tbuckley/cabot-search huggingface dataset:
Dissemination of breast cancer knowledge and expertise from NCI-CCC tumor boards with community oncologists.
Authors: Maitri Kalra, Meghan Sri Karuturi, Rachel Catherine Jankowitz, Kelly Elizabeth McCann, Mei Wei, Sarah Schellhorn Mougalian, Debu Tripathy, Adam Brufsky, Carlos Hernando Barcenas, Sara A. Hurvitz, Parvin F. Peddi, Norah Lynn Henry, Samir Housri, Nadine Housri
Journal: Journal of Clinical Oncology (2018)

e18575 Background: Tumor boards (TB) at National Cancer Institute Designated Comprehensive Cancer Centers (NCI-CCC) are an important source of multidisciplinary education and expert knowledge, however, this knowledge is not systematically documented and made accessible to oncologists in the community. Using an online oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at NCI-CCCs to provide educational benefit to the oncology community. Methods: We designed a process with oncologists at the MD Anderson, University of Pittsburgh, UCLA, University of Utah, and Yale Cancer Centers to document and share discussions from breast cancer TBs focused on areas of controversy and practice variation on theMednet.org, a social Q&A website of over 5,300 US oncologists. Faculty members translated TB discussions into concise non-case based Q&A on theMednet. Answers were peer reviewed by experts at other institutions, indexed and stored for easy search retrieval, and disseminated in a weekly email newsletter to registered medical oncologists. Engagement was measured in Q&A views and helpful and agree votes. Reach was measured by the number of unique oncologists viewing Q&A. Answers were analyzed for reference sources. Results: Between 12/2016 and 1/2018, 55 answers to 50 questions were posted from 5 NCI-CCCs and shared with 1,994 medical oncologists. Twenty-nine academic breast oncologists peer reviewed answers. Answers were viewed by 856 oncologists at 550 institutions in 49 states. This included 469 community practices. All questions were focused on topics not addressed by NCCN or ASCO guidelines or on controversy in guidelines. Forty-seven percent of answers cited published research and 62% cited clinical experience.The median time from research publication date to Q&A on theMednet was 10.5 months (range 0.1-96). Conclusions: Through an online Q&A platform, experts at NCI-CCCs document, peer-review, and disseminate clinical experience, new research, and important knowledge outside the walls of academic cancer centers to oncologists across the US. Access to up to date, expert knowledge can significantly impact patient care in community practices.
Efficacy of anti-CD19 chimeric antigen receptor modified T(CAR-T) cell therapy in Chinese patients with relapsed/refractory acute lymphocytic leukemia in a multicenter trial.
Authors: Lei Xiao, He Huang, Xiaojun Huang, Xiaoyan Ke, Yu Hu, Junmin Li, Qing Zhang, Yongxian Hu, Qian Jiang, Jiong Hu, Hongmei Jing, Xiaohong Zhang, Zhao Wu
Journal: Journal of Clinical Oncology (2017)

7028 Background: r/r B-ALL was reported as the most-threatening disease because of the low disease free survival even treatment with allogeneic hematopoietic stem cell transplantation. For overcoming conventional therapies limitation, autologous CD19CAR-T was performed in our clinical trials to induce remission in patients with r/r disease. 30 patients (from 7 clinical centers, in China) as volunteers with r/r B-ALL were treated by autologous CD19 CAR-T. Methods: 5 juveniles and 25 adults with r/r ALL received autologous CD19 targeted CAR-T, the doses between 1.03 × 10 6 CAR-T cells/kg and 10.09 × 10 6 CAR-T cells/kg. These 30 cases(from 7 clinical centers, in China) were treated with CAR-T cells from May. 8 2015 to January. 4 2017 (Table1). Patients were monitored for a response. Highly standardized CAR T cell preparation protocol and manageable CRS in most were kept for no significant difference in 7 clinical centers. Results: After treated with CAR-T, a total of 30 cases (5 juveniles and 25 adults coming from 7 clinical centers, in China) with r/r B-ALL were all detected the CAR-T cells proliferated in the blood and bone marrow. The results showed that complete remission (CR) is 26/30(86.67% ) between day7-14 after CD19 CART cell infusion, and 25/30(83.33%) cases arrived at MRD negative. There is about 1/3 of the total cases receiving a repeat infusions following initial ones since these patients have no safety concerns. Additionaly, the severe Cytokine release syndrome (CRS) was 8/30(26.67%) of cases and 24/30(80%) of cases was seen CRS. The anti-IL6R agent tocilizumab and Methylprednisolone were effective confrontation Severe CRS. Conclusions: This is the first multicentre report to our knowledge of successful treatment of r/r ALL with anti-CD19 CAR T cells in China. Even r/r B-ALL with high-burden leukemia patients also was effective and associated with a high remission rate after infused autologous CD19 CAR-T).(NCT 02813837).
CanStem303C trial: A phase III study of napabucasin (BBI-608) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC).
Authors: Axel Grothey, Manish A. Shah, Takayuki Yoshino, Eric Van Cutsem, Julien Taieb, Ruihua Xu, Niall C. Tebbutt, Alfredo Falcone, Andres Cervantes, Laura Borodyansky, Chiang Li
Journal: Journal of Clinical Oncology (2017)

TPS3619 Background: Cancer stem cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapeutics, including 5-FU and irinotecan. Encouraging anticancer activity in advanced CRC was observed in a phase Ib/II (Bendell et al, GI ASCO 2017) study of 63 pts with disease control rate (DCR) of 93% (28/30) and overall response rate (ORR) of 33% (10/30) in FOLFIRI-naïve pts who have had an on-study RECIST evaluation. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia. Methods: This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of napabucasin+FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) is permissible per investigator choice. Pts must have failed 1 prior line of therapy with oxaliplatin and a fluoropyrimidine +/- bev for metastatic disease. Pts are randomized 1:1 to receive napabucasin 240 mg PO BID plus FOLFIRI bi-weekly, or FOLFIRI bi-weekly (bev may be added to FOLFIRI by investigator choice) and stratified by geography, time to progression on 1 st -line therapy, RAS mutation status, bev as part of study treatment and primary tumor location. Treatment will continue until disease progression, or another discontinuation criterion. Primary endpoint is overall survival (OS) in the general study population (ITT) (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive (biomarker+) population, progression free survival (PFS) in the ITT population, PFS in biomarker+ population, ORR and DCR in the ITT and in biomarker+ populations, safety and quality of life. Also, blood and tumor archival tissue will be assessed for PK and biomarker analyses. Global enrollment is underway. Clinical trial information: NCT02753127.
Determining the disappearance rate of creatine kinase (CK) in the dog.
Authors: R Roberts
Journal: Circulation (1990)

Maximal Exercise Testing Safety "The Safety of Maximal Exercise Testing," by Gibbons et al,' provided very detailed statistics on the safety of exercise testing in a low-risk population.According to the authors, the major differ- ence between this study and all others evaluating the safety of exercise testing is that this is the first large-scale study to evaluate the complications associated with exercise testing without the use of surveys from numerous facilities.This, however, is not the case; in 1987, we published data on the safety of exercise testing performed on high-risk patients at four separate health-care centers of the CIGNA Healthplan of California.2 Between January 1980 and June 1985, data regarding the safety of exercise testing were directly documented immediately after each of 10,577 exer- cise tests.This prospective study gathered exercise test informa- tion directly via stress test raw data sheets that included the patient's name, age, sex, diagnosis, complications, maximal heart rate achieved, percent of the predicted maximal heart rate, protocol used, test date, patient effort, medications used, and date and location of cardiac catheterization, if performed.This infor- mation allowed us to thoroughly assess the complications observed during and after exercise testing of patients (41% of whom had documented coronary artery disease) in our laboratories.Analysis of the documented data revealed a morbidity rate of 3.8 per 10,000 exercise tests and a mortality rate of 0.9 per 10,000 tests.The CIGNA study, therefore, demonstrates that the study of the safety of exercise testing by direct documentation has been previously performed and was unfortunately not cited in the article by Gibbons et al.In addition, as Gibbons et al demonstrated in a low-risk population, we have demonstrated in a high-risk population that maximal exercise testing can be performed safely when 1) contraindications to testing are followed; 2) end points for testing are well defined; 3) the patient's signs and symptoms are thor- oughly assessed before, during, and after the exercise test; and 4) properly trained professionals perform the exercise test.
Free circulating DNA in patients with advanced gastric cancer during systemic chemotherapy.
Authors: Savia Raquel Costa Normando, Fernando Luiz Affonso Fonseca, Waldec Jorge David, Pamela de Oliveira Delgado, Julio Cesar Lemes de Oliveira, Ana Katherine Soares Barbosa Rodrigues, Felipe Melo Cruz, Auro Del Giglio
Journal: Journal of Clinical Oncology (2016)

e15517 Background: Locally advanced unresectable and metastatic gastroesophageal cancers are not curable conditions for which systemic chemotherapy is the backbone of therapy. Useful biomarkers to predict prognosis and monitor chemotherapy response are necessary to improve its clinical management. We conducted a pilot study to analyze the potential for total plasma free circulating DNA (fcDNA) as a possible biomarker in patients with metastatic and advanced unresectable gastric cancer. Methods: We included 30 patients with histologically diagnosed locally advanced unresectable or metastatic gastric cancer. We obtained samples from each patient before chemotherapy and at every three months after that until disease progression or death. We quantified total plasma fcDNA using GeneQuant RNA/DNA Calculator - Amersham Pharmacia Biotech (Biochrom) Ltd, USA. We utilized the RECIST criteria 1.1 to analyze the response to treatment. Results: We evaluated ten normal controls matched for age for cfDNA levels and found them to have significantly lower levels of cfDNA than the patients before chemotherapy (p = 0.00024). We arbitrarily choose the 90% percentile of fcDNA distribution levels of the normal healthy controls matched for age as the cut-off value to call a sample negative or positive for fcDNA. We did not find any correlation between the expression of cfDNA and overall survival, disease-free survival (DFS) and RECIST response categories. However, we observed that patients who converted from cfDNA positive before chemotherapy to cfDNA negative after three months tended to have a longer DFS (p = 0.09) as compared to those who persisted positive. Conclusions: The values of total plasma cfDNA in locally advanced unresectable and metastatic gastroesophageal cancers do not seem to be of prognostic value, Further study of the tumoral fraction of total fcDNA may improve the prognostic potential of this biomarker.
Evaluation of fixed-dose regimens of seribantumab in patients with solid tumors.
Authors: Bambang Adiwijaya, Walid Kamoun, Sara Ghassemifar, Sergio Santillana, Lecia V. Sequist, Peter A. Kaufman, Johannes Ettl, Joyce F. Liu, Michaela Jane Higgins, J. Marc Pipas
Journal: Journal of Clinical Oncology (2018)

2524 Background: Seribantumab (MM-121) is an anti-ErbB3 human monoclonal antibody being tested as an anti-cancer therapy for patients with high expression of heregulin mRNA in NSCLC (SHERLOC study, 3g every 3 weeks [Q3W]+docetaxel) and in and in HR+/ HER2- metastatic breast cancer (mBC) (SHERBOC study, 3g every 2 weeks [Q2W]+fulvestrant). Here we aimed to evaluate seribantumab dose regimens based on PK and safety. Methods: Pharmacokinetics (PK) and safety were evaluated for fixed and weight-based dose: in NSCLC, 3 g Q3W vs. 20 mg/kg Q2W; in mBC, 3 g Q2W vs. 40 mg/kg loading dose, followed by 20 mg/kg QW. PK was quantified using nonlinear mixed effect with the following covariates: sex, race, age, weight, dose, study, and hepatic functions. Adverse events (AEs) were evaluated for associations to PK and weight: Grade 1+ and 3+ diarrhea, fatigue, hypokalemia, hypomagnesemia, nausea, pulmonary embolism, rash, stomatitis, and vomiting. Results: Seribantumab PK from 499 patients in 7 previous trials identified associations with sex and weight. Fixed and weight-based doses showed similar variability. With higher weight, weight-based dose resulted in higher exposure (average concentration [Cavg] and maximum concentration [Cmax]), and fixed dose resulted in lower exposure. Steady-state Cmax were higher with 3 g than with 20 mg/kg; these values were comparable to Cmax with 40 mg/kg. Steady-state Cavg were equal to or higher for fixed dose than comparable weight-based dose. All doses tested had minimum concentrations (Cmin) higher than the nonclinical target concentration of 100 mg/L. Among AEs evaluated, significant associations with seribantumab exposure were observed for G1+ diarrhea, fatigue, nausea, rash, and stomatitis. Weight-based dose showed higher AE rates with increasing weight. Fixed dose is predicted to reduce AE rates in high-weight patients and to increase AE rates in low-weight patients, with the latter rates still lower than those in patients with high weight dosed by weight. Conclusions: The recommended dose of seribantumab is 3 g Q3W+docetaxel in NSCLC and 3 g Q2W+fulvestrant in mBC. The fixed dose of seribantumab allows acceptable concentrations and safety profiles and potentially reduces drug waste and dosing errors.
Dietary inflammatory index and breast cancer risk by menopausal status and histological subtype.
Authors: Adela Castello, Nitin Shivappa, Amparo Ruiz, Ana Casas, Ana Lluch Hernandez, José Manuel Baena-Cañada, Silvia Antolin, Pedro Sánchez Rovira, Manuel Ramos Vazquez, Jose Angel Garcia-Saenz, Antonio Anton, Montserrat Munoz, Ana de Juan, Carlos Jara-Sanchez, Jesus Vioque, Beatriz Perez-Gomez, James R. Hébert, Virginia Lope, Miguel Martin, Marina Pollan
Journal: Journal of Clinical Oncology (2018)

1521 Background: Inflammation plays an important role in cancer development. The Dietary Inflammatory index (DII) reflects the inflammatory potential of diet. We examined the association between the DII and breast cancer (BC) risk by menopausal status and histological subtype. Methods: Epi-GEICAM is a nation-wide case-control study that collected epidemiologic information, including diet, of 973 BC cases from 23 hospitals individually matched to 973 controls by age and residence. Cases were sub classified by tumor subtype: 1) Estrogen Receptor(ER)+ or Progesterone Receptor(PR)+ with Human Epidermal Growth Factor Receptor 2(HER2)-; 2) HER2+; and 3) ER-,PR-&HER2-. The association of the calorie density adjusted DII score (0-10) with BC risk was evaluated using conditional logistic regression models, adjusted by alcohol, body mass index, age at menarche, physical activity, smoking habit, education, history of breast alterations, family history of BC, age at first delivery and menopausal status. Heterogeneity of the effects by menopausal status was tested including an interaction term between this variable and the DII. Multinomial logistic regression models -adjusted for age, hospital, and the same set of potential confounders described above- were used to evaluate the association of the DII score with each of the intrinsic BC subtypes. In all cases associations were analyzed both, as categorical (grouping the DII into quartiles of its distribution among controls) and continuous (1-point increase) variables. Results: Women whose diet was more pro-inflammatory showed higher BC risk (OR4th quartile(Q4)vs 1st quartile(Q1)= 1.39; 95%CI = 1.05-1.84; p-trend = 0.023). This effect seemed to be confined to premenopausal women (ORQ4vsQ1= 1.52; 95%CI = 1.05-2.21; p-trend = 0.030) and it was stronger for HER2+ (ORQ4vsQ1= 1.46; 95%CI = 0.92-2.32; p-trend = 0.050) and ER-,PR-&HER2- (ORQ4vsQ1= 2.72; 95%CI = 1.45-5.10; p-trend = 0.006) tumors than for ER+/PR+&HER2- (ORQ4vsQ1= 1.24; 95%CI = 0.92-1.67; p-trend = 0.145) tumors. Conclusions: A diet that promotes inflammation might be associated with higher BC risk, especially among premenopausal women and for the most aggressive tumors (HER2+ and ER-, PR-&HER2-).
Frequency of cancer therapy-related late effects among long-term Wilms' tumor survivors in a 20-year period at the Instituto Nacional de Pediatria, Mexico city, Mexico.
Authors: Araceli Castellanos-Toledo, Juan Pablo Nuñez-Mondragón, Jose de Jesus Figueroa Carbajal, Rocio Cardenas-Cardos
Journal: Journal of Clinical Oncology (2018)

e22508 Background: Therapy with surgery, chemotherapy and radiation-therapy (RT) cures more than 90% of Wilms' tumor (WT) children, however, despite adequate rationalization of these treatments, risk of presenting therapy-related short- and long-term sequelae remains latent and intensifies over time and may not become apparent until years later as the child matures. Our results provided a notion of therapy-related late effects in our WT patients and a guide for their approach and prevention. Methods: Retrospective and clinical study of late effects among WT survivors treated at Instituto Nacional de Pediatría between 1990-2010. Results: Forty-eight patients were included, 26 girls (54%) and 22 boys (46%). At diagnosis, median age was 32.4 months (6-96 months), 2 had associated genetic syndromes (AGS), Denys-Drash and Beckwith-Wiedemann syndromes, there were 4 (8.3%) stage-I, 3 (6.2%) stage-II, 20 (41.6%) stage-III, 14 (29%) stage-IV (pulmonary metastases) and 7 (14.5%) stage-V. Three (6.2%) had diffuse anaplasia. All patients received a clinical-trials-NWTSG-based treatment. Median follow-up time was 10-year (5-20-year range). EFS and OS rates over 10-year for unilateral and bilateral WT were 83.3% and 88.9%, and 60% and 85.7%, respectively. Chronic conditions development cumulative incidence among long-term WT survivors was 18.4%. There were 2% doxorubicin-induced late cardiotoxicity ( > 250mg/m2 TCD, RR 0.16), 4.1% no-related AGS end-stage renal disease, and 8.3% RT-related musculoskeletal disorders (RR 0.7). There were not RT-induced lung damage or second malignancies. Twenty-year mortality rate was 16.1%. Conclusions: Long-term WT survivors at our institution have a morbidity and mortality risk and survival rates similar to survivors population of other countries. Due increased number of worldwide WT survivors, a lifelong surveillance systematic plan for these patients is necessary in all hospitals treating childhood cancer, focused on prevention, early diagnosis and treatment of their chronic comorbid health conditions.
Abiraterone +/- cabazitaxel in defining complete response in prostatectomy (ACDC-RP) trial.
Authors: Anthony M. Joshua, Neil Eric Fleshner, Joseph Chin, Urban Emmenegger, Martin E. Gleave, Sebastien J. Hotte, Joan Sweet, Colin Collins, Paul Christopher Boutros, Mathieu Lupien, Trevor John Pugh, Kim N. Chi
Journal: Journal of Clinical Oncology (2017)

TPS5095 Background: Given recent advances in the management of de novo metastatic hormone-sensitive prostate cancer with both docetaxel and abiraterone, as well as evidence of significant activity of cabazitaxel in the post-abiraterone castrate-resistant setting, we hypothesized that the addition of cabazitaxel to neoadjuvant abiraterone will improve pathological complete response rates by overcoming mechanisms of resistance in localized high-risk prostate cancer. Aim: To determine the relative efficacy of the addition of cabazitaxel to abiraterone in the neoadjuvant treatment of prostate cancer to achieve a complete response. Methods: Open label, randomized, 2-arm multi-centre, phase 2 clinical trial. Primary endpoint: Pathological complete response rate (pCR). Secondary endpoints: surgical outcomes (positive margins, extracapsular extension, seminal vesicle or nodal involvement), pharmacodynamic markers in residual tumour (apoptosis, androgen receptor expression, localization, and signaling), biomarkers (intra-prostatic androgen levels), and safety. Design: Study participants will be randomized in a 1:1 ratio to receive either: Arm A: Abiraterone (1000 mg/day), prednisone (5 mg b.i.d.), leuprolide (22.5 mg s.c. every 3 months), and cabazitaxel (25 mg/m 2 starting at week 2, with 6 mg pegfilgrastim 24 h following cabazitaxel) or Arm B: Abiraterone (1000 mg/day), prednisone (5 mg b.i.d.) and leuprolide (22.5 mg s.c. every 3 months). Assessments will take place biweekly for the first 12 weeks, then monthly until the prostatectomy (scheduled for 24 weeks following start of treatment). Target accrual is 88 participants within 36 months. Study is powered to detect a 15% difference with 85% power, assuming a one-sided type 1 error rate of 20%. A 6 patient safety run-in is included. As of Jan 2017, 1 site is open in Canada, with 4 additional Canadian sites and 1 site in Australia pending. To date, 4 participants are randomized and undergoing treatment. ACDC-RP is an investigator-initiated trial led by the Princess Margaret Urology Trials Group with funding from Ontario Institute for Cancer Research (OICR) and in-kind contributions from Janssen and Sanofi. Clinical trial information: NCT02543255.