored to further improve intracranial activity in melanoma patients.
SYST-09 IMPACT OF END-STAGE RENAL DISEASE AND CONCOMITANT DIALYSIS ON THE EFFICACY OF IMMUNOTHERAPY IN BRAIN METASTASES PATIENTS: A PROPENSITY-MATCHED SURVIVAL ANALYSIS
Authors: Baroz Angel , Bhanja Debarati , Stahl Caleb , Wilding Hannah , Mansouri Alireza 
Published: August 2022

Abstract

INTRODUCTION
Mounting evidence demonstrates the therapeutic promise of immunotherapies (ITs) for brain metastases (BM). However, there is concern that stringent eligibility criteria in these clinical studies have selected against patients with comorbid conditions. As a result, it remains unclear if these results are truly applicable to the general population, particularly in individuals with end-stage renal disease (ESRD) on dialysis. Therefore, we sought to determine the impact of concomitant dialysis treatment and IT on overall survival (OS) of patients with BM.

METHODS
Data were collected from TriNetX (TriNetX, Inc., Cambridge, MA), a global research network that aggregates clinical data from 92 healthcare organizations. Independent variables included ‘secondary malignant neoplasm of brain’, ‘ipilimumab’, ‘pembrolizumab’, ‘ESRD’, ‘dependence on renal dialysis’, and ‘dialysis services and procedures’. Patients with BM receiving IT were dichotomized by dialysis use. Cohorts were propensity matched on age, gender, and race. Kaplan-Meier analyses and log rank tests were conducted to assess overall survival (OS) and survival probability over a five-year period.

RESULTS
Of the 14,368 confirmed BM patients treated with IT, 95 (0.6%) began dialysis within three months of IT initiation. Propensity matching established 95 patients in each cohort. The dialyzed cohort had a median OS of 277 days with a survival probability of 11.6%, compared to the non-dialyzed group with a median OS of 419 days and survival probability of 40.29% (p=0.109; hazard ratio 1.422, 95% confidence interval, 0.923-2.191, p=0.891). A separate comparison cohort was created to compare ESRD diagnosis with or without dialysis (n=56 and n=106 respectively). The comparison cohorts did not show a difference in median OS and survival probability (p=0.49).

CONCLUSION
Despite their health complexities, individuals with ESRD, with or without dependence on dialysis, may nonetheless derive a similar survival benefit from ITs. Therefore, we advocate for greater inclusion of patients with advanced comorbidities in clinical trials to assess for real-world safety and efficacy outcomes.