tbuckley/cabot-search huggingface dataset:
Risk factors associated with metastatic site failure in patients with high-risk neuroblastoma.
Authors: John Thomas Lucas, Daniel Victor Wakefield, Michael Doubrovin, Yimei Li, David Cooper, Bogdan-Alexandru Manole, Teresa Santiago, Sara Michele Federico, Thomas E. Merchant, Andrew M. Davidoff, Matthew J. Krasin, Barry L. Shulkin, Victor M. Santana, Wayne Lee Furman
Journal: Journal of Clinical Oncology (2017)

10557 Background: This retrospective study sought to identify predictors of metastatic site failure (MSF) in patients with high-risk (HR) neuroblastoma (NB). Methods: Seventy-six patients with HR NB treated on prospective trials at from 1997 to 2014 were eligible for inclusion. All patients were treated with induction chemotherapy (chemo) with surgery followed by myeloablative chemo &amp; stem cell rescue. Primary &amp; metastatic site (MS) RT were applied according to institutional protocol. CT &amp; I-123 MIBG scans were used to assess Curie scores at diagnosis, post-induction, post-transplant &amp; failure. Overall (OS), &amp; progression-free survival (PFS) were described using the Kaplan-Meier estimator. Cox proportional hazards frailty (cphfR) &amp; CPH regression (CPHr) were used to identify covariates predictive of MSF &amp; new site MSF. Results: Forty-two (55%) patients had documented MSFs. Consolidative MS RT was applied to 30 MSs in 10 patients. Original site MSF occurred in 146 of 383 (38%) &amp; 18 of 30 (60%) non-irradiated &amp; radiated MSs respectively. Original site MSF occurred in post-induction MIBG avid lesions in 68 of 81 (84%) &amp; 12 of 14 (85%) non-irradiated &amp; radiated MSs respectively. The median OS &amp; PFS were 61 mo (95% CI 42.6-NR) &amp; 24.1 mo (95% CI 16.5-38.7). Univariate cphfR identified an increased hazard for original MSF when MIBG avid following induction chemo (HR 4.9, 95%CI 1.1-20.9, p = 0.03) &amp; transplant (HR 7.3 95%CI 1.8-30.2, p = 0.006) relative to lesions that cleared after induction. Notably, MS RT nor site location did not modify the hazard for MSF. Multivariate CPHr identified inability to undergo transplant (HR 32.4 95%CI 9.3-96.8, p &lt; 0.001) &amp;/or maintenance chemo (HR 5.2, 95%CI 1.7-16.2, p = 0.005) &amp; the presence of lung metastases (HR 4.4 95%CI 1.7-11.1, p = 0.002) at diagnosis as predictors of new site MSF. The new MSF free survival at 3 years was 25% vs. 87% in patients with high-risk factors relative to those without the risk factors suggesting limited benefit of consolidative MS RT in this population. Conclusions: Metastatic lesions that remained MIBG avid following induction chemo &amp; post-transplant had an increased hazard for MSF. Consolidative site RT likely has limited benefit in patients with HR features.
Pharmacogenomic determinants of cetuximab and oxaliplatin pharmacokinetics during combined intravenous cetuximab (IV-Cet) and triplet hepatic artery chronomodulated infusion in patients (pts) with initially unresectable liver metastases from colorectal cancer (uLM-CRC) (EU OPTILIV trial).
Authors: Abdoulaye Karaboue, Raphael Saffroy, Christophe Desterke, Mohamed Bouchahda, Pasquale Innominato, C. N. J. Focan, Etienne Chatelut, Gilles Paintaud, Gerard A. Milano, Antoinette Lemoine, Francis Levi
Journal: Journal of Clinical Oncology (2017)

e14082 Background: Triplet HAI with IV-Cet achieved 29.7% complete uLM-CRC resections (R0+R1) and an overall median survival (OS) of 25.7 months in previously treated pts. While the high antitumour efficacy of this new regimen involved direct exposure of LM to the HAI drugs and their potentiation by cetuximab, haematological and intestinal toxicities mostly related to systemic exposure (Lévi, Ann Oncol 2016; Clin Pharmacokin 2016). Methods: To identify potential pharmacogenomics (PG) determinants of toxicity-related systemic exposure to the HAI drugs, 207 single nucleotide polymorphisms (SNPs) from 34 pharmacology genes were analysed in blood mononuclear cells (ADME PGx, MassArray platform, Sequenom, USA) from 11 pts undergoing a first course of chronomodulated triplet HAI and iv-CET (Levi et al. Clin Pharmacokinet 2016). Relations between SNPs and main pharmacokinetics parameters and toxicities were determined using ANOVA or Fisher Exact test. Results: Nine toxicity-related polymorphic genes were identified in the 52 pts of the PG study (ASCO, submitted). Here we investigated whether any of these polymorphic genes modified PK in 4F and 7M (33-72 yo) with WHO performance status 0-1. ABCB1 (rs1045642) was the only polymorphic gene that was significantly associated with both pharmacokinetics and toxicity in this study population. Conclusions: ABCB1 polymorphisms might contribute to the systemic hematologic toxicity of the combined IV-HAI regimen through altering cetuximab and oxaliplatin disposition, yet without affecting efficacy. Consideration of ABCB1 polymorphism could help optimize OPTILIV delivery in individual patients. Clinical trial information: NCT00852228. [Table: see text]
Does hypertension history in patients with advanced gastric cancer has an impact on clinical outcomes following apatinib treatment? A subgroup analysis based on data from Ahead-G201 study.
Authors: Tienan Yi, Jin Li, Shukui Qin, Lu Wen, Junsheng Wang, Wenying Deng, Guifang Zhang, Tongfu Jia, Yi Ba, Haijun Zhong, Jianwei Yang, Xiaoyan Lin, Yu-Xian Bai, Yifu He, Zhong Xie, Xiangyuan Wu, Feng Ye, Likun Liu, Yong Huang, Mei Wang
Journal: Journal of Clinical Oncology (2018)

e16022 Background: Hypertension (HTN) is one of the most common adverse events (AEs) associated with apatinib treatment in gastric carcinoma. However, few studies focus on the effect of HTN history on the safety and efficacy of apatinib treatment in advanced gastric cancer. We used available data from a phase IV study of Ahead-G201 to analyze this issue. Methods: As the cut-off date of Dec 21, 2017, a total of 1468 patients (pts) were enrolled in Ahead-G201 study. Incidence of AEs and clinical efficacy outcomes were compared between pts with HTN history and those without. Results: Among 1468 enrolled pts, 248 were found with HTN history, and 1220 were free of HTN prior to apatinib treatment. Significant differences in age, sex, body mass index, disease duration, and diabetes history were found between pts with HTN history and those without. 166 (66.9%) pts with HTN history were found with drug-related AEs (DRAEs) of all grades, which had no significant difference compared to pts without (742, 60.8%). However, pts with HTN history showed an obviously higher incidence of grade 3-4 DRAEs (35.9 vs. 27.1%, p = 0.0069), DRAEs associated with dose modification (36.7 vs. 29.2%, p = 0.0230), DRAEs associated with dose interruption or discontinuation (9.3 vs. 5.3%, p = 0.0264) and severe AEs (25.8 vs. 18.9%, p = 0.0187) than those without. For efficacy, the median PFS and OS in pts with HTN history were 4.1 (95%CI, 3.0-5.3) and 6.1 (95%CI, 4.8-7.6) mos, in pts without HTN history were 4.1 (95%CI, 3.1-4.6) and 6.6 (95%CI, 5.8-7.2) mos, respectively. There was no significant difference. Multivariate analysis also indicated that HTN history was not significantly associated with either PFS or OS in advanced gastric cancer pts following apatinib treatment. Conclusions: Current results suggested that HTN history may not affect clinical outcomes associated with apatinib treatment in previously treated advanced gastric cancer. However, the presence of HTN history may increase the risk of DRAEs, which indicated that close attention should be paid to these pts during apatinib treatment. Clinical trial information: NCT02426034.
Prospective, non-interventional study on the influence of adherence measures on the therapy with abiraterone acetate (AA) + prednisone/prednisolone (P) in patients with metastatic, castration resistant prostate carcinoma.
Authors: Henrik Suttmann, Susan Feyerabend, Jochen Gleissner, Andreas Huebner, Edmund A.M. Neugebauer, Tim Mathes, Werner Baurecht, Natasha Schuier
Journal: Journal of Clinical Oncology (2016)

e16525 Background: AA is a blocker of androgen biosynthesis, which is highly effective in men with mCRPC in prolonging PFS and OS. Oncology experiences an increase in oral cancer drugs treatments, for which monitoring of therapy adherence is more difficult and is known to decline over the treatment duration, although it is important for a long term success. The objective of this NIS is to assess the influence of adherence measures on the therapy with AA+P under routine conditions in comparison to a group without adherence measures. We report data of the second interim analysis: the rate of therapy discontinuations after 3 and 6 months due to non-adherence. Methods: This is a prospective, non-interventional study. 780 patients at 100 German study sites are to be included for the observation of a standard therapy with AA+P. 390 patients are to participate in the adherence program (Group A), and 390 patients are treated without special adherence program (Group B). The study centers are equally randomly assigned 1:1 through cluster randomization. Primary endpoint is the
Abstract 19235: Rare Missense Mutations of ABCG5/ABCG8 Raise Cholesterol and Phytosterol Levels and Increase the Risk of Coronary Artery Disease
Authors: Anna Helgadottir, Kristjan F Alexandersson, Gudmundur Thorgeirsson, Isleifur Olafsson, Olof Sigurdardottir, Gudmundur Eyjolfsson, Patrick Sulem, Unnur Thorsteinsdottir, Hilma Holm, Daniel F Gudbjartsson, Kari Stefansson
Journal: Circulation (2016)

Background and objective: Sequence variants in genes involved in absorption of cholesterol and other sterols may promote understanding of the impact of dietary components, as opposed to endogenous ...
A phase 3 study comparing polatuzumab vedotin plus R-CHP versus R-CHOP in patients with DLBCL (POLARIX).
Authors: Herve Tilly, Christopher Flowers, Jonathan W. Friedberg, Charles Herbaux, Franck Morschhauser, Laurie Helen Sehn, Jeff Porter Sharman, Marek Trněný, Lijia Wang, Calvin Lee, Gilles A. Salles
Journal: Journal of Clinical Oncology (2018)

TPS7589 Background: R-CHOP remains the standard of care in patients (pts) with previously untreated diffuse large B-cell lymphoma (DLBCL). However, pts with high-risk disease have poorer outcomes with R-CHOP. Polatuzumab vedotin (pola) is an antibody-drug conjugate targeting CD79b; it delivers the antimitotic agent MMAE and is being evaluated as a replacement strategy for vincristine within the R-CHOP regimen. In a phase Ib/II study in higher risk DLBCL pts, pola + R-CHP produced promising efficacy across different subtypes of DLBCL and a safety profile similar to that observed in the R-CHOP arm of the GOYA study (Tilly H, et al. Hematol Oncol 2017; Vitolo U, et al. J Clin Oncol 2017). Methods: This is a multicenter, randomized, double-blind, placebo-controlled, phase 3 study in pts with previously untreated DLBCL. Pts (planned N = 875) aged 18-80 years with CD20-positive DLBCL (including DLBCL not otherwise specified [NOS], germinal center B-cell like [GCB], and activated B-cell like [ABC] subtypes), ECOG performance status 0–2, and IPI score 2–5, will be randomized 1:1 to one of two treatment groups, stratified by IPI score (2 versus 3–5), bulky disease and geographical region. Arm A will receive pola 1.8 mg/kg on Day 1 plus R-CHP (standard dosing schedule) plus vincristine placebo for 6 cycles; Arm B will receive R-CHOP (standard dosing schedule) with pola placebo for 6 cycles. In both arms, R will be administered as monotherapy in cycles 7 and 8. The primary endpoint is progression-free survival, as assessed by the investigator, using the Lugano classification (Cheson B, et al. J Clin Oncol 2014). Secondary endpoints include PET-CT complete response rate at end of treatment assessed by an independent review committee, event-free survival due to efficacy reason, 2-year PFS rate, and overall survival. PET-CT and CT scans will be obtained at screening, after 4 cycles (planned interim assessment), and 6–8 weeks after end of study treatment. Patient follow-up will continue for 5 years after end of treatment. Enrolment began November 2017. Clinical trial information: study is funded by F. Hoffmann-La Roche Ltd; Clinical trial information: NCT03274492.
TCT-82 Race-based Disparities in the Management and Outcomes of Cardiogenic Shock Complicating Acute Myocardial Infarction: A 15-Year National Study
Authors: Saraschandra Vallabhajosyula, Saarwaani Vallabhajosyula, Gregory Barsness, Shannon Dunlay, Chet Rihal, David Holmes, Abhiram Prasad
Journal: Journal of the American College of Cardiology (2018)
Characterization of actionable somatic alterations in microdissected gynecologic carcinosarcomas.
Authors: Rachel N. Grisham, Sarah Chiang, Ronglai Shen, Rajmohan Murali, Catherine A. Shu, Douglas A. Levine, Tara Soumerai, David Michael Hyman, Martee Leigh Hensley, Michael F. Berger, Carol Aghajanian, Gopa Iyer
Journal: Journal of Clinical Oncology (2016)

5594 Background: Gynecologic carcinosarcomas (CS) are rare tumors most often arising in the uterus or ovary that histologically contain both carcinomatous and sarcomatous components. CS is thought to develop from sarcomatous differentiation of a high-grade carcinoma. We sought to define the genomic profile within the individual sarcomatous and carcinomatous components of CS to determine whether these two histologically distinct components display a shared genomic lineage. Methods: Following institutional approval, 10 cases of gynecologic CS were identified with adequate FFPE archival tissue available to allow for dissection of the carcinomatous, sarcomatous and normal components of individual tumors. Macrodissection and laser capture microdissection were performed as needed to isolate the relative components. The sarcomatous and carcinomatous components were separately analyzed using the MSK-IMPACT next generation exon capture sequencing platform. Matched tumor and normal specimens were used to identify somatic mutations and copy number variations. Results: Seven uterine and 3 ovarian CS tumors were analyzed. All were primary tumors with 6 showing homologous and 4 heterologous differentiation. Sixty-six unique somatic mutations were identified in a total of 44 genes with an average of 6.4 mutations (median 5; range 2-16) identified per tumor. An average of 4.9 mutations (median 4; range 2-9) was identified in the carcinomatous component of each tumor and an average of 3.9 mutations (median 3; range 1-9) in the sarcomatous component. Copy number analysis identified a high rate of aneuploidy with 17 samples with ploidy > 2.5 and 8 samples with ploidy > 3. Commonly mutated genes included TP53, PIK3CA, ARID1A, and KRAS. These mutations were concordant between the carcinomatous and sarcomatous components of individual tumors in TP53: 78% (7/9), PIK3CA: 75% (3/4), ARID1A: 100% (1/1), KRAS: 100% (1/1) of tumors harboring these alterations. Conclusions: A high level of concordance of driver gene mutations was observed between the sarcomatous and carcinomatous components of individual CS tumors. Indicators of chromosomal instability and actionable mutations were identified.
Effect of very low doses of chemotherapeutic drugs on proangiogenic factors in tumor cells.
Authors: Muge Ocal, Fatma Gizem Sonugur, Cansu Babahan, Samira Abdi Abgarmi, Fikri Icli, Hakan Akbulut
Journal: Journal of Clinical Oncology (2017)

e23013 Background: The efficacy of the metronomic use of conventional chemotherapeutic drugs in the clinic has been linked to their anti-angiogenic activity. However, the dose level for the metronomic use of the drugs with regard to anti-angiogenic activity is not known. In the current study, we aimed to study the effects of very low doses of 5-florouracil (5-FU), irinotecan and oxaliplatin on the synthesis of pro-angiogenic factors in tumor cells. Methods: We first determined the IC50 doses of 5-FU, irinotecan, and oxaliplatin in human tumor cell lines (HT-29: colon cancer cells, MCF-7: breast cancer cells and LNCaP: prostatic carcinoma cells). Then we applied the drugs to the assigned cells at the dose levels of IC50, -1log, -2log and -3log of IC50. The effects of the drugs on both gene expression and protein secretion levels of pro-angiogenic genes including vascular endothelial growth factor A (VEGF-A), basic-fibroblast growth factor (bFGF), matrix metalloproteinase-9 (MMP-9), platelet-derived growth factor-beta (PDGF-B), interleukin-8 (IL-8) and factor secretion by real-time PCR and sandwich ELISA. Results: The IC50 levels of 5-FU, irinotecan, and oxaliplatin in tumor cells were found as shown in the Table. We found that -1logIC50 dose level of 5-FU efficiently suppressed the pro-angiogenic genes both at the gene expression and protein secretion levels. However, the -2logIC50 and -3logIC50 dose levels of both irinotecan and oxaliplatin significantly inhibited gene expression and protein secretion. Conclusions: In conclusion, our results suggest that irinotecan and oxaliplatin could be used as anti-angiogenic agents at the very low doses. The -1logIC50 dose for 5-FU and the -2log and -3logIC50 doses of irinotecan and oxaliplatin could be further tested in animal models and clinical trials. Table. The IC50 dose levels of the drugs in tumor cell lines. [Table: see text]
TCT-257 Impact of Percutaneous Coronary Intervention of Ostial vs Non-ostial Lesions on Short and Long-term Clinical Outcomes
Authors: Kareem Abdelshafi, Seung-Woon Rha, Ji Young Park, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, None ahmed mashaly, Yoonjee Park, Won Young Jang, Woo Hyeun Kim, Eun Jin Park, Ja Yeon Choi, Jin Oh Na, Cheol Ung Choi, Eung Ju Kim, Chang Gyu Park, Hong-Seog Seo
Journal: Journal of the American College of Cardiology (2018)
Artificial nutrition in palliative care cancer patients.
Authors: Bernard Lobato Prado, Andrea Z Pereira, Sandra Elisa Adami Gonçalves, Sonia Perez Cendon Filha, Fabiana Lucio, Polianna M R Souza
Journal: Journal of Clinical Oncology (2018)

e22190 Background: Enteral or parenteral nutrition are artificial nutrition (AN) do not improve the quality of life or overall survival of advanced cancer patients in the end-of-life. Instead, they are a potential source of morbidity, and current guidelines recommend that withdrawal should be considered. Emotional, cultural and religious values may influence the decision of suspending AN. Objectives: To evaluate the frequency of AN use among advanced cancer patients receiving inpatient palliative care over the last 5 years. Methods: We retrospectively reviewed the medical charts of 467 consecutive adult advanced cancer care patients receiving palliative care by a mobile consultation team, and that died during hospitalization between 2014 and 2017, at Hospital Israelita Albert Einstein, a tertiary care general hospital in São Paulo, Brazil Results: 467 eligible were evaluable. 65% were elderly (mean = 65±16 years), 51% were female, and 58% were catholic. 30% were at the end-of-life. The majority had leukemia, breast or gastrointestinal cancers (11-12%). 23% received AN (13% enteral and 10% parenteral). We evaluated our patients with Karnofsky test (mean = 51±22), ECOG (mean = 2,3±1,1) and PPS(mean = 54±21,5). In the end of life, 10% used parenteral nutrition and 15% enteral nutrition. We used less AN in end-of-life patients (p < 0,005). Its use decreased from year 2014 to 2017 (p < 0,005). No other significant associations were found between the use of AN, and patients demographics or clinical characteristics. Conclusions: 23% of palliative cancer care patients that died at our institution received AN. Its use is decreasing over the years. This reduction might have been a consequence of continuing education of health care providers involved in the care of these patients.
A retrospective analysis of carboplatin plus etoposide in patients with adrenal cortical carcinoma.
Authors: Matthew T. Campbell, Emily Lemke, Khaled M. Elsayes, Bana Bazerbashi, Amishi Yogesh Shah, Mouhammed Amir Habra
Journal: Journal of Clinical Oncology (2018)

e16591 Background: Unresectable/metastatic adrenal cortical carcinoma (ACC) is a rare malignancy with limited treatment options. The current standard of care is to provide etoposide, doxorubicin, cisplatin (EDP) with mitotane. However, many patients due to severity of Cushings syndrome or impaired renal function are not candidates for cisplatin based chemotherapy. Here we present our findings using carboplatin plus etoposide in 12 patients (pts) with ACC. Methods: We performed a retrospective review of 12 pts treated at MD Anderson Cancer Center from 2004-2017 who received carboplatin plus etoposide. Baseline characteristics were tabulated. An independent radiologist evaluated disease response using RECIST v1.1 and determined overall response rate (ORR). Overall survival from the time of initiation of chemotherapy was calculated using Kaplan Meier technique. Statistical analysis was performed using Microsoft Excel and GraphPad Prism Results: Of the 12 pts, 6 were male, the median age was 49.4 (range: 18-75), 6 were hormonally active (5 cortisol, 1 testosterone producing), 11 had metastatic disease, 3 had primary in place. 3 pts had received previous chemotherapy and 8 pts had failed treatment with mitotane. Glomerular filtration rate was below 60ml/minute in 5 of 12 pts (41.7%), and ECOG performance status was ≥ 2 in 3 of 12 (33%) patients. The median number of metastatic sites was 1.5, with 7 of 12 (58.3%) with lung metastasis, 4 of 12 (33.3%)with liver metastasis, and 3 out of 12 (25%) with bone metastasis. The median number of cycles of carboplatin plus etoposide was 5 (range 3-11), 7 out of 12 (58.3%) with concurrent mitotane. Best ORR was partial response in 4/12 (33%), stable disease 4/12 (33%), and progressive disease 4/12 (33%), of note 3 responses seen in hormonally active disease and in one patient previously treated with EDP. The median OS was 17.2 months. Conclusions: Carboplatin plus etoposide has activity in patients with ACC and should be considered in patients with conditions making them ineligible to receive cisplatin.