tbuckley/cabot-search huggingface dataset:
A retrospective analysis of patients with poor-risk germ cell tumor (PRGCT) treated at Indiana University from 1990 to 2011.
Authors: Nabil Adra, Aabha Oza, Costantine Albany, Sandra Althouse, Nasser H. Hanna, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2014)

4557 Background: Based on the International Germ Cell Cancer Collaborative Group (IGCCCG), PRGCT represents 14% of germ cell tumors with a 5-year survival of only 48% and 5-year PFS of 41%. PRGCT is defined by primary mediastinal non-seminomatous germ cell tumor (PMNSGCT), non-pulmonary visceral metastasis (NPVM), AFP > 10,000 or hCG > 50,000. This analysis attempts to identify subsets of patients with more or less favorable outcomes among the poor risk groups. Methods: Retrospective analysis of all patients with testicular cancer seen at Indiana University from 1990-2011. 411 patients with PRGCT identified of whom 211 received initial therapy at Indiana University. Median follow-up time was 35.3 months. We analyzed the following variables: primary site testis/retroperitoneal T/RP (169) vs. PMNSGCT (42), no NPVM (109) vs. NPVM (102), PMNSGCT with no metastasis (18) vs. PMNSGCT with distant metastasis (24), and single criterion (128) vs. multiple criteria (83) for PRGCT. Results: Mean age 29, mean AFP 9,449, mean hCG 169,087. 20% had PMNSGCT, 48% NPVM. Patients with NPVM had significantly worse PFS. Patients with PMNSGCT had significantly worse OS compared to patients with other primary sites. Multiple different criteria for poor risk disease carried significantly worse impact on PFS when compared to having a single criterion for poor risk disease. Patients with PMNSGCT with distant metastasis had worse PFS. Conclusions: Our results for patients with PRGCT treated at Indiana University from 1990-2011 are superior to the IGCCCG patients treated from 1975-1990. Patients with PRGCT treated after 1990 had better outcome compared to 1975-1990 with a 5-year survival of 74% and PFS of 54%. Our data indicate that patients with NPVM, PMNSGCT, more than one criteria for poor risk disease, or PMNSGCT with distant metastasis have a worse outcome compared to other PRGCT subgroups. 5-yr PFS 5-yr OS P value All patients 54% 74% No NPVM vs NPVM 60% vs 49% 78% vs 71% PFS 0.06; OS 0.2 PMNSGCT vs T/RP 46% vs 56% 57% vs 78% PFS 0.69; OS 0.002 Single criterion vs multiple criteria for poor-risk disease 60% vs 45% 78% vs 69% PFS 0.03; OS 0.12 PMNSGCT vs PMNSGCT + metastasis 69% vs 36% 78% vs 45% PFS 0.06; OS 0.16
T3 PEPTIDE, AN ACTIVE FRAGMENT OF TUMSTATIN, STIMULATES MIGLATION OF CARDIAC FIBROBLASTS AND EXERTS CYTOPROTECTIVE EFFECT ON H9C2 CARDIOMYOBLASTS
Authors: Jumpei Yasuda, Kana Fukui, Muneyoshi Okada, Hideyuki Yamawaki
Journal: Journal of the American College of Cardiology (2017)
Influence of variant allele frequency (VAF) on the phenotypic penetrance of TP53 mutations in myeloid malignancies.
Authors: David Andrew Sallman, Rami S. Komrokji, Christine Vaupel, Najla Al Ali, Jeffrey E. Lancet, Alan F. List, Jeff Hall, Eric Padron
Journal: Journal of Clinical Oncology (2015)

7091 Background: The clinical implementation of next generation sequencing (NGS) has allowed for the quantitative detection of clinically significant somatic mutations in myeloid malignancies. However, the clinical relevance of the VAF in these mutations is unknown. Here we investigate the role of TP53 VAF in MDS and AML which is a recognized adverse prognostic feature associated with a complex karyotype. Methods: A training set of NGS profiled MDS or AML cases were retrospectively identified from the Moffitt Cancer Center MDS database. A validation set was obtained from WHO defined MDS cases profiled at Genoptix. Clinical variables and outcomes of MDS patients were characterized at the time of sample procurement. Fisher’s exact and t-tests were used for comparative analyses. Kaplan-Meier estimates were used to estimate overall survival and analyzed from the date of mutation identification. Results: From May 2013 to October 2014, 43 patients of 252 screened cases were identified in our training set with a TP53 mutation. The mean VAF across duplicate libraries was 39.8%. As previously reported, TP53 mutation was strongly associated with complex karyotype (70% vs 6%, p < .0001). When parsed by VAF, 100% of TP53 mutated patients with a VAF > 40% had complex cytogenetics in comparison to 50% of patients with a VAF < 20% (p = .0016). Further, patients with complex cytogenetics had a significantly increased VAF (median 49% vs 18%, p = .0009). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 102 days versus an OS that was not reached in patients with lower VAF (p = .04). The validation set (n = 150) confirmed the training set findings (p < .0001). Additionally, RUNX1mutations were associated with thrombocytopenia (p < .0001) and VAF more strongly predicted the presence of thrombocytopenia (p = .04), suggesting that allelic burden influences phenotype penetration across multiple genes. Conclusions: Consideration of TP53 VAF improves prognostic precision compared to binary mutational analysis alone. This study supports inclusion of VAF at point of care for TP53 and other recurrent mutations.
Decision analysis of contralateral prophylactic mastectomy for women with sporadic, unilateral, early-stage breast cancer.
Authors: Kalatu R Davies, Abenaa M. Brewster, Patricia A. Parker, Isabelle Bedrosian, Melissa Crosby, Susan K. Peterson, Yu Shen, Robert Joseph Volk, Scott B. Cantor
Journal: Journal of Clinical Oncology (2015)

e12572 Title: Decision analysis of contralateral prophylactic mastectomy for women with sporadic, unilateral, early-stage breast cancer Background: An increasing number of women with sporadic, unilateral, early-stage breast cancers are choosing to undergo contralateral prophylactic mastectomy (CPM). The aim of this study was to compare overall survival outcomes between CPM and no CPM with continued surveillance following treatment of a primary breast cancer to assist clinical decision-making. Methods: We created an individual-based, state-transition Markov model. We considered women treated for sporadic stage I, II, or III, estrogen receptor (ER) positive and ER-negative breast cancer at ages 40, 50, 60, and 70. To simulate overall survival outcomes for breast cancer patients, we implement an initial 10-year risk period for the development of contralateral breast cancer (CBC) and mortality from the primary or CBC following treatment for the primary and CBC. We incorporated adjustments for mortality probabilities to account for time since treatment for the primary cancer and/or a CBC. Microsimulation trials estimated the average life expectancy (LE) for each strategy. Results: The incremental benefit of CPM compared to no CPM ranged from 0.03 to 0.22 years for women with stage I breast cancer, 0.06 to 0.21 years for stage II, and 0.01 to 0.15 for stage III breast cancer. Greater gains in LE were observed for women < 60 and for stage I, ER-negative cancer; however, the differences were not statistically significant. Sensitivity analysis on LE benefit resulted in a maximum LE difference of 0.37 year for a 40-year-old woman with stage I breast cancer and varying annual risk of CBC. Conclusions: Microsimulation modeling results suggest that CPM provides marginal LE gains for women with early stage breast cancer. The gains in LE decreased with increasing patient age and stage and there was no significant LE gain for ER-positive or ER-negative breast cancer for women ages 50-70. The impact of these results on shared decision making about CPM is an area of active investigation.
CORONARY ARTERY CALCIUM AND INCIDENT HYPERTENSION IN A POPULATION-BASED COHORT: THE MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
Authors: Amer I. Aladin, Mahmoud Al Rifai, Shereen H. Rasool, Zeina Dardari, Joseph Yeboah, Khurram Nasir, Matthew Budoff, Bruce M. Psaty, Roger Blumenthal, Michael Blaha, John W. McEvoy
Journal: Journal of the American College of Cardiology (2017)
Triptolide Induces Cell Death Independent of Cellular Responses to Imatinib in Blast Crisis CML Cells and Sensitizes Imatinib.
Authors: Duncan H. Mak, Wendy D. Schober, Wenjing Chen, Jorge E. Cortes, Hagop M. Kantarjian, Michael Andreeff, Bing Z. Carter
Journal: Blood (2007)
CHILDBIRTH RELATED COMPLICATIONS IN WOMEN WITH HYPERTROPHIC CARDIOMYOPATHY
Authors: Amitoj Singh, Sahil Agrawal, Kanika Samra, Sajeev Saluja, Uzma Tariq, Lohit Garg, Rasha Aurshiya, Mark Fegley, Yugandhar Manda, Sudip Nanda, Jamshid Shirani
Journal: Journal of the American College of Cardiology (2017)
Phase II study of paclitaxel and cisplatin in advanced esophageal cancer: A Chinese esophageal cancer group
Authors: J. Huang, G. R. Cai, J. M. Zhang, W. J. Wang, T. Da Chu, Y. Sun
Journal: Journal of Clinical Oncology (2004)

4173 Background: Esophageal cancer is not common in western countries, but it is one of the most frequent malignancies and the second leading cause of death from cancer in china. Paclitaxel is one of the most active single agents in the treatment of metastatic esophageal cancer. We performed a phase II trial of paclitaxel in combination with cisplatin for esophageal cancer. The antitumor response, toxicity and survival of patients treated with the two-drug regimen were evaluated. Methods: 28 patients with advanced, surgically unresectable, or metastatic squamous cell of the esophagus were enrolled. 25 patients had no priorchemotherapy. 3 patients had previous adjuvant chemotherapy. Patients received paclitaxel 175mg/m2 by 3-hour infusion day 1, and cisplatin 40mg/m2 daily days 2 through 3. Granulocyte colony-stimulating factor (G-CSF) was not routinely a administered unless the patient had neutropenia. Treatment was recycled every 21 days. Results: 28 patients (male/female, 27/1; median age 55, range 38–76 ) completed a median of 4 cycles, and 27 patients were evaluable for response (CR 14.8% PR 40.7%, SD 25.9%, PD18.5%). Toxicity was manageable with dose attenuation. 7 patients required a dose altenuation for toxicity. There were one toxic death due to grade 4 neutropenia. Conclusion: The combination of paclitaxel and cisplatin is active and a well tolerated regimen. No significant financial relationships to disclose.
A phase I trial of ZD1839 (Z), capecitabine (Cp), and celecoxib (Cel): Preliminary results of an amended schedule
Authors: M. Basche, A. S. Pierson, S. Holden, L. Gore, C. O'Bryant, S. Raj, M. Morrow, D. Gustafson, J. Dancey, S. G. Eckhardt
Journal: Journal of Clinical Oncology (2004)

3159 Background: Angiogenesis is essential for tumor growth and metastasis. Distinct pro-angiogenic pathways are targeted by Cel (a cyclooxygenase-2 inhibitor), Z (an epidermal growth factor receptor tyrosine kinase inhibitor that results in reduced vascular endothelial growth factor expression), and Cp (a prodrug of 5-fluorouracil (5FU) activated by thymidine phosphorylase, a tumor-associated pro-angiogenic molecule). This abstract reports the results of an amended treatment schedule based on preclinical data suggesting that antitumor effects are sequence dependent. In vitro synergistic effects were observed when ZD1839 was administered prior to 5FU, additive effects with concomitant administration, and antagonistic effects when administered after 5FU. Methods: This phase I trial assesses the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), pharmacokinetic interactions, and biologic effects of the combination of Z (250–500 mg/day days 1–14), Cp (1000 mg/m2- 2000 mg/m2/day days 8–21), and Cel (400 mg twice daily days 1–28) given in 28-day cycles. Results: Eleven patients (pts) have been enrolled and completed 29 treatment courses (crs). Median age was 66 (range 52–77) and median performance status was 1 (range 0–1). Dose-limiting toxicity (DLT) occurred in 1of 6 pts treated with ZD1839 250mg, Cp 1500mg/m2, and Cel 400mg and 1 of 1 pt treated with ZD1839 250mg, Cp 2000mg/m2, and Cel 400mg. DLT consisted of Gr 3–4 diarrhea and Gr 3 fatigue Additional Gr 3 toxicities considered to be possibly related to treatment include Gr3 hand-and-foot syndrome (HFS) in 2 courses. Grade 1–2 toxicities include fatigue (10 crs), acneiform rash (9 crs), diarrhea (8 crs), HFS (7 crs), and mucositis (5 crs). Three patients maintained stable disease for ≥ 5 cycles (adenocarcinoma unknown primary, gallbladder, and rectal cancer). Conclusions: Accrual is ongoing to determine the MTD. Tumor biopsies will then be obtained to assess effects on tumor metabolism and gene expression. No significant financial relationships to disclose.
A phase II trial of PS-341 in metastatic breast cancer (MBC)
Authors: M. Cristofanilli, A. M. Gonzalez-Angulo, K. N. Nealy, D. Booser, L. Pusztai, R. D. Walters, G. N. Hortobagyi, J. Reuben, D. Esseltine, J. Wright
Journal: Journal of Clinical Oncology (2004)

3102 Background: The ubiquitin proteasome pathway plays an important role in cell cycle regulation, cancer growth and metastases representing a novel target for therapy. PS-341 (Bortezomib -Velcade) is a depeptidyl boronic acid inhibitor with high specificity for the proteasome and represents the first agent of this class approved for treatment of hematologic neoplasms. We initiated a Phase 2 single Institution trial testing PS-341 in minimally pretreated metastatic breast cancer (MBC). Methods: Twelve patients (pts) with minimally treated (1 previous regimen) measurable disease were enrolled and treated with PS-341 at 1.5mg/m2 intravenously bi-weekly for 2 consecutive weeks in a 21-day cycle. Pts. were evaluated clinically every 3 weeks to assess toxicity. Correlative studies include: level of 20-S proteasome activity in whole blood lysate before and after 1 hour of administration of the first dose (expressed as specific chymotryptic activity, SpA). Additionally we plan for evaluation of angiogenic and inflammatory cytokines (IL-12p70, TNF-α, IL-6, IL-1B, IL-8). Results: Ten pts are evaluable, 1 died early from disease complications and 1 is still on treatment. The median age was 54 years, (range 30–72 years). Nine pts had predominant visceral disease. 20-S proteasome inhibition compared to the pre-dose administration was documented in all cases. The median number of cycles of PS-341 was 2 cycles, (range 1–5 cycles). There were 1 stable disease (SD) and 9 progressive diseases (PD). The median time-to progression (TTP) was 47 days (range 17–110 days). The most common Grade 3–4 toxicities included: fatigue 70% (n=7) and skin rash 40% (n=4). The median time of onset of the skin rash was 11 days (range 10–27 days). Conclusions: PS-341 inhibits 20S-proteasome in pts with MBC. Administered in this schedule seems to have an acceptable tolerance, but little activity. The role of this agent in the management of breast cancer should be explored using combination with cytotoxics or other biological agents. No significant financial relationships to disclose.
ENDO-EPICARDIAL VERSUS ENDOCARDIAL-ONLY APPROACH FOR FIRST VENTRICULAR TACHYCARDIA ABLATION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF SAFETY AND EFFICACY OUTCOMES
Authors: Rhanderson Cardoso, Gilson Fernandes, Guilherme Nasi, Joao Braghiroli, Andre D'Avila
Journal: Journal of the American College of Cardiology (2017)
Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors
Authors: Sharareh Gholamin, Siddhartha S. Mitra, Abdullah H. Feroze, Jie Liu, Suzana A. Kahn, Michael Zhang, Rogelio Esparza, Chase Richard, Vijay Ramaswamy, Marc Remke, Anne K. Volkmer, Stephen Willingham, Anitha Ponnuswami, Aaron McCarty, Patricia Lovelace, Theresa A. Storm, Simone Schubert, Gregor Hutter, Cyndhavi Narayanan, Pauline Chu, Eric H. Raabe, Griffith Harsh, Michael D. Taylor, Michelle Monje, Yoon-Jae Cho, Ravi Majeti, Jens P. Volkmer, Paul G. Fisher, Gerald Grant, Gary K. Steinberg, Hannes Vogel, Michael Edwards, Irving L. Weissman, Samuel H. Cheshier
Journal: Science Translational Medicine (2017)

Anti-CD47 antibody is effective for treating malignant pediatric brain tumors without detectable toxicity in patient-derived xenograft models.
Screening for lung cancer: Feasibility study of a randomized trial comparing low dose spiral CT and chest X-ray
Authors: B. Milleron
Journal: Journal of Clinical Oncology (2004)

7183 Background: Low dose spiral CT (LDCT) efficacy has been demonstrated in many open studies for detection of early stage lung cancers with a four times higher sensitivity than chest X-ray. However, the impact of LDCT screening on the lung cancer mortality has not yet been evaluated and can be demonstrated only with randomized studies comparing LDCT and chest X-ray. Such a study will require the recruitment and consent of 40,000 subjects and is obviously expensive. In France, a preliminary study started on October, 2002 to determine the feasibility and the future management of such a trial. Methods: 1000 subjects were to be included within 2 yrs, randomized between LDCT (Group 1) and chest X-ray (Group 2), and followed up for two years by General Practitioners (GP) with 3 radiological screens (M0, M12, M24). Inclusion criteria were: asymptomatic male or female, between 50 and 75 yrs, current or former smokers, with a more than 15 cig/day during 20 years at least. Results: At year one, 81 GP had included 612 subjects (among which 68% were current smokers and 32% former smokers), with a sex ratio of 2.4 (70% male). At this time data are only available for 353 subjects: at least one non-calcified nodule has been detected for 89/180 subjects (49.5%) in Group 1 and 12/173 (7%) in Group 2. The size of the biggest nodule in Group 1 was: 10 mm, in19 (10.6%). Six lung cancers have been identified in Group 1 and one in Group 2. Conclusions: These preliminary findings confirm the feasibility of a GP recruitment of 40,000 subjects in a 10 yr-trial. High percentage of abnormalities detected in LDCT stress the need for careful follow-up procedures. No significant financial relationships to disclose.
Different-dose docetaxel plus cisplatin as first-line chemotherapy and then maintenance therapy with single-agent docetaxel for advanced non-small cell lung cancer (TFINE study, C-TONG 0904).
Authors: Li Zhang, Shun Lu, Ying Cheng, Zhihuang Hu, Zhiwei Chen, Gongyan Chen, Xiaoqing Liu, Jinji Yang, Li Zhang, Jia Chen, Meijuan Huang, Min Tao, Gang Cheng, Cheng Huang, Caicun Zhou, Weimin Zhang, Hong Zhao
Journal: Journal of Clinical Oncology (2013)

8015 Background: Docetaxel (75 mg/m 2 ) has been reported as first-line and maintenance treatment for Western population with advanced NSCLC. Different doses of docetaxel (60 mg/m 2 ) are currently delivered in Asian population. Pharmacogenomics alterations in taxanes disposition in different ethnic groups may explain this difference. TFINE study was to evaluate the efficacy, safety, and tolerability of docetaxel in the maintenance setting, and to identify the preferable dose of docetaxel in Asian population. Methods: Previously untreated patients, aged between 18 and 75 years, histologically or cytologically confirmed advanced NSCLC with PS of 0-1 were included. Patients were initially randomized (R1, 1:1) to receive cisplatin (75 mg/m 2 ) plus docetaxel of 75 mg/m 2 or 60 mg/m 2 for 4 cycles. Patients with disease control after the initial treatment were subsequently randomized (R2, 1:2) to best supportive care (BSC) or maintenance docetaxel of 60 mg/m 2 for up to 6 cycles. Genomic DNA was prospectively collected from all enrolled patients. The primary endpoint was PFS since R2, and the secondary endpoints included ORR, overall survival, and toxicity. This study is registered with ClinicalTrials.gov (NCT01038661). Results: This randomized study was undertaken in 15 centers in China. A total of 378 patients were enrolled to R1 and 184 patients (48.7%) were enrolled to R2 (61 vs. 123). Maintenance docetaxel plus BSC significantly prolonged PFS compared with BSC (5.4 months [95% CI 2.8, 7.0] vs. 2.8 months [1.8, 3.1]; P=0.002). The difference of ORR during initial chemotherapy was not significant, with 32.4% in the 60 mg-group and 33.7% in 75 mg-group (P=0.80).The data concerning the overall survival and toxicity, together with the information of pharmacogenomics alterations, will be presented in the meeting subsequently. Conclusions: Maintenance therapy with docetaxel is well tolerated and offers improved PFS in patients with advanced NSCLC.The dose of 60 mg/m 2 of docetaxel demonstrated similar efficacy and better tolerability than that of 75 mg/m 2 and should be preferred in Asian population. Clinical trial information: NCT01038661.
Benefit in progression-free survival (PFS) to expect based on CA125 reduction at week 6 in recurrent ovarian cancer (ROC) patients: CALYPSO phase III trial data (a GINECO-GCIG study).
Authors: Melanie Wilbaux, Emilie Henin, Olivier Colomban, Amit M. Oza, Eric Pujade-Lauraine, Gilles Freyer, Michel Tod, Benoit You
Journal: Journal of Clinical Oncology (2013)

5547 Background: Prediction of the expected survival benefit based on CA125 change in treated recurrent ovarian cancer (ROC) patients would be very useful. It may help for early selection of the best drug candidates during drug development, and for clinical trials. We used mathematical modeling to: 1) quantify the links between CA125 kinetics and progression-free survival (PFS) benefit, and 2) to estimate the CA125 decline required to observe a 50% PFS improvement. Methods: CALYPSO randomized phase III trial database, comparing 2 platinum-based regimens in ROC patients was used. The cohort was randomly split into a “learning dataset” (N=356) to estimate model parameters and a “validation dataset” (N=178) to validate model performances. A full parametric survival model was developed to quantify the links between tumor size changes; CA125 kinetics; prognostic factors and PFS. The predictive performance of the model was evaluated with simulations on the validation dataset. Results: PFS from 534 ROC patients was properly described by a parametric model with log-logistic distribution. The factors significantly linked to PFS were fractional changes in CA125 (ΔCA125) and in tumor size (ΔTS) from baseline at week 6; baseline CA125 (CA125 BL ); and patient therapy free interval. By reducing this model, ΔCA125 was a better predictor of PFS than ΔTS. Simulations verified the predictive performance of this model. Patients should achieve at least 49% ΔCA125 decline induced by treatment to observe 50% PFS improvement. This effect was independent on treatment arm. Conclusions: This is the first drug-independent parametric survival model quantifying links between PFS and CA125 kinetics in ROC. The CA125 modeled decline required to observe a 50% improvement in PFS in treated ROC patients was defined. It may be a surrogate marker of PFS gain, and may embody an early predictive tool for go/no go drug development decisions and for clinical trials. Validation in other datasets is warranted.