tbuckley/cabot-search huggingface dataset:
Abstract 13543: Brain Injury in Adolescents With Single Ventricle Heart Disease Compared to Healthy Controls
Authors: Nancy A Pike, Sudhakar Tummala, Marie K Poulsen, Nancy J Halnon, Alan B Lewis, Rajesh Kumar
Journal: Circulation (2015)

Background: Adolescents with single ventricle heart disease (SVHD), who have undergone staged surgical palliation, have increased risk for neurocognitive deficits. However, the type and location of brain injury in SVHD adolescents remains unclear. Purpose: Examine brain injury, using Diffusion Tensor Imaging (DTI) based axial (gray matter injury) and radial diffusivity (white matter injury) procedures in adolescents with SVHD who have undergone surgical palliation compared to controls. Methods: Six SVHD (age 16.2±1 years; 4 males; BMI 20±3.5 kg/m2), and 8 controls (age 16.2±1 years; 4 males; BMI 25.4±8.1 kg/m2) were examined via brain DTI on a 3T MRI. No subject had a history of prematurity, cardiac arrest, ECMO use, genetic syndrome, head trauma or severe developmental delays. Whole-brain axial/radial diffusivity maps were calculated. Statistics consisted of ANCOVA, with age and gender as covariates (uncorrected threshold, p &lt; 0.005). Results: Increased axial diffusivity in SVHD compared to controls were found in several brain sites that include frontal gyrus (p=.03), temporal gyrus (p=.01), parahippocampal gyrus (p=.008), occipital gyrus (p=.02), insular cortex (p=.04), cerebellar cortex (p=.004), pons (p=.02), and cingulate gyrus (p=.006) (Fig1). Increased radial diffusivity appeared in frontal gyrus (p=.01), cingulate gyrus (p=.001), corpus callosum (p=.04), cerebellum (p=.004), temporal gyrus (p=.004), parahippocampal gyrus (p=.004), and pons (p=.004) (Fig2). Conclusions/Implications: Brain injury was more extensive in gray matter than white matter and was located in autonomic and cognitive areas of the brain in adolescents with SVCHD. These findings indicate that the neurocognitive deficits commonly reported in SVCHD are likely related to brain injury. Further investigation is needed to clarify these relationships and to evaluate potential interventions to repair and/or protect these brain regions in this high risk patient population.
Leukocyte telomere length is associated with survival and drug resistance in lung adenocarcinoma patients treated with EGFR-TKIs
Authors: M. Yang, J. Li, N. Zhang
Journal: Annals of Oncology (2018)

Background: Gefitinib is currently one of the mostly used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for treating non-small cell lung cancer. However, the factors that predict treatment prognosis and drug resistance to EGFR-TKIs remain elusive. The objective of this study is to exam the association between leukocyte relative telomere length (RTL) and prognosis or drug resistance of advanced lung adenocarcinoma to gefitinib treatment. Methods: In this study, three hundred and sixty-nine patients with stage IIIB or IV lung adenocarcinoma were recruited between January 2009 and June 2013. All patients were treated with gefitinib orally at a daily dose of 250 mg as first-line monotherapy. Leukocyte RTL of each patient was measured using quantitative polymerase chain reaction (qPCR) protocol on an ABI PRISM 7900HT Sequence Detection System (Applied Biosystems) and calculated according to Cawthon's formula. Differences in patients' characteristics were calculated by Pearson's χ2 tests or Student's t test. Cox proportional hazard regression analyses were used to calculate univariate and multivariate hazard ratios (HRs). Survival differences were examined using the log-rank test. Two-sided P < 0.05 indicated a significant difference. Results: Among 369 patients, EGFR mutations were positive in 181 patients (49.1%). Compared to long RTL, short leukocyte RTL was significantly associated with poor prognosis in all patients after gefitinib treatment (overall survival: 12.9 months vs. 17.8 months, P = 1.2 × 10-4; progression free survival: 7.8 months vs. 13.0 months, P = 0.043). Additionally, statistically significant association between short leukocyte RTL and shorten OS still existed among the EGFR mutant patients with gefitinib treatment (HR = 1.65, 95% CI = 1.28-2.12; P = 0.006). Besides EGFR mutation status, short RTL also contributed to significantly elevated risk of gefitinib primary resistance (HR = 1.50, 95% CI = 1.05-2.15, P = 0.027). Conclusions: Our results highlight the potential of leukocyte RTL as a novel biomarker in advanced lung adenocarcinoma treated with EGFR-TKIs and the possibility of patient-tailored decisions based on leukocyte RTL. Legal entity responsible for the study: Ming Yang. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Effect of a genomic classifier on treatment decision-making among patients with biochemical recurrence after radical prostatectomy: Results from the multicenter prospective PRO-IMPACT study.
Authors: John L. Gore, Marguerite Du Plessis, Maria Santiago-Jimenez, Kasra Yousefi, Darby J. S. Thompson, David Y. T. Chen, William R. Clark, Michael E. Franks, Lawrence Ivan Karsh, Adam S. Kibel, Brian R. Lane, Yair Lotan, William Thomas Lowrance, Paul Maroni, Scott David Perrapato, Edouard John Trabulsi, Robert J. Waterhouse, Elai Davicioni, Daniel W. Lin
Journal: Journal of Clinical Oncology (2016)

e16558 Background: Patients and providers have tremendous uncertainty as they decide on the appropriate timing for intervention with salvage radiation therapy (SRT) for suspected local recurrence after radical prostatectomy (RP). We prospectively evaluated the impact of a previously validated genomic classifier (the Decipher test, henceforth referred to as GC) which predicts metastasis risk after RP, on urologists’ decision-making for SRT. Methods: 75 salvage patients were enrolled into the study by 43 urologists; 19 community and academic practices. We included patients with rising PSA after RP. Physicians provided a management recommendation prior to obtaining GC and again upon receiving results. Patients complete validated surveys on decisional quality and PCa-related anxiety and are followed for one year. In this interim analysis, we evaluated the pre-and post-GC visits. Results: Results were available for 69 patients. Median patient age at enrollment was 64 years; 45% had pathologic T3 stage classification and 49.3% had positive surgical margins at RP. Median 5-year predicted probability of metastases by GC was 5.9% (interquartile range [IQR] 2.8%-12.1%). GC classified 35%, 32%, and 33% as low-, intermediate-, and high-risk, respectively. Without GC, 58%, 33% and 8.7% of patients were recommended for observation, SRT, and other treatments, respectively. 39% (95% confidence interval 28-52%) of management recommendations changed post-GC, including 29% of GC low-risk patients and 65% of GC high-risk patients. Decisional Conflict Scale (DCS) scores decreased (indicating higher decision quality) after exposure to GC results (median DCS pre-GC 28 [IQR 21-42] compared with 21 [IQR 2-28] post-GC, p < 0.001). Conclusions: Knowledge of GC results was associated with treatment decision-making among patients with recurrence after RP. Patients found to be low risk for metastases by GC had higher rates of observation recommendations and patients at high risk had higher rates of SRT recommendations. Decision quality was improved among patients considering SRT after RP exposed to GC. Clinical trial information: NCT02080689.
Characteristics and outcomes of resected pancreatic cystadenocarcinoma: 1,205 cases from the National Cancer Data Base.
Authors: Jiping Wang, Xuefei Wang, Lianne Heuthorst, Thomas E. Clancy, Christopher Pezzi
Journal: Journal of Clinical Oncology (2017)

4129 Background: Cystadenocarcinoma (CAC) of the pancreas is a rare pancreatic and therefore there is limited data on the characteristics, treatment and prognosis of this disease. Methods: Patients who underwent resection for CAC (n = 1,205) between 2003 and 2012 were identified from National Cancer Data Base. The clinicopathological characteristics and treatment outcomes were compared to patients with resected ductal adenocarcinoma (DAC) (n = 15,696). Cox-proportional hazard model was used to adjust for potential prognostic factors. A nomogram was constructed and validated to predict the outcomes of patients with CAC by using multiple variable Cox-proportional model and receiver operating characteristics curve methods. Results: Compared with resected DAC, patients with resected CAC are diagnosed at a younger age (58.7 vs. 61.2, p &lt; 0.0001); female predominant (63.7% vs. 48.8%, p &lt; 0.0001); more often Black (15.0% vs. 9.3%, p &lt; 0.0001);had larger tumor (0-2, 2-4 and &gt; 4cm:17.5%, 24.3%, 53.5% vs. 16.8%, 48.3% , 32.1%, respectively, p &lt; 0.0001); have less total number of examined lymph nodes (10.6 vs. 14.5, p &lt; 0.0001) and fewer positive lymph nodes(0.6 vs. 2.3, respectively). CAC patients were less likely to receive chemotherapy (28.8% vs. 62.5%, p &lt; 0.0001) and radiation therapy (16.4% vs. 36.9%, p &lt; 0.0001). CAC patients had significantly better overall survival than those with DAC (5 year survival: 55.6% vs. 17.3%, p &lt; 0.0001). The survival advantage was primarily seen in patients with early stage disease (5 year survival: 70.9% vs. 36.9% in stage I patients, p &lt; 0.0001, and 32.7% vs. 14.5% in stage II patients, p &lt; 0.0001 respectively) and persisted after adjusting the known prognostic factors including age, AJCC staging, Charlson-Deyo score, type of surgery, chemotherapy, tumor size, and lymph node ratio (adjusted hazard ratio: 0.43, 95% confidence interval: 0.39-0.48, p &lt; 0.0001). Conclusions: Patients with CAC had significantly better survival than those with pancreatic DAC even after controlling for known prognostic factors. The proposed nomogram could accurately predict patients’ outcome and may be used as a tool for clinical decision making.
Abstract 12170: Paced-QRS fragmentation as a Novel Predictor for Ventricular Fibrillation in Patients With Brugada Syndrome
Authors: Naoya Kataoka, Koichi Mizumaki, Yasushi Tuzino, Yosuke Nakatani, Tamotsu Sakamoto, Kunihiro Nishida, Hiroshi Inoue
Journal: Circulation (2015)

Introduction: In patients with Brugada syndrome, conduction abnormalities could serve as a substrate for ventricular fibrillation (VF) and fragmented QRS appears to be a predictor of VF. Hypothesis: Therefore, we hypothesized that right ventricular apical pacing (RVP) could enhance or unmask the QRS fragmentation in the right precordial leads and paced-QRS fragmentation might predict a risk of VF in patients with Brugada syndrome. Methods: Eighteen consecutive male patients who underwent ICD implantation were categorized into 10 patients with spontaneous VF (group VF(+)) and 8 patients without VF (group VF(-)). The number of spikes within the QRS complex in leads V1-V2 and the duration of QRS fragmentation in lead V1 were evaluated (with 0.05-150 Hz filters) during both sinus rhythm (SR) and during RVP using ICD at VVI 80 bpm or 110 bpm. Results: Sum of spikes in lead V1-V2 was not significantly different between groups VF(+) and VF(-) during SR; however, it was greater in VF(+) than VF(-) during RVP at VVI 80 bpm (7.0±2.8 vs 2.9±5.2, p = 0.04) and VVI 110 bpm (10.7±3.7 vs 2.4±3.2, p = 0.01). The duration of QRS fragmentation in lead V1 was longer in VF(+) than VF(-) at VVI 110 bpm (173±32 ms vs 45±44 ms, p = 0.006). In VF(+), sum of spikes (V1-V2) was higher and the duration of QRS fragmentation (V1) was longer at VVI 110 bpm compared to VVI 80 bpm (10.1±3.7 vs 7.0±2.8, p = 0.02 and 173±32 ms vs 111±39 ms, p = 0.02, respectively). According to ROC analysis, sum of spikes ≥ 3.5 most accurately predicted spontaneous VF with sensitivity of 100% and specificity of 87.5%. Conclusions: Right ventricular apical pacing enhanced or unmasked QRS fragmentation in the right precordial leads in patients with Brugada syndrome. Therefore, paced-QRS fragmentation could be a novel predictor for spontaneous VF in patients with Brugada Syndrome.
PRODIGE 52-UCGI 29-CCTG/CO.27 (IROCAS): A multicenter, international, randomized phase III trial comparing adjuvant modified (m)FOLFIRINOX to mFOLFOX6 in patients with high-risk stage III (pT4 and/or N2) colon cancer (a UNICANCER GI-PRODIGE trial).
Authors: Jaafar Bennouna, Thierry Andre, Laurent Miglianico, Loic Campion, Laurent Mineur, You Heng Lam, Sandrine Hiret, Pascal Artru, Olivier Bouche, Florence Borde, Albert Aleba, Laetitia-Shanna Rajpar, Christine Rebischung, Yann Touchefeu, Petr Kavan, Sharlene Gill, Tim Asmis, Claire Jouffroy-Zeller, Jean-François Emile, Julien Taieb
Journal: Journal of Clinical Oncology (2018)

TPS3622 Background: According to the IDEA trial (Shi Q et al. ASCO 2017;LBA1), 6-month adjuvant chemotherapy should remain the standard in stage III T4 or N2 colon cancer. The relatively poor survival in this high-risk subgroup (3-year disease-free survival ([DFS] rate, 66%) and the potential synergistic efficacy of 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (demonstrated in stage IV colon and pancreatic cancers) suggest FOLFIRINOX as a regimen of particular interest in this setting. Methods: This multicenter, international, phase III trial (NCT02967289) conducted in 47 centers in France and Canada, plans to include 640 patients, aged 18 to 70 years, ECOG performance status ≤1, within 42 days (start treatment, within 56 days) after curative-intent R0 surgical resection of a pT4N1 or pT1-4N2 colon adenocarcinoma. Patients are randomized (1:1; minimization method) between adjuvant mFOLFIRINOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², and 5-FU 2.4 g/m²over 46 h) or mFOLFOX6 (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU bolus 400 mg/m2 then 2.4 g/m²over 46 h), every two weeks for 24 weeks (12 cycles). Patients will be followed up for 5 years after the end of adjuvant chemotherapy. A gain of 9% in 3-yr DFS (primary endpoint) is expected (74% in the experimental arm vs. 65% in the control arm; α, 5% [two-sided log-rank test]; 1-b, 80%). Secondary endpoints include 2-yr DFS, overall survival, and toxicity. Since April 2017, 49 patients have been enrolled to date (accrual period, 4 years). Clinical trial information: NCT02967289.
Uridine triacetate as a lifesaving antidote for overdoses and severe early-onset 5-fluorouracil and capecitabine toxicities.
Authors: Wen Wee Ma, Wasif M. Saif, Thomas H. Cartwright, Marwan Fakih, Bassel F. El-Rayes, Thomas King, Julie Vanas, Reid von Borstel, Michael K. Bamat, James Posey
Journal: Journal of Clinical Oncology (2016)

e21689 Background: Uridine triacetate was approved by FDA in 2015 for adult and pediatric patients who exhibit early-onset, severe or life-threatening toxicities or who receive an overdose of 5-fluorouracil or capecitabine. Uridine triacetate is an oral prodrug of uridine, a direct antagonist of 5-FU, that dilutes and competes with toxic 5-FU metabolites, particularly FUTP incorporation into RNA, reducing morbidity and mortality due to 5-FU and capecitabine. Increased susceptibility to 5-FU/capecitabine can lead to rapid, early-onset toxicity caused by factors such as: impaired clearance; DPD deficiency (3-5% of the population); and elevated OPRT (which converts 5-FU to toxic intracellular 5-fluorouridine nucleotides). Life-threatening or lethal 5-FU overdose occurs due to infusion pump errors, dosage miscalculations, accidental and suicidal ingestion of capecitabine. Methods: 173 patients overdosed with 5-FU or capecitabine (n = 147); or who showed early onset of severe toxicities (n = 26) were treated with uridine triacetate in 2 clinical trials. Patients were to receive uridine triacetate (10g q6h for 20 doses) starting up to 96h post-5-FU/capecitabine. Clinical endpoints included survival, time to resumption of chemotherapy, and safety. Results: A total of 163/173 (94%) patients treated with uridine triacetate recovered fully (within 30 days), including rapid reversal of severe cardiotoxicity (e.g. multiple cardiac arrests; LVEF of 5%) and neurotoxicity (e.g. coma, encephalopathy, ataxia), in addition to recovery from mucositis and leukopenias. Historical comparators for overdose patients (n = 47) were obtained from publicly-available sources. Of those with outcome data, 38/42 (90%) died. Of the 166 uridine triacetate-treated patients with a diagnosis of cancer, 53 resumed chemotherapy in < 30 days (median 19.5 days post-5-FU), indicating rapid recovery from toxicity. Adverse reactions in patients receiving uridine triacetate were vomiting (10%), nausea (5%), and diarrhea (3%). Conclusions: In these studies, uridine triacetate was a safe and effective life-saving antidote for capecitabine and 5-FU overexposure, and facilitated rapid resumption of chemotherapy.
Improved coping to mediate the positive effects of integrated palliative care on quality of life and depression.
Authors: Jamie M. Jacobs, Joseph A. Greer, Areej El-Jawahri, Ryan David Nipp, Emily R. Gallagher, William F. Pirl, Elyse R. Park, Alona Muzikansky, Juliet Jacobsen, Vicki A. Jackson, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2017)

10023 Background: In a recent trial, early integrated palliative care (PC) improved quality of life (QOL) and reduced depression symptoms in patients with newly-diagnosed incurable lung and gastrointestinal (GI) cancer. The mechanisms by which PC benefits these outcomes are unclear. Therefore, we examined whether early integrated PC improved patients’ coping strategies and the degree to which changes in coping mediated intervention effects on patient-reported QOL and depression symptoms. Methods: From 5/2011 to 7/2015, we enrolled 350 patients with newly diagnosed incurable lung or non-colorectal GI cancer in a randomized trial of early PC integrated with oncology care vs. oncology care alone at Massachusetts General Hospital. Patients completed self-report measures of QOL (Functional Assessment of Cancer Therapy-General), depression symptoms (Patient Health Questionnaire-9), and use of active and avoidant coping strategies (Brief Cope) at baseline, 12, and 24 weeks. Linear regression was used to assess the effects of the early PC intervention on active and avoidant coping strategies. A multiple mediation regression with bias-corrected bootstrapping was modeled to examine whether changes in use of coping strategies mediated intervention effects on QOL and depression symptoms. Results: Compared to oncology care, early integrated PC improved patients’ use of active coping and reduced use of avoidant coping strategies. Improvements in 24-week QOL in patients assigned to PC were mediated by increased use of active coping strategies (indirect effect = 1.27, bootstrapped SE = 0.65, 95% CI [0.31, 2.86]), but not by decreased use of avoidant coping. Similarly, PC-related reductions in 24-week depression symptoms were mediated by increased use of active coping strategies (indirect effect = -0.39, bootstrapped SE = 0.20, 95% CI [-0.89, -0.08] but not by decreased use of avoidant coping. Conclusions: Patients with newly diagnosed incurable cancer who received early integrated PC showed increased use of active coping strategies, which led to improved QOL and depression symptoms. PC may improve QOL and mood by providing patients with the skills to cope effectively with life-threatening illness. Clinical trial information: NCT01401907.
Predictive value of circulating tumor DNA in locally advanced rectal cancer patients receiving neoadjuvant radiochemotherapy.
Authors: Min Li, WeiWei Xiao, Grace Q. Zhao, Zhiwei Guo, Xuexi Yang, Shengrong Lin, Kang Ying, Ming Li, Yuan-Hong Gao
Journal: Journal of Clinical Oncology (2017)

e15125 Background: Neoadjuvant radiochemotherapy (RCT) is rapidly becoming the preferred treatment for patients diagnosed with late-stage locally advanced rectal cancer (LARC). Presently, tumor regression grades (TRG) is used to characterize treatment responsiveness; patients with low TRG scores have been shown to receive no benefit from surgery. To-date, however, there exists no reliable method for identifying low TRG-scoring patients without surgery. Here we propose the use of circulating tumor DNA (ctDNA) to identify low TRG-scoring patients to reduce overtreatment and improve quality of life. Methods: 30 LARC patients undergoing neoadjuvant RCT were prospectively enrolled in our study. Plasma was collected before treatment, immediately preceding cycle 3 chemotherapy, and 2 weeks following cycle 4 chemotherapy. Tumor tissue was also collected before treatment start. CtDNA and tumor DNA were sequenced using Accu-Act, a 61-gene NGS panel. Tumor response was classified as TRG1-5 according to Mandard classification system. Somatic mutation profiles were correlated with tumor response. The accuracy of ctDNA and tumor DNA in predicting TRG scores was calculated using the change of allele frequency. The predictive value of ctDNA was also compared to that of standard CEA and CA199 assays. Patients with CEA and CA199 scores below threshold were also considered for evaluation. Results: 18 of the 30 LARC patients enrolled had complete ctDNA profiling test among whom 13 had already undergone surgery. 17 somatic mutations were identified from the 10 patients with TRG scores of either 1, 2, or 3. Predictive accuracy of pretreatment ctDNA profiling was 70%, compared to that of CEA analysis (66%) and CA199 analysis (50%). TRG prediction using ctDNA successfully evaluated half of patients for whom CEA analysis failed to predict the change in tumor burden. Conclusions: Our findings suggest ctDNA mutation profiling may be a powerful tool for predicting TRG in LARC patients undergoing RCT. Further studies are needed to validate the utility of ctDNA in identifying patients who can be spared from unnecessary surgical treatment in LARC. Clinical trial information: NCT02031939.