tbuckley/cabot-search huggingface dataset:
Long-term survival (over 10 years) of inoperable/metastatic GISTs: A retrospective series of 141 patients (pts) of the french sarcoma group (FSG).
Authors: Florence Duffaud, Edouard Auclin, Antoine Italiano, Julien Mancini, Francois Bertucci, Nicolas Penel, Marc Pracht, Guillaume Vogin, Olivier Collard, Emmanuelle Bompas, Bruno Landi, Thibaud Valentin, Loic Chaigneau, Maud Toulmonde, Antoine Adenis, Isabelle Laure Ray-Coquard, Maria Rios, S Bastien Salas, Axel Le Cesne, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2017)

11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM) introduction. The aim of this study was to analyse the clinico-biological characteristics of GIST pts alive &gt; 10 years (yrs) after diagnosis (dx) of metastases (mets) and identify possible factors associated with long-term survival. Methods: Pts were identified from 2 sarcoma databases; NetSarc and ConticaGIST. Clinical data prospectively registered in the databases were supplemented with retrospective review of medical records. Results: We identified 141 pts (75 men, 66 women) with median age 54 (17-84) yrs and median ECOG 0 (0-2). Primary tumors (T) were all CD117+, and mainly gastric or intestinal (64 &amp; 45 pts), with median size 10 (2-40) cm, CD34+ (82 pts), mitoses/50 HPF ≤ 5 (n = 36), or &gt; 5 (n = 81). Genotype was documented in 82 (58%) pts with 73 (89%) KIT mutations (in exons 11,9 and 12 of 69, 3, and 1 pts respectively) and 9 WT KIT. 129 (91%) T were resected, 124 upfront, 5 post IM, with R0/R1/R2 resections in 61, 11, and 10 pts. Mets were mainly hepatic or peritoneal (78 &amp; 51 respectively). 1 st line TKI was given to 139 pts: 130 received IM; 88 (63%) within a clinical trial (CT), 41 (29%) had mets resection. Second, 3 d and 4 th line TKI were given to 81, 51 and 37 pts respectively, comprising 27, 7 and 10 from CT. Median number of TKIs was 2 (0-7), but 60 (44%) pts received only 1 st line with no GIST progression within or after 10 yrs. 2 pts never received TKI but had mets resection. After median FU of 14.3 yrs (10-34.5), 104 remain alive, 37 died. Mean and Median OS from initial dx are 24 yrs (CI95% 21.6-27) and 20,8 yrs. Median PFS on TKIs are 127, 29, 21 and 22 mos on 1 st , 2 d , 3 d and 4 th line of TKI. In univariate analysis no factor is significantly associated with OS, but T size (≤ 10 vs &gt; 10 cm) and oligometastatic disease (≤5 vs &gt; 5 mets) are borderline significant (p = 0.056 and 0.07), and good PS (ECOG ≤ 1) at 2 d line TKI initiation is associated with better PFS (p = 0.03). Conclusions: This large series of long-term ( &gt; 10 yrs) survivors of metastatic GIST shows a high proportion of mets resection and a longer duration of PFS for TKI at any line. In this selected population, no prognostic factor is associated with long OS.
FOBT compared to FIT in reducing colorectal cancer (CRC) incidence.
Authors: Sarmad Sadeghi, David I. Quinn, Heinz-Josef Lenz, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2016)

e18119 Background: It is thought that CRC incidence reduction (IR) and cancer mortality reduction (CMR) associated with screening (Scr) with colonoscopy (CS) and flexible sigmoidoscopy (FS) are derived from adenoma detection as opposed to invasive cancer and down-staging. While traditionally FIT is felt to be superior to FOBT, and neither one is empirically linked to IR, if a positive Scr is followed by CS the subjects are expected to accrue the IR and CMR benefits of CS. Methods: To test this hypothesis, a Markov model was built to represent the CRC incidence and its natural history in the US general population. Study perspective was societal and costs and effects were discounted (Dis) at 3%. 8 Scr strategies (ST) were compared to No Scr. Dis Life Years (LY), IR, CMR, and Dis costs of Scr and total costs of care were measured. Incremental cost effectiveness ratios (ICERs) were calculated. Results: FOBT or FIT resulted in IR and CMR due to diagnostic CS prompted by false positive (FP) Scr. Despite being more sensitive (.82 vs .64) and specific (.97 vs .90) FIT is inferior to FOBT in IR (6% vs 12%) and CMR (12% vs 17%). Compared to No Scr, FOBT 2 was the most cost effective (CE) ST. When FS was included, it became the most CE ST with ICER of $32K, and when CS was included, it dominated all other STs. Conclusions: Stool testing can reduce CRC incidence. FIT detects more cancers than FOBT. Yet, it is inferior to FOBT in IR, MR, and LY gained underlining the importance adenoma detection and removal as a result higher FP rates of FOBT. Strategy Comparative Effectiveness Costs Cost Effectiveness Status (Rank-ICER $) Dis LY CRC IR (%) CMR (%) Cancer Care Scr Without CS or FS With FS With CS and FS No Scr 15.205 0 0 3415 0 D D D ST 1: FOBT 15.215 12 17 3078 86 D D D ST 2: FIT 15.211 6 12 3180 123 D D D ST 3: FOBT + FS 15.217 14 19 3012 158 D D D ST 4: FIT + FS 15.214 8 14 3106 232 D D D ST 5: FOBT 2 15.218 12 20 2979 75 U (1-0) U (1- 0) D ST 6: FIT 2 15.215 5 14 3093 93 D D D ST 7: FOBT 2 + FS 15.219 13 21 2949 178 U (2 - 67,297) D D ST 8: FIT 2 + FS 15.217 7 17 3026 230 D D D FS 15.221 11 21 2875 270 U (1- 32,229) D CS 15.227 23 34 2335 526 U (1- 0) FOBT: Fecal Occult Blood Test, FIT: Fecal Immunochemical Test. Stool tests are done annually or at the interval listed. D: Dominated. U: Undominated.
Computer extracted features on H&E images to improve biochemical recurrence prediction of Kattan nomogram for prostate cancer patients following radical prostatectomy: Preliminary findings.
Authors: George Lee, Robert W. Veltri, Guangjing Zhu, Jonathan I. Epstein, Kenneth J. Pienta, Anant Madabhushi
Journal: Journal of Clinical Oncology (2016)

11556 Background: Of the 75,000 cases of prostate cancer annually treated by radical prostatectomy (RP) in the United States, 30% will experience biochemical recurrence (BCR). Gleason scoring (GS), a qualitative and subjective system, is currently the strongest individual predictor of BCR. The goal of this study was to evaluate whether computationally derived quantitative histomorphometry (QH) features from both within tumor and adjacent benign regions could together improve the BCR prediction capability of extant nomograms. Methods: This study comprised of 70 patients (22 BCR and 48 non-recurrence (NR)) followed up to 14 years, T2 or T3 stage, and GS 6 to 9. For each patient, we investigated 242 features describing nuclear shape, architecture, and disorder calculated from H&E stained TMA core images sampled from tumor and cancer-adjacent normal-appearing benign fields. The top 10 features (8 from benign field and 2 from tumor field) were selected using a Wilcoxon Rank-Sum test and used to train a random forest classifier to predict BCR. Results: The QH features predicted BCR with a classification AUC of 0.74, outperforming GS (AUC = 0.72). Combining QH features with each of GS, and multivariate Kattan and Stephenson scores significantly (p < 0.05) improved BCR prediction. Low correlation was observed between the QH features and GS (r = 0.04), Kattan (r = 0.22), and Stephenson (r = 0.13) scores. Conclusions: We found that the combination of QH features from within the tumor and adjoining benign regions was able to better predict BCR compared to Gleason score and also improved the prediction performance of established nomograms. Our data also appears to suggest that morphology of tumor adjoining benign regions is important in predicting prognosis for these tumors. Future work will focus on validating these findings on an independent test set. Mean AUC, 95% CI of BCR predictions using QH features combined with post-surgical clinical predictors. Gleason Sum Kattan Stephenson Without QH 0.72 (0.68-0.76) 0.85 (0.84-0.87) 0.81 (0.78-0.83) With QH 0.82 (0.76-0.88) 0.91 (0.89-0.93) 0.87 (0.85-0.89)
Abstract 19074: Prevalence of Age-Advanced Coronary Artery Disease on Coronary CT Angiography
Authors: Ali M Agha, Jean-Paul Bryant, Maria Marquez, Melissa Kendall, William Sensakovic, Julie Pepe, Jeremy R Burt
Journal: Circulation (2017)

Introduction: Little is known about the prevalence or risk factors associated with “age advanced” CAD (defined as CAD in men < age 40 and women < age 50). Hypothesis: The prevalence of CAD in this ...
Hope and distress to predict patient-centered outcomes among adolescent and young adult patients with cancer.
Authors: Abby R. Rosenberg, Miranda Bradford, Kira O'Neil Bona, Claire M Wharton, Michele Shaffer, Joanne Wolfe, Kevin Scott Baker
Journal: Journal of Clinical Oncology (2016)

10580 Background: Distress screening is standard in clinical in oncology; however, we know little about its relationship to patient-centered outcomes among adolescents and young adults (AYAs). Methods: In a multi-center, prospective, survey-based study, English-speaking AYAs (14-25 years-old) with non-CNS cancer and their parents were surveyed at diagnosis (T1) and 3-6 months later (T2). Patient-Reported Outcomes included the Kessler-6 psychological distress, Snyder Hope, and PedsQL Quality of Life (QOL) scales, plus queries of normal developmental behaviors such as intimate relationships. We dichotomized Kessler-6 scores (no distress vs moderate-serious distress) and created a composite hope/distress scale where higher scores reflect greater hope and lower distress. Associations between T1 distress or composite scores and T2 outcomes were estimated with logistic or linear regression modeling. Results: Respondents included 37 (88%) eligible patients (mean age 18, SD 2, 57% male) and 39 parents (mean age 49, SD 7, 74% mothers). T1 composite hope/distress scores predicted later distress more strongly than T1 distress alone, and only the composite predicted later QOL. For example, participants with distress at T1 more commonly reported distress at T2 (OR 3.2, 95% CI 1.0-10.5) but had similar T2 QOL scores (p > 0.3 for differences in mean scores). Each 5 point increase in T1 composite scores corresponded to lower odds of distress at T2 (OR 0.4, 95% CI 0.5-0.8), 2-point higher total, and 6-point higher pain-hurt related QOL scores (p < 0.01 for both). Comparing the highest and lowest quartiles of composite scores at T1 suggested important differences in outcomes at T2 (Table). Conclusions: Distress at diagnosis may predict distress later during cancer therapy, but multi-dimensional screens incorporating other (positive) psychosocial constructs may better predict QOL and other patient-centered outcomes. Quartile of Composite Hope/ Distress at T1* % (N) of participants distressed at T2† Mean total QOL (95% CI)*† Mean pain- hurt QOL (95% CI) *† % (N) of AYAs with intimate relationships Highest 8 (1/13) 77 (61-94) 79 (32-127) 100 (3/3) Lowest 60 (9/15) 66 (58-75) 46 (12-80) 40 (2/5) *higher scores better; †p ≤ 0.05
Effects of <i>CYP2A6</i> genotype and plasma level of 5-chloro-2,4-dihydroxipyridine (CDHP) on pharmacokinetics (PK) of tegafur (FT) and 5-fluorouracil (5-FU) in the patients treated by S-1
Authors: K. Fujita, W. Yamamoto, H. Endo, F. Nagashima, W. Ichikawa, T. Miya, K. Araki, K. Kodama, M. Narabayashi, Y. Sasaki
Journal: Journal of Clinical Oncology (2007)

2504 Background: S-1, which is an oral anticancer agent comprised of FT, CDHP and potassium oxonate, is one of the most widely prescribed agents in the treatment of gastric and colorectal cancer in Japan. CYP2A6 is involved in the bioactivation of FT to 5-FU. Dihydropyrimidine dehydrogenase which is responsible for the detoxification of 5-FU is inhibited by CDHP to increase plasma exposure of 5- FU. The dose of S-1 is determined by body surface area (BSA) of the patients. We prospectively analyzed contribution of CYP2A6 genotype, plasma level of CDHP, and BSA on the PK of FT and 5-FU. Methods: Forty Japanese patients with metastatic/ recurrent cancers who received S-1 were enrolled. Genetic polymorphisms in CYP2A6 (*4, *7 and *9) related to deficient or reduced activity were analyzed. CYP2A6 genotypes were defined as wild (*1/*1), one-reduced allele (*1/*4, *1/*7 or *1/*9) and two-reduced alleles (*4/*4, *4/*7, *4/*9, *7/*7, *7/*9 or *9/*9). On the first day of the treatment, plasma concentration of FT, 5-FU and CDHP were measured. Multivariate linear regression analysis was used identifying association or correlation between oral clearance (CL/F) for FT or area under the time-concentration curve (AUC) for 5-FU and possible factors including CYP2A6 genotype, AUC for CDHP and patient’s characteristics including BSA. Results: CL/F for FT was significantly associated with CYP2A6 genotype (ANOVA, P=0.0000787, R 2 =50.1%), but not with other factors. CL/F for FT in patients with one- and two-reduced allele(s) were significantly lower than that in wild patients (P=0.0126 and 0.000128, respectively; Wilcoxon test). AUC for 5-FU was significantly correlated with AUC for CDHP (ANOVA, P=0.000534, R 2 =39%), but not with others. AUC for CDHP was correlated with creatinine clearance (Ccr) (ANOVA, P=0.00056, R 2 =27.2%). Conclusions: PK of FT and 5-FU are significantly affected by CYP2A6 genotype and exposure of CDHP, respectively. In addition, AUC for CDHP, which is correlated with Ccr, is the more critical factor to regulate AUC for 5-FU than BSA. Ccr-based dosing will be more rational than the conventional BSA-based dosing in the prescription of S-1. No significant financial relationships to disclose.
Health care associated infections (HAIs) a growing challenge in low-middle-income countries: A Brazilian prospective cohort study.
Authors: Jose Iran Costa, Maria Julia Gonçalves Mello, Isabella R . da Cunha Barros, Camila jacó Ramos, Naiá de miranda Neves, Jurema Telles O Lima
Journal: Journal of Clinical Oncology (2017)

e18253 Background: Healthcare associated infections (HAIs) are responsible for morbidity and mortality among oncologic patients. The aim of this study was to determine the risk factors and the profile of HAI in patients admitted in cancer center. Methods: a prospective cohort study approved by the institution’s ethics committee.It was completed standardized initial assessment and conducted telephone follow-up after thirty days and sixty days from hospital discharge records and supplemented with analysis and hospital information system.Data were analyzed using Cox proportional hazards models. Results: 220 patients between 20 and 87 years of IMIP Adult Oncology service, from December 2015 to June 2016. Among the 220 cancer patients included in the study, the prevalence of HAI was 73.6% and the mortality was 40.4%. 90% percent of patients were initially treated at emergency service. Elderly patients had a higher risk of developing HAI(p &lt; 0.001) as well as people who had longer period of hospitalization(p &lt; 0.001), advanced cancer, people who reported fever on admission, who were diagnosed with Febrile neutropenia(p &lt; 0.001) .The most frequent infections were urinary tract infection, followed by pneumonia and bloodstream infections, which are caused most commonly by Gram-negative microorganisms, and Klebsiella pneumoniae ESBL the most common.Conclusions: HAI is a prevalent problem in the whole course of cancer care with significant morbidity and mortality. Health professionals, especially in the emergency department, must be able to identify and appropriately treat HAI. Bacterial multidrug resistance was prevalent, and may be in the future because of great loss of scientific advances made in the oncology area to date. Institutional policies for prevention, surveillance and HAI therapy must be priority in cancer population.
Lipidomic profile of colorectal cancer patients by matrix-assisted laser desorption/ionization mass spectrometry (MALDI/MS).
Authors: Nora Manoukian Forones, Patrcia Valeria Serafim, Adiel Figueiredo, Augusto Azzolini, Aledson Vitor Felipe, Edson Lo Turco, Ismael DCG Silva
Journal: Journal of Clinical Oncology (2016)

e15089 Background: Colorectal cancer (CRC) is the second cause of cancer, worldwide and frequently diagnosed at advanced stage. Identification of lipid targets may lead to the development of new biomarkers for CRC. Aim: to identify circulating lipids able to discriminate CRC patients as well as to predict metastatic spread to lymph nodes. Methods: Lipids were extracted from plasma of 40 patients with CRC, 12 polyps (P) and 32 controls (normal colonoscopy). MALDI-TOF MS was applied for the lipidomic profiling. Univariate (ANOVA) and multivariate ROC curve and principal component analysis [PCA] workflows were applied to the dataset, using MetaboAnalyst 3.0.The ions were identified according to the class of lipids using the online database Lipid Maps (http://www.lipidmaps.org). Results: Multi and univariate ROC curve analysis applied to training set, revealed the presence of lipids able to discriminate CRC from controls (healthy+P) with sensitivity = 100%, specificity = 100%, PPV = 100%, NPV = 100%, Average Accuracy (100-fold CV) = 1 and 1000-fold Permutation Statistics p = 0.00055. The identified blood signature was then applied to the validation set that replicated the results with sensitivity = 100%, specificity = 100%, PPV = 100%, NPV = 100%, Average Accuracy (100-fold CV) = 1 and 1000-fold Permutation Statistics p = 4.61787e-5. Additionally, the same metabolomics strategy was able to discriminate metastatic spread to lymph nodes with sensitivity = 88.89%, specificity = 87.88%, PPV = 66.67%, NPV = 96.55%, Average Accuracy (100-fold CV) = 0.832 and 1000-fold Permutation Statistics p = 0.01. Eight ions were the most important lipids and belong to the class of flavonoids, glycerophospholipids and fatty acids, 6 were downregulated in CRC patients. The lipid profile of the P compared to the controls had a less accuracy (74%). Conclusions: The identified lipidomic signatures differentiate CRC from healthy controls and patients witm polyps as well as identify, previously from surgery, patients at higher risk of metastatic spread to lymph nodes. However, were not able to differentiate patients with polyps from controls. The knowledge of the alteration in lipids may aid the discovery of new biomarkers
Biomaterials: Bioinspired Mineral–Organic Bioresorbable Bone Adhesive (Adv. Healthcare Mater. 17/2018)
Authors: Alina Kirillova, Cambre Kelly, Natalia von Windheim, Ken Gall
Journal: Advanced Healthcare Materials (2018)

In the article 1800467 by Ken Gall and co-workers, a novel bio-inspired bioresorbable bone adhesive is introduced, which cures in minutes in an aqueous environment, provides high bone-to-bone adhesive strength, and facilitates osteointegration. Its use may inspire innovative clinical treatments of bone fractures and fusions with and without implants.
Multimodality therapy in IIIA-N2 NSCLC: Factors associated with treatment selection and survival.
Authors: Andrew Brandmaier, Elizabeth Mauer, Paul J. Christos, Dattatreyudu Nori, Silvia Formenti, Himanshu Nagar
Journal: Journal of Clinical Oncology (2016)

8550 Background: Multimodality therapy is recommended in the management of clinical stage IIIA-N2 non-small cell lung cancer (NSCLC). However, the optimal combination and sequence of treatments and their relative outcomes is not clear. We examined patterns of care, outcomes of different treatment regimens, and associated socieconomic and clinicopathologic factors. Methods: Patients with clinical stage IIIA-N2 NSCLC were identified in the National Cancer Database from 2004-2013 and stratified based on treatment regimens. Four treatment cohorts were evaluated: definitive chemoradiation (CR), neoadjuvant chemoradiation followed by surgery (CRS), neoadjuvant chemotherapy followed by surgery (CS), and surgery followed by adjuvant therapy (SA). The impact of clinicopathologic factors and treatment sequencing on overall survival (OS) was analyzed using Cox regression and multivariate analysis. Results: A total of 28,147 patients met inclusion criteria. The frequency of treatment courses was: 71% CR, 8.8% CRS, 3.9% CS and 16.5% SA. Median OS was 21 months with a median follow-up of 19.3 months (0-131 months). The 2-year OS rate for each treatment cohort was: 38.6% CR, 66.7% CRS, 68.7% CS, and 60.3% SA. Multivariate analysis showed OS was associated with age, race, gender, Charlson-Deyo comorbidity index (CD), laterality, grade, clinical T stage, and treatment cohort. Improved OS was associated with patients that received CRS or CS (HR 0.8 p < .0001). Receipt of surgery was associated with age, race, gender, CD, insurance status, facility type and region, laterality, grade, clinical T stage and histology. Conclusions: The majority of patients with IIIA-N2 NSCLC were treated with CR. Patients who received neoadjuvant therapy followed by surgery had improved OS including when controlling for age and comorbidity index. Further randomized prospective trials in this population are needed to evaluate sequencing of multimodality therapy and the contribution of surgery to OS.
Effect of post-discontinuation therapy (PDT) on survival in metastatic gastric-gastroesophageal junction (G-GEJ) adenocarcinoma patients from the RAINFALL trial: An exploratory analysis.
Authors: Kohei Shitara, Manish A. Shah, Maria Di Bartolomeo, Sara Lonardi, Salah-Eddin Al-Batran, Eric Van Cutsem, David H. Ilson, Ian Chau, Maria Alsina, Jill Lacy, Daisuke Takahari, Naotoshi Sugimoto, Johanna C. Bendell, Zev A. Wainberg, Mustapha Tehfe, David Raymond Ferry, Ran Wei, Richard A. Walgren, Mayukh Das, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2018)

4044 Background: The global, randomized, placebo (PL)-controlled phase 3 RAINFALL trial evaluated if addition of ramucirumab (RAM) to first-line (1L) cisplatin plus fluoropyrimidine (chemo) improved survival. Imbalances in PDT (including cross over) could confound OS analysis comparison of 1L therapies. We report the PFS & OS, as previously disclosed at ASCO-GI 2018, and investigated the impact of PDT on survival in a post-hoc analysis. Methods: Study blinding was continued until final OS data-lock. Investigators could choose any treatment for PDT. To compare OS from randomization as well as from the start of second-line (2L) treatment (Landmark OS), PDT were categorized into RAM or Non-RAM containing, RAM+paclitaxel(PTX), or All Others. Analyses were stratified by ECOG PS, primary tumor location, disease measurability & geographic region. Results: 326 pts were randomized to chemo+RAM (8 mg/kg iv D1, D8, every 21d) & 319 pts to chemo+PL (ITT, N= 645). The primary endpoint of investigator-assessed PFS was met (HR, 0.75; 95% CI 0.61–0.94; p = 0.011; median, 5.7 vs 5.4 mo) while no OS benefit was observed (HR, 0.96; 95% CI 0.80–1.16; p = 0.68; median, 11.2 vs 10.7 mo). 150 pts (46%) in the RAM arm received PDT compared to 164 (51%) in the PL arm. Subgroup results are summarized in Table. Conclusions: PDT use was balanced in both arms. OS from Randomization and Landmark OS is numerically higher in patients who received RAM containing PDT compared to Non-RAM PDT. Despite the small sample size, the results are consistent with previously demonstrated OS benefit with RAM+PTX as 2L therapy. Clinical trial information: NCT02314117.Summary of PDT* Results (any subsequent line). Median months, (95% CI) (n) Median months, (95% CI) (n) All PDT pts All Non-PDT pts OS from Randomization 13.4 (12.8, 15.2) 314 7.1 (6.5, 7.8) 331 OS from Randomization RAM Containing Non-RAM Containing 1L RAM 16.2 (11.7, 19.4) 40 13.2 (11.9, 16.3) 110 1L PL 14.9 (12.6, 18.9) 53 13.0 (11.4, 15.0) 111 Landmark OS RAM + Paclitaxel All Others 1L RAM 9.6 (6.0, 14.6) 37 6.5 (5.7, 7.9) 113 1L PL 8.6 (5.2, 10.9) 46 6.8 (5.5, 7.8) 117 * = overall, the most frequent PDTs included: PTX, RAM, & irinotecan in both arms