tbuckley/cabot-search huggingface dataset:
Trends in the receipt of guideline care and survival for women with ovarian cancer.
Authors: Joan Warren, Linda C Harlan, Edward Lloyd Trimble, Jennifer Stevens, Melvin Grimes, Kathleen A Cronin
Journal: Journal of Clinical Oncology (2017)

5540 Background: Guideline care has been found to improve survival for women with ovarian cancer, yet many women do not receive appropriate care. We assessed trends in the receipt of guideline care and 2-year cause-specific survival for women diagnosed with ovarian cancer. Methods: This retrospective cohort analysis used National Cancer Institute’s Patterns of Care studies data for women diagnosed with primary ovarian cancer in 2002 and 2011 (weighted n=6867). Data included patient characteristics, type of treatment, and provider characteristics. We used logistic regression to evaluate the association of year of diagnosis with receipt of guideline surgery, multiagent chemotherapy, or both. Two-year cause-specific survival, 2002-2013, was assessed using SEER data. Results: Forty-six percent of women received stage-appropriate surgery, unchanged from 2002 to 2011. The percent of women seeing a gynecologic oncologist (GO) 2002 to 2011 increased from 43% to 77%, 53.6% of women who saw a GO received stage-appropriate surgery. The percent of women with Stages IC-IV cancer who received both stage-appropriate surgery and multiagent chemotherapy increased significantly from 31% in 2002 to 38% in 2011. From 2002 to 2011, 2-year cause-specific ovarian cancer survival did not improve for Stages I/II cancers, with slight improvement for Stages III/IV cancers. Conclusions: There has been modest improvement in the receipt of guideline care for women with ovarian cancer, 2002-2011. However, current treatment falls far short of clinical recommendations and may explain limited improvement in 2-year cause-specific survival. There has been a marked increase in the percent of women consulting a GO and seeing a GO increased the chances of receiving guideline care. However many women who consulted a GO did not receive guideline care. There needs to be a better understanding of the decision-making process about treatment during the consultation with GOs and other factors precluding receipt of guideline care.
Efficacy of up-front hematopoietic cell transplantation in peripheral t-cell lymphoma, not otherwise specified (PTCL-NOS): A National Cancer Database analysis.
Authors: Bhagirathbhai R. Dholaria, Ambuj Kumar, Ernesto Ayala, Michale Jain, Lubomir Sokol, Julio C. Chavez, Mohammad Hussaini, Mohamed A. Kharfan-Dabaja, Taiga Nishihori
Journal: Journal of Clinical Oncology (2018)

7578 Background: Peripheral T cell lymphoma-not otherwise specified (PTCL NOS) is the most common subtype of mature T cell lymphoma in the Western World with inferior survival compared to the B-cell lymphomas. Herein, we studied the impact of up-front hematopoietic cell transplantation (HCT) on PTCL-NOS survival outcomes. Methods: The National Cancer Database (NCDB) with PTCL-NOS incident cases from 2004-2015 was used. We compared the outcomes of patients receiving chemotherapy only versus chemotherapy coupled with a consolidative autologous (auto) or an allogeneic (allo) HCT. Those without any form of chemotherapy treatment (n = 1823) were excluded from the analysis. Results: A total of 5252 PTCL-NOS patients were identified; 4812 received chemotherapy only and 440 received chemotherapy and a HCT (auto-HCT = 410; allo-HCT = 30). HCT recipients were more likely to be younger (median age, 55 vs. 63 years), had lower Charlson/Deyo co-morbidity score, of the white race, had a higher median household income, be treated at an academic facility and had private insurance. IPI and Ann-Arbor stage distribution were not significantly different between the groups. The median overall survival (OS) for all patients, chemotherapy alone and chemotherapy + HCT was 17.2 months, 14.7 months and not reached, respectively.(p< 0.001) The 10-year OS was 15% and 52% for chemotherapy alone and chemotherapy + HCT group, respectively (p< 0.001). There was no significant difference in OS between auto-HCT and allo-HCT patients (p =0.93). After adjusting for baseline characteristics in Cox-regression model, HCT (Hazard ratio (HR) = 0.36, 95% confidence interval (CI): 0.20-0.65, p =0.001) was associated with improved OS. IPI-intermediate (HR = 1.9, 95% CI: 1.2-2.9, p =0.008) or IPI-high (HR = 3.5, 95% CI: 2.1-5.8, p< 0.001) were associated with poor OS. Conclusions: In this large US-based analysis, up-front HCT was an independent prognostic factor associated with improved OS of PTCL-NOS. Efforts to ensure early referral to transplant centers and education on the role of HCT to both our patients and hematologists to optimize the access to HCT are urgently needed.
Abstract 13695: Global Electrical Heterogeneity Risk Score Predicts Sudden Cardiac Death in the General Population
Authors: Larisa G Tereshchenko, Jonathan Waks, Colleen Sitlani, Elsayed Soliman, Muammar Kabir, Elyar Ghafoori, Charles Henrikson, Nona Sotoodehnia, Tor Biering-Sørensen, Sunil Agarwal, David Siscovick, Wendy Post, Scott Solomon, Alfred Buxton, Mark E Josephson
Journal: Circulation (2015)

Background: The majority of sudden cardiac deaths (SCDs) in the general population occur in asymptomatic individuals. Our goal was to develop and validate a SCD risk score for use in the general population. Methods: The prospective Atherosclerosis Risk in Communities (ARIC) study [n=15,366; age 45-64 yr; 45% male; 73% white; 5% prevalent coronary heart disease (CHD), median 14 yrs of follow-up] was used for risk score development. ECG markers of global electrical heterogeneity (GEH) [sum absolute QRST integral (SAI QRST), spatial ventricular gradient (SVG), and spatial QRS-T angle] were measured on standard 12-lead ECGs and abnormal values were derived using the Youden index. Competing risk models were evaluated using C-statistics, integrated discrimination improvement, net reclassification improvement (NRI), and Akaike Information Criterion. Internal cross-validation was performed in 5 partitions. Adjudicated SCD was the primary outcome. Results: Overall SCD incidence was 1.51 (95% CI 1.35-1.69) per 1,000 person-yrs. The most accurate risk model included gender-, race-, and CHD-specific GEH ECG parameters [SAI QRST, spatial QRS-T angle, and SVG direction (azimuth and elevation)], demographics (sex, race, age≥55 y), clinical characteristics (CHD, diabetes, hypertension, stroke), QTc interval, and 1 interaction term (abnormal SVG azimuth in age≥55 yrs). C-statistic was 0.842 (95% CI 0.814-0.859) in the whole cohort and ranged 0.782-0.866 in 5 cross-validation partitions. The risk score classified 10-yr SCD risk as low (0 to &lt;1%), intermediate (1-10%), and high (&gt;10%) in 65.5%, 32.3%, and 2.2% of participants, respectively. With addition of GEH ECG markers to clinical/demographic factors C-statistic increased from 0.813 to 0.837 (p=0.004), 28/311 (9%) of participants were appropriately reclassified from intermediate to high risk, and only 4/311 (1.3%) were inappropriately reclassified from high to intermediate risk. NRI was 13.3% (P&lt;0.001). The score was highly specific (98.2%) for SCD, and predicted SCD better than non-sudden cardiac death. Negative predictive value for SCD was up to 99.5%. Conclusion A risk score using basic clinical characteristics and novel GEH ECG parameters accurately predicted SCD in the general population.
Primary tumor sidedness associates with prognosis of patients with brain metastases of colorectal cancer.
Authors: Anna Sophie Berghoff, Pedro Ferreira, Hanna Plazer, Georg Widhalm, Peter Birner, Rupert Bartsch, Gerald W. Prager, Christoph Zielinski, Matthias Preusser
Journal: Journal of Clinical Oncology (2017)

3562 Background: Brian metastases (BM) are a rare but devastating complication of colorectal cancer. We aimed to analyse prognostic factors in patients suffering from colorectal cancer (CRC) BM. Methods: Patients with histological proven CRC and BM were identified from the brain metastasis database of the Comprehensive Cancer Center Vienna. Clinical characteristics including established prognostic factors were retrieved by chart review. Established clinical prognostic scores for BM patients including the graded prognostic assessment (GPA) and the GPA for gastrointestinal tumours (GI-GPA) were calculated based on clinical characteristics as previously published. Results: 215 (male: 125/215 (58.1%); female 90/215 (41.9%)) patients with CRC BM were available for this study. The following established clinical prognostic factors showed a significant association with median overall survival (OS) times from BM diagnosis: number of brain metastases (n = 1: 6 months; n = 2-3: 4 months; n &gt; 3: 3 months; p = 0.001), age at BM diagnosis ( &lt; 65 years: 6 months; &gt; 65 years: 4 months; p = 0.047), extracranial disease (present: 4 months; absent: 8 months; p = 0.002) and Karfnofsky performance score (KPS &lt; 70%: 3 months; KPS &gt; 70%: 5 months; p = 0.002), graded prognostic assessment (GPA) class (class I: 15 months; class II: 13 months; class III: 4 months; class IV: 4 months) and the gastro-intestinal disease-specific GI-GPA (class I: 11 months; class II: 6 months; class III: 6 months; class IV: 3 months; p &lt; 0.001). In addition, the location of the primary tumour in the left colon (n = 176 (81.9%); 5 months) was associated with significantly longer median overall survival times from diagnosis of BM than primary tumour location in the right colon (n = 39 (18.1%); 3 months; p = 0.010). Primary tumor sidedness (HR 0.577; 95% CI 0.397-0.841; p = 0.004) remained a strong prognostic factor at multivariate analysis independently of GI-GPA (HR 0.718; 95% CI 0.612-0.842). Conclusions: Primary tumor sidedness is an independent prognostic factor in patients with CRC BM and should be included in disease-specific prognostic scores.
Phase I/II study of nab-paclitaxel (<i>nab</i>-P) with cisplatin (C) and thoracic radiation (TRT) in patients with locally advanced NSCLC: Safety results of phase I part.
Authors: Hidetoshi Hayashi, Masakazu Ogura, Takashi Niwa, Satoshi Ikeo, Takashi Yokoi, Yoshitaro Torii, Kunio Okamoto, Yosuke Tamura, Kaoru Tanaka, Yasuhito Fujisaka, Isao Goto, Hiroyasu Kaneda, Takayasu Kurata, Hiroshige Yoshioka, Kazuhiko Nakagawa
Journal: Journal of Clinical Oncology (2016)

e20042 Background: Concurrent platinum-based chemotherapy with thoracic radiation therapy (TRT) is well established with standard therapy in locally advanced NSCLC pts. Nanoparticle albumin-bound paclitaxel (nab-P) is a cremophor-free formulation of paclitaxel designed to improve intra-tumor delivery. This phase I/II trial evaluates the safety and efficacy combination of nab-P + C + TRT in pts with unresectable stage III NSCLC. Methods: In phase I part, pts with inoperable Stage IIIA or IIIB NSCLC, PS 0-1, and aged < 75 years entered escalating dose cohorts in a modified 3+3 design of nab-P weekly, beginning at 50 mg/m2 and increasing by 10 mg/m2 increments, in combination with C (75mg/m2) tri-weekly for 6 weeks and concurrent RT 60 Gy/30 fractions. Pts optionally received 2 cycles of consolidation therapy with full dose nab-P (100 mg/m2 weekly for 3 weeks) and C (75mg/m2 on day 1) every 21d. The DLT period is defined as the concurrent chemoradiation period. Primary endpoint for phase I part is determination of the recommended dose (RD) of nab-P in concurrent phase. Results: Twelve pts were treated at 3 dose levels (3 pts for 50mg/m2 and 60mg/m2, 6 for 70 mg/m2). One patient experienced DLT (Grade 3 esophagitis) at 70mg/m2 dose of nab-P. During concurrent treatment, a total of 5 patients experienced the esophagitis of grade 2, which was the most frequent adverse event. As the other toxicities were also generally mild, as shown in table. No grade 4 toxicities and deaths were observed. After concurrent period, grade 2 or 3 radiation pneumonitis was observed in 2 and 1 pts, respectively. All pts were evaluable for response with 1 CR, 10 PR and 1 SD. Conclusions: The RD of weekly nab-P was determined to be 70mg/m2. A Phase II study to further evaluate this regimen is underway. Clinical trial information: 000012531.Adverse event during concur rent CRT Nab-PTX 50 mg/ m2 (n = 3) Nab-PTX 60 mg/ m2 (n = 3) Nab-PTX 70 mg/m2 (n = 6) Grade1/2 Grade3 Grade1/2 Grade3 Grade1/2 Grade3 Leukopenia 2 1 2 1 5 1 Neutropenia 2 1 3 5 Thrombocytopenia 1 Anemia 2 2 2 Nausea 1 1 5 Vomiting 1 Anorexia 1 1 5 Fatigue 2 1 2 Creatinine increase 1 Sensory neuropathy 1 Esophagitis 2 1 5 1 Dermatitis 2 3 1 Pneumonitis (including after concurrent period) 2 1 1 2
The prognostic impact of plasma methylated HOXA9 in patients with advanced non-small cell lung cancer.
Authors: Sara Witting Christensen, Torben Hansen, Christa Haugaard Nyhus, Henrik Hager, Ole Hilberg, Rikke Fredslund Andersen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2018)

e24063 Background: The Homeobox A9 (HOXA9) gene encodes transcription factors, and methylation of this gene has been proposed as a diagnostic biomarker in lung cancer. The aim of the present study was to investigate the prognostic impact of HOXA9 methylation in patients with advanced non-small cell lung cancer (NSCLC). Methods: Patients with advanced NSCLC were treated with first-line standard therapy. Blood was drawn at baseline and progression. Plasma was stored at -80° C until analyses. DNA was extracted and following bisulfite conversion HOXA9 was analysed by methylation specific PCR. The percentage of methylated HOXA9 was assessed both as a categorical and a numeric variable. Progression free survival (PFS) and overall survival (OS) calculated from start of treatment were end-points. Results: A total of 279 patients were included. HOXA9 methylation increased during treatment in 57% of the patients. The median HOXA9 methylation percentage at baseline was 1.95 (95% confidence interval (CI) 1.30-2.90) and at progression 2.50 (95% CI 1.41-3.20), p = 0.061. HOXA9 methylation was detected in 79% of the patients at baseline. Median PFS for this group was 4.8 months (95% CI 3.8-5.4) compared to 6.1 months (95% CI 5.5-7.2) for patients without HOXA9 methylation, p = 0.0004. Accordingly, median OS was 7.9 months (95% CI 7.1-8.7) and 17.2 months (95% CI 9.7-20.2), p = 0.0012, respectively. Simple Cox regression analyses (numeric variable) demonstrated a prognostic impact of HOXA9 methylation on PFS, hazard ratio (HR) 1.0149 (95% CI 1.0050-1.0249), p = 0.0031, and OS, HR 1.0194 (95% CI 1.0096-1.0292), p = 0.0001, respectively. Multiple Cox regression analysis confirmed an independent prognostic impact of HOXA9 methylation on OS, HR 1.0143 (95% CI 1.0024-1.0264), p = 0.0189. Conclusions: Baseline HOXA9 methylation may serve as a valuable prognostic marker in patients with advanced NSCLC. Everyday application calls for further clinical trials.
Outbreak of multiple strains of non-O157 Shiga toxin-producing and enteropathogenic Escherichia coli associated with rocket salad, Finland, autumn 2016
Authors: Sohvi Kinnula, Kaisa Hemminki, Hannele Kotilainen, Eeva Ruotsalainen, Eveliina Tarkka, Saara Salmenlinna, Saija Hallanvuo, Elina Leinonen, Ollgren Jukka, Ruska Rimhanen-Finne
Journal: Eurosurveillance (2018)

In August 2016, an outbreak of Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) with 237 cases occurred in the Helsinki metropolitan area, Finland. Gastroenteritis cases were reported at 11 events served by one catering company. Microbiological and epidemiological investigations suggested rocket salad as the cause of the outbreak.H11 and EPEC O111:H8 strains isolated from food samples containing rocket were identical to the patient isolates. In this outbreak, the reported symptoms were milder than considered before for STEC infection, and the guidelines for STEC control measures need to be updated based on the severity of the illness. Based on our experience in this outbreak, national surveillance criteria for STEC have been updated to meet the practice in reporting laboratories covering both PCR-positive and culture-confirmed findings. We suggest that EPEC could be added to the national surveillance since diagnostics for EPEC are routinely done in clinical laboratories.
A clinical study to evaluate the efficacy and safety of docetaxel with ribavirin in patients with progressive castration resistant prostate cancer who have previously received docetaxel alone.
Authors: Takeo Kosaka, Takahiro Maeda, Toshiaki Shinojima, Hirohiko Nagata, Ryuichi Mizuno, Mototsugu Oya
Journal: Journal of Clinical Oncology (2017)

e14010 Background: We have previously reported a novel cell reprogramming approach, named drug efficacy reprogramming, as a new model for identifying candidate antitumor drugs targeting cancer stemness related gene network and identified ribavirin as a candidate drug for overcoming docertaxel resistant castration resistant prostate cancer.This non-randamized and open-labelled pilot clinical study explored the safety and efficacy of ribavirin, anti-virus drug, in combination with docetaxel in patients with progressive CRPC. Methods: In this clinical study, patients received intravenous docetaxel 60-70 mg/mm2 on day 1 of 3-6 weeks cycles plus Ribavirin 600 mg twice daily. The primary endopoint was safety, PSA response and objective response rate. Secondary end ponts included health-related quality of life overall survival.Patients with progressive CRPC based on PSA and/or radiographic criteria, PS 0-1, normal renal and hepatic function were eligible. Results:Five patients were enrolled in this study. Medium age was 73. Median serum PSA concentration was 53.1 ng/ml (range: 5.1-370.5).The median cycle and total dose of docetaxel received before the study was 31 cycles and 3625 mg, respectively. 80% of patients who had disease progression during docetaxel treatment. The median time from last docetaxel dose to disease progression before the participation was 1.5 months.Safety: Medium number of treatment cycles were 7 (range: 3-8) cycles. Grade 3/4 adverse events requiring dose modification were not observed. Grade 3 anemia and neutropenia were seen in two patients. Common adverse events were less than Grade 2. Efiicacy: 3 (60%) had some degree of PSA decline and 2 (40%) had a decline of ≧30 %. Median follow-up was 10.0 month. Median progression free survival was 6 month. Conclusions: This combination was well tolerated with promising response rate, justifying further investigation in docetaxel resistant CRPC. Clinical trial information: UMIN000012521.
The relationship between metastatic sites and progression free survival of nivolumab in non-small cell lung cancer patients.
Authors: Motohiro Tamiya, Akihiro Tamiya, Hidekazu Suzuki, Takako Inoue, Yoshihiko Taniguchi, Kenji Nakahama, Takayuki Shiroyama, Shun-ichi Isa, Kazumi Nishino, Norio Okamoto, Toru Kumagai, Tomonori Hirashima, Shinji Atagi, Fumio Imamura
Journal: Journal of Clinical Oncology (2017)

e20679 Background: Nivolumab (Nivo) is applicable for all metastatic or unresectable non-small cell lung cancer (NSCLC), however only some patients benefit from it. Therefore, identifying biomarkers predicting efficacy is a crucial topic in the “real world’’ setting. We conducted a retrospective study to analyze the impact of metastatic status on the effect of Nivo in NSCLC patients. Methods: This is a retrospective multicenter study conducted by the three medical centers in Japan. All patients treated with Nivo from January 2016 to July 2016 in these centers were retrospectively reviewed. We collected clinical data including age, sex, smoking history, performance status (PS), and metastatic cites (lymph nodes: lym, liver, brain, bone, pleural effusion, and intrapulmonary metastasis: lung) at the time of starting Nivo treatment. We investigated relationship between metastatic sites and progression free survival (PFS) of Nivo. Patients were followed-up until 30 th September 2016. Results: Two hundred and one patients treated with Nivo were enrolled. At the time of administration of Nivo, median age was 68 years old, 137 patients were male, 155 patients had history of smoking status, 152 patients were PS 0 or 1, and 46 patients had squamous cell carcinoma (SQ). For all participants, median PFS was 2.5 months. In univariate analysis, female (hazard ratio (HR): 1.43, 95% confidence interval (CI): 1.02-2.00; p = 0.036), never-smoker (HR: 1.51 , 95% CI: 1.05 – 2.17; p = 0. 0262), PS 2 or more (HR: 1.68, 95% CI: 1.17-2.41; p = 0.0045), metastasis to liver (HR: 2.02, 95% CI: 1.30-3.15; p = 0.0015), brain (HR: 1.42, 95% CI: 0.99-2.03; p = 0.0574), bone (HR: 1.42, 95% CI: 1.01-1.98; p = 0.0642), lung (HR: 1.57, 95% CI: 1.13-2.20; p = 0.0076), and malignant pleural effusion (HR: 1.47, 95% CI: 1.06-2.04; p = 0.0195) had significantly correlated with poor PFS. In multivariate analysis, liver metastasis (HR: 1.59, 95% CI: 0.97-2.61; p = 0.0642) and malignant pleural effusion (HR: 1.47, 95%CI: 1.04–2.07; p = 0.0294) had significantly correlated with poor PFS. Conclusions: Liver metastasis and malignant pleural effusion were independent poor prognostic factors of Nivo treatment in NSCLC patients. (UMIN-ID: UMIN000025908)
In vivo localization of miR-34 delivered via liposomal MRX34: chromogenic in situ hybridization (CISH) results in a preclinical model and liver biopsies from phase I patients.
Authors: Desiree' Martin, Kevin Kelnar, Andreas G. Bader
Journal: Journal of Clinical Oncology (2016)

e14074 Background: Each microRNA (miRNA) modulates the expression of hundreds of genes across distinct cellular pathways. This broad activity gives miRNA-based therapy the potential to simultaneously repress multiple oncogenic processes in the tumor microenvironment, including growth and proliferation, resistance, cancer stem cells, metastasis, and immune evasion. The naturally occurring tumor suppressor miR-34a has been shown to down-regulate expression of > 30 oncogenes (eg, MET, MEK1, PDGFR-α, CDK4/6, BCL2, WNT 1/3, NOTCH1, CD44), as well as genes involved in tumor immune evasion (eg, PD-L1, DGKζ). MRX34, a liposome-encapsulated miR-34a mimic, is a potential first-in-class miRNA therapy for cancer. Methods: We developed a CISH staining method to visualize cellular and sub-cellular localization of miR-34a following MRX34 treatment. Tissue concentrations of miR-34a were determined on corresponding tissue slides using micro-dissection, extraction-free RNA isolation, and qRT-PCR. The combined protocol was applied to tissues (tumor, normal liver, bone marrow) extracted post-treatment with MRX34 or dilution buffer control from an orthotopic (Huh-7) mouse HCC model (n = 3 each treatment and control per dose level). Pre- and post-treatment liver biopsies from patients (n = 4) with advanced HCC who received IV infusions of MRX34 in the MRX34-101 phase I trial (NCT01829971) were subjected to CISH only (due to limited available tissue). Results: In the orthotopic mouse HCC model (Huh-7), miR-34a levels in tumor, normal liver, and bone marrow increased by > 2 orders of magnitude as early as 2 min after tail vein injection of MRX34, with localization to the cellular cytoplasm. CISH showed similarly increased miR-34a in tumor and normal liver in the post-treatment biopsies from phase I HCC patients receiving MRX34 infusions, also localized to the cellular cytoplasm. Conclusions: Our results demonstrate MRX34-mediated delivery of miR-34a to tumor and normal tissue, both in a preclinical model of HCC and in liver biopsies from patients with advanced HCC treated systemically with MRX34 in a first-in-human trial of miRNA cancer therapy.