tbuckley/cabot-search huggingface dataset:
Body composition among adult survivors of pediatric abdominal and pelvic tumors in the St. Jude Lifetime Cohort.
Authors: Carmen Louise Wilson, Wassim Chemaitilly, Wei Liu, Melissa M. Hudson, Deokumar Srivastava, Leslie L. Robison, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2016)

10574 Background: In the general population, adverse changes in body composition are associated with reduced physical function, metabolic impairment and mortality. However, little is known about changes in body composition among adult survivors of non-hematological malignancies diagnosed in childhood. Methods: Participants included 347 long-term survivors with a history of abdominal or pelvic tumors. Using dual X-ray absorptiometry, relative lean mass (LM) was calculated by dividing lean mass by height (m2) and calculating race- age- and sex-standardized z-scores using data from NHANES. Multiple linear regression, stratified by sex, was used to evaluate associations between treatment (abdominal/pelvic radiation, alkylators, anthracyclines), lifestyle factors (smoking, activity levels and daily caloric consumption) and LM. Results: The median age at follow-up was 29.6 (range: 18.7-55.1) years and median time from diagnosis was 24.2 (range: 10.7-50.0) years. Forty-four percent of participants had received abdominal/pelvic radiation. Fifty-eight percent and 51% of male and female survivors had a BMI ≥ 25 kg/m2, respectively. For survivors with BMI ≥ 25 kg/m2, LM did not differ significantly from normative data in males (z-score = 0.06 [±0.76], p = 0.462) and was increased relative to normative data in females (z-score = 0.24 [±0.91], p = 0.01). Among survivors with a BMI < 25 kg/m2, mean LM was reduced among both males (z-score = -1.70 [±1.11], p < 0.001) and females (z-score = -1.64 [±1.02], p < 0.001). In multivariable analyses, males survivors who were exposed to abdominal/pelvic radiation (Estimate = -1.10, standard error [SE] = 0.23, p < 0.001) or who smoked (Estimate = -0.53, SE = 0.23, p = 0.020) had an increased risk of low LM when compared to males not exposed to radiation or non-smokers. Only exposure to abdominal/pelvic radiation was associated with an increased risk of low LM among females (Estimate = -0.76, SE = 0.24, p = 0.002). Conclusions: Survivors with BMI < 25 kg/m2 have low LM compared to US normative data. Further studies are required to understand the impact of low LM on metabolic profile and physical function among survivors of pediatric solid tumors.
Predictive factors for prolonged response to olaparib as maintenance therapy in ovarian cancer patients with <i>BRCA</i> mutations.
Authors: Sana Intidhar Labidi-Galy, Thibault De La Motte Rouge, Olfa Derbel, Elsa Kalbacher, Anita Wolfer, Timothee Olivier, Ketty Hu, Olivier Tredan, Hemerson Guevara, Fernando Bazan, Victoire De Castelbajac, Jean-Damien Combes, Pauline Vaflard, Louise Crivelli, Valerie Bonadona, Valeria Viassolo, Lisa Golmard, Adrien Buisson, Manuel Rodrigues, Isabelle Laure Ray-Coquard
Journal: Journal of Clinical Oncology (2018)

5558 Background: To investigate clinical factors predictive for prolonged progression-free survival (PFS) in ovarian cancer (OC) patients carrying BRCA mutations and receiving olaparib as a maintenance therapy. Methods: Multicentric (7 cancer centers) international (France and Switzerland) retrospective study of OC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. Results: One hundred and fifteen patients were included. Median age was 60 years. There were 92 BRCA1 carriers, 22 BRCA2 carriers and one patient had double mutation of BRCA1 and BRCA2 genes. Ninety-two percent had serous carcinomas. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Median follow-up was 9.8 months. Ninety percent of the patients were platinum-sensitive: 24% had platinum-free interval (PFI) at 6-12 months and 65% had PFI > 12 months. Responses to platinum-based chemotherapy before olaparib as maintenance therapy were: SD (15.7%), PR (52.2%) and CR (32.2%). In multivariate analysis, factors predictive for prolonged PFS under olaparib were: CR (HR = 0.13; 95%CI 0.06-0.28; p< 10-3), PFI > 12 months (HR = 0.43; 95%CI 0.26-0.73; p= 0.002) and BRCA2 mutations (HR = 0.42; 95%CI 0.24-0.94; p= 0.033). Conclusions: Complete response to platinum before olaparib, PFI > 12 months, and BRCA2 mutations are predictive for prolonged PFS in BRCA carriers who received olaparib as maintenance therapy.
Clinical relevance of c-MET overexpression in patients with residual rectal cancer after preoperative chemoradiotherapy.
Authors: Byung Woog Kang, An Na Seo, Keun Hur, Young Hun Choi, Eun Hye Lee, Jong Gwang Kim, Yee Soo Chae, Soo Jung Lee
Journal: Journal of Clinical Oncology (2016)

e15106 Background: This study was designed to explore the clinical and prognostic impact of c-MET expression in residual disease after preoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: Thesurgical specimens of 145 patients with residual rectal cancer after preoperative CRT, between January 2006 and January 2011 at the Kyungpook National University Hospital, were analyzed. To assess c-MET expression, immunohistochemistry was carried out on whole section tissues. KRAS exon 2 (codon 12 and 13) and BRAF V600E mutational status, and microsatellite instability (MSI) were determined using polymerase chain reactions. Results: Of the eligible 135 patients, c-MET over-expression was observed in 59.3% (n = 80), and was associated with lower T category (p = 0.041), circumferential resection margin (CRM) negativity (p = 0.006), and absence of perineural invasion (p = 0.045). However, c-MET over-expression had no correlation with KRAS and BRAF mutation status, or with MSI status (all p > 0.05). In univariate analysis, c-MET over-expression was significantly associated with favorable rectal cancer-specific survival (RCSS) (p = 0.045) and disease-free survival (DFS) (p = 0.021). Notably, Multivariate analysis revealed that c-MET over-expression was independently associated with favorable DFS (p = 0.025, hazard ratio = 2.189, 95% confidence interval = 1.102-4.347). Conclusions: c-MET over-expressionin residual rectal cancer after preoperative CRT had favorable prognostic influence. Although further studies were needed to validate our results, our data might aid in understanding the approaches for anti-MET therapy in patients with residual rectal cancer after preoperative CRT.
A study of thymidylate synthase gene expression as a biomarker for the treatment of esophageal adenocarcinoma.
Authors: Staci Beamer, Zoran Gatalica, Joanne Xiu, Dawn E. Jaroszewski, Melissa Stanton, Rish Pai, Murli Krishna, Mathew Thomas, Helen J. Ross, Thai Huu Ho
Journal: Journal of Clinical Oncology (2017)

e15563 Background: Expression of thymidylate synthase (TS), a target of fluoropyrimidine-based (5-FU) chemotherapy, has prognostic value in colorectal adenocarcinoma. Its value as a biomarker in treatment of esophageal adenocarcinoma (EAC) is unknown. With widespread adoption of CROSS trial protocol for treatment of EAC, 5-FU is frequently omitted from regimens. We retrospectively analyzed the association between TS protein expression and clinical outcomes in EAC. Methods: TS expression levels were measured by immunohistochemistry in formalin-fixed paraffin-embedded specimens from 35 primary EAC patients from 2 institutions (range 5/2006-1/2016); at time of diagnosis and surgical resection (33 neoadjuvant chemoradiation and 2 surgery alone). TS expression higher than 1+, 5% was read as positive. Mean follow up was 1323 days (range 263-3677). TS expression correlated with treatment response and survival in patients treated with and without 5-FU therapy (log-rank test, Kaplan-Meier method). Results: In the cohort of 35 patients, 21 patients (60%) had pretreatment positive TS expression. Overall survival (OS) for TS negative patients was 1216 days versus 974 days for TS positive (p = 0.15). In the 23 patients treated with 5-FU, TS-negative patients had a trend towards longer overall survival compared to TS-positive patients, mean OS (1272 days versus 743 days, p = 0.08). In the group of 12 patients not treated with 5-FU, 2 patients showed negative TS staining. Neoadjuvant chemoradiation was performed in 33/35 patients. Downstaging was observed in 69% (9/13) of patients with negative pre-treatment TS levels versus 55% (11/20) in pre-treatment TS positive patients (p = 0.48). In 23 patients treated with 5FU, 9/12 (75%) were downstaged in the TS-negative cohort versus 6/11 (45%) in the TS-positive cohort (p = 0.21). In the 5FU treatment group, complete response was seen in 2 patients with negative TS staining. Conclusions: Low TS expression in EAC patients trended towards improved survival and tumor downstaging, particularly in patients treated with neoadjuvant 5-FU and platinum based therapy. Prospective data and greater patient numbers may be necessary to demonstrate statistical significance.
Frequent germline <i>BRCA1/2</i> mutations in women with ovarian cancer and the need for insurance coverage of genetic testing: A Hellenic Society of Medical Oncology (HeSMO) national program.
Authors: Georgios Lypas, Zacharenia Saridaki, Emmanouil S. Saloustros, Michael Liontos, Evangelos Bournakis, Christos Papandreou, Evangelos Lianos, Haralabos Kalofonos, Elena Maragouli, Gerasimos Aravantinos, Nikolaos Xenidis, Charalampos Andreadis, Eleni Stergiou, Alexandros Bokas, Cedric Gouedard, George Nasioulas, Fotini Papageorgiou, Athanasios Athanasiadis, Ioannis Varthalitis, Ioannis Boukovinas
Journal: Journal of Clinical Oncology (2018)

e13525 Background: Most international scientific organizations and guidelines recommend genetic counseling and testing for women with epithelial ovarian cancer. Identification of BRCA1/2 mutation carriers provides important information, guiding treatment decisions for patients, and prevention/risk reduction strategies for their families. Genetic testing is not reimbursed by the state health insurance provider in Greece. Methods: Patient enrollment required: a) histopathological diagnosis of non-mucinous, high grade ovarian, salpingeal & primary peritoneal cancer at any age & b) diagnosis or 1st relapse date, not earlier than July 2014. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large rearrangements & deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA). The project was industry supported. Results: From March 2015 to January 2018, 708 patients were enrolled and tested. One hundred and forty seven (20.7%) mutation carriers were identified, 102 (14.4%) in BRCA1 and 45 (6.3%) in BRCA2 gene. BRCA1 mutation carriers were significantly younger at diagnosis (median age 49 years; range: 37-77), compared to BRCA2 carriers (58; range:38-80) & sporadic cases (59; range:22-88). Twenty three mutation carriers (15.8%) reported a negative family history for cancers associated with the BRCA1/2 hereditary cancer syndrome. Variants of uncertain significance (class 3) were detected in 38 patients (5.3%). Conclusions: Recommendation for genetic testing for all women with ovarian cancer is further supported through the findings of this study, and is incorporated in the National Guidelines, issued by HeSMO. Testing reimbursement from the national health care insurance provider is actively pursued, as it will provide a unique opportunity for patients and their families to receive important treatment and risk reduction information.
Utilization of a web-based supportive oncology training curriculum for healthcare professionals (HCPs).
Authors: Shelly S. Lo, Betty Roggenkamp, Kristin Hasson, Julia Rachel Trosman, Carol A. Rosenberg, Teresa Lillis, Eileen Knightly, Mary Pasquinelli, Lauren Allison Wiebe, James Gerhart, Frank J. Penedo, Joanna Martin, Patricia A. Robinson, Amy Scheu, Rosa Berardi, Christine B. Weldon
Journal: Journal of Clinical Oncology (2018)

59 Background: A challenge in supportive oncology is training the HCP workforce. The Coleman Supportive Oncology Collaborative clinicians (faculty) from 25 institutions (academic, community &amp; safety net) developed a unique and easily accessible supportive oncology training curriculum (Trosman JR JNCCN 2017). Methods: Using data provided by The National Comprehensive Cancer Network (NCCN) Continuing Education team, we evaluated completion rates of survivorship and supportive oncology education courses using simple frequencies. Results: Over 4748 on-line courses were completed (pretest, course, post-test, evaluation) of 7184 accessed. Of 4748 courses, nurses completed 45%, physicians 17%, advance practice clinicians 16%, and others 22% (social workers, chaplains, MAs). Course completion improved from 65% to 69% after articles describing collaborative work were published in Cure and Oncology Nursing News, p = 0.0014. Conclusions: A variety of HCPs successfully completed supportive oncology guideline education via the NCCN’s education portal. These on-line courses are an efficient way to train HCPs in supportive oncology. Curriculum advertising improves course completion.[Table: see text]
Abstract P199: Alcohol Consumption Modified the Effect of Leptin on Blood Lipids: A Mendelian Randomization Study
Authors: Luqi Shen, Jose Cordero, Jia-Sheng Wang, Ye Shen, Changwei Li
Journal: Circulation (2018)

Objective: The current study aimed to evaluate the relation between leptin and serum lipids, and to explore whether alcohol consumption modifies the effect of leptin on lipids. Method: We conducted a Mendelian randomization analysis to the baseline data for 3,780 participants of the Framingham Heart Study Generation III cohort. A genetic risk score (GRS) for leptin was generated by summing leptin increasing alleles of 3 single-nucleotide polymorphisms, weighted by their corresponding effect sizes on leptin reported by Kilpelainen et al. For those taking lipid lowering medications, total cholesterol (TC) was adjusted as TC/0.8, and low density lipoprotein (LDL) was imputed by replacing the adjusted TC into the Friedewald equation. Leptin and triglycerides (TG) were log transformed. Associations between the GRS and leptin, leptin and imputed lipids, and GRS and imputed lipids were assessed, respectively, by multivariate linear regression models, controlling for age and sex in basic model and additionally controlling for education, smoking, drinking, and physical activity in the fully adjusted model. Interactions between the GRS and alcohol drinking was evaluated by adding an interaction term, GRS*drinking, in the fully adjusted model. Sensitivity analyses were performed among those not taking lipid or glucose lowering medications. Result: In univariate analyses, the GRS was significantly associated with leptin (Beta=1.44, P =4.55E-4), but not with age ( P =0.33), sex ( P =0.62), education ( P =0.37), smoking ( P =0.59), drinking ( P =0.42), or physical activity ( P =0.80). Leptin was significantly associated with age and sex adjusted LDL (Beta=7.29, P =5.95E-38), high density lipoprotein (HDL) (Beta=-4.30, P =4.35E-62), TG (Beta=0.22, P =1.05E-119), and TC (Beta=8.06, P =1.72E-36). The GRS for leptin was associated with HDL (Beta=-16.72, P =0.01), but not LDL (Beta=2.64, P =0.85), TG (Beta=-0.35, P =0.16), or TC (Beta=-23.34, P =0.15), in partially adjusted model. In the fully adjusted model, association between the GRS and HDL was still significant (Beta=-16.70, P =0.01). When stratified by drinking status, the GRS for leptin was significantly associated with reduced LDL (Beta=-99.26, P =0.02), TG (Beta=-2.4, P =0.002), and TC (Beta=-156.10, P =0.001) among non-current drinkers, and reduced HDL (Beta=-19.98, P =0.005) among current drinkers, adjusting for age and sex. After further adjustment, these associations were still significant. In the fully adjusted model, significant interactions between the GRS and alcohol drinking were identified for LDL ( P =0.02), TG ( P =0.005), and TC ( P =0.008). Sensitivity analyses among those not taking lipid or glucose lowering medications revealed similar associations. Conclusion: Out study provided evidence for a causal relationship between leptin and lipids, and an interaction effect of alcohol drinking on leptin and lipids associations.
Primary tumor location and efficacy of second-line therapy after initial treatment with FOLFIRI in combination with cetuximab or bevacizumab in patients with metastatic colorectal cancer- FIRE-3 (AIOKRK0306).
Authors: Dominik Paul Modest, Sebastian Stintzing, Ludwig Fischer von Weikersthal, Thomas Decker, Alexander Kiani, Ursula Vehling-Kaiser, Salah-Eddin Al-Batran, Tobias Heintges, Christoph Kahl, Gernot Seipelt, Frank Kullmann, Martina Stauch, Werner Scheithauer, Swantje Held, Clemens Giessen-Jung, Andreas Jung, Thomas Kirchner, Volker Heinemann
Journal: Journal of Clinical Oncology (2017)

3525 Background: FIRE3 compared 1 st -line therapy with FOLFIRI plus either cetuximab (arm A) or bevacizumab (arm B) in 592 patients (pts) with KRAS exon 2 wild-type metastatic colorectal cancer (mCRC). Second-line therapies appeared more successful in arm A compared to arm B. The impact of primary tumor location on this observation is unclear. Methods: Pts. were stratified for primary tumor site (left- vs. right-sided). Duration of 2 nd -line therapy was calculated as time from first to last application. Progression-free survival (PFS2nd) and overall survival (OS2nd) of second-line therapy) were evaluated by Kaplan-Meier method and compared by log rank test as well as Cox regression. All analyses were performed in the RAS wild-type population of the trial and reported according to drug sequences. Results: 272 of 400 pts. (68%) received 2 nd -line therapy, of those 206 (109 in arm A, 97 in arm B) pts. presented left-sided, whereas 66 (26 in arm A, 40 in arm B) pts. presented right-sided primaries. PFS2nd was markedly longer in pts. with left-sided as compared to right-sided primary tumors (6.0 (95% CI: 5.5-6.7) vs. 3.4 (95% CI: 3.0-5.8) months, hazard ratio (HR): 0.64 (95% CI: 0.47-0.87), P = 0.005). Differences in PFS2nd between study-arms were evident in pts. with left-sided primaries (arm A: 7.3 (95% CI: 6.4-7.7) vs. arm B: 5.3 (95% CI: 4.3-5.9) months, HR: 0.61 (95% CI: 0.44-0.84), P = 0.002), but not in pts. with right-sided primaries (arm A: 4.0 (95% CI: 3.0-6.3) vs. arm B: 3.3 (95% CI: 2.6-5.8) months, HR: 1.09 (95% CI: 0.62-1.90). Consistent observations were also made for treatment duration and OS2nd. Conclusions: This retrospective analysis indicates that treatment duration and efficacy of second-line therapy are associated with primary tumor location. Efficacy of second-line therapy was significantly greater in pts. with left-sided tumors as compared to right sided tumors. This difference was driven by superior activity of second-line regimens of arm A compared to arm B in left-sided tumors. Our observations confirm the strong prognostic value of primary tumor location in mCRC across treatment lines. Clinical trial information: NCT00433927.
A phase II, double-blind study of galunisertib+gemcitabine (GG) vs gemcitabine+placebo (GP) in patients (pts) with unresectable pancreatic cancer (PC).
Authors: Davide Melisi, Rocio Garcia-Carbonero, Teresa Macarulla, Denis Pezet, Gael Deplanque, Martin Fuchs, Jorg Trojan, Helmut Oettle, Mark Kozloff, Ann Cleverly, Ivelina Gueorguieva, Durisala Desaiah, Michael M. F. Lahn, Al Blunt, Karim A. Benhadji, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

4019 Background: In vivo preclinical models, transforming growth factor-beta (TGFβ) inhibitors enhanced gemcitabine activity. In this study, patients (pts) with Stage II to IV unresectable PC were treated with GG or GP to evaluate their efficacy and safety. Methods: Pts were randomized 2:1 (stratified for ECOG PS, disease stage and previous gemcitabine use) to GG or GP. Oral galunisertib 150 mg BID was given as intermittent dosing (14 days on/14 days off per cycle); gemcitabine was administered per label. The primary endpoint was overall survival (OS). Using a Bayesian augmented control (BAC) design assuming a hazard ratio (HR) of 0.7 for OS, the study had 90% power to identify if the probability of HR < 1 was > 0.85. Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), biomarkers and safety (CTCAE v4). Results: 156 pts were randomized to GG (N = 104) or GP (N = 52). Baseline characteristics were balanced between groups. HR based on BAC was 0.8 with 95% credible interval (0.60, 1.09) and PR (HR < 1) = 0.92, indicating a positive study. Efficacy data are summarized in the table. For the subgroup of pts with baseline TGFβ1 levels ≤ 4224 pg/mL (n = 117), median OS was 10.9 vs 7.2 months (GG vs GP) with unadjusted HR (95% CI) = 0.68 (0.44, 1.04), logrank p = 0.076). The most frequent CTC grade 3/4 adverse events possibly related to study treatment (GG vs GP) were anemia (7.8% vs 13.5%), neutropenia (32.0% vs 26.9%) and thrombocytopenia (7.8% vs 9.6%). 46% vs 43% of pts had > 50% decrease in CA19-9 and 43% vs 41% had > 50% decrease in TGFβ1 (GG vs GP). For both biomarkers a reduction in concentration correlates with improved OS. Conclusions: GG resulted in improvement of OS and PFS in pts with PC, with a manageable toxicity profile as compared to GP. TGFβ1 and CA19-9 reduction correlated with OS. Pts with lower levels of TGFβ1 may have greater benefit from treatment with galunisertib. Clinical trial information: NCT01373164. GG GP Median (95% CI) OS (months) 9.10 (7.43, 12.2) 7.59 (4.04, 9.92) HR (95% CI) OS 0.89 (0.61, 1.30) Median (95% CI) PFS (months) 3.65 (2.86, 5.39) 2.79 (1.81, 3.68) Unadjusted logrank p = 0.215 HR (95% CI) PFS 0.80 (0.55, 1.15) ORR (95% CI) (%) 8.7 (4.0, 15.8) 1.9 (0.1, 10.3) Fisher's exact P = 0.116
TCT-8 Fate of deferred lesions using state-of-art percutaneous coronary revascularization in patients with de novo three vessel disease: lesion level analysis at 2 years of the SYNTAX II study
Authors: Norihiro Kogame, Simon Walsh, Manel Sabate, Justin Davies, Maciej Lesiak, Raul Moreno, Ignacio Cruz-Gonzalez, Nick West, Jan Piek, Yuki Katagiri, Taku Asano, Rodrigo Modolo, Ply Chichareon, Chun-Chin Chang, Carlos Collet, Javier Escaned, Adrian Banning, Yoshinobu Onuma, Patrick Serruys
Journal: Journal of the American College of Cardiology (2018)