bluuebunny/crossref_metadata_2025_split huggingface dataset:
NIMG-24. RANO CRITERIA DETECTS EARLY PROGRESSION SOONER THAN MODIFIED RANO CRITERIA IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Youssef Gilbert , Lim-Fat Mary Jane , Bay Camden , Arnaout Omar , Bi Wenya Linda , Cagney Daniel , DeSalvo Matthew , Castro L Nicolas Gonzalez , Guenette Jeffrey , Lee Eudocia Quant , McFaline-Figueroa J Ricardo , Potter Christopher , Reardon David , Cloughesy Timothy , Ellingson Benjamin , Rahman Rifaquat , Huang Raymond , Wen Patrick 
Published: November 2021

Abstract

BACKGROUND
Accurate response criteria are crucial for determining treatment efficacy. The response assessment in neuro-oncology (RANO) criteria was developed to standardize response assessment in neuro-oncology. Modified RANO (m-RANO) criteria were recently proposed to address some limitations of the initial criteria including the use of a post-radiation baseline and an additional scan to confirm progression. We sought to identify differences in the association of progression-free survival (PFS) and overall survival (OS) using RANO and m-RANO criteria.

METHODS
We conducted a retrospective review of newly diagnosed glioblastoma (GBM) patients treated at Dana-Farber Cancer Institute from January 2013 until December 2019. Patients with available clinical and imaging data obtained before initiation of treatment, after radiation completion and at intervals of 1 to 3 months were included. MRIs were evaluated by two independent readers, and PD dates determined using RANO and m-RANO criteria.

RESULTS
552 patients were included. 97.1% of the tumors were IDH wild-type. MGMT promoter was unmethylated in 51.4%, methylated in 35.1% and undetermined in 8.5%. Median OS among patients was 18.1 months. 72 patients (13%) did not have PD at the end of the study. 83 patients had treatment change while being clinically stable and without a confirmation scan and were excluded from the final analysis. PFS was 8.2 months with RANO and 8.4 months with mRANO. Difference in PD dates between RANO and m-RANO was detected in 76 patients (14%), where PFS was 3.5 months with RANO and 5.1 months with m-RANO. These patients had a worse median OS than those with identical RANO and m-RANO PD dates (15.2 vs. 22.4 months, p&lt; 0.0001).

CONCLUSION
RANO and m-RANO criteria resulted in identical PFS for most patients. 14% of patients had discordant PD dates and a worse prognosis. These patients progressed early, and their PD was identified sooner with RANO criteria.
NIMG-29. ELEVATION OF GLUTAMINE AND CITRATE BY MR SPECTROSCOPY IS AN IMAGING BIOMARKER OF RAPID CELL PROLIFERATION IN GLIOMAS
Authors: Tiwari Vivek , Askari Pegah , Maher Elizabeth , Choi Changho 
Published: November 2021

Abstract
Prior studies suggested glutamine metabolism in cancers may be altered to meet the high demands of nucleotide biosynthesis in cancers. We conducted 1H MR spectroscopy in 18 glioma patients and analyzed the metabolic data together with post-gadolinium MRI and cell proliferation rate (MIB-1 label index). The optimized MRS (TE 97 ms PRESS) provided well discernible signal of glutamine at 2.45 ppm and a negative-polarity signal of citrate at 2.6 ppm, without considerable overlaps with neighboring signals. The 18 patients had biopsy-proven anaplastic gliomas or glioblastomas. Concurrent elevation of glutamine and citrate was identified in 15 gliomas. These gliomas presented with enhancement in post-gadolinium MRI, indicative of broken blood-brain barrier (BBB). The 15 gliomas were grouped as subset-1 while the other 3 gliomas that had elevated citrate without elevation of glutamine were grouped as subset-2. Citrate level was significantly different between the two subsets of gliomas (1.4+/-0.5 vs. 1.6+/-0.4 mM). However, subst-1 had significantly higher choline (4.7+/-1.8 vs. 1.6+/-0.3 mM, p&lt; 0.01) and higher MIB-1 compared with subset-2. Given that choline is a cellularity marker, a finding of high choline and high MIB-1 with elevation of glutamine and citrate suggests that the tumors have high tumor cellularity and cell multiplication competence. Of the 18 gliomas, 13 were IDH mutated with elevated 2HG. The glutamine and citrate levels in IDH-mutant gliomas were not significantly different from those in IDH wildtype gliomas. In conclusion, high-grade gliomas undergo a metabolic rearrangement of concurrent elevation of glutamine and citrate to attain malignant characters such as high cellularity, rapid cell proliferation, and BBB breakdown. IDH mutant and IDH wildtype gliomas may share a common metabolic rearrangement of glutamine-mediated citrate elevation to attain malignancy. Measurements of glutamine and citrate may serve a potential imaging biomarker for aggressive gliomas.
NIMG-33. VOLUMETRIC TUMOR MEASUREMENTS ARE SUPERIOR TO 2D BIDIRECTIONAL MEASUREMENTS IN THE EVALUATION OF IDH INHIBITION IN DIFFUSE GLIOMAS: EVIDENCE FROM A PROSPECTIVE PHASE I TRIAL OF IVOSIDENIB
Authors: Ellingson Benjamin , Kim Grace , Brown Matt , Lee Jihey , Salamon Noriko , Steelman Lori , Hassan Islam , Pandya Susan , Chun Saewon , Wen Patrick , Mellinghoff Ingo K , Goldin Jonathan , Cloughesy Timothy 
Published: November 2021

Abstract
Since IDH mutant (mIDH) low-grade gliomas (LGGs) progress slowly and patients have a relatively long survival, testing of new therapies in clinical trials based solely on survival can take more than 20 years. Guidance on therapeutic evaluation using LGG RANO criteria recommends serial bidirectional (2D) measurements on a single slice; however, questions remain as to the best approach for evaluating LGGs in clinical trials including use of volumetric (3D) measurements, which would theoretically allow for more accurate measurements of irregular shaped lesions and allow readers to better assess areas of change within these tumors. A total of 21 (out of 24) non-enhancing, recurrent mIDH LGGs with imaging pre- and post-treatment enrolled in a phase I, multicenter, open-label study to assess the safety and tolerability of oral ivosidenib (NCT02073994) were included in this exploratory ad hoc analysis. 2D bidirectional and 3D volumetric measurements were centrally evaluated by one of 3 radiologists at an imaging CRO using a paired read and forced adjudication paradigm. The effects of 2D vs. 3D measurements on progression-free survival (PFS), growth rate measurement variability, and reader concordance and adjudication rates were then quantified. 3D volumetric measurements had significantly longer estimates of PFS (P=0.0181), more stable (P=0.0063) and considerably lower measures of tumor growth rate (P=0.0037), the highest inter-reader agreement (weighted Kappa=0.7057), and significantly lower reader discordance rates (P=0.0002) with comparable recommended LGG RANO 2D approaches. In summary, 3D volumetric measurements are better for determining response assessment in LGGs due to longer PFS and more stable measures of tumor growth rates (i.e. less “yo-yo-ing” of measurements over time causing fewer erroneous calls of progression and more accurate growth rates), highest inter-reader agreement, and lowest reader discordance rates. Future studies will focus on validating this in a larger cohort and determining whether these measurements better reflect clinical benefit.
NIMG-50. DEUTERIUM METABOLIC IMAGING OF THE ALTERNATIVE LENGTHENING OF TELOMERES PATHWAY REPORTS ON TUMOR BURDEN AND PSEUDOPROGRESSION IN LOW-GRADE GLIOMAS
Authors: Taglang Céline , Batsios Georgios , Mukherjee Joydeep , Tran Meryssa , Gillespie Anne Marie , Hong Donghyun , Ronen Sabrina , Luchman Hema Artee , Pieper Russell , Viswanath Pavithra 
Published: November 2021

Abstract
Glioma patient management relies heavily on magnetic resonance imaging (MRI). However, MRI is often inadequate for assessment of tumor burden and pseudoprogression. Non-invasive methods that report on molecular pathways such as telomere maintenance that drive tumor proliferation are needed. Among brain tumors, low-grade astrocytomas (LGAs) use the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. The goal of this study was to identify ALT-linked metabolic alterations that can be exploited for non-invasive magnetic resonance spectroscopy (MRS)-based imaging of LGAs. We examined the patient-derived BT257 model and compared neurospheres that are ALT-dependent (BT257 ALT+) with those in which the ALT pathway has been silenced (BT257 ALT-). Our studies suggest that expression and activity of the rate-limiting glycolytic enzyme phosphofructokinase-1 are significantly higher in BT257 ALT+ neurospheres relative to ALT-, an effect that is associated with elevated glucose flux to lactate. Studies indicate that poly(ADP-ribose) polymerase inhibitors such as niraparib selectively induce telomeric fusion and cell death in ALT-dependent cells. We find that the telomeric fusion-mediated cytotoxicity of niraparib is associated with significantly reduced glycolytic flux in BT257 ALT+ neurospheres. We then examined whether 2H-MRS using [6,6’-2H]-glucose, which is a clinically translatable method of imaging glycolytic flux, can be used to monitor the ALT pathway in vivo. [6,6’-2H]-glucose flux to lactate is elevated in tumor relative to normal brain in mice bearing orthotopic BT257 tumors. Importantly, following treatment of BT257 tumor-bearing mice with niraparib, lactate production from [6,6’-2H]-glucose is significantly reduced at early timepoints when alterations in tumor volume cannot be observed by MRI, pointing to the ability of [6,6’-2H]-glucose to report on pseudoprogression in vivo. Collectively, our studies mechanistically link the ALT pathway with elevated glycolytic flux via phosphofructokinase-1 and identify deuterium metabolic imaging as a novel, non-invasive method of imaging tumor burden and treatment response in LGAs in vivo.
NIMG-59. RADIOMICS-PREDICTED T CELL DYNAMICS STRATIFY SURVIVAL AFTER DENDRITIC CELL VACCINE THERAPY FOR PRIMARY GLIOBLASTOMA
Authors: Bond Kamila , Hawkins-Daarud Andrea , De Leon Gustavo , Curtin Lee , Urcuyo Javier , Singleton Kyle , Clark-Swanson Kamala , Sereduk Christopher , Tran Nhan , Hu Leland , Parney Ian , Swanson Kristin 
Published: November 2021

Abstract

INTRODUCTION
Dendritic cells (DCs) are potent antigen presenting cells that can be exploited to initiate an adaptive anti-tumoral immune response. DC vaccine clinical trials for primary glioblastoma (GBM) have reported prolonged progression-free survival without any impact on overall survival (OS). We report a radiomics approach that identifies a subpopulation of patients with prolonged OS in clinical trial MC1272.

METHODS
Twenty adults with primary GBM undergoing standard-of-care therapy were enrolled in MC1272. Autologous DCs were pulsed with allogenic GBM cell lines to generate vaccines that were administered for up to twelve cycles. Standard brain imaging was obtained at the initiation of treatment and two months afterwards. An independent cohort of image-localized biopsies underwent RNA sequencing followed by cellular deconvolution to estimate T cell abundance. A machine learning model was trained to predict intratumoral T cell abundance from imaging features, and the model was applied to MC1272 patient imaging.

RESULTS
Voxelwise predictions of T cell abundance were generated for each patient’s pre- and post-treatment images. The difference in total intratumoral T cell abundance between imaging timepoints classified patients into increasing or decreasing T cell groups. Patients whose T cells increased had longer OS (median, 21 months) than those whose T cells decreased (median, 10 months; p=0.0035). The significance remained in a Cox proportional hazards analysis that adjusted for patient age and sex (p=0.011).

CONCLUSIONS
A spatially-resolved radiomics model detected that an intratumoral T cell influx after DC vaccine therapy was associated with prolonged OS. The “post-treatment” imaging in this study was obtained a mere two months after DC vaccine initiation, suggesting that our radiomics model can provide an early indication of treatment responsiveness and prognosis in these patients.
NCMP-15. IMMUNE CHECKPOINT INHIBITOR ENCEPHALITIS: A RETROSPECTIVE COHORT STUDY
Authors: Clarke Nathan , Chen Merry 
Published: November 2021

Abstract

OBJECTIVE
To review our institution’s experience with immune check point inhibitors (ICI) in patients with all cancer types and describe the incidence and outcomes of encephalitis associated with its use.

METHODS
We performed a single-center retrospective chart-review identifying patients who developed encephalitis within 12 weeks of treatment with an ICI.

RESULTS
Between 2011 to 2020 we identified 842 unique patients treated with an ICI with 32 patients (3.8%) developing encephalitis associated with treatment. The median time to diagnosis was 20 days post infusion (13-24 days IQR) and 3 infusions (2-4 IQR). No specific treatment was more significantly associated with encephalitis than the rest with the combination of ipilimumab and nivolumab (10 of 176, 5.68%) being the most common, and single agent nivolumab (9 of 222, 4.05%) and pembrolizumab (8 of 271, 2.95%) being slightly less frequent. By class PD-1 inhibitors were the most common treatment associated (n=18, 3.76%), however there was no one specific class more significantly associated with increased rates of encephalitis when comparing this to inhibitors of PD-L1 (n=2, 1.16%), CTLA-4 (n=2, 5.00%), or combination of PD-1/CTLA-4 (n=10, 6.02%) (p=0.26). Patients were treated with discontinuation of the therapy alone (n=7), high dose steroids alone (n=10), or a combination of high dose steroids, IVIG, or plasma exchange (n=15). The effects were typically reversible or non-disabling with the average 90-day ECOG score being 1.8. There were 8 patients (25%) who developed severe debility (n=4) or death (n=4).

CONCLUSION
Encephalitis is a rare complication associated with ICI therapies. Overall, there was no apparent specific drug or class more at risk of causing this complication. As ICI therapy is used more in practice, we will likely see a greater number of cases of ICI encephalitis and need to be aware of how it presents, diagnose, and treat appropriately to avoid permanent disability.
NCMP-16. MANAGEMENT AND LONG-TERM OUTCOMES OF PATIENTS WITH RECURRENT STROKE-LIKE EPISODES AFTER CRANIAL RADIOTHERAPY
Authors: Neth Bryan , Lachance Daniel , Uhm Joon , Ruff Michael 
Published: November 2021

Abstract
Stroke-Like Migraine Attacks after Radiation Therapy (SMART) is a descriptive clinical entity consisting of transient hemispheric dysfunction. We were interested in pragmatic management patterns for patients with Recurrent Stroke-Like Episodes (R-SLE) of transient negative neurologic symptoms after cranial radiotherapy (RT) to define optimal management strategy and assess long-term outcomes. We conducted a retrospective review of all patients with recurrent negative neurologic symptoms after cranial RT who were treated at Mayo Clinic (Rochester), with follow-up extending until February 2021. Descriptive statistics and Chi-Square analysis was performed to assess for differences between patients with clinical cessation of symptoms, death, progressive encephalopathy and therapeutic class, patient and primary treatment characteristics (i.e. whole brain RT). We identified 27 patients with R-SLE after RT. 25 patients were included in analyses. Median age at diagnosis was 28.7 years (3.0-65.8 years, SD: 15.0 years). Median time from RT to symptom onset was 14.6 years (3.3-30.5 years, SD: 8.9 years). The most common presentations included hemiparesis (55.6%), hemisensory loss (22.2%), transient visual field loss (33.3%), encephalopathy (18.5%), and aphasia (22.2%). Antiseizure medications were most used for management of R-SLE (92%) followed by anti-platelets (68%), verapamil (52%), statins (48%), glucocorticoids (24%), antivirals (20%), and ACE inhibitors/angiotensin receptor blockers (16%). Beta blockers were not used. Verapamil use was frequently associated with clinical cessation of recurrent events with cessation being achieved in 64.7% of patients on verapamil versus 35.3% not on verapamil (p=0.0638). Other medical interventions did not approach clinical or statistical significance. Progressive encephalopathy was more common in patients without clinical cessation (87.5% vs. 23.5%, p=0.0026). All patients who died at last follow-up had progressive encephalopathy. We found cessation of recurrent negative neurologic symptoms after cranial RT in most patients. Verapamil use was associated with clinical cessation. Progressive encephalopathy was more common in patients without clinical cessation of recurrent events.
NCMP-18. FIXED PTOSIS AS A SYMPTOM OF MYOSITIS SECONDARY TO CHECKPOINT INHIBITION
Authors: Aaroe Ashley , Tummala Sudhakar 
Published: November 2021

Abstract

BACKGROUND
A growing number of patients with cancer receive checkpoint inhibitor (CPI) based immunotherapy. Peripheral nervous system toxicities including myositis, myasthenia gravis and inflammatory neuropathy are distinct from their non immunotherapy-related equivalents, with unique clinical presentations and therapeutic considerations.

METHODS
Patients with CPI myositis and non-fatigable ptosis were identified, and clinical data was retrospectively extracted from the electronic medical record in compliance with MD Anderson Cancer Center Institutional Review Board guidelines.

RESULTS
14 patients were identified. Average maximum creatine kinase (CK) was 3571 U/L (range 20-19,794). 9 patients had electromyography and nerve conduction studies documented in our system; all had electrodiagnostic evidence of myopathy and two had evidence of concomitant myasthenia gravis by electrodecrement. Two muscle biopsies revealed myositis with inflammatory T-cell infiltrate. 6 had positive anti-striated muscle antibody titers, 9/14 had concomitant myocarditis, 2 had hepatitis, 2 had pneumonitis and 1 had thyroiditis. All received high dose steroids, 11 received plasma exchange, 4 received rituximab, 4 received tacrolimus and 2 received tocilizumab. 7/14 patients died (50%). Mean time from initial neurology consultation for symptoms to death was 6.46 months (range .3-24). 5 patients had documented clinical stabilization or mild improvement on post-discharge follow-up.

CONCLUSIONS
While ptosis in patients receiving CPI can initially suggest myasthenia gravis, in patients with rapid onset and ultimately fixed deficits there should be a high index of suspicion for immunotherapy related restricted localized myositis. Myositis may coincide with other toxicities, such as myocarditis and pneumonitis, and can be fatal despite aggressive treatment. Deficits persist on post-discharge follow-up, suggesting protracted recovery for patients who survive.
NCOG-08. BIOPSY-ONLY GLIOBLASTOMA (BO-GBM) AS A HETEROGENEOUS GROUP OF PATIENTS
Authors: Harlay Vincent , Loundou Anderson , Boucard Céline , Petrirena Gregorio , Barrie Maryline , Campello Chantal , Autran Didier , Padovani Laeticia , Figarella Dominique , Boissonneau Sébastien , Dufour Henry , Baumstark Karine , Tabouret Emeline , Chinot Olivier 
Published: November 2021

Abstract

BACKGROUND
“Biopsy-only” glioblastoma is associated with a heterogeneous functional and survival outcome. It is an understudied group of patients which has been reported to represent 21% of histologically confirmed GBM in the US National Cancer Data Base. Pattern of care included radiotherapy-temozolomide (RT-TMZ) completed in 15% of patients, any other form of oncologic treatment in 60%, and supportive care alone in 25% of patients. Our objective was to explore treatment and prognosis of BO-GBM.

MATERIAL AND METHODS
Patients with BO-GBM included in a prospective regional glioma SIRIC cohort in 2014-2017 were retrospectively reviewed for patient characteristics, MRI finding, treatment allocation and delivery. PFS and OS were analyzed.

RESULTS
Of 535 patients included in the cohort, 449 patients were included at initial surgery, of which 158 patients (35%) underwent biopsy only. Of 158 patients, 18 were excluded for missing data leaving 139 patients for the present analysis. Fifty-four (39%) were referred to RT-TMZ, 68 (49%) considered unfitted for RT received chemotherapy upfront (CT-UF), 17 (12%) were referred to palliative care. Groups differed at baseline for age (mean 60 and 68 years, for RT-TMZ, CT-UF respectively); KPS (70, 60 for RT-TMZ, CT-UF); mean tumor surface (793, 1420 mm2 for RT-TMZ, CT-UF); and tumor extension (bilateral in 6.4% and 29.3% for RT-CT and CT-UF respectively). Median OS was 14 months (95% CI, 9.65-18.71) and 8 months (95% CI, 4.62-7.67) for RT-TMZ, CT-UF respectively.

CONCLUSION
Inoperable GBM constitute a large and heterogeneous population in which one third of patients are amenable to standard of care, with survival outcome close to the one of patients who underwent surgery. Patients considered unfit for RT-CT at diagnosis exhibit a poor survival outcome. Thus, reliable criteria are needed to help selecting patients for adequate treatment while new strategies are warranted for BO-GBM unfit for RT.
NCOG-27. STATUS AS A CLINICAL TRIAL PARTICIPANT AND OUTCOME IN IDH-WILDTYPE GLIOBLASTOMA
Authors: Pan Peter , Joanta-Gomez Adela , Iwamoto Fabio , Welch Mary , Haggiagi Aya , Donovan Laura , Barbaro Marissa , Yuen Carlen , Lassman Andrew 
Published: November 2021

Abstract

INTRODUCTION
Standard of care for glioblastoma consists of surgery, followed by combined chemoradiation and adjuvant chemotherapy, as per the seminal EORTC study from 2005. Clinical trial patients, being a population selected for functional status, hepatic function, renal function, and lack of other malignancies, may have improved outcome over the general treated population.

METHOD
Single center retrospective analysis of status as a clinical trial patient in the upfront setting and other clinical factors/biomarkers, analyzed for correlation with outcomes (PFS/OS) in IDH-wildtype glioblastomas.

RESULTS
82 patients with IDH-wildtype glioblastoma were identified between 2014 and 2020, treated with standard of care or with an upfront clinical study (43% women; median age 66 years, range 35-91 years of age). 22 patients (27%) were treated with upfront clinical study. Status as a patient treated in an upfront clinical study did not correlate with outcome (hazard ratio HR PFS 0.99, CI 0.57-1.7, p=0.97; HR OS 1.09, CI 0.56-2.1, p=0.81). Frontal lobe was most frequently involved (n=36, 44%), followed by parietal lobe (n=33, 40%). Age was not a strong predictor of survival (R2 0.01). No statistically significant correlation was observed between outcome and laterality or location. MGMT promoter methylation was associated with improved PFS (HR 0.56, CI 0.33-0.94, p=0.03) and OS (HR 0.40, CI 0.19-0.85, p=0.02), with mPFS 6 months vs 9 months and mOS 16 months vs 20 months (unmethylated vs methylated respectively).

CONCLUSION
In this retrospective cohort of IDH-wildtype glioblastomas, age, tumor laterality, and tumor location were not significant predictors of outcome. MGMT promoter methylation predicted for superior PFS/OS. Patient selection for clinical studies are influenced by entry criteria, however at least in this retrospective review, status as a clinical study patient in the upfront setting did not correlate with outcome compared to patients treated with upfront standard of care.