tbuckley/cabot-search huggingface dataset:
EMBR-03. PINEOBLASTOMA: A POOLED OUTCOME STUDY OF NORTH AMERICAN AND AUSTRALIAN THERAPEUTIC DATA
Authors: Jordan Hansford, Jie Huang, Andrew Dodgshun, Bryan Li, Eugene Hwang, Sarah Leary, Amar Gajjar, Katja Von Hoff, Raelene Endersby, Olivia Wells, Alison Wray, Rishi Kotecha, David Raleigh, Schuyler Stoller, Sabine Mueller, Steven Schild, Pratiti Bandopadhayay, Maryam Fouladi, Eric Bouffet, Annie Huang, Arzu Onar, Nicholas Gottardo
Journal: Neuro-Oncology (2021)

Abstract Background Pineoblastoma (PB) is a rare embryonal brain tumour most often diagnosed in young children. To date, no clinical trials have been conducted specific to pediatric PB. Collaborative studies performed over the past 30 years have included PB in studies accruing for other embryonal tumours, primarily medulloblastoma (MB), but also including the entity formerly known as CNS-PNET and atypical teratoid rhabdoid tumors. Each of these studies have included only a small number of children with PB, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. Patients and Methods Published centrally reviewed series with sufficient treatment and outcome data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact and Wilcoxon-Mann-Whitney tests, and Spearman correlations were used as appropriate. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analysis. Results We describe a 30-year review of the reported clinical features of PB and a pooled centrally reviewed, cohort analysis of cases (n=178) from the Children’s Oncology Group (COG) (n=82) groups and several published, centrally reviewed institutional series (n=96). We find young children &amp;lt;3 years of age have a dramatically poorer outlook compared to older children (5-year OS 16.2% +/- 5.3% vs 67.3% +/- 5%) confirming new and novel approaches are needed in future clinical trials for this at risk group. Interestingly, male gender was predictive of worse outcome possibly suggestive of gender specific subgroup risks that needs validation in future studies. Assessment of radiation therapy is not possible as the vast majority of children under age three did not receive any form of radiation therapy. Conclusion Given the relative scarcity of this tumor and the emerging data on subgroups of pineoblastoma, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.
Abstract 19092: Natriuretic and Matrix Remodeling Biomarker Modeling for the Prediction of 30 Day Heart Failure Readmissions
Authors: William S Bradham, Sean Collins, Shi Huang, Frank Harrell, Gregory Fermann, Matthew Sperling, Karen Miller, Douglas Sawyer, Neal Weintraub, Alan Storrow, Frank Spinale
Journal: Circulation (2017)

Introduction: Hospital readmission for heart failure (HF) is an increasingly important quality metric; influenced by clinical status, but also by socioeconomic issues, caregiver assistance, and med...
An Integer Weighted Genomic Mutation Score (GMS) Using Next Generation Sequencing Is Predictive of Prognosis in Intermediate Risk AML Patients
Authors: Akash Mukherjee, Xinyu Nan, Joe Ensor, Jasleen K. Randhawa, Sai Ravi Kiran Pingali, Arthur William Zieske, Randall J Olsen, Betty Chung, Swami P. Iyer
Journal: Blood (2017)
Tumor immunotherapy and multi-mode therapies mediated by medical imaging of nanoprobes
Authors: Yang Xuan, Meng Guan, Shubiao Zhang
Journal: Theranostics (2021)

Immunotherapy is an effective tumor treatment strategy that has several advantages over conventional methods such as surgery, radiotherapy and chemotherapy. Studies show that multifunctional nanoprobes can achieve multi-mode image-guided multiple tumor treatment modes. The tumor cells killed by chemotherapies or phototherapies release antigens that trigger an immune response and augment the effects of tumor immunotherapy. Thus, combining immunotherapy and multifunctional nanoprobes can achieve early cancer diagnosis and treatment. In this review, we have summarized the current research on the applications of multifunctional nanoprobes in image-guided immunotherapy. In addition, image-guided synergistic chemotherapy/photothermal therapy/photodynamic therapy and immunotherapy have also been discussed. Furthermore, the application potential and clinical prospects of multifunctional nanoprobes in combination with immunotherapy have been assessed.
Breast cancer survivorship and level of institutional involvement utilizing integrative oncology.
Authors: Terri Crudup, Linna Li, Jennifer Wright Dorr, Elizabeth Lawson, Rachel Stout, Pedram Vazifeh Niknam, Judi Jones, Robert Steen, Lynn L Lu, Susan Casner, Yi Wang, James Scott, Shelby Zanine, Stacey Robertshaw, Gabriella Broderick, Simarpreet Singh, Jingsong Lu, Li Zhou, Vaishali Palommella, Wayne Jonas
Journal: Journal of Clinical Oncology (2021)

e18588 Background: A growing body of evidence has shown that a Whole Person Integrative Oncology approach, adding the use of complementary and lifestyle therapies to cancer treatments, benefits patients by improving patient-reported outcomes and potentially extending overall survival. This study aims to investigate the relationship between the survival outcomes of breast cancer patients and the level of involvement in Integrative Oncology at the institutions treating those patients. Methods: Between January 2013 and December 2014, 4,815 breast cancer patients were available for survival analysis using an established claims-based method. These patients were filtered to include those with clear mapping to treating oncologists and treating institutions. To measure each institution’s level of Integrative involvement, a scoring system was developed with the Samueli Foundation and oncologists from each institution were surveyed on the education, availability, and financing of 12 complementary and lifestyle approaches during the treatment timeframe. Statistical analysis using multivariate modeling with logistic regression and a lasso approach were employed. 19 variables across region, patient demographics, and institutional profile were included. Model coefficients are exponentiated and presented as odds-ratios, with less than one having a negative impact on survival and greater than one improved survival. Results: We identified 173 patients mapping to 103 institutions and 103 oncologists who responded to our survey. Median age of breast cancer patients was 51 (range: 32-76). 14 of the patients (8%) were identified as metastatic. The 5-year overall survival among the Low scoring institutions was 89%, Low-Mid 96%, Mid-High 96%, High 95%. Chi square testing across these cohorts showed no statistically significant difference between them. On multivariate modeling, age, geography, metastatic status, academic setting, and Integrative score were predictors of 5-year survival. The most significant 9 variables are shown in Table. Having metastatic disease, treatment at a non NCCN designated facility, treatment at Midwest or Western Region predicts for lower 5-year survival. Older age, treatment at an academic setting, and having a High or Low-Mid Integrative score are predictors of improved survival. Conclusions: This study suggests that in addition to traditional predictors of survival such as metastatic disease and younger age, patients receiving treatment at an institution that supports Integrative Oncology programs may be associated with improved survival. More work is needed to evaluate the relationship between Integrative Oncology and cancer treatment outcomes.[Table: see text]
Next generation sequencing in ovarian cancer patients: Does personalized medicine improve oncological outcomes?
Authors: Tamar Safra, Dov Hershkovizh, Eliya Shachar, Lyri Adar, Miriam R. Brezis, Yuval Raviv, Lee Galmor, Shira Peleg Hasson
Journal: Journal of Clinical Oncology (2021)

5553 Background: Ovarian cancer (OC) is the second most common gynecologic malignancy and the most common cause of gynecologic cancer mortality in the United States. Homologous recombination deficiency (HRD), including the BRCA mutations, are found in 50% of OC tumors. Next generation sequencing (NGS) provides understanding the underlying molecular and genetic patterns to improve OC treatment. This study examines the prognostic and predictive biomarkers identified with NGS in hopes to improve OC patients outcomes. Methods: The patient cohort included 890 consecutive OC patients treated between 2002 and 2020,at the Tel-Aviv Medical Center. We retrospectively evaluated patients with histopathologically confirmed OC. Cox models were used to analyze the clinical impact of various mutations and biomarkers among OC patients with and without FoundationOne CDx NGS testing, by assessing overall survival (OS), progression free survival (PFS), and physicians' timing preferences for referral to NGS testing. Results: Among the 890 OC patients, 103 (11.57%) completed NGS molecular testing. The median OS among patients with and without NGS testing, adjusted for age, stage and recurrence status, was 73.36 and 68.50 months, respectively (P =.02). The median PFS was 17.23 and 17.43 months, respectively (P =.77). We also evaluated physicians' preferences regarding timing of molecular profiling, upon diagnosis, after first recurrence and at advanced line of treatment in 31.95%, 36.08% and 26.8% of practitioners, respectively. Of the patients who completed NGS, 48 (52.75%) harbored actionable mutations, and 21 patients (43.75%) received matched targeted therapy. Forty-five patients were microsatellite stable (MSS) (45%), 55 with undetermined status (55%) and 0 patients with MSI-H. Forty-one (71.93%) patients had low ( &lt; 5) tumor mutation burden status (TMB), 16 (28.07%) intermediate (5-15) and none with high ( &gt; 15) TMB. There was no noticeable survival difference when comparing low with intermediate TMB (P = 0.3). Loss of heterozygosity (LOH) was a significant prognostic biomarker. Patients with high LOH (hLOH &gt; = 16%) had longer OS compared to low LOH (lLOH &lt; 16%), 99.02 vs. 50.23 months, respectively (P &lt;.005). Patients with hLOH and BRCA mutations (BRCA+) had longer OS compared to hLOH/BRCA WT (BRCA-), lLOH/BRCA+, and lLOH/BRCA-, with an unreached median OS of 91.5 vs. 60.48 vs. 45.21 months, respectively (P =.005). Conclusions: Our work demonstrates the clinical benefit of NGS personalized medicine as a cornerstone of future treatment strategies in OC. Our study suggests an OS benefit among the NGS tested cohort. We identified LOH as a prognostic biomarker. Prospective studies evaluating larger cohorts are necessary to generate a more extensive evaluation of additional prognostic and predictive biomarkers among OC patients.
RNA-Sequencing Reveals a Distinct Transcriptomic Signature for Giant Cell Myocarditis and Identifies Novel Druggable Targets
Authors: Kaushik Amancherla, Juan Qin, Yu Wang, Margaret L. Axelrod, Justin M. Balko, Kelly H. Schlendorf, Robert D. Hoffman, Yaomin Xu, JoAnn Lindenfeld, Javid Moslehi
Journal: Circulation Research (2021)
Randomized study of electric hand warmer (EHW) versus observation to avoid discomfort during scalp cooling for chemotherapy-induced alopecia (CIA) prevention.
Authors: Luciana Castro G. Landeiro, Rodrigo Dienstmann, Matheus Costa e Silva, Michele Gonçalves, Priscila Viana, Ana Paula dos Santos, Adriana de Castro, Andrea Teixeira, Maira Costa, Ceci da Silva, Pamela Souza Almeida Malta, Roberto Mathias Machado, Clarissa Mathias
Journal: Journal of Clinical Oncology (2021)

12108 Background: CIA has been reported as the most disturbing adverse event of cancer treatment by most women receiving chemotherapy. Many strategies have been tested to minimize CIA, among which scalp cooling has proven high effectiveness. However, discontinuation rates of this technology vary from 3% to 13%, mostly due to headache, cold sensation and pain. EHW could be used to mitigate these side effects, produce heat on demand and a warming sensation. The primary objective of this study is to evaluated the impact of EHW device on the general comfort of breast cancer patients while on scalp cooling during chemotherapy treatment. Methods: Patients were randomly assigned to EHW use or observation. Thermal, sensory and general comfort were measured with pragmatic questionnaires after each chemotherapy infusion: neutral or hot as favorable thermal responses; comfortable and very comfortable as favorable sensory responses; finally, favorable outcomes in both thermal and sensory comfort questionnaires defined a positive result on the general comfort. We evaluated the impact of age (≤ or &gt; 50 years), alopecia (grade 0 or 1/2), chemotherapy regimen (with or without taxanes) and EHW use (yes or no) in the different comfort scales using Logistic Regression (LR) models. Results: Forty women with early or locally advanced breast cancer were assigned to EHW (n = 20) or observation (n = 20) during neo(adjuvant) chemotherapy. Median age was 53 years, 67.5% concluded university education, 52.5% had comorbidities. Most patients had stage II disease (55%), largely ER/PR+ HER2- disease (67.5%), followed by triple negative (22.5%), and HER2+ (10%). Most frequent regimen was ACdd-Tdd (42.5%). Thirty-one patients (77.5%) continued scalp cooling during entire chemotherapy regimen (alopecia &lt; grade 3). A favorable thermal response was seen in 79% of EHW applications as compared to 50% in control arm (odds ratio [OR] 3.79, P &lt;.001). Sensory comfort was satisfactory in 82% of EHW applications as compared to 74% with control (OR 1.62, P =.1). General comfort was favorable in 73% of EHW applications as compared to 44% in control arm (OR 3.4, P &lt;.001). Age, alopecia grade and taxane use did not significantly impact on comfort measures. Conclusions: Our study suggests that an EHW has a consistent favorable impact on thermal and general comfort of breast cancer patients under scalp cooling technology to prevent CIA. This simple device can improve patient´s quality of life and eventually avoid scalp cooling discontinuation due to discomfort.
Core Cross‐Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages
Authors: Tobias A. Bauer, Natalie K. Horvat, Oriana Marques, Sara Chocarro, Christina Mertens, Silvia Colucci, Sascha Schmitt, Luca M. Carrella, Svenja Morsbach, Kaloian Koynov, Federico Fenaroli, Peter Blümler, Michaela Jung, Rocio Sotillo, Matthias W. Hentze, Martina U. Muckenthaler, Matthias Barz
Journal: Advanced Healthcare Materials (2021)

Abstract Iron is an essential co‐factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine ‐block‐ poly( S ‐ethylsulfonyl‐ l ‐cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly( S ‐ethylsulfonyl‐ l ‐cysteine) block, yielding glutathione‐responsive core cross‐linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparticles display preferential uptake, sustained intracellular iron release, and induce a strong inflammatory response. This response is also demonstrated in vivo when nanoparticles are intratracheally administered to wild‐type C57Bl/6N mice. Most importantly, the controlled release concept to deliver iron oxide in redox‐responsive CCPMs induces significantly stronger macrophage activation than any other iron source at identical iron levels (e.g., Feraheme), directing to a new class of immune therapeutics.
Clinicopathological features and treatment of perivascular epithelioid cell tumor.
Authors: Ying Lin, Xin Liu, Xiaowei Zhang, Yong Chen, Chunmeng Wang, Shengping Wang, Jian WANG, Zhiguo Luo
Journal: Journal of Clinical Oncology (2021)

e23538 Background: Perivascular epithelioid cell tumor (PEComa) is a rare form of mesenchymal neoplasms. No clinical trial of large sample size regarding medical treatment of PEComa has been reported so far. Previous retrospective studies with small sample size have showed efficacy of mTOR inhibitors as treatment of PEComa. This study aimed to analyze the clinicopathological features of PEComa, and the efficacy of mTOR inhibitor in advanced PEComa. Methods: Medical information of patients diagnosed with PEComa and treated in Fudan University Shanghai Cancer Center were collected. Survival analysis was performed by Kaplan-Meier method. Radiological response was assessed according to RECIST version1.1. Results: A total of 17 patients were treated in our center during June 2007 to June 2020. PEComa mostly occurs in middle-aged women. The most common primary sites are pelvis, lung and abdomen. Relapse usually occurs within 2 years after radical surgery. Radical surgery is the main treatment for PEComa of limited stage, and remains the main option for those with limited recurrent lesions. Of the 13 patients with advanced malignant PEComa in our cohorts, the objective response rate of mTOR inhibitors in advanced malignant PEComa was 45.5%, and median progression-free survival was 27.7 months (95% CI 4.7-50.5 months). 2 patients discontinued mTOR inhibitor treatment due to pneumonitis combined with dyspnea and fever respectively. Conclusions: For advanced malignant PEComa, mTOR inhibitors are effective. Lung toxicity of mTOR inhibitor should be monitored.
A PAncreatic cancer screening study in individuals with New-onset or DeteriOrating diabetes MEllitus (PANDOME study).
Authors: Richard C. Frank, Tammy Lo, Dugho Jin, Cornelius Ferreira, Ramanathan Seshadri, Xiang Da (Eric) Dong, James Bauman, Naveen Anand, Ronald Lee
Journal: Journal of Clinical Oncology (2021)

TPS10607 Background: Pancreatic adenocarcinoma (PC) has a persistently high mortality as it presents in the advanced stages and has largely not benefited from the genomic and immunotherapeutic revolutions in oncology. Improvements in screening to detect early stage cancers are therefore urgently needed. Screening studies such as those from the International CAPS Consortium have demonstrated improved survivals in hereditary high risk individuals. In the sporadic population, individuals with new-onset diabetes (NOD) or long-standing deteriorating diabetes (DD) are at substantially increased risk of PC in the 12 months following these diagnoses and have been proposed as target populations for screening efforts. This trial will study the benefits of PC screening in the latter populations in a community setting. Methods: Individuals ≥ 50 years of age with either NOD or DD will be eligible. Criteria for NOD (within the past 12 months) include: fasting blood glucose ≥ 126 mg/dL, random blood glucose ≥ 200 mg/dL, or HbA1c ≥ 6.5%, with confirmed prior normal values. For those without prior glycemic values, a HbA1c ≥ 7.0% is required. Transition from pre-diabetes requires an increase in HgA1c of ≥ 0.5%. DD is defined by an increase in HbA1c of ≥ 2% within the past six months that is not associated with medication non-compliance or weight gain. Study participants will undergo every 6 months: evaluation by an APRN, testing for anxiety and depression and blood donation for biobanking purposes. High resolution MRI/MRCP with gadolinium will be performed at study entry and annually for 2 years. Images will be reviewed at a multi-disciplinary tumor board consisting of body-image certified radiologists, interventional gastroenterologists, hepatobiliary surgeons and medical oncologists. MRI results will be classified according to a novel PANC-RADS system. High-risk pancreatic findings will be further interrogated by endoscopic ultrasound (EUS). Study endpoints include detection rate of high-risk lesions, referrals for EUS and surgery and detection of incidental findings leading to unnecessary procedures. Adverse psychological impacts will be assessed through HADS testing. Target accrual: 500 patients within 3 years. Clinical trial information: NCT03937453 .
Induction of antigen-specific tolerance by nanobody–antigen adducts that target class-II major histocompatibility complexes
Authors: Novalia Pishesha, Thibault Harmand, Liyan Y. Smeding, Weiyi Ma, Leif S. Ludwig, Robine Janssen, Ashraful Islam, Yushu J. Xie, Tao Fang, Nicholas McCaul, William Pinney, Harun R. Sugito, Martin A. Rossotti, Gualberto Gonzalez-Sapienza, Hidde L. Ploegh
Journal: Nature Biomedical Engineering (2021)
Prevalence of the concurrent administration of contraindicated medications in patients with cancer treated with tyrosine kinase inhibitors (TKIs): A pilot study from the IU Simon Comprehensive Cancer Center.
Authors: Dana Alhaffar, Yan Han, Julianne Darling, Todd C. Skaar, Christopher A. Fausel, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2021)

e18714 Background: Polypharmacy may result in drug-drug interactions that reduce efficacy or increase toxicities to patients. Tyrosine kinase inhibitors (TKIs), which is standard therapy for many patients with cancer, have interactions with many commonly prescribed drugs (including proton pump inhibitors [PPIs] and cytochrome inhibitors/inducers) which alter their metabolism. Methods: Retrospective study of 100 consecutively chosen patients with advanced cancer treated with TKIs were identified. Patients &lt; 18 years of age, participating in clinical trials, or taking an investigational treatment for their cancer were excluded. TKI start date and concurrent medications were identified from chart reviews. Documentation was undertaken to record co-administration of drugs that could prolong QT interval, PPIs, and CYP3A inhibitors and inducers. QT prolonging medications were divided into those with known risk (KR), conditional risk (CR), and probable risk (PR). IUSM Clinical Pharmacology Flockhart table was utilized for cytochrome drug interactions. All three categories of cytochrome inhibitors (strong, moderate, and weak) were included in the analysis. The primary objective was to estimate the percentage of patients treated with TKIs co-administered these classes of drugs with a potential for harmful drug-drug interaction. Results: Median age of 100 pts was 57 and median duration of treatment with the TKI was 441 days. 85 of 100 pts receiving TKIs for their cancer were also prescribed at least 1 drug with the potential for drug-drug interaction, including 39 with a QT prolonging drug with known risk and 25 with a CYP3A inducer or inhibitor. 53% had documentation of EKG while on TKI treatment. Conclusions: Most patients in this chart review were co-administered TKIs with other agents with a potential for harmful drug-drug interactions. Continual monitoring of medications is necessary to optimize efficacy of TKIs and reduce the chance for harmful side effects.[Table: see text]