tbuckley/cabot-search huggingface dataset:
Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients.
Authors: David Dewei Yang, Brandon Arvin Virgil Mahal, Christopher Sweeney, Quoc-Dien Trinh, Felix Yi-Chung Feng, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2017)

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and &gt; 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and &gt; 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and &gt; 20.0 ng/mL (P Gleason*PSA interaction &lt; 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA &gt; 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P &lt; 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; P ADT*PSA interaction = 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.
Intermediate prognosis in metastatic germ cell tumors (IPGCT): Outcome and prognostic factors.
Authors: Christoph Alexander Seidel, Gedske Daugaard, Alexey Tryakin, Andrea Necchi, Marcus Hentrich, Gabriella Elisabeth Cohn-Cedermark, Olof Stahl, Margarida Brito Goncalves, Arthur Gerl, Karin Oechsle, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2017)

4560 Background: The IGCCCG classification published in 1997 is based on data from the 1970-80s. Approximately 25% of metastatic GCT patients belong to the intermediate prognosis category, that was associated with a 5-year overall survival (OS) rate of 79%. However, more recent data suggest significant changes. We have thus performed an international registry of IPGCT patients to analyze current treatment, outcome, and potential prognostic factors. Methods: Data of IPGCT patients, diagnosed between 1979-2012, were retrospectively collected from 14 centers. Treatment and outcome before and after implementation of IGCCCG were analyzed. For patients diagnosed since 1997 prognostic factors were investigated by uni- and multivariate analysis to test whether current patients or subgroups may require less intensive treatment. Results: This registry includes 637 patients: group 1 diagnosed prior 1997 (n = 237), and group 2 since 1997 (n = 400). Mean follow-up duration was 128.4 months (IQR: 168.9). Patients in group 1 and 2 received first-line treatment with BEP (median 4 cycles; range 1 - 6) in 98% and 97%, respectively. Response to chemotherapy (CR and marker negative PR) was similar: 91% group 1; 94% group 2; (p = 0.233), but survival curves were significantly superior in group 2 associated with a 5-year OS rate of 87% (group 2) and 81% (group 1), respectively (p = 0.011; 95%CI 294-317). Recurrence rates were higher in group 1 (36% versus 24%; p = 0.001). Patients treated with 3 cycles BEP (n = 58) in both groups had a similar outcome concerning OS compared to patients treated with 4 cycles (n = 489) (p = 0.415). Uni- and multivariate analysis revealed LDH levels &lt; 2.0 UNL prior chemotherapy (p = 0.018; HR 0.35) and an adequate tumor marker decline at days 18-21 (half-life) of first cycle (p = 0.025; HR 2.58) as independent prognosticators, both associated with 5-year OS rates of 94%, respectively. Conclusions: Outcome of intermediate patients seems improved after implementation of the IGCCCG classification and less intensive regimes may also be sufficient. Here, patients treated with 3xBEP had a non-inferior outcome. A baseline LDH &lt; 2.0 UNL and an adequate tumor marker decline after first treatment cycle can be used for further stratification.
Association of Gleason Grade With Androgen Deprivation Therapy Duration and Survival Outcomes
Authors: Amar U. Kishan, Xiaoyan Wang, Wendy Seiferheld, Laurence Collette, Kiri A. Sandler, Howard M. Sandler, Michel Bolla, Philippe Maingon, Theo De Reijke, Gerald E. Hanks, Nicholas G. Nickols, Matthew Rettig, Alexandra Drakaki, Robert E. Reiter, Daniel E. Spratt, Patrick A. Kupelian, Michael L. Steinberg, Christopher R. King
Journal: JAMA Oncology (2018)

Androgen deprivation therapy (ADT) improves survival outcomes in patients with high-risk prostate cancer (PCa) treated with radiotherapy (RT). Whether this benefit differs between patients with Gleason grade group (GG) 4 (formerly Gleason score 8) and GG 5 (formerly Gleason score 9-10) disease remains unknown.To determine whether the effectiveness of ADT duration varies between patients with GG 4 vs GG 5 PCa.Traditional and network individual patient data meta-analyses of 992 patients (593 GG 4 and 399 GG 5) who were enrolled in 6 randomized clinical trials were carried out.Multivariable Cox proportional hazard models were used to obtain hazard ratio (HR) estimates of ADT duration effects on overall survival (OS) and distant metastasis-free survival (DMFS). Cause-specific competing risk models were used to estimate HRs for cancer-specific survival (CSS). The interaction of ADT with GS was incorporated into the multivariable models. Traditional and network meta-analysis frameworks were used to compare outcomes of patients treated with RT alone, short-term ADT (STADT), long-term ADT (LTADT), and lifelong ADT.Five hundred ninety-three male patients (mean age, 70 years; range, 43-88 years) with GG 4 and 399 with GG 5 were identified. Median follow-up was 6.4 years. Among GG 4 patients, LTADT and STADT improved OS over RT alone (HR, 0.43; 95% CI, 0.26-0.70 and HR, 0.59; 95% CI, 0.38-0.93, respectively; P = .03 for both), whereas lifelong ADT did not (HR, 0.84; 95% CI, 0.54-1.30; P = .44). Among GG 5 patients, lifelong ADT improved OS (HR, 0.48; 95% CI, 0.31-0.76; P = .04), whereas neither LTADT nor STADT did (HR, 0.80; 95% CI, 0.45-1.44 and HR, 1.13; 95% CI, 0.69-1.87; P = .45 and P = .64, respectively). Among all patients, and among those receiving STADT, GG 5 patients had inferior OS compared with GG 4 patients (HR, 1.25; 95% CI, 1.07-1.47 and HR, 1.40; 95% CI, 1.05-1.88, respectively; P = .02). There was no significant OS difference between GG 5 and GG 4 patients receiving LTADT or lifelong ADT (HR, 1.21; 95% CI, 0.89-1.65 and HR, 0.85; 95% CI, 0.53-1.37; P = .23 and P = .52, respectively).These data suggest that prolonged durations of ADT improve survival outcomes in both GG 4 disease and GG 5 disease, albeit with different optimal durations. Strategies to maintain the efficacy of ADT while minimizing its duration (potentially with enhanced potency agents) should be investigated.
Ventricular Arrhythmias in Cardiac Sarcoidosis
Authors: David R. Okada, John Smith, Arsalan Derakhshan, Zain Gowani, Satish Misra, Ronald D. Berger, Hugh Calkins, Harikrishna Tandri, Jonathan Chrispin
Journal: Circulation (2018)

The diagnosis of cardiac sarcoidosis (CS), especially in cases where there is limited or no extracardiac involvement, is challenging. Patients with CS are at increased risk of ventricular arrhythmias and sudden cardiac death. Several techniques for risk stratification for sudden cardiac death have been proposed in this population, including advanced cardiac imaging and electrophysiology study. Clinical ventricular arrhythmias in patients with CS may be treated with immunosuppressant therapy, antiarrhythmic drugs, catheter ablation, or implantable cardioverter-defibrillator placement. This article will provide an update on techniques for diagnosing CS, risk stratifying patients with CS for sudden cardiac death, and treating patients with CS with ventricular arrhythmias, focusing on evidence that has become available since publication of the 2014 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated With Cardiac Sarcoidosis.
TCT-213 Carotid Revascularization in Patients with Contralateral Carotid Occlusion: a Systematic Review and Meta-analysis
Authors: Seth Avner, Stefanos Giannopoulos, Pavlos Texakalidis, Damianos Kokkinidis, Nikolaos Chaitidis
Journal: Journal of the American College of Cardiology (2018)
Sputum exosomes: promising biomarkers for idiopathic pulmonary fibrosis
Authors: Makon-Sébastien Njock, Julien Guiot, Monique A Henket, Olivier Nivelles, Marc Thiry, Franck Dequiedt, Jean-Louis Corhay, Renaud E Louis, Ingrid Struman
Journal: Thorax (2018)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease of unknown aetiology which leads rapidly to death. As diagnosis of IPF is complex, we aimed to characterise microRNA (miRNA) content of exosomes from sputum of patients with IPF. Using miRNA quantitative PCR array, we found a substantial dysregulation of sputum exosomal miRNA levels between patients with IPF and healthy subjects and identified a unique signature of three miRNAs. Interestingly, we found a negative correlation between miR-142-3p and diffusing capacity of the lungs for carbon monoxide/alveolar volume. This is the first characterisation of miRNA content of sputum-derived exosomes in IPF that identified promising biomarkers for diagnosis and disease severity.
Survival analysis of a phase IB/II study of everolimus and metformin for patients with advanced cancer.
Authors: Remco Jurriaan Molenaar, Tim van de Venne, Mariette Weterman, Ron Mathot, Heinz-Josef Klumpen, Dirk Richel, Johanna Wilmink
Journal: Journal of Clinical Oncology (2017)

e14020 Background: Fundamental research suggests that a combination of everolimus and metformin has synergistic anti-tumour effects with lower chances of drug resistance. Methods: 9 patients with advanced refractory cancer received everolimus and metformin in a 3+3 dose-escalation scheme. Objectives were to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, toxic effects, pharmacokinetics and anti-tumour efficacy. Results: We enrolled 9 patients who stayed on the study for a median duration of 48 days (range: 4-78). 6 patients discontinued due to toxicity and 3 patients because of progressive disease. 4 out of 9 patients experienced a DLT and we terminated patient enrollment. Metformin was eliminated slower and metformin trough concentrations were higher when co-administered with everolimus than as single-agent (half-life: 9.3 h vs 4.3 h; P= .03 and C trough : 0.47 mg/l vs 0.2 mg/l; P =.01). After 9 weeks of treatment, 3 patients were still on study and all had stable disease as evaluated using CT scans and RECIST criteria. The 3 patients that received everolimus and metformin for at least 9 weeks had a significantly longer survival than the 5 patients who had to stop study treatment prematurely due to toxicity (median overall survival: 184 days vs 82 days; P= .048). Conclusions: The combination of everolimus and metformin is poorly tolerated in patients with advanced cancer. This may be due to pharmacokinetic interactions between everolimus and metformin and has implications for diabetic cancer patients that are treated with these drugs. Patients that tolerated the combination survived longer than patients who did not, suggesting that the combination of an mTOR inhibitor and metformin is clinically effective against cancer. This advocates for future clinical trials with combinations of other mTOR inhibitors and biguanides. [Table: see text]
Abstract 951: A Rapid Delayed-Rectifier Current Activator Ameliorates Repolarization and Suppresses Arrhythmias in Rabbit Models of Acquired Long QT Syndrome: A Novel Therapeutic Approach Targeting Underlying Ionic Mechanisms
Authors: Thomas Goldin Diness, Yung-Hsin Yeh, Xiao-Yan Qi, Denis Chartier, Yukiomi Tsuji, Rie Schultz Hansen, Morten Grunnet, Stanley Nattel
Journal: Circulation (2007)

Background: Impaired cardiomyocyte repolarization leads to prolonged action potentials reflected as long QT (LQT) intervals associated with increased susceptibility to Torsades de Pointes (TdP). Current pharmacological treatment of LQT syndrome is often inadequate. This study evaluated the antiarrhythmic effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, IKr, in two rabbit models of spontaneous TdP related to abnormal IKr function. Methods and Results: We used two clinically-relevant rabbit models of spontaneous TdP to which we infused NS1643 or vehicle (VCL): 3-week AV block with ventricular bradypacing; dofetilide (DOF) induced IKr inhibition in methoxamine-sensitized rabbits. Bradypaced rabbits developed frequent ventricular ectopy and TdP. Infusion of NS1643 (45 mg/kg/hr) completely suppressed arrhythmic activity and shortened the QT interval, whereas VCL had no effect (Fig A and B). NS1643 (35 mg/kg/hr) reduced the number of ectopic beats and episodes of ventri...
A situation where hepatocellular carcinoma (HCC) may be more common in women than men: Clinical and genetic patterns of non risk-factored HCC.
Authors: Imane Hassan El Dika, James J. Harding, Marinela Capanu, Michael F. Berger, Dafna Rebibo, Matthew Rusek, Joanne F. Chou, Eileen Mary O'Reilly, Leonard Saltz, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2017)

e15614 Background: Men are classically diagnosed with HCC three times more frequently than women. The gender difference persists after adjusting for confounding risk factors of viral hepatitis and alcoholic cirrhosis, presumably due to protective role of estrogens in women. In rare and unclear circumstances, HCC can arise in patients with no identified risk factor. Methods: Archival FFPE samples from patients with HCC and no underlying liver disease who consented to an IRB-approved protocol from 2014 onward were analyzed using the MSK-IMPACT platform, a hybridization capture based next generation sequencing assay for targeted deep sequencing of all exons and selected introns of &gt; 400 key cancer genes. Tumor and matched normal libraries were sequenced on an Illumina HiSeq 2500. Sequencing output was processed using a custom analysis pipeline. Demographic and treatment data was prospectively collected. Fisher’s exact tests were performed to look for associations between clinical characteristics and genetic alterations. Results: 16 patients were identified with 12 (75%) women affected versus 4 men only. Median age at diagnosis was 64 years. 5 (21%) patients had concomitant other malignancy, being melanoma, lymphoma, mesothelioma, rectal and prostate adenocarcinoma. 75% of patients underwent upfront surgery while only 12% presented with metastatic disease. Median number of genetic mutations was 4. Genetic sequencing did not reveal a specific molecular signature in this subgroup of patients; TERT and CTNNB1 were the most commonly mutated genes, found in 37% of cases. Median follow-up was 20 months and all patients were alive at last follow-up. Conclusions: In contrast to HCC in the general population, we found that HCC in the absence of risk factors is diagnosed more commonly in women than men in this small cohort. Patients in this cohort appear to live longer which can be attributed to normal underlying liver function or different disease biology. The pattern and number of genetic mutations reported herein are not different from those previously reported in risk-factored HCC. The study of a larger cohort of this non-previously defined non-risk factored HCC is warranted.
Are National Comprehensive Cancer Network (NCCN) Evidence Blocks (EB) Affordability Ratings (AR) representative of real-world costs? An evaluation of advanced non small cell lung cancer (aNSCLC).
Authors: Scott David Ramsey, Pei-Jung Lin, Yeun Mi Yim, William Bruce Wong, Ning Wu, Daniel Sheinson, Joshua T. Cohen
Journal: Journal of Clinical Oncology (2018)

6512 Background: The NCCN EB are designed to provide AR on the overall cost of drug treatments (tx), including medication, administration, supportive care, side effect management and hospitalization. This study characterized the relationship between real-world costs of aNSCLC tx and NCCN AR. Methods: We used the Truven MarketScan claims database to identify patients (pts) treated with aNSCLC tx evaluated by the NCCN EB from 2006-2011. We estimated mean per patient per month (PPPM) cost (including inpatient, outpatient, and pharmacy costs) for each regimen, adjusted for patient characteristics using generalized linear models with log-link gamma. Tx regimens were grouped into their respective NCCN EB AR. Weighted linear regression was used to examine the correlation between adjusted mean PPPM costs per regimen and NCCN AR. Results: The study identified 15,574 pts (mean age: 65 [SD = 11], 53% male). The mean PPPM cost per regimen ranged from $12,188 to $66,996 (mean $22,782, median $16,412). EGFR and ALK tx and generic chemotherapy had different AR despite having similar mean PPPM costs (EGFR/ALK: $13,665-$27,782, AR 2; chemo: $16,175-$28,195, AR 3-4). The mean PPPM costs per regimen by AR had low correlation (R2= -0.34) and was not statistically significant (p = 0.13). Pairwise comparisons show a significant difference in mean PPPM costs between AR 1 and other groups; there were no significant differences in mean PPPM costs among AR 2, 3, and 4. Conclusions: Real-world costs are often inconsistent with the NCCN AR. Given the intended use of NCCN EB to inform tx decisions and value discussions between providers and pts, our results suggest that the NCCN AR need to be further refined and validated. NCCN AR Mean PPPM (95% CI) Difference vs. AR = 2 Difference vs. AR = 3 Difference vs. AR = 4 AR 1: Very Expensive (n = 860) $40,084 ($31,123, $49,044) -$19,230* -$15,226* -$19,734* AR 2: Expensive (n = 2177) $20,854 ($17,755, $23,953) -- $4,003 -$505 AR 3: Moderately expensive (n = 3155) $24,857 ($21,349, $28,365) -- -- -$4,508 AR 4: Inexpensive (n = 9307) $20,349 ($18,517, $22,182) -- -- -- AR 5: Very inexpensive (n = 0) -- -- -- -- * p < 0.01
Impact of clostridium difficile infection on mortality among gastrointestinal (GI) and lung cancers.
Authors: Stuthi Perimbeti, Prateeth Pati, Sridevi Rajeeve, Qian Wang, Rishi Shrivastav, Karan Jatwani, Michael Rainone, Erika Correa, Mariola A. Vazquez Martinez, Vivek Modi, Kristine Marie Ward, Michael Styler, Neilanjan Nandi, Maneesh Rajiv Jain
Journal: Journal of Clinical Oncology (2018)

e18735 Background: Clostridium Difficile Infection (CDI) resulted in almost half a million cases, 83,000 re-infections and 29,000 deaths in 2011. Limited studies have shown increased incidence of CDI in patients with malignancies and autologous stem cell transplant. While solid organ malignancies such as of the lung and gastrointestinal tract are major causes of morbidity and mortality, there is a paucity of studies demonstrating the mortality due to CDI infections in these patients. Our study aims to examine the association of CDI and mortality in lung and gastrointestinal (GI) cancers Methods: Adult admissions with a primary diagnosis of esophageal, gastric, colorectal, lung cancers and secondary diagnosis of CDI were extracted from the NIS database using ICD-9 codes from 1999-2014 (N = 58090, weighted = 2860896). The sample was weighted to approximate the full inpatient population of the U.S. over the time period. Bivariate and multivariate analysis were performed using Chi square test and Cox proportional hazard respectively to estimate the in-hospital mortality percentage and hazard ratio of mortality among the above cancers with and without CDI. Results: Conclusions: Patients with gastric cancer have the highest mortality due to CDI which may be explained in part due to altered local and systemic immunity. Active research needs to be conducted to investigate and control the pathophysiological mechanisms of CDI of the GI tract since the trends of hospitalizations and mortality with CDI are continuing to rise each year. Due to the advent of many novel therapeutic agents, the survival rates of solid tumors have been consistently rising and controlling CDI may further improve quality of life and life expectancy. Table 1: Comparison of in-hospital mortality among GI cancers and lung cancer Cancer Without CDI With CDI P value Esophageal 11.36 19.17 0.0001 Gastric 8.86 12.37 0.0001 Colorectal 4.33 9.40 0.0001 Lung 12.55 22.55 0.0001 Table 2: Hazard ratio of Mortality in patients with CDI in comparison to patients without CDI Cancer HR of death with CDI (95% CI) P value Esophageal 1.43(1.05-1.92) 0.0001 Gastric 1.53(1.23-2.02) 0.0001 Colorectal 1.22(1.10-1.41) 0.0001 Lung 1.22(1.19-1.30) 0.0001