tbuckley/cabot-search huggingface dataset:
Identification and Functional Analysis of Novel miRNA Target Genes That Control Mesenchymal Stem Cell Function
Authors: Maria Roubelakis, Dimitra Zagoura, Ourania Trohatou, Pantelis Zotos, Vassiliki Bitsika, Sophia Kossida, Kalliopi I Pappa, Aristidis Antsaklis, Nicholas P. Anagnou
Journal: Blood (2008)
A comparison of neoadjuvant TP (nTP; docetaxel, T; cisplatin, P) versus nTPF in patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC).
Authors: J. Fayette, E. Lavergne, S. Chabaud, B. Favier, D. Girodet, P. Zrounba
Journal: Journal of Clinical Oncology (2011)

e16006 Background: nTPF is a standard induction chemotherapy for LAHNSCC but only proposed to patients (pts) in good health, younger than 70 years, without comorbidities including important weight loss. The aim of this exploratory study was to evaluate the impact of 5FU suppression in LAHNSCC pts, non eligible for nTPF treatment, in terms of safety and efficacy. Methods: Between December 2005 and November 2009, 14 pts with LAHNSCC were treated with nTP (T and P 75 mg/m2, both d1) q3 weeks, with prophylactic G-CSF for 3 cycles (C) in our institution. Study population was described and survival analysis was performed using the Kaplan Meier method. Results: Median age at diagnosis was 59 years [42-75]. Pts received nTP rather than nTPF because of denutrition, history of cardiovascular disease or advanced age. Tumor localizations were: oral cavity (7%), oropharynx (29%), hypopharynx (43%), larynx (7%) and rhinopharynx (14%). Eight (57%) pts were inoperable. Three pts had only one C (1 due to toxicity and 2 because radiochemotherapy was planed after this first C), 1 received 2 C (grade 3 mucositis and progression) and 3 received 4 C. Three pts required secondary hospitalization after the first C (2 for febrile neutropenia and 1 for grade 4 colitis). No febrile neutropenia neither secondary hospitalization were observed during the following C. Five pts (36%) had CR and 7 (50%) reached PR for an ORR of 86%. We observed 1 PD and 1 SD (the pt benefited from radical surgery and was still alive). All pts, except one, were irradiated including 10 (77%) with potentialization (4 with q1w cisplatin, 4 with q3w cisplatin, 2 with cetuximab). None needed temporary interruption of radiotherapy but 5 had to stop chemotherapy before the radiotherapy’s end because of toxicity. No toxic death occurred. After potentialization, 11 pts (92%) had CR. We list 3 progressions (2 relapse and 1 progression during induction). These 3 pts died and 11 were still alive. With a median follow-up of 25 months (95% CI [15-35]), 2-year OS was 73% (95% CI [37 – 91]). Conclusions: These preliminary and encouraging results raise the interest for a future comparison between nTP and nTPF regimen in pts with LAHNSCC.
Epidemiologic differences among colon cancer patients diagnosed before age 85 those diagnosed after age 85.
Authors: R. J. Edmonds, S. Subbiah, A. K. Ganti, P. T. Silberstein
Journal: Journal of Clinical Oncology (2011)

e19684 Background: There is little data concerning the survival and rate of surgical resection of individuals diagnosed with colon cancer over the age of 85. Methods: The SEER 17 Database 1988-2003 malignant behavior colon (excluding rectal) cancer cases were used to analyze the epidemiological differences between patients diagnosed over the age of 85 and younger peers. Tumors recorded were as follows using AJCC Staging 3rd edition. Results: Surgery was performed at 99% in both age groups for stages I-III. SEER records data on approximately 28% of the U.S. population, therefore by extrapolation, approximately 3,490 colon cancer patients over the age of 85 received surgery per year in the United States. Surgical resection was associated with improved survival in Stages I-III for both age groups (ANOVA p<.0001), as well as those over the age of 100 at diagnosis (Table). The largest cohort were Stage II patients; those who received surgery had a median survival of: 117.75 months (pts <85); 39.64 months (pts >85); 7.5 months (pts <100). Conclusions: Stage at presentation, surgical resection rates are very similar in both age groups. Surgical resection was associated with improved survival in both age groups, and lack of surgery led to inferior outcomes in both groups. Patients over the age of 85 appeared to have benefitted from surgery when compared to those who did not receive surgery. About 3,500 patients over the age of 85 per year in the United States have colon cancer surgery and their survival is about 1/3 that of younger patients. Surgery performed No surgery performed 0-84 85+ 100+ 0-84 85+ 100+ Stage 1 Survival in months 154.22 50.11 38.5 55.79 9.75 4 n 30,286 3,004 9 258 94 2 Stage 2 Survival in months 117.75 39.64 7.5 8.17 3.25 N/A n 47,795 7,237 29 274 61 0 Stage 3 Survival in months 64.13 20.16 4.25 17.13 6 0.5 n 40,365 4,436 25 141 20 1
Incidence, management, and resolution of noninfectious pneumonitis in BOLERO-2.
Authors: Yoshinori Ito, Shinzaburo Noguchi, Ines Deleu, José Baselga, Gabriel N. Hortobagyi, Thomas Denis Bachelot, Norikazu Masuda, Barbara Pistilli, Kathleen I. Pritchard, Hiroji Iwata, Michael Gnant, J F Eakle, Tibor Csõszi, Vichien Srimuninnimit, Puttisak Puttawibul, Fausto Roila, Ashok Panneerselvam, Tanya Taran, Tarek Sahmoud, Hope S. Rugo
Journal: Journal of Clinical Oncology (2013)

561 Background: The BOLERO-2 trial showed that adding everolimus (EVE) to exemestane (EXE) more than doubled progression-free survival (PFS) without reducing quality of life versus placebo (PBO) + EXE alone in postmenopausal women with hormone-receptor–positive (HR + ), HER2-negative (HER2 – ) advanced breast cancer (ABC) progressing on/after nonsteroidal aromatase inhibitor (NSAI) therapy. Although generally well tolerated, mTOR inhibitors such as EVE have been associated with noninfectious pneumonitis (NIP). Methods: Patients (pts) were randomized 2:1 to receive EVE+EXE or PBO+EXE. Incidence and severity of NIP, consequent dose interruptions/adjustments, study drug discontinuations, and time to resolution were recorded. Results: Median duration of exposure to EVE was 24 weeks with median dose intensity of 8.6 mg/d. Pulmonary adverse events (AEs) of any grade (NIP, interstitial lung disease, lung infiltration, pneumonia, or pulmonary fibrosis) were recorded in 97 of 482 pts (20%) in the EVE+EXE arm versus 1 of 238 pts (&lt;1%) in the PBO+EXE arm. Of these, 16% of pts (77 of 482) in the EVE+EXE arm versus 0 in the PBO+EXE arm had a diagnosis consistent with NIP. In the EVE+EXE arm, grade 1 (no symptoms), grade 2 and 3 NIP occurred in 7%, 6% and 3% of pts, respectively, and no grade 4 events were reported. Complete resolution of NIP to grade ≤1 was recorded for all but 4 pts for whom NIP was still observed at last follow-up before study discontinuation. Overall, in the EVE+EXE arm, NIP was recorded as the reason for dose interruption and treatment discontinuation in 7.5% and 5.6% of pts, respectively. Conclusions: Data from BOLERO-2 support the combination of EVE and EXE to significantly prolong PFS in postmenopausal women with HR + , HER2 – ABC progressing on/after NSAI. The incidence of NIP in this study was generally consistent with reports from other oncology settings, was of mild to moderate severity, and was generally reversible with appropriate interventions and temporary dose modifications. Patient and healthcare provider education for early diagnosis and management of NIP are highly recommended. Clinical trial information: NCT00863655.
Age, race, BMI, and pathologic complete response following neoadjuvant chemotherapy: An analysis of four alliance clinical trials.
Authors: Erica T Warner, Karla V. Ballman, Aman Buzdar, Lisa A. Carey, William M. Sikov, Carrie Strand, Ann H. Partridge
Journal: Journal of Clinical Oncology (2015)

33 Background: Pathologic complete response (pCR) is an important prognostic indicator and surrogate endpoint, particularly for patients with hormone receptor-negative breast cancer. Previous studies have suggested differential response to pre-operative therapy by age and body mass index (BMI), though no association has been seen by race. We assessed associations of age at diagnosis, BMI and race with pCR accounting for breast cancer subtype. Methods: Women enrolled in four clinical trials of neoadjuvant chemotherapy (CALGB 40601 and 40603; ACOSOG Z1031 and Z1041) were eligible for this analysis. Age, race, and BMI were abstracted from patient records at baseline. Tumor subtype was assessed using immunohistochemical staining and/or fluorescence in situ hybridization. Logistic regression models were used to determine the association of race/ethnicity and age at diagnosis with pCR, the absence of residual invasive disease in the breast after neoadjuvant chemotherapy, adjusting for subtype (HER2+, ER+/ HER2-, triple negative), age, study arm, lymph node status, tumor size, and tumor grade. Results: 1,146 women with a mean age of 51.5 years were included. 156 (13.6%) were of black race. 590 (51.5%) of tumors were HER2+, 169 (14.7%) were ER+/HER2- and 387 (33.8%) were triple negative. In multivariate analyses controlling for tumor characteristics and other factors, black race (OR: 1.07, 95% CI: 0.67-1.70), age (OR: 0.99, 95% CI: 0.97-1.00) and BMI (OR: 0.99, 95% CI: 0.96-1.01) were not significant predictors of pCR. Similar associations we observed when stratified by subtype, and we found no interaction between age and black race (p=0.06), black race and BMI (p=0.54) or age and BMI (p=0.73). Conclusions: After accounting for tumor characteristics, we observed no differences in pCR rates according to race, age or BMI.
Phase II trial of fixed-dose rate gemcitabine, bevacizumab, and concurrent 30 gy radiotherapy as preoperative treatment for potentially resectable pancreatic adenocarcinoma.
Authors: George Van Buren, Ramesh K. Ramanathan, Alyssa M Krasinskas, Ryan Smith, Gerard J. Abood, Yongli Shuai, Douglas M. Potter, Nathan Bahary, Barry C. Lembersky, Amer H Zureikat, David L. Bartlett, Herbert Zeh, Arthur J Moser
Journal: Journal of Clinical Oncology (2012)

258 Background: Effective multimodality treatment for localized pancreatic cancer is elusive. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with short-course radiotherapy (RT) and the angiogenesis inhibitor bevacizumab (BEV) would improve margin negative surgical outcomes and complete pathological response rates. Methods: Multisite phase II trial evaluating all potentially-resectable pancreatic adenocarcinoma without major arterial involvement or portal venous occlusion. Dual primary endpoints included complete pathological response and margin negative resection rates of 10% and 80%. Subjects received FDR GEM on days 1, 15, and 29 combined with BEV (10 mg/kg IV), followed on day 43 by BEV and concurrent 30 Gy RT (3 Gy/fraction) over 10 days. After restaging, subjects underwent laparoscopy and possible resection after day 85. Stopping criteria required continuous monitoring of serious wound complications. Results: 58 subjects enrolled, of which 29 (50%) had suspected venous involvement. 57 completed treatment without dose-limiting toxicity or delays in surgery. Two grade 4 (3.4%) and 17 grade 3 toxicities (28.8%) occurred. Four patients progressed before surgery. 54 subjects underwent laparoscopy; ten had unexpected carcinomatosis, and one was unresectable. 43 subjects were resected (74%; 33 pancreatico-duodenectomy, 8 distal pancreatectomy, 1 total pancreatectomy, 1 Appleby); 19 (44%) required portal vein resection. Margin negative outcome was achieved in 38 (88%, 95% CI: 75%-96%) with one complete pathological response (2.3%; 95% CI: 0.1%- 12%) and seven (6 grade 3; 1 grade 4) wound complications (13%). Median overall survival (OS) was 16.3 months (95% CI: 13.9 -22.1) and 21.3 months (95% CI: 15.0-32.9) after resection. Median progression-free survival (PFS) was 5.7 months (95% CI: 3.9-9.1) and 9.9 months (95% CI: 5.7 to 14.1) after resection, with 7 local and 21 distant recurrences. Conclusions: Combination therapy was well-tolerated and was within statistical design parameters for the primary endpoints despite a significant proportion of borderline tumors.
Using radiologic response to predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy.
Authors: Shingo Hatakeyama, Hayato Yamamoto, Akiko Okamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2014)

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to &lt;pT2 was 37 (49%) in responders, 5 (13%) in non-responders group. Radiologic response was a strong predictor of DFS and OS. A 5-year advantages of DFS and OS in responders vs. non-responders were 88% and 86% vs. 64% and 69%, respectively (P=0.021 and P=0.013). Multivariate analysis showed radiologic response was the independent factor for DFS and OS. Conclusions: Radiological response post carboplatin-based neoadjuvant chemotherapy is associated with OS in patients with MIBC.
Palonostron with aprepitant plus dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) during gemcitabine/cisplatin (GC) in urothelial cancer (UC) patients: A multi-institutional retrospective study in Japan.
Authors: Hiroshi Kitamura, Atsushi Takahashi, Hiroshi Hotta, Ryuichi Kato, Yasuharu Kunishima, Fumiyasu Takei, Hiroki Horita, Naoya Masumori
Journal: Journal of Clinical Oncology (2014)

362 Background: GC combination chemotherapy of is a standard regimen for advanced UC. Although this is a highly emetogenic chemotherapy, there has been no study concerning antiemetic prophylaxis for CINV during GC. The aims of this study were to evaluate CINV during GC and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-HT3 receptor antagonists and dexamethasone. Methods: We conducted a retrospective multi-institutional review of the medical records of 122 patients who received GC for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled CINV events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake. Nausea, vomiting, and anorexia were classified using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Results: A total of 75 and 47 patients were treated with first-generation 5-HT3 receptor antagonists (ondansetron or granisetron) plus dexamethasone (group 1) and palonosetron with dexamethasone plus aprepitant (group 2), respectively. There was no significant difference in age, sex, or the dose of cisplatin between the 2 groups. Patients in group 2 had significantly higher CR (defined as no emetic episodes and no rescue medication use) rates than those in group 1 during the overall phase in the first cycle (85.7% versus 65.3%, p=0.012) and all cycles (78.7% versus 50.7%, p=0.0019) of GC. Patients in group 2 were more likely to achieve more favorable CINV control, e.g., a lower grade of nausea, vomiting, or anorexia, lower incidence of rescue therapy required, and shorter time to become CINV-free, than patients in group 1. Conclusions: This study shows that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in UC patients treated with GC than first-generation 5-HT3 receptor antagonists plus dexamethasone.
Gingkolide B is a potential therapeutic agent in ovarian cancer through PAF-PAFR signaling pathways
Authors: B. Ye, W. Jiang, S. C. Mok, D. Cramer
Journal: Journal of Clinical Oncology (2008)

16538 Background: Our previous studies have identified Ginkgo Biloba as a chemopreventivepotential alternative agent for ovarian cancer. prevention. Ginkgolide B is a well-known natural inhibitor of Platelet-Activating Factor (PAF)−a potent proinflammatory phospholipid with multiple pathological effects. PAF and its receptor (PAFR) oftenhave been often activated expression of oncogenes, proliferation, angiogenesis, invasion and metastasis. Our goal in this study was to explore is to define ginkgolide B as a as potential agent in ovarian cancer therapy through and PAF-PAFR pathways. as new target for ovarian cancer therapy. Methods: Quantitative PCR (qRT-PCR) was performed for gene expression analysis in ovarian cell lines. Laser captured microdissected tissue from cancer patients was processed for RNA extraction and qRT-PCR.ovarian cancer patient groups. Western blot and IHC were used to measure PAFR protein expression in cancer cell lines and tissue micro-arrays. In vitro proliferation and invasion assays were performed with of treatment ginkgolide B, PAFR antibody and siRNA. Ginkgolide B induced Aanti-cancer efficacy of ginkgolide B was evaluated in xenograft mice. Results: PAFR expression was were significantly increased in 9 of 13 cancer cell lines (up to 10,000-fold) but were not detected in all normal HOSE and mucinous cells. PAFR was significantly (p<0.0001) overexpressed (10–1000 fold) in early and late stages serous, endometrioid and clear cell type ovarian cancers, but not in mucinous cancer patients. Interestingly, PAF-induced cell proliferation and invasion were dependent on are PAFR-expression dependent and was significantly blocked by ginkgolide B or and PAFR antibody. It may due to competitive to PAFR and turn on pleiotropic tyrosine phospho-EGFR/Src/FAK/Paxillin signaling pathways. After 8 weeks ginkgolide B treatment (1.0 mg/mice per day) in mice with xenograft ovarian tumors, the average tumor mass was 0.27g/mice (n=6) (p<0.05) compared to the control mice group 2.2 g/mice (n=6). Conclusions: Our in vitro and in vivo study strongly suggests that PAF-PAFR is a potential therapeutic target for ovarian cancer. Ginkgo and the derived active ginkgolide B could be potential alternative therapeutic agents for future clinical trial. No significant financial relationships to disclose.
Phase II study of everolimus in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum.
Authors: D. Yoon, M. Ryu, Y. Park, H. Lee, C. Lee, J. Lee, B. Ryoo, H. Chang, T. Kim, Y. Kang
Journal: Journal of Clinical Oncology (2011)

93 Background: To evaluate feasibility with activity and toxicities of everolimus, a novel inhibitor of mammalian target of rapamycin (mTOR), in patients with advanced gastric cancer (AGC) who failed chemotherapy including both fluoropyrimidine and platinum (FP). Methods: Fifty-four patients were enrolled between Jul 2008 and Feb 2010. Everolimus, 10 mg daily, was given until disease progression or unacceptable toxicity. Primary objective was to determine 4-month progression-free survival (PFS) and secondary objectives were to investigate response rate, toxicity and overall survival OS rate. Pre- (n = 28) and on-treatment (n = 19) tumor biopsies were evaluated for phosphorylated (p) mTOR, pS6 kinase1, pS6 and eukaryotic initiation factor 4E binding protein 1 expression. Results: A total of 180 cycles of everolimus were administered with a median of 2 (range, 1-20) cycles in each patient. Two patients (3.7%) achieved confirmed partial response and 19 patients (35.2%) showed stable disease, resulting in a disease control rate of 38.9%. At a median follow-up duration of 8.7 months in surviving patients (range, 3.0–19.4 months), a 4-month PFS rate was 18.4% with a median PFS of 1.7 months (95% CI, 1.5-2.2 months) and a median OS time was 8.3 months (95% CI, 4.5-12.1 months). Peritoneal metastasis (Hazard ratio [HR], 3.97; 95% CI, 1.54-10.23; p = 0.010) and low expression level of pS6 Ser240/4 at baseline (HR, 7.64; 95% CI, 2.591-22.51; p = 0.001) were significantly associated with shorter PFS time. Treatment was in general well tolerated. Toxicities of grade 3/4 included anemia (9.4%), thrombocytopenia (9.4%), hepatic dysfunction (11.3%) and pulmonary toxicities (one interstitial pneumonitis and a diffuse alveolar hemorrhage [DAH] case). The DAH and cardiopulmonary dysfunction in another case resulted in treatment-related mortalities. Conclusions: Everolimus monotherapy showed modest activity against AGC refractory to FP. pS6 Ser240/4 might be a potential biomarker for the clinical activity of everolimus. The toxicity profile was generally mild. However, careful monitoring for treatment-related pulmonary complication seems to be required. [Table: see text]