tbuckley/cabot-search huggingface dataset:
P05.82 Clinical decision making. The route from an ontology to a prediction model for stereotactic radiotherapy: PRE.M.I.S.E. (PREdiction Models in Stereotactic External Radiotherapy)
Authors: F Bianciardi, S Chiesa, B Tolu, S Longo, G Minniti, B Nardiello, F Cellini, F Rea, P Gentile, V Valentini
Journal: Neuro-Oncology (2018)

It becomes more and more clear that people with the same cancer can have different forms of the disease, so responses to treatment and their toxicity can vary. Beside the widely accepted and old fashioned clinical guidelines, personalized medicine needs the DSS (Decision Support System) to be implemented in order to offer a valuable assistance in clinical decision making and in daily practice. DSS are represented by softwares, apps, nomograms all based on the creation of predictive models (PM) that require standardization of data collection. Ontology represents a fundamental tool to establish a common language without knowing, beforehand, which one of the described features could be the most relevant for a specific hypothesis. Through the creation of a ontology for a specific technique [Stereotactic Radiotherapy (SRT)], this multicentric study aims at collecting standardized data in order to build up a predictive model. We started focusing on brain metastases SRT. The first two centres involved selected personnel in order to create a multidisciplinary team made of physicians, physicist, nurses and therapists. They meet twice a month. The first step of the project was to identify variables, validate them and built up the ontology. The second step was to implement a system that defines variables characteristics and the relationships among them. The semantic web technology was put into practice and the team is now collecting data on a dedicated software called BOA (Beyond Ontology Awareness) with its own WEB platform. The future development is to involve other RT centres to combine multiple datasets. The drafted ontology is made up of more than 130 variables related with brain SRT, including both general “brain” nomenclature and SRT specific features. All the features were collected and organized in three levels (‘registry’, ‘procedural’ and ‘research’ level) that classify all the information in order to easily diversify queries. The BOA Web platform was shared between the first two centers involved and data collection process is ongoing by using Case Report Form (CRF). We drafted a brain SRT ontology in order to create a common language with the aim of enlarging our databases by involving different centres in collecting clinical data. The creation of a centralized multicentre large database is therefore essential for the development of ad hoc prediction tools. The aim is to implement a system that analyse large heterogeneous datasets to develop and validate multifactorial models that are able to assist clinical decision making based on specific pre-treatment characteristics in each individual patient.
Effects of exercise on dyspnea and cancer-related fatigue in patients with prostate cancer.
Authors: Calvin Cole, Luke Joseph Peppone, Ian Kleckner, Po-Ju Lin, Richard Francis Dunne, Chunkit Fung, Kah Poh Loh, Matthew Asare, Karen Michelle Mustian, Gary R. Morrow
Journal: Journal of Clinical Oncology (2017)

e16580 Background: Dyspnea and fatigue are two of the most common symptoms reported by patients with advanced cancer. Patients with dyspnea report an inability to complete activities of daily living (ADL) and impaired quality of life (QOL). Exercise has been shown to reduce cancer-related fatigue (CRF); however the relationships between dyspnea, CRF, ADL and QOL are unclear. The purpose of this study is to examine the effect of exercise on dyspnea, CRF, ADL and QOL. Methods: A secondary data analysis was performed on a two-arm randomized controlled trial investigating the influence of exercise on prostate cancer patients treated with hormone (androgen deprivation therapy) and/or radiation therapy. Exercise for Cancer Patients (EXCAP © ) is a 6 week home-based program that includes progressive aerobic and resistance band training. Participants were randomly assigned to usual care with EXCAP © or usual care only (UC). Dyspnea, CRF, ADL and QOL were measured using the Multidimensional Fatigue Symptom Inventory (MFSI) and a Clinical Symptom Inventory (SI) at pre- and post-intervention. Results: Participants included 57 sedentary prostate cancer patients, average age 67 ± 8 years. Mean changes in dyspnea showed a positive, association with mean changes in CRF (SI r = .525; p &lt; .01, MFSI r = .327; p = .08) in the EXCAP group but not in the UC group. Dyspnea changes were also positively associated with changes in exercise behavior (r = .590; p &lt; .01), ADL (r = .684; p &lt; .01), and QOL (r = .532; p &lt; .01) in the EXCAP group, no association was found in the UC group. Furthermore, exercisers who reported the greatest improvements in dyspnea also reported greater improvements in CRF = 2.2 (p &lt; .05), ADL = 1.8 (p &lt; .01), and QOL = 2.4 (p = .01). Conclusions: Exercise-induced improvements in dyspnea are associated with improvements in CRF, ADL and QOL in prostate cancer patients. Additional research is needed to further understand these results. NCORP UG1 CA189961, R25 CA102618, DOD PC061518 Clinical trial information: NCT00815672.
Association of family history and survival in patients with colorectal cancer.
Authors: Dawn Q. Chong, Barbara L. Banbury, Amanda I. Phipps, Xinwei Hua, Jonathan Kocarnik, Ulrike Peters, Sonja Berndt, Wen-Yi Huang, John D. Potter, Martha L. Slattery, Emily White, Peter T. Campbell, Tabitha A. Harrison, Polly A. Newcomb, Andrew T. Chan
Journal: Journal of Clinical Oncology (2016)

3594 Background: A family history of colorectal cancer (CRC) in first-degree relatives (FDRs) increases the risk of CRC. However, beyond rare hereditary CRC syndromes, the influence of family history on CRC survival remains uncertain. Methods: We conducted a pooled analysis of 5,010 incident CRC cases from 6 prospective cohort studies and 2 population-based case-control studies within the International Survival Analysis in CRC Consortium (ISACC). Cox proportional hazards models were used to estimate overall survival (OS) and CRC-specific survival (CSS) in relation to family history of CRC in FDRs, and number of affected FDRs, adjusting for age, gender, body mass index, smoking status, use of aspirin/non-steroidal anti-inflammatory drugs, history of screening endoscopy, stage at diagnosis, tumor location and study site. We conducted subgroup analyses by age, gender, tumor location and stage. Results: 819 (16.3%) patients reported a family history of CRC. There were 1,580 (31.5%) total deaths over a median follow-up time of 4.6 years, of which 1,046 (66.2%) were due to CRC. Individuals with a family history of CRC were more likely to have undergone screening endoscopy (p < 0.001), have proximal colon tumors (p = 0.04) and non-metastatic CRC (p = 0.003). Having a family history of CRC was not associated with OS [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.89-1.19] or CSS (HR 1.13; 95% CI 0.95-1.36) after multivariate adjustment. Compared to patients without a family history, those with ≥ 2 affected FDRs had a HR of 0.92 (95% CI 0.59-1.43) for OS, and HR of 0.98 (95% CI 0.55-1.76) for CSS. There was no association between age at diagnosis of the affected FDR with OS (ptrend = 0.47) or CSS (ptrend = 0.16). In subgroup analyses, family history was associated with worse CSS in individuals diagnosed at age ≤ 70 years (HR 1.45; 95% CI 1.11-1.89), and in patients with distal colon cancer (HR 1.45; 95% CI 1.03-2.04). Conclusions: Among CRC patients,family history is generally not associated with CRC survival. However, family history may be associated with worse prognosis in individuals diagnosed at age ≤ 70 years, and in patients with distal colon cancer, suggesting a possible distinct pathogenic mechanism underlying a common genetic predisposition.
P01.134 Extracranial spread of glioblastoma as the initial manifestation of the disease: case report and literature review
Authors: C M Domingos, J C Rato, O Rebelo, H Tão
Journal: Neuro-Oncology (2018)

Glioblastomas are the most frequent and most aggressive primary brain tumors, representing one of the main causes of morbidity and mortality in neurosurgical practice. At the time of diagnosis the spread of these tumors is described as locally invasive, with penetration through the dura mater and invasion of extracranial structures rarely occurring (less than 2% of the cases). The authours describe a case of a brain tumour in a right handed 63-year-old woman complaining with headaches, dysarthria and paresthesia involving left V2 territory. Enhanced MRI showed a solid lesion involving Meckel’s cavum and transdural spread through foramen ovale invading extracranial structures, and a large cystic component compressing left temporal lobe with surrounding vasogenic edema, initially interpreted as a giant trigeminal neurinoma with cystic component. Pre and post-operatory imaging features of the tumor are showed. The patient underwent surgery with removal of both solid and cystic components. After surgery she improved from headache and dysarthria, maintaining discrete paresthesia in the aforementioned trigeminal territory after surgery. Histopathological examination showed cells of variable dimensions with nuclear atypia and abundant mitoses. There were hypercellular areas with elongated cells forming bundles between collagen and reticulin fibers, with necrosis phenomena, vascular microproliferation and leptomeningeal infiltration. The tumor showed intense positivity for the glial fibrillary acidic protein (GFAP) and negativity for the mutation of isocitrate dehydrogenase 1 (IDH1). Final histopathological diagnosis was wild type glioblastoma with meningeal invasion (WHO grade IV). Histological images of the tumor are showed. After surgery patient was referred to adjuvant therapies. Extradural spread of glioblastomas occurs late in the course of the disease (on average 2 years after diagnosis), usually after craniotomies performed for excision of the lesion. However primary extradural spread of these tumors at the time of diagnosis is a rare phenomenon, with few cases being reported in the literature. The authors reviewed the literature reported cases and summarized the three pathways of dissemination at the moment of diagnosis: 1) by direct erosion of the dura mater; 2) through peri-vascular spaces or peri-neural sheaths of cranial or spinal nerves; 3) through dural slits in temporal fossa created by intracranial hypertension due to large volume tumours.
Interrogating MEK inhibition in a KRAS-mutant lung cancer patient-derived xenograft (PDX) resource.
Authors: Philip C. Mack, Jonathan Riess, Rebekah A Burich, Mingshan Cheng, Hongyuan Yang, Yu Li, Susan D. Airhart, Carol J. Bult, James G. Keck, Joel H Graber, David R. Gandara
Journal: Journal of Clinical Oncology (2016)

e20561 Background: Constitutively activating KRAS mutations (mt) comprise ~28% of lung adenocarcinoma. Despite their accepted role as oncogenic drivers, effective targeted intervention remains elusive. KRAS mts are heterogeneous, with multiple amino acid substitutions differentially associated with patient smoking status and tumor biology, modified further by variable gene amplification levels and co-mt patterns. To identify characteristics of KRAS-mt lung cancers that benefit from MEK inhibition, we investigated the activity of trametinib in a heterogeneous series of KRAS-mt PDX models selected for differences in genomic makeup. Methods: Clinically annotated patient tumor (biopsy, resection or pleural effusion) was implanted subcutaneously into the flank of NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. The resultant PDXs were analyzed for driver mts (JAX 358 CTP panel); copy number variants and global RNA expression (Affymetrix arrays; RNA sequencing). PDX cohorts (n = 6-10) were treated with trametinib at 2-3mg/kg p.o. QDx5/week for 4 weeks, with follow-up until tumors reached pre-determined size. Parallel pharmacodynamic (PD) studies were conducted at 4 & 24h in select models by immunoblotting. Results: To date, 18 KRAS-mt PDX lung cancer models have been established, harboring KRAS G12C, G12D, G12A, G12S or G13R substitutions. 16 models co-harbored TP53mts. Other co-mts of interest included STK11, ATM, Keap1 & BRCA1/2 disrupting mutations, and one model with PI3K E542K. 37% exhibited KRAS gene amplification. Trametinib induced statistically significant tumor growth inhibition in 5 of 9 models tested to date. Characteristics of responsive models included non-G12C KRAS mt with concurrent gene amplification. PD analysis revealed reduction in both MEK and ERK phosphorylation in responsive models. Non-responders showed negligible effect on pERK. Conclusions: In KRAS-mt lung cancer PDX models, single-agent trametinib resulted in partial growth inhibition in 5 of 9 models, concomitant with downregulation of pERK. The preserved tumor heterogeneity and genomic complexity of PDXs provides an ideal preclinical platform to model strategic combinations of targeted regimens for KRAS-mt lung cancer.
A combination of computer extracted measurements of prostate capsule shape and tumor texture on MRI to predict biochemical recurrence post treatment.
Authors: Rakesh Shiradkar, Soumya Ghose, Andrei Purysko, Anant Madabhushi
Journal: Journal of Clinical Oncology (2017)

e16554 Background: Prostate cancer (PCa) biochemical recurrence (BCR) occurs in a significant proportion of men after treatment and is associated with increased mortality. Identifying PCa patients at risk of BCR following definitive therapy may help identify patients who might benefit from adjuvant therapy. Multi-parametric MRI (mpMRI) is being increasingly used in pre-treatment staging and risk stratification of PCa. In this work, we sought to explore whether a combination of computer extracted features relating to prostate capsule shape and tumor texture from pre-treatment mpMRI is predictive of BCR post treatment. Methods: This single center and retrospective study included 80 men with PCa who underwent pre-treatment 3T mpMRI and were followed for &gt; 3 years post treatment. These men were grouped into a training set D 1 (N = 50, 25 each of BCR+ and BCR-) and an independent validation set D 2 (N = 30, 10 BCR+ and 20 BCR-). The prostate capsule and cancer region of interest (ROI) were annotated on mpMRI by a single experienced radiologist. Shape features (curvature and orientation) were extracted from a surface of interest where statistically significant differences were observed between BCR+ and BCR- patients in the training set. Radiomic features for capturing tumor textural patterns (including 1 st and 2 nd order statistics, Gabor and Haralick) were extracted from within the radiologist annotated cancer ROIs. Features from D 1 were used to train random forest classifiers, one each with shape (C s ) and radiomic (C R ) features. A fused Bayesian classifier (C R+S ) was created by integrating decisions from both C s and C R . Results: The classifiers C s , C R and C R+S were evaluated on independent validation set D 2 , resulting in area under the curve (AUCs) of 0.71, 0.81 and 0.84 respectively. C s added value in patients who had extra prostatic spread of PCa, but suffered from mpMRI intensity artefacts that affected performance of C R . Conclusions: Integrating prostate capsule shape and tumor radiomic features from pre-treatment mpMRI enabled prediction of PCa BCR after treatment. Multi-site validation is needed to establish the robustness of the approach.
Impact of tumor location and variables associated with overall survival in patients with colorectal cancer.
Authors: Cassia B Wang, Amit Merchea, Faisal Shahjehan, Dorin Colibaseanu, Jordan Cochuyt, Zhuo Li, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2018)

e15651 Background: Our study investigated the demographic characteristics of Mayo Clinic Colon and Rectal Cancer Registry patients and sought to associate tumor location with overall survival. Methods: Using the cohort of patients seen at all three sites of Mayo Clinic (Minnesota, Arizona and Florida) from 1972-2015, we obtained 28,006 colorectal adenocarcinoma patient records. Overall survival of patients with colorectal cancer was analyzed by sidedness (left vs. right) and (left vs. right vs. rectum). Kaplan Meier analysis was conducted on all demographic and cancer variables to trace survival over a 35-year period. Subgroups within variables were compared to each other using the log-rank test and considered significantly different at p < 0.05. Cox proportional hazard regression analysis was used to assess the impact of tumor location while controlling for age, year of diagnosis, sex, tumor stage, and tumor grade. Results: Overall survival differed significantly within all variables studied after Kaplan Meier analysis (p < 0.0001). Survival was higher in the left-side group when evaluated by tumor sidedness, and rectal cancer patients had the highest median survival (100.5 months). Right-sided cancer patients had the worst prognosis in both tumor location analyses with a median survival of 76.1 months. Conclusions: These observations confirm some of the previous and recent studies on sidedness of colorectal cancer patients. This initial study provides a platform to investigate more the biological and clinical factors associated with tumor location. Merging this dataset with other available datasets and previously conducted studies within the institution (e.g. pathology, tumor genetics, transplant etc.) will provide a robust platform for multiple future studies and collaborations.
Longitudinal precision oncology experience in solid tumors at the Cleveland Clinic.
Authors: Meena Sadaps, Pauline Funchain, Haider Mahdi, Petros Grivas, Amy Pritchard, Stefan Klek, Bassam N. Estfan, Jame Abraham, George Thomas Budd, James Stevenson, Nathan A. Pennell, Alok A. Khorana, Brian James Bolwell, Davendra Sohal
Journal: Journal of Clinical Oncology (2018)

e18710 Background: Precision oncology approaches to selecting therapies are increasingly being used, but there are limited data on benefit to patients. We expand on our initial prospective cohort data in solid tumors [JNCI. 2015; 108(3)], and evaluate impact on clinical outcomes, including survival. Methods: We conducted a retrospective cohort study of 600 consecutive patients seen at the Cleveland Clinic from 2013 to 2016 for treatment of incurable solid tumor malignancies for whom tumor genomic profiling was performed using FoundationOne (Cambridge, MA). Therapeutic recommendations by our multidisciplinary genomics tumor board were reviewed. Data analyzed included subsequent therapy (Tx) and overall survival (OS). Results: The median age of the study population was 59 (range, 14-94) years, 308 (51.3%) were female, and 533 (88.8%) were Caucasian. Lung (20.3%), breast (16.5%), colorectal (13.3%), and head & neck (9.5%) cancers were most common. Median time from initial diagnosis was 1.7 years, and a median of 2 prior lines of Tx had been used. Based on sequencing results, genomics-driven-Tx (G) was recommended in 310 (51.7%) patients. After results, 313 (52.2%) patients started a new Tx; of these, 95 (30%; 15.8% overall) received G and 218 (70%) received non-genomics-driven-Tx (NG). The most common targets for G were HER2 (n = 14), BRAF (12), PIK3CA/PIK3R/PTEN (9), EGFR (8), and ALK, CDK and RET (5 each). For G vs NG groups, on-label, off-label, and clinical trial Tx were 23% vs 88%, 47% vs 3%, and 30% vs 9%, respectively. Median OS for patients receiving no Tx after tumor genomic profiling was 5.5 months; for the NG and G groups, it was 14.6 (p < 0.001) and 18 months (p < 0.001), respectively (p = 0.5 for G vs NG). The use of G increased from 10% in our initial cohort (N = 250) to 20% in the subsequent cohort (p < 0.01). Conclusions: Tumor genomic profiling influenced treatment in 15.8% of patients in this cohort, and use of G increased over time. More patients received Tx via clinical trials in the G cohort. These data compare favorably to prior reports and highlight the importance of targeted therapy trials to improve precision oncology’s impact.
Abstract 19889: Critical Role of Endoplasmic Reticulum Stress-STING-IRF3 Pathway in Smooth Muscle Cell Phenotype Switch in Aortic Aneurysm and Dissection
Authors: Yun Mao, Lin Zhang, Pingping Ren, Swapna Krishnamoorthy, Michelle Zhang, Christopher Guardado, Joseph Coselli, Scott LeMaire, Ying Shen
Journal: Circulation (2016)

Introduction: A significant feature of sporadic aortic aneurysm and dissection (AAD) development is smooth muscle cell (SMC) phenotype switch that results in SMC contractile dysfunction. Endoplasmi...
A phase 1/2, open-label dose-escalation study of liposomal irinotecan (nal-IRI) plus 5- fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) in patients with previously untreated metastatic pancreatic cancer (mPAC).
Authors: Andrew Peter Dean, Zev A. Wainberg, Ramesh K. Ramanathan, Patrick McKay Boland, Kabir Mody, Bin Zhang, Bruce Belanger, Floris A de Jong, Stephan Braun
Journal: Journal of Clinical Oncology (2018)

4111 Background: nal-IRI+5-FU/LV is effective for patients with mPAC after disease progression following gemcitabine-based therapy. The current study (NCT02551991) is a phase 1/2, open-label trial to assess the safety, tolerability, and dose-limiting toxicities (DLT) of nal-IRI+5-FU/LV+OX (NAPOX) for the first-line treatment of patients with mPAC and to determine Phase 3 dosing. Methods: NAPOX is being evaluated in patients ≥18 yrs with previously untreated mPAC, with an ECOG performance status ≤1 and adequate organ function. Three of 4 dose-escalation cohorts of NAPOX, dosed on day 1 and 15, have been initiated. Safety and tolerability are the primary endpoints of this study, with assessment of exploratory efficacy signals. Results: As of 10 Nov 2017, 24 patients (Cohort A: n = 7; Cohort B: n = 7; Cohort C: n = 10) have received ≥1 dose of NAPOX (median age: 66.0 yrs, range: 44–78 yrs). Five patients reported ≥1 DLT (Cohort A: n = 2/7; Cohort B: n = 1/7; Cohort C: n = 2/10). The most frequent treatment-emergent adverse events (TEAEs) were gastrointestinal (GI) disorders (Cohort A: 71%; Cohort B: 71%; Cohort C: 60%). Grade 3 or 4 TEAEs were GI disorders (Cohort A; 43%; Cohort B: 14%; Cohort C: 50%) and neutropenia (Cohort A: 43%; Cohort B: 29%; Cohort C: 40%). The best overall response was partial response (PR) in 6/24 patients (Cohort B: n = 3/7; Cohort C: n = 3/10). In Cohort B (the lowest and most tolerable cohort), n = 5/7 patients reached disease control (PR or stable disease > 16 weeks), with n = 4/7 patients were treated for ≥24 weeks. Conclusions: Initial analysis suggests a well-tolerated dose and promising antitumor clinical activity of NAPOX. Dose escalation and expansion is ongoing. Clinical trial information: NCT02551991. Dose Current Patients Grade 3/4 TEAEs Cohort nal-IRI (mg/m2) 5-FU/LV (mg/m2) Oxaliplatin (mg/m2) Dosed (n) Ongoing (n) Neutropenia (n) Diarrhea (n) Vomiting (n) Nausea (n) A 80 2,400 / 400 60 7 0 3 3 1 0 B 60 2,400 / 400 60 7 2 2 1 0 0 C 60 2,400 / 400 85 10 3 4 3 3 2 D* 65 2,400 / 400 70 - - - - - - * Cohort not yet initiated