tbuckley/cabot-search huggingface dataset:
NIMG-51. CONVENTIONAL MRI RADIOMIC FEATURES IMPROVE PROGNOSTICATION AND ARE PREDICTIVE OF H3 K27M STATUS IN DIPG
Authors: Christopher Tinkle, Chih-Yang Hsu, Edward Simpson, Jason Chiang, Xiaoyu Li, Jesse Armstrong, Michael Soike, Michael Young, Zhaohua Lu, Amar Gajjar, Thomas Merchant, Alberto Broniscer, Suzanne Baker, Zoltan Patay, John Lucas
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Genomic profiling of DIPG suggests distinct and clinically relevant molecular subgroups based on the presence and isoform of histone H3 K27M mutation. We evaluated the impact of radiomic features on the classification and prognostication of 81 histologically confirmed and centrally reviewed DIPG. METHODS We utilized a combination of manual and automatic segmentation (DeepMedic) to define tumor volume and Pyradiomics for computation of radiomic features. Imaging feature stability was assessed by calculating concordance correlation coefficient (CCC) for each radiomic parameter from two separate pretreatment MRIs. Bootstrapped least absolute shrinkage and selection operator (LASSO) was used for feature selection. Classification and prognostication models, incorporating H3 status and clinical variables, were developed using random forest, Cox proportional hazards, and deep learning algorithms and assessed for goodness of fit using the c-index. RESULTS Eighty of 386 imaging features demonstrated stability (CCC, p&amp;lt; 0.001) between pretreatment scans. LASSO identified 26 prognostic imaging features and 38 and 57 imaging features predictive of the presence of H3 K27M mutation and H3 K27M isoforms, respectively. Using five-fold cross validation, the accuracy of distinguishing H3 K27M mutant and WT tumors was 85% and 77% for H3.3 K27M, H3.1 K27M, and WT tumors. C-index for prognostication was 0.77 for Cox, 0.55 for random forest, and 0.72 for deep learning. All models were more predictive than the Jansen survival prediction model. CONCLUSIONS Stable, predictive radiomic features may be a surrogate for H3 status and enhance current prognostication of DIPG. Model validation in cohorts of prospectively treated patients with DIPG is ongoing.
LGG-04. A PHASE II RE-TREATMENT STUDY OF SELUMETINIB FOR RECURRENT OR PROGRESSIVE PEDIATRIC LOW-GRADE GLIOMA (pLGG): A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY
Authors: Jason Fangusaro, Arzu Onar-Thomas, Shengjie Wu, Tina Young Poussaint, Roger Packer, Lindsay Kilburn, Ibrahim Qaddoumi, Girish Dhall, Ian F Pollack, Alicia Lenzen, Sonia Partap, Maryam Fouladi, Ira Dunkel
Journal: Neuro-Oncology (2020)

Abstract The PBTC conducted a re-treatment study (NCT01089101) evaluating selumetinib (AZD6244, ARRY-142886), a MEK I/II inhibitor, in children with recurrent/progressive pLGG. Eligible patients must have previously enrolled on PBTC-029 or PBTC-029B and progressed after coming off treatment with selumetinib. Patients must have maintained stable disease (SD) for ≥12 courses or had a sustained radiographic response (partial or complete) during their first exposure to selumetinib. Thirty-five eligible patients (median age: 13.11 years [range 7.96–25.33]) were enrolled, 57% of whom had optic pathway or hypothalamic target lesions. At the time of submission, median duration of treatment was 18 courses (range 2–48) and 21 subjects remained on therapy. Best responses reported to date are 6/35 (17%) partial response, 22/35 (63%) SD and 7/35 (20%) progressive disease with a 2-year progression-free survival of 75.7 + 8.3%, which met the design parameters for success. The most common attributable toxicities were grade 1 diarrhea, elevated AST, hypoalbuminemia, elevated CPK, maculo-papular rash, fatigue, paronychia, ALT elevation, acneiform rash and grade 2 CPK elevation. Rare grade 3 toxicities included CPK elevation (3), lymphopenia (2), paronychia (2) and ALT elevation (2). There was only one grade 4 CPK elevation. Five patients (14%) required dose reductions due to toxicity. There does not appear to be a notable difference in toxicities observed during initial selumetinib therapy versus re-treatment. In pLGG that has recurred/progressed following treatment with selumetinib, re-treatment with selumetinib appears to be effective with 80% of patients again achieving response or prolonged stable disease. Long-term follow-up is ongoing.
68Ga-Fibroblast Activation Protein Inhibitor, a Promising Radiopharmaceutical in PET/CT to Detect the Primary and Metastatic Lesions of Chromophobe Renal Cell Carcinoma
Authors: Yizhen Pang, Jihong Wei, Qihang Shang, Liang Zhao, Haojun Chen
Journal: Clinical Nuclear Medicine (2020)

18F-FDG PET/CT was performed to locate the primary lesion in a 71-year-old man with bone metastasis. However, no abnormal 18F-FDG activity likely presenting the primary tumor was observed. 68Ga-fibroblast activation protein inhibitor PET/CT was then performed for further detecting the primary tumor, which showed a higher activity in lesions of bone metastases than 18F-FDG. Additionally, another lesion with intense uptake was observed in the inferior pole of right kidney, likely presenting the primary tumor. A renal biopsy revealed the diagnosis of chromophobe renal cell carcinoma. This case highlighted that 68Ga-fibroblast activation protein inhibitor could be a promising radiopharmaceutical in the diagnosis of renal cell carcinoma.
Building a Better Clinician Value-Based Payment Program in Medicare
Authors: Kenton J. Johnston, Jason M. Hockenberry, Karen E. Joynt Maddox
Journal: JAMA (2020)

This Viewpoint reviews problems and successes to date in Medicare's value-based payment programs, and argues for global payment structures across populations, settings, and episodes of care to improve quality, patient-centered outcomes, and efficiency while not disadvantaging safety-net clinicians.
HGG-05. REGRESSION OF RECURRENT GLIOBLASTOMA AFTER BORON NEUTRON CAPTURE THERAPY AND CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY IN A CHILD
Authors: Hsin-Hung Chen, Yi-Wei Chen
Journal: Neuro-Oncology (2020)

Abstract A 6 y/o girl with recurrent multifocal glioblastoma received 3 times of boron neutron capture therapy (BNCT) and chimeric antigen receptor (CAR)–engineered T cells targeting the tumor-associated antigen HER2. Multiple infusions of CAR T cells were administered over 30 days through intraventricular delivery routes. It was not associated with any toxic effects of grade 3 or higher. After BNCT and CAR T-cell treatment, regression of all existing intracranial lesions were observed, along with corresponding increases in levels of cytokines and immune cells in the cerebrospinal fluid, but new lesions recurred soon after the treatment. This clinical response continued for 14 months after the initiation of first recurrence.
SURG-12. PREDICTORS OF SURVIVAL AND UTILITY OF INTRAOPERATIVE MRI FOR RESECTION OF GRADE II ASTROCYTOMAS AND OLIGODENDROGLIOMAS: A MULTICENTER ANALYSIS
Authors: Alexander Yahanda, Bhuvic Patel, Amar Shah, Daniel Cahill, Garnette Sutherland, John Honeycutt, Randy Jensen, Keith Rich, Joshua Dowling, David Limbrick, Ralph Dacey, Albert Kim, Eric Leuthardt, Gavin Dunn, Gregory Zipfel, Jeffrey Leonard, Matthew Smyth, Mitesh Shah, Steven Abram, John Evans, Michael Chicoine
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Few studies use large, multi-institutional patient cohorts to examine the role of intraoperative MRI (iMRI) in the resection of grade II gliomas. We assessed the impact of iMRI and other factors on overall survival (OS) and progression-free survival (PFS) for newly-diagnosed grade II astrocytomas and oligodendrogliomas. METHODS Retrospective analyses of a multicenter database assessed the impact of patient-, treatment-, and tumor-related factors on OS/PFS. RESULTS 232 resections (112 astrocytomas, 120 oligodendrogliomas; 135 males; mean age 36.2 ± 0.9 years) were analyzed. Oligodendrogliomas had longer OS (p&amp;lt; 0.001) and PFS (p=0.009) than astrocytomas. Multivariate regression showed that extent of resection (EOR), including gross-total (GTR) versus near-total (NTR) resection (p=0.02, HR: 0.64, 95% CI: 0.25-.79) and GTR versus subtotal resection (STR) (p=0.006, HR: 0.23, 95% CI: 0.08-0.66), was associated with longer OS. GTR versus NTR (p=0.04, HR: 0.49, 95% CI: 0.29-.85), GTR versus STR (p=0.02, HR: .54, 95% CI: .32-.91) and iMRI use (p=0.02, HR: 0.54, 95% CI: 0.32-0.92) were associated with longer PFS. Frontal (p=0.048, HR: 2.11, 95% CI: 1.01-4.43) and occipital/parietal (p=0.003, HR: 3.59, 95% CI: 1.52-8.49) locations were associated with shorter PFS (versus temporal). Kaplan-Meier analyses showed longer OS with increasing EOR (p=0.03) and 1p/19q gene deletions (p=0.02). PFS improved with increasing EOR (p=0.01), GTR versus NTR (p=0.02), and resections above STR (p=0.04). Factors influencing adjuvant treatment (35.3% of patients) included age (p=0.002, OR: 1.04) and EOR (p=0.037, OR: 0.41 for NTR versus STR; p=0.003, OR: 0.39 for GTR versus STR), but not glioma subtype or location, as determined by logistic regression. Additional tumor resection after iMRI was performed in 105/159 (66%) iMRI cases, yielding GTR in 54.5% of these cases. CONCLUSIONS EOR significantly improves OS and PFS for patients with grade II astrocytomas and oligodendrogliomas. Intraoperative MRI may improve EOR and was associated with increased PFS.
SWK-08. DELAYED DIAGNOSIS OF CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN: PERSPECTIVE FROM THE FRONTLINE
Authors: Manisha Jogendran, Rebecca Ronsley, Ran D Goldman, Sylvia Cheng
Journal: Neuro-Oncology (2020)

Abstract Delayed diagnosis of CNS tumors in children is well documented, partially due to challenges in recognizing rare diagnoses. Our objective was to describe Canadian family physicians’ attitudes and confidence in diagnosing and managing pediatric CNS tumors. A standardized questionnaire was administered at a Canadian national family physicians’ conference. Items were based on observations from our institutional study of prediagnostic symptomatic interval in pediatric CNS tumors. 449 surveys were completed. 302/443 (68%) physicians practice in cities. 153/447 (34%) report encountering parents that inquire about their children having brain tumors. 261/449 (58%) have not managed a pediatric brain tumor. 153/447 (34%) report they are not confident, 255/447 (57%) somewhat confident and 39/447 (9%) confident in managing a suspected brain tumor in a stable child. 259/447 (58%) would refer directly to a hospital/specialist. The reported median time for suspicion of a brain tumor was 8–14 days for children with vomiting and/or headache and 1 day for children with seizure and/or ataxia. 410/447 (97%) report not knowing any guidelines to help with management. 235/447 (53%) suggested barriers they experience to include 52/235 (22%) wait times for imaging/specialists, 37/235 (16%) geographical location of the child, 27/235 (12%) knowledge, 25/235 (11%) access to imaging/specialist, and 15/235 (6%) patient-related factors or system barriers, and 8/235 (3%) specialist attitudes. 68/235 (29%) identified no barriers in their practice. This study provides insight into family physicians’ perceived challenges and barriers in diagnosing and managing new suspected pediatric CNS tumors. Educational effort and overcoming systemic perceived barriers may increase physicians’ confidence.
DIPG-34. SUPER ELONGATION COMPLEX AS A TARGETABLE DEPENDENCY IN H3K27M+ DIFFUSE MIDLINE GLIOMA
Authors: Nathan Dahl, Etienne Danis, Ilango Balakrishnan, Dong Wang, Angela Pierce, Faye Walker, Ahmed Gilani, Natalie Serkova, Krishna Madhaven, Susan Fosmire, Adam Green, Nicholas Foreman, Sujatha Venkataraman, Rajeev Vibhakar
Journal: Neuro-Oncology (2020)

Abstract Mutations in the histone 3 gene (H3K27M) are the eponymous driver in diffuse intrinsic pontine gliomas (DIPGs) and other diffuse midline gliomas (DMGs), aggressive pediatric brain tumors for which no curative therapy currently exists. To identify specific epigenetic dependencies within the context of the H3K27M mutation, we performed an shRNA screen targeting 408 genes classified as epigenetic/chromatin-associated molecules in patient-derived DMG cultures. This identified AFF4, a component of the super elongation complex (SEC), as necessary for DMG cells to maintain growth and self-renewal. We hypothesized that aberrant SEC expression occurs as a consequence of the H3K27M mutation and that this dysregulated SEC signaling overcomes repressive transcriptional regulation in order to suppresses differentiation and promote self-renewal of DMG tumor stem cells. We interrogated the role of AFF4 in DMG using an shRNA lentiviral approach. We demonstrate a significant decrease in in vitro clonogenicity and stem cell maintenance following AFF4 depletion. We employed RNA-seq-based gene set enrichment analysis to delineate differentiation programs under SEC regulatory control. Finally, we sought to determine whether CDK9, the catalytic subunit of the SEC, represents a therapeutic vulnerability in DMG. Using RNA polymerase II ChIP-seq, we demonstrate that CDK9 pharmacologic inhibition restores regulatory Pol II pausing, promotes cellular differentiation, and leads to potent anti-tumor effect both in vitro and in patient-derived xenograft models. These studies present a biologic rationale for the translational exploration of CDK9 inhibition as a promising therapeutic approach.
MBCL-38. UNUSUAL EXTRANEURAL METASTASIS OF PEDIATRIC EMBRYONAL TUMORS: TWO CASE REPORTS
Authors: Aaron Goldberg, Chenue Abongwa, Jody Pathare, Clay Hoerig, Michael Muhonen, Joffre Olaya, Amar Gajjar, Krista Warren, Ramesh Patel, Hollie Lai, William Loudon, Ashley Plant
Journal: Neuro-Oncology (2020)

Abstract We report two cases of unusual extraneural metastasis in patients with embryonal tumors without central nervous system disease progression and prolonged survival. The first patient presented at 16 years of age with atypical teratoid rhabdoid tumor of the cervical spine. The tumor was confirmed to have loss of INI1, SMARCB1 deletion of exons 1–3, and heterozygous deletion of 22q11.2. The patient received treatment initially per ACNS0333 with high dose chemotherapy and tandem autologous transplants. The patient developed a biopsy-confirmed liver metastasis six months from diagnosis and, subsequently, had disease progression including liver metastases, bony lesions, muscle involvement, and lung nodules. Two and a half years from diagnosis the patient has still not had a relapse in the CNS. The second patient presented with medulloblastoma isolated to the posterior fossa at 11 years of age and was treated on SJMB03 protocol with craniospinal irradiation and high dose chemotherapy. He had his first recurrence in the temporal lobe three years post treatment. He had multiple recurrences in the brain over the next five years treated with re-resections, adjuvant chemotherapy, and gamma knife radiotherapy. He then developed cervical lymphadenopathy, bony lesions, liver lesions, and lung nodules. Cervical lymph node biopsy confirmed medulloblastoma. Next generation sequencing from recurrent tumor showed somatic mutations in p53, KDM6A, and PPP2R1A. Fourteen years from treatment, he has now developed a temporal lobe lesion. These cases are notable for prolonged survival despite widely metastatic disease and genomics predicting poor prognosis as well as metastatic disease disproportionate to CNS disease.
NURS-08. A CASE REPORT OF RARE AND PROFOUND ANTEROGRADE AMNESIA IN A PAEDIATRIC SURVIVOR OF A BIFOCAL NON GERMINOMATOUS GERM CELL TUMOUR AND DIABETES INSIPIDUS
Authors: Elizabeth Bland
Journal: Neuro-Oncology (2020)

Abstract We present the case of a 12yo female who presented to the emergency department with increasing agitation, confusion, fluctuating GCS, hydrocephalus, and deranged electrolytes. MRI revealed tumour in pineal region and filling the third ventricle. Biopsy and tumour markers confirmed the diagnosis of bifocal Non Germinomatous Germ Cell Tumour (NGGCT). The diagnosis was complicated with the secondary diagnoses of diabetes insipidus and profound permanent anterograde amnesia. Whilst DI is common in NGGT in pineal region, anterograde amnesia is a very rare condition in paediatrics. Thus there is paucity of literature available to the clinicians to know how much improvement to expect or how to target rehabilitation whilst undergoing curative therapy, chemotherapy and craniospinal irradiation; however the importance of a consistent and coordinated nursing and allied health team approach with structure and errorless learning must be initiated from the beginning if independence is to be achieved.
Machine learning can predict disease manifestations and outcomes in lymphangioleiomyomatosis
Authors: Saisakul Chernbumroong, Janice Johnson, Nishant Gupta, Suzanne Miller, Francis X. McCormack, Jonathan M. Garibaldi, Simon R. Johnson
Journal: European Respiratory Journal (2020)

Background Lymphangioleiomyomatosis (LAM) is a rare multisystem disease with variable clinical manifestations and differing rates of progression that make management decisions and giving prognostic advice difficult. We used machine learning to identify clusters of associated features which could be used to stratify patients and predict outcomes in individuals. Patients and methods Using unsupervised machine learning we generated patient clusters using data from 173 women with LAM from the UK and 186 replication subjects from the US National Heart, Lung, and Blood Institute (NHLBI) LAM registry. Prospective outcomes were associated with cluster results. Results Two- and three-cluster models were developed. A three-cluster model separated a large group of subjects presenting with dyspnoea or pneumothorax from a second cluster with a high prevalence of angiomyolipoma symptoms (p=0.0001) and tuberous sclerosis complex (TSC) (p=0.041). Patients in the third cluster were older, never presented with dyspnoea or pneumothorax (p=0.0001) and had better lung function. Similar clusters were reproduced in the NHLBI cohort. Assigning patients to clusters predicted prospective outcomes: in a two-cluster model the future risk of pneumothorax was 3.3 (95% CI 1.7–5.6)-fold greater in cluster 1 than cluster 2 (p=0.0002). Using the three-cluster model, the need for intervention for angiomyolipoma was lower in clusters 2 and 3 than cluster 1 (p&lt;0.00001). In the NHLBI cohort, the incidence of death or lung transplant was much lower in clusters 2 and 3 (p=0.0045). Conclusions Machine learning has identified clinically relevant clusters associated with complications and outcome. Assigning individuals to clusters could improve decision making and prognostic information for patients.
Antibody profiling of patients with prostate cancer reveals differences in antibody signatures among disease stages
Authors: Hemanth K Potluri, Tun Lee Ng, Michael A Newton, Jin Zhang, Christopher A Maher, Peter S Nelson, Douglas G McNeel
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Previous studies of prostate cancer autoantibodies have largely focused on diagnostic applications. So far, there have been no reports attempting to more comprehensively profile the landscape of prostate cancer-associated antibodies. Specifically, it is unknown whether the quantity of antibodies or the types of proteins recognized change with disease progression. Methods A peptide microarray spanning the amino acid sequences of the gene products of 1611 prostate cancer-associated genes was synthesized. Serum samples from healthy male volunteers (n=15) and patients with prostate cancer (n=85) were used to probe the array. These samples included patients with various clinical stages of disease: newly diagnosed localized prostate cancer (n=15), castration-sensitive non-metastatic prostate cancer (nmCSPC, n=40), castration-resistant non-metastatic prostate cancer (n=15) and castration-resistant metastatic disease (n=15). The patients with nmCSPC received treatment with either standard androgen deprivation therapy (ADT) or an antitumor DNA vaccine encoding prostatic acid phosphatase. Serial sera samples from these individuals were also used to probe the array, to secondarily determine whether this approach could be used to detect treatment-related changes. Results We demonstrated that this peptide array yielded highly reproducible measurements of serum IgG levels. We found that the overall number of antibody responses did not increase with disease burden. However, the composition of recognized proteins shifted with clinical stage of disease. Our analysis revealed that the largest difference was between patients with castration-sensitive and castration-resistant disease. Patients with castration-resistant disease recognized more proteins associated with nucleic acid binding and gene regulation compared with men in other groups. Our longitudinal data showed that treatments can elicit antibodies detectable by this array, and notably vaccine-treated patients developed increased responses to more proteins over the course of treatment than did ADT-treated patients. Conclusions This study represents the largest survey of prostate cancer-associated antibodies to date. We have been able to characterize the classes of proteins recognized by patients and determine how they change with disease burden. Our findings further demonstrate the potential of this platform for measuring antigen spread and studying responses to immunomodulatory therapies.
Impact of treatment delay due to the pandemic of COVID-19 on the efficacy of immunotherapy in head and neck cancer patients
Authors: Gaili Chen, Qiuji Wu, Huangang Jiang, Zheng Li, Xinying Hua, Xiaoyan Hu, Haijun Yu, Conghua Xie, Yahua Zhong
Journal: Journal of Hematology & Oncology (2020)

Immunotherapy has been a new standard for recurrent/metastatic head and neck cancers (R/M HNC). One of the prominent characteristics of cancer immunotherapy is the induction of immune memory followed by endured treatment response. However, whether and how a treatment delay would impact on the efficacy of immunotherapy has not been well determined. During the outbreak of COVID-19, a number of cancer patients in Wuhan, the epicenter of the pandemic in China, had experienced long-lasting city lockdown and delay of immunotherapies. Here, we retrospectively analyzed 24 HNC patients treated with immune checkpoint inhibitors in our cancer institute prior to the outbreak of COVID-19 who were re-evaluated after the restoration of regular medical care. Of these 24 patients, 10 patients had achieved complete response (CR) or partial response (PR), 12 patients had achieved stable disease (SD), and 2 patients had received just one cycle treatment without efficacy evaluation before treatment delay. The median delay was 3.75 months (range 1.73-8.17 months). Re-evaluation after treatment delay revealed that ten patients (10/10) who achieved CR or PR, two patients (2/2) who received just one cycle treatment without efficacy evaluation and seven patients (7/12) who achieved SD before outbreak of COVID-19 maintained tumor response after treatment delay. Among the rest five patients who had achieved SD, four patients were re-evaluated as progressive disease (PD) due to treatment delay and one patient died after treatment interruption without re-evaluation. Our results from a small cohort of R/M HNC patients showed that treatment delay of three to four months might have mild, if any, impact on the efficacy of immunotherapy for patients with controlled disease.