tbuckley/cabot-search huggingface dataset:
Robotic-assisted laparoscopic prostatectomy in obese patients: The Columbia University experience
Authors: A. W. Levinson, D. B. Samadi, S. M. Collins, A. E. Urdaneta, E. T. Goluboff, M. C. Benson
Journal: Journal of Clinical Oncology (2006)

14619 Background: In addition to being more likely to be found with more aggressive prostate cancer (PCa), obese patients (OPs) face challenges with treatment options for localized PCa. Several studies have shown that open radical retropubic prostatectomy, pure laparoscopic, and robotic-assisted laparoscopic prostatectomy (RALP) may be associated with increased operative times, blood loss, and even a higher rate of capsular incision. We examined our own experience with the surgical and pathologic outcomes of OPs undergoing transperitoneal RALP at our institution. Methods: We queried the Columbia University IRB approved database for transperitoneal RALPs performed by a single fellowship trained laparoscopic oncologist (DS) for which body mass index (BMI) data was available. We identified patients who met the CDC definition of obese (BMI &gt; or = 30 kg/m 2 ) at the time of surgery. We compared surgical and pathologic outcomes between these OPs and NOPs. Of note, operative time was defined as the time from initial trocar placement to skin closure, and does not include robotic set-up time. Results: BMI data was available for 78% of RALP patients in the database. We identified 22 OPs (mean BMI 32.7 (30.1 to 46.7)) and 112 NOPs (mean BMI 25.6). One patient in each group was converted to open. There were no statistically significant differences in the surgical outcomes of mean blood loss, operative time or length of stay for the OPs vs. NOPs (179cc v. 191cc, 213min v. 221min, and 1.4d vs. 1.7d, respectively). There was no significant difference in preoperative PSA, pre-treatment MSKCC 5yr progression-free probability, pre or post-operative Gleason sum, margin status, or perioperative complications. There was a trend towards increased prostatic volume in OPs vs NOPs (51cc vs 44cc, p = 0.10). Conclusions: Unlike a prior robotic, pure laparoscopic and ORRP series, OPs who received transperitoneal RALP at our institution had no statistically significant increases in blood loss, operative time or perioperative complications when compared to their non-obese cohorts. We believe RALPs may be safely recommended to OPs as an option for treatment of localized prostate cancer. No significant financial relationships to disclose.
Abstract 13832: Prognostic Value of Plasma Concentration of Soluble Thrombomodulin, a Marker for Endothelial Damage, in Patients Undergoing Elective Coronary Angiography for Suspected Coronary Artery Disease
Authors: Shigeru Matsui, Junnichi Ishii, Ryuunosuke Okuyama, Tousei Hashimoto, Kousuke Hattori, Hideki Kawai, Masanori Okumura, Hiroyuki Naruse, Sadako Motoyama, Hideo Izawa, Yukio Ozaki
Journal: Circulation (2012)

Background: Thrombomodulin is a transmembrane protein expressed constitutively in endothelial cells. In spite of being mostly located on endothelial cells of arteries, there is, however, a small am...
Irinotecan combined with infusional 5-fluorouracil and high-dose leucovorin (FOLFORI) for the treatment of advanced gastric carcinoma as the first-line chemotherapy
Authors: U. Yilmaz, I. Oztop, A. Alacacioglu, A. Yaren, O. Tarhan, I. Somali
Journal: Journal of Clinical Oncology (2005)

4164 Background: Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is need for newer regimens. Methods: Twenty-five chemo-naive patients (pts) with stage IV AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m2 over 30 minutes on day (d) 1 combined with leucovorin 200 mg/m2 over 2 h followed by 5-FU 400 mg/m2 bolus and 600 mg/m2 as 22 h infusion on d 1 and 2. The treatment was administered every 14 day until progression or intolerable toxicity. Results: Twenty-five pts (17 male/8 female); median age 54 (range 25–77), 22 pts with PS 0–1 and 3 pts with PS 2), received a total of 230 courses of chemotherapy (median 9; range 1–18). Objective response was observed in 9 pts (36%), all being partial. Median progression-free survival (PFS), 1 and 2 year PFS rates were respectively 9.3 months (mo), 28.4% and 15.3%. Median overall survival (OS), 1 and 2 year OS rates were respectively 12.6 mo, 48.0% and 17.8%. As serious adverse events, grade 3–4 neutropenia was observed in 5 pts (20.0%), grade 3 diarrhea in 4 (16.0%) pts. No treatment-related death occurred. Conclusions: FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC. No significant financial relationships to disclose.
Translational disequilibrium as an interference marker to study miRNA and methylation silencing of APRIN, a stem cell regulator in breast cancer microchimerism
Authors: P. Geck, V. Denes, M. Pilichowska, A. Makarovskiy, G. A. Carpinito
Journal: Journal of Clinical Oncology (2009)

11109 Background: Gene silencing is universally observed in cancer and involves promoter DNA methylation. We found that a cohesin-related stem cell regulator, APRIN (Pds5B) was silenced in breast cancer clinical samples. Surprisingly, in 40% of these samples DNA methylation was not involved. Furthermore, in some breast cancer cell lines the APRIN protein was silenced without transcript downregulation or promoter methylation. This “translational disequilibrium” has been frequently reported with other proteins, but without mechanistic explanations. Recent results with RNA interference indicate that gene repression through microRNAs (typically mismatched) is mostly translational without transcript degradation. We propose, therefore, that the puzzling translational disequilibrium phenomenon is a new form of epigenetic silencing by miRNA mechanisms. We aim (i) to verify miRNA epigenetics of APRIN silencing in breast cancer cell lines; (ii) to study clinical breast cancer samples for methylation vs. miRNAs mechanisms in APRIN translational disequilibrium; and (iii) to investigate if miRNA silencing of APRIN affects a fetal embryonic stem cell pool in breast cancer (microchimerism). Methods: (i) We used miRNA mimics and miRNA inhibitors in breast cancer cell lines to verify specific miRNA involvement in APRIN silencing. (ii) We used immunohistochemistry with bisulfite converted DNA for methylation and microdissected RNA for microRNA interference studies from 56 clinical breast cancer samples. (iii) We used Y-chromosome markers on microdissected DNA for fetal microchimerism studies. Results: (i) We found that in breast cancer cell lines with APRIN translational disequilibrium a set of microRNAs correlate with APRIN silencing. (ii) We found miRNA related mechanisms in about 35 percent of breast cancer samples where APRIN was silenced and (iii) APRIN may specifically affect stem cells of fetal origin in the mother's mammary gland and contribute to cancer. Conclusions: The novel miRNA-based mechanism maybe a new epigenetic factor of gene silencing in cancer. We experimentally confirmed a set of APRIN specific miRNAs and established preliminary correlations with fetal microchimerism in breast cancer. No significant financial relationships to disclose.
Biomarkers for cetuximab-based neoadjuvant radiochemotherapy in advanced rectal cancer.
Authors: D. Vallbohmer, P. P. Grimminger, D. Yang, K. D. Danenberg, P. Danenberg, D. Arnold, J. H. Machiels, C. Roedel, V. Velenik, H. Lenz
Journal: Journal of Clinical Oncology (2010)

3563 Background: Recent phase II trials in locally advanced rectal cancer patients have shown that cetuximab-based neoadjuvant radiochemotherapy is feasible but without a significant improvement of clinical outcome. In order to identify a subgroup of patients with a marked benefit,we assessed gene expression of factors involved in tumor growth (EGFR), angiogenesis (VEGF, VEGFR1, VEGFR2d), DNA repair (ERCC1) and drug metabolism (TS) as well as KRAS gene mutation status to characterize molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation followed by surgery. Methods: 130 patients with locally advanced rectal cancer who were enrolled in phase II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Tumor tissue was obtained prior to neoadjuvant and after surgical therapy. Histomorphologic regression was defined using a modified Dworak regression system (grade 0/1: nonresponse; grade 4: complete response). After microdissection and extraction of the RNA/DNA, intratumoral gene expression levels and KRAS mutation status were analyzed. Results: Asignificantly decrease of TS, VEGFR1 and VEGFR2d expression was detected during neoadjuvant therapy (p < 0.02). High pre-therapeutic VEGF expression was significantly correlated with nonresponse (p = 0.033). KRAS mutations were found in 42 % of the patients. The mutation status (wild type [wt] vs. mutant [mt]) was significantly correlated with response: patients with a wt-status showed more frequently a complete response to neoadjuvant treatment (p = 0.025). In patients with a wt-status, high VEGF and EGFR mRNA expressions were significantly associated with complete response (p < 0.04). KRAS transversions (tv) vs. wt-status was also associated with tumor regression: nonresponse was more common in patients with KRAS tv (p = 0.007). Conclusions: This study suggests pretherapeutic intratumoral EGFR and VEGF mRNA expression as well as KRAS mutation status to be predictive markers for tumor response to neoadjuvant cetuximab-based chemoradiation of patients with locally advanced rectal cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Response Genetics Bristol-Myers Squibb, ImClone Systems, Merck KG Response Genetics Bristol-Myers Squibb, ImClone Systems, Merck KG, Merck Serono, Roche, sanofi-aventis Merck, Roche, sanofi-aventis
Respect of Average Relative Dose Intensity Correlates with Survival in Diffuse Large B Cell Lymphoma Patients Treated by CHOP: A National Retrospective Study (1995–2000).
Authors: Andre Bosly, Bron Dominique, Van Hoof Achiel, De Bock Robbrecht, Berneman Zwi, Ferrant Augustin, Verhoef Gregor
Journal: Blood (2004)
A multicentric randomized phase III study to evaluate the equivalence between lanreotide PR 60 mg vs lanreotide Autogel 120 mg in well-differentiated neuroendocrine tumours (NETs)
Authors: E. Bajetta, G. Procopio, L. Catena, L. Ferrari, S. Ricci, S. Iacobelli, G. Cartenì, F. De Braud, P. Loli, P. Vezzadini
Journal: Journal of Clinical Oncology (2004)

4154 Background: Somatostatin analogues represent the treatment of choice for inoperable well-differentiated NETs, mainly for symptomatic patients (pts). Methods: Sixty pts with histologically proven well-differentiated NETs (accordingly to the WHO classification) were randomized to receive lanreotide prolonged release (PR) 60 mg every 3 weeks or the new drug formulation Autogel (ATG) 120 mg every 6 weeks, Primary end point was to show the equivalence between the PR and the ATG formulations in terms of clinical, symptomatic and biochemical responses. Secondary endpoints were the evaluation of tolerability, progression-free and overall survival. The estimated accrual of 30 pts for each randomization arm was achieved, accordingly to the test of Dunnet and Gent for proving the non-inferiority of the lanreotide ATG formulation. Pts were treated until progression. Globally, 40 males and 20 females were studied (median age 61, range 29–81). Primary tumour site: small bowel 37%, pancreas 27%, lung 13%, unknown 18% and others 5%. Most of the pts were pretreated: 54% with octreotide and 22% with chemotherapy. Thirty-one percent of pts had carcinoid syndrome and 85% of pts had increased levels of chromogranin A. Results: Accrual was accomplished with 30 pts receiving lanreotide PR 60 mg and 30 pts lanreotide ATG 120 mg. Six pts are still on treatment. Partial tumour responses were observed in 7% (95% C.I.: 2–16%) and 0 pts treated with PR and ATG formulation, respectively. Disease stabilization was demonstrated in 75% (C.I.: 59–90%) and 77% (C.I.: 62–92%) of the pts (PR vs ATG) and disease progression in 20% (C.I.: 6–34%) and 23% (C.I.: 8–38%) of the pts (PR vs ATG). Both the formulation allowed an adequate biochemical control. There were no side effects leading to a treatment discontinuation. Conclusion: Our preliminary data seem to demonstrate a similar clinical efficacy of lanreotide ATG 120 mg with respect to lanreotide PR 60 mg. No significant financial relationships to disclose.
A prospective study of the interaction between p53 genotype and overall survival in patients with colorectal cancer liver metastases (CRCLM) with and without neoadjuvant therapy (oxaliplatin and capecitabine/5-FU): A p53 research group study
Authors: D. Kandioler, N. Pilat, S. Kappel, T. Gruenberger, F. Laengle, M. Mittlboeck, B. Herberger, I. Kuehrer, R. Jakesz, F. Muehlbacher
Journal: Journal of Clinical Oncology (2009)

e15003 Background: Mutations in the p53 gene have been suggested as both a marker of tumour aggressiveness and a means of predicting response to chemotherapy. Unfortunately, there remains no clear evidence that p53 gene mutation affects cancer survival rates. Methods: We sought to evaluate whether mutation in the p53 gene is a marker of more aggressive tumours or of chemotherapeutic failure. Between 2001 and 2003 we collected data prospectively on 76 patients with CRCLM at a single institution. Patients considered to be technically operable were included. 51 patients received preoperative therapy with oxaliplatin plus 5-FU or capetcitabine and 25 were treated with surgery only. Treatment decision was based on the preference of the surgeon or the patient. The groups did not differ in age, chronicity of CRCLM, staging and grading of the primary colorectal cancer. The p53 gene was assessed in all tumours through complete direct gene sequencing (Exon 2–11 including splice sites). Results: For entire cohort the p53 gene mutation rate was 55%, and the median survival was 44.2 months. The overall death rate was 51%. There were 14 (41%) deaths in patients with a normal p53 gene compared to 25 (60%) deaths in patients with mutations in this gene (Logrank P=0.079). For patients that received only surgical treatment the overall death rate was 48% and was unaffected by the presence of p53 gene mutation (Logrank P=0.54). For patients who received neoadjuvant chemotherapy, median survival was 44 months if they had a normal p53 gene compared to only 20 months in patients with p53 gene mutations. The unadjusted hazard ratio for death was 3.24 in the p53 mutation group compared those with a normal p53 gene (95 percent confidence interval 1.5 to 7.0; P=0.045). The adjusted hazard ratio for death in patients with a p53 gene mutation receiving neoadjuvant chemotherapy was 5.5 (95% CI 2.3 to 13.2; P=0.0042). Conclusions: In CRCLM patients receiving neoadjuvant chemotherapy, the p53 gene mutation predicts overall survival. Our data suggests an interaction between the p53 gene and chemotherapy in patients with colorectal liver metastasis. No significant financial relationships to disclose.
A phase II study of a novel anti-tubulin, E7389, in patients with advanced non-small cell lung cancer (NSCLC)
Authors: A. Das, A. Spira, N. Iannotti, M. Savin, E. Zang, K. Datta, G. Shapiro, M. Patturajan, S. Silberman
Journal: Journal of Clinical Oncology (2006)

7106 Background: E7389, a synthetic analog of halichondrin B that was isolated from a marine sponge, has broad anti-proliferative activity at nanomolar levels and a unique profile of tubulin interactions. Methods: This is an open-label, single-arm, stratified phase II study of E7389 in patients with measurable, recurrent and/or metastatic NSCLC who progressed during or after platinum-based doublet chemotherapy. E7389 (1.4 mg/m 2 ) was administered as a bolus IV on days 1, 8, and 15 of a 28-day cycle to 72 patients (cohort 1) in stratum I (55 taxane pretreated patients) and stratum II (17 taxane-naive patients) and on Days 1 and 8 of a 21-day cycle (cohort 2), providing an additional 22 patients in stratum I. The primary efficacy endpoint was objective response rate to E7389 monotherapy. Results: As of 9 December 2005, 94 evaluable patients received E7389. Nineteen tumors were classified as squamous cell carcinomas, 39 as adenocarcinomas, and 36 were large cell carcinomas or unclassified. The median number of cycles completed was 3. Fifteen patients completed 6 or more cycles and 75 patients underwent tumor assessments after cycle 2. Major toxicities related to study drug included myelosuppression, nausea, fatigue, dehydration, arthralgias, dyspnea, and peripheral neuropathy. Based on RECIST criteria, 6 partial responses (PR) were observed among 94 evaluable patients (PR rate = 6.4%, 95% CI: 2.8%, 12.8%). For 33 patients the best response was stable disease (SD rate = 35.1%, 95% CI: 25.5%, 45.1%). Disease control rate (PR + SD) was 41.5% (95% CI: 31.4%, 51.7%). For cohort 1, the 12-week progression free survival rate was 57.2%. As of 9 December 2005, median PFS time was 108 days (95% CI = 55, min-max = 1–239+). Cohort 2 is being followed to estimate their 12-week PFS. The correlation of beta tubulin isotype, stathmin, microtubule-associated protein 4 (MAP4) and tau protein mRNA expression with tumor responses is on-going. Conclusions: Based on this data, E7389 has been shown to be safe and effective in the treatment of NSCLC patients. Updated information and results of molecular correlations of responses will be presented. [Table: see text]
Improved Response Rate with Bortezomib Consolidation After High Dose Melphalan: First Results of a Nordic Myeloma Study Group Randomized Phase III Trial.
Authors: Ulf-Henrik Mellqvist, Jan Westin, Peter Gimsing, Oyvind Hjertner, Stig Lenhoff, Edward Laane, Kari Remes, Hlif Steingrimsdottir, Niels Abildgaard, Lucia Ahlberg, Kristina Carlsson, Inge Marie Dahl, Karin Forsberg, Tobias Gedde-Dahl, Henrik Gregersen, Astrid Gruber, Nina Guldbrandsen, Einar Haukås, Olle Linder, Hareth Nahi, Ingerid Nesthus, Nilsaage Toffner-Clausen, Raija Silvennoinen, Niels Frost Andersen, Ingemar Turesson, Anders Waage
Journal: Blood (2009)
Combining glycolytic inhibitors with chemotherapy: Phase I trial of 2-deoxyglucose and docetaxel in patients with solid tumors
Authors: L. E. Raez, J. Rosenblatt, J. Schlesselman, V. Langmuir, G. Tidmarsh, C. Rocha-Lima, K. Papadopoulos, J. O’Connor, P. Baldie, T. Lampidis
Journal: Journal of Clinical Oncology (2005)

3190 Background: Although hypoxia is known to contribute to tumor cell resistance to chemotherapeutic agents by slowing growth, it also provides a window of selectivity for glycolytic inhibitors, such as 2-deoxy-D-glucose (2DG). Thus, the combination of chemotherapy and 2DG (to selectively kill slowly dividing cells) is expected to be more effective than either agent alone. We previously demonstrated this in mouse xenografts of human osteosarcoma and lung cancer cell lines with 2DG + adriamycin and 2DG + paclitaxel (CancerRes;.2004 64:31–4). Methods: We designed a phase I clinical trial with the following aims: (1) To determine the maximum tolerated dose (MTD) of daily oral doses of 2DG given alone and in combination with weekly docetaxel (DC) in patients (pts) with advanced solid malignancies who failed chemotherapy previously; (2) To evaluate the pharmacokinetics (PK) of 2DG after single and multiple doses when given alone and in combination with weekly DC and (3) To evaluate the biologic effect of 2DG alone and in combination with weekly DC on tumor uptake of 18F-fluorodeoxyglucose using positron-emission tomography. 2DG was administered daily for 7 days every other week starting at a dose of 2mg/kg, and DC was administered at 30mg/m2 for 3 of every 4 weeks beginning Day 1/Week 2. Results: To date 12 pts with various types of malignancies. i.e. breast, head and neck, lung, and adenoid cystic carcinoma have entered the trial. A modified accelerated titration design was used where single subjects were enrolled at different dose levels and each dose level was increased by 100% until dose-limiting toxicity (DLT) occurred in one subject at 64mg/kg (transient asymptomatic Grade 3 hyperglycemia). However this patient was found to be glucose intolerant. Nonetheless, 3 pts began 2DG treatment at one dose level lower (32mg/kg) and dose escalations were reduced to a 40% increase. No DLT or serious adverse events have occurred in the cohort at 32 mg/kg and dose escalation is continuing. PK analysis did not reveal any interaction between 2DG and DC to date. Two pts have achieved disease stabilization (1 NSCLC and 1 adenoid cystic carcinoma). Conclusions: The combination of 2DG and DC appears to be feasible and safe. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Threshold Aventis, Threshold Threshold Aventis Aventis
A Phase 1 and Correlative Biological Study of CSL360 (anti-CD123 mAb) in AML
Authors: Andrew W. Roberts, Simon He, Kenneth F Bradstock, Mark S Hertzberg, Simon T S Durrant, David Ritchie, Ian D. Lewis, Paula Marlton, Andrew J McLachlan, Trina M Yeadon, Samantha J Busfield, Megan J Barnden, Roslyn Davis, Sarah Hosback, Danijela Mirosa, Mark Biondo, Simone Bamford, Mark DeWitte, Russell Basser
Journal: Blood (2008)
Combination treatment of paclitaxel, cisplatin and infusional 5-fluorouracil (PCF) as first-line chemotherapy for metastatic or recurrent gastric cancer: Prospective multicenter clinical trial
Authors: M. Jin, X. D. Zhang, Y. Q. Shu, J. Liang, J. W. Yang, L. Chen, W. G. Cao, G. M. Shi, C. Y. Guo, F. C. Zhang
Journal: Journal of Clinical Oncology (2007)

15035 Background: Paclitaxel has been shown to be effective in patients with advanced gastric cancer. We assess the combination of paclitaxel (Anzatax®, Mayne Pharma), infusional 5-fluorouracil and Cisplatin as first-line chemotherapy for metastatic or recurrent gastric cancer. Methods: Patients with previously untreated metastatic gastric adenocarcinomas are eligible. Fifty patients received paclitaxel (Anzatax®, Mayne Pharma) 150mg/m2 by 2-hour infusion day 1, cisplatin 15 mg/m 2 daily days 1 through 5, and 5- fluorouracil by continuous infusion at a dose of 600 mg//m 2 daily days 1 through 5. Cycles were repeated every 3weeks until progression. Objective tumor responses, duration of response, time to progression, and toxicity profile are the end points evaluated in this study. Results: Total 50 patients were enrolled (41 men, 9 women). The median age was 59 years (range 32 - 75). All patients had ECOG performance status (PS) 0–2 and adequate organ functions. 50 patients completed one-six cycles (mean 3 cycles). Forty-four patients were evaluable and all patients were assessable toxicity. In these 44 assessable patients, 1 CRs and 14 PRs were obtained, resulting in an overall response rate of 34%. 19 patients (43.2%) had stable disease, and 3 patients (8.9%) progressed. The tumor control rate was 77.3%. The median time to progression(TTP) was 5 months. The major (Grade 3–4) toxicities were neutropenia (22%) and anorexia (4%). There were no treatment-related deaths were recorded in all patients. The median and overall survival times are now being followed up and the results will be announced during the ASCO 2007 annual meeting. Conclusion: The combination of paclitaxel (Anzatax®, Mayne Pharma), cisplatin,and 5-FU has substantial antitumor activity in advanced gastric cancer. The toxicity of this regimen is within acceptable range, but no remarkable response rate was noted. Paclitaxel is an important new agent in the treatment of gastric cancer, and further evaluation of this agent in combination chemotherapy is warranted. No significant financial relationships to disclose.