tbuckley/cabot-search huggingface dataset:
Quantitative functional imaging by dynamic contrast enhanced ultrasonography (DCE-US) in patients with GIST treated by thyrosine kinase inhibitor (TKI)
Authors: L. Chami, N. Lassau Mrs, S. Koscielny, B. Benatsou, A. Roche, A. Le Cesne
Journal: Journal of Clinical Oncology (2008)

10552 Background: To determine the best quantitative parameters of DCE-US for predicting the early functional response at D1, D7, D15 in GIST treated by TKI and to compare to the Pet-CT performed at 1 month. Methods: Twenty patients were treated by a targeted treatment AB1010 in phase II. DCE-US was performed before treatment and at 1, 7, 15 days, 1, 2 months and every 2 months. Contrast uptake was acquired using VRI perfusion software after SonoVue (Bracco) bolus injection. Time-intensity curves (TIC) were determined using linear raw-data from CHI-Q (Toshiba) software. Seven parameters were extracted from the modelized TICs: peak intensity, areas under the curve, under the wash-in, under the wash-out, (corresponding all to the blood volume), time to peak intensity, slope of the wash- in (both corresponding to the blood flow), mean transit time. CT ( RECIST) were performed before treatment and at 2 months and every 2 months. Pet-CT were performed before and at 1 month in 14 patients. The variation was estimated between D0 and D1, D7, D15 for each functional DCE-US parameter. A non parametric sum-rank test was used to test the significance of the variation. Results: Twenty patients were included with a maximal follow-up of 30 months. Nineteen patients were treated at least 1 year. A total of 221 DCE-US were performed. At D 15, 5 parameters were significantly modified: AUC (p=0.004), area under the wash-in (p=0.002), area under the wash-out (p=0.002), time to peak intensity (p=0.005), slope of the wash-in (p=0.003). Among the 14 patients evaluated by Pet-CT, only 11 have a tumoral fixation. Among these, at 1 month: no modification of SUV was found in 4 patients (PFS < 18 months), and SUV was normalized in 7 patients (PFS >18 months). The functional parameters by DCE-US correlated to the blood volume were modified at D7 (increased and decreased for 4 and 7 patients, respectively). Conclusions: This study allows us to determine 5 relevant quantitative functional parameters calculating by DCE-US to early evaluate the targeted treatment in GIST at D15. The decrease of 3 parameters at D7 was able to predict the response on Pet-Ct at 1 month. No significant financial relationships to disclose.
Impact of crossover and baseline prognostic factors on overall survival (OS) with abiraterone acetate (AA) in the COU-AA-302 final analysis.
Authors: Charles J. Ryan, Matthew Raymond Smith, Karim Fizazi, Fred Saad, Cora N. Sternberg, Christopher Logothetis, Eric Jay Small, Joan Carles, Thomas W. Flaig, Mary-Ellen Taplin, Celestia S. Higano, Paul L. De Souza, Johann Sebastian De Bono, Thomas W. Griffin, Peter De Porre, Youn Choi Park, Jinhui Li, Thian San Kheoh, Arturo Molina, Dana E. Rathkopf
Journal: Journal of Clinical Oncology (2015)

142 Background: AA + prednisone (P) significantly increased OS, time to opiate use, and was well tolerated at the COU-AA-302 final analysis. Here we further characterize OS benefit adjusting for crossover therapy and for baseline prognostic factors. Methods: Patients (N = 1,088) were randomized 1:1 to receive AA (1 g) + P (5 mg po BID) vs P. Co-primary end points were radiographic progression-free survival and OS. Median time to events with 95% CI was estimated using the Kaplan-Meier method. Stratified log-rank test was used to test the difference in treatment effect. Adjustment for crossover utilized the iterative parameter estimate (IPE) and impact of baseline prognostic factors was examined via the multivariate Cox proportional hazard model. Results: With a median follow-up of 49.2 months and 741 deaths (96% of required), AA + P significantly reduced the risk of death vs P (19%) and prolonged median OS (34.7 vs 30.3 months) (Table). 44% of patients initially receiving P alone subsequently received AA + P as crossover per protocol (17%) or as subsequent therapy (27%). IPE adjustment resulted in a 26% reduction in the risk of death (Table). By multivariate analysis, AA + P treatment led to a 21% reduction in the risk of death; baseline prostate-specific antigen (PSA), lactate dehydrogenase (LDH), hemoglobin, alkaline phosphatase (ALP), bone metastases, and age were significant OS prognostic factors (Table). Conclusions: AA + P yielded a statistically significant improvement in OS. Greater improvement in OS was observed after adjusting for the 44% of patients originally on P who ultimately received AA + P. Adjusting for baseline prognostic factors also demonstrated an AA + P OS benefit. Clinical trial information: NCT00887198. [Table: see text]
Is diabetes mellitus (DM) associated with worse outcomes in pancreatic cancer (PC)?
Authors: O. O. Olowokure, M. S. Beg, S. Ali, A. Tandra, M. M. Safa, K. Havlin, S. A. Ahmad
Journal: Journal of Clinical Oncology (2010)

4114 Background: Previous studies suggest that patients with DM have worse oncologic outcomes than those who do not. To address this issue in PC, we performed a systematic review of a large cancer database. Methods: The Veterans Affairs (VA) Central Cancer Registry (VACCR) aggregates cancer data from more than 120 VA centers across the United States. We queried the VACCR for PC cases between 1995 and 2008, and cases with DM were identified. Data were analyzed using biostatistical software SPSS. Kaplan-Meier curves were used for estimates of overall survival (OS) and chi square for comparison of categorical variables. Results: There were 8,466 cases of PC identified. Comorbidity data was available for 4,728 cases and DM was present in 1,326 (28%). Males comprised 97.7% while 77.3% were white. Two groups were similar in race, sex, and primary site. OS in DM was 4.2 vs. 3.6 months (mo) in non-DM (p=0.048). OS between DM and non-DM was 6.7 vs. 6.5 mo (p=0.5) for early stage and 2.5 vs. 2.1 mo for stage 4 (p=0.02). DM cases were more likely to receive chemotherapy and radiation (37.9% vs. 33.5% and 15.2% vs. 12.2% (see Table). Cox regression analysis revealed DM, age, race, site, gender, stage, chemotherapy, surgery, were independent predictors of survival while radiation was not. Conclusions: According to this retrospective review, PC patients with DM do not have worse OS than non-DM in the VA system. We suggest evaluating this association in a large prospective fashion. Diabetics (n=1,326) Nondiabetics (n=3,402) p value Age (years) 67.8 66.9 0.01 Stage 0 n (%) 2 (0.2) 8 (0.3) 0.06 1 8 (0.8) 35 (1.3) 2 8 (0.8) 42 (1.6) 3 137 (13.7) 334 (12.7) 4 635 (63.3) 1,563 (59.6) Missing 213 (30.2) 641 (24.4) Sex Male 1,295 (97.7) 3,322 (97.6) 0.9 Female 31 (2.3) 80 (2.4) Race White 1,053 (79.4) 2,636 (77.5) 0.3 Black 240 (18.1) 680 (20) Other 33 (2.5) 86 (2.5) Site Head 707 (53.3) 1,745 (51.3) 0.132 Body 151 (11.4) 327 (9.6) Tail 154 (11.6) 419 (12.3) Missing/Other 314 (23.7) 911 (26.8) Rx Chemo Yes 37.9% 33.5% 0.005 No 62.1% 66.5% Radiation Yes 15.2% 12.2% 0.006 No 84.8% 87.8% Surgery Yes 15.6% 15.5% 0.9 No 84.4% 84.5% Survival (mo) p; Median 4.2 3.5 0.048 Stage 1-3 6.7 6.5 0.5 Stage 4 2.5 2.1 0.02 12-mo (%) 8.4 8.3 18-mo (%) 5.4 4.8 No significant financial relationships to disclose.
Phase I study of ixabepilone in combination with capecitabine in Japanese patients with metastatic breast cancer previously treated with an anthracycline and a taxane.
Authors: J. Watanabe, J. Horiguchi, N. Masuda, K. Aogi, R. Sato, T. Tokudome, R. A. Peck
Journal: Journal of Clinical Oncology (2010)

e13095 Background: Ixabepilone is a new class of nontaxane tubulin polymerization agents and is approved as both monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer (MBC) in the United States. Primary objective of this study was to establish the maximum tolerated dose (MTD) and the recommended dose (RD) of ixabepilone plus capecitabine in Japanese MBC patients (pts) previously treated with an anthracycline and a taxane. Methods: Ixabepilone (Ixa) was administered intravenously over 3 hours on day 1 and capecitabine (Cap) was given orally twice daily from days 1 to 14. Treatment cycles were repeated every 3 weeks. Three cohorts were planned as follows: Ixa 32 mg/m2+ Cap 1,650 mg/m2, Ixa 40 mg/m2+ Cap 1,650 mg/m2 and Ixa 40 mg/m2 + Cap 2,000 mg/m2 respectively. If no dose-limiting toxicity (DLT) was observed within 3 pts in the cohort, another 3 pts were enrolled and treated in next cohort. Results: Nine MBC pts, median age of 58 (range 30-69), with ECOG PS 0-1 received treatments at median 10 cycles (2-12). Grade (G) 3 neutropenia was observed in all pts and G4 neutropenia was seen in 5 pts; however, no febrile neutropenia was documented. Nonhematologic toxicities were mild to moderate except for G3 fatigue (2 pts) and G3 AST elevation (1 pt). No DLTs were observed, therefore the MTD, consistent with RD, was determined as ixabepilone 40 mg/m2 and capecitabine 2,000 mg/m2. Of the 9 pts, 1 had complete response, 4 had partial response, 2 had stable disease, and 2 had disease progression. All 3 pts at the maximum dose level responded (1CR, 2PR) and had long treatment duration (12 cycles). Conclusions: Ixabepilone in combination with capecitabine was well tolerated and highly active in Japanese MBC patients previously treated with both an anthracycline and a taxane. The recommended phase II dose of the combination is ixabepilone 40 mg/m2and capecitabine 2,000 mg/m2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
BNIP3L (Nix) expression in colon cancer
Authors: J. E. Littlejohn, D. Jupiter, X. Cao, L. Zhang, M. Shabahang, W. R. Smythe
Journal: Journal of Clinical Oncology (2009)

e15097 Background: Microenvironmental adaptation to hypoxic conditions is critical for a cell to survive in a growing solid tumor. BNIP3L (Nix) mediates apoptosis during hypoxia in cancer cell lines, and Nix knockdown promotes tumor growth in-vivo through decreased apoptosis and increased proliferation, suggesting a means by which cells can adapt. Little is known specifically about Nix expression and its importance in human colon cancer. To gain insight into expression of this gene in colon tumors, the present study analyzed mRNA microarray data from 227 colon tumors and 22 normal colon tissue samples and queried differential expression of Nix. These results were compared to the protein levels present in human colon tumors. Methods: mRNA expression of 227 human colon tumors (made available by the Expression Project for Oncology (expO)) and 22 normal colon samples (retrieved from the Gene Expression Omnibus (GEO)) was analyzed. These samples were hybridized to the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array, assaying 17,726 NCBI Entrez genes. Immunohistochemistry was performed on human tissue microarray CO701 (US Biomax, Inc.) containing 62 tumor samples. Results: Nix mRNA levels were shown to increase from normal to cancer (log-fold change of 0.961, Benjamini-Hochberg FDR adjusted p &lt; 0.001). IHC demonstrated variable levels of Nix present in colon tumors: 38/62 (61.3%) of tumors stained positive for Nix while 24/62 (38.7%) were negative. Conclusions: We have shown that mRNA levels of Nix are upregulated in the transition from normal colon tissue to cancer but that protein levels in tumors demonstrate variable expression. This suggests that silencing of Nix occurs at various stages of tumorigenic progression and results in isolated populations of cells within a growing tumor that are uniquely resistant to apoptosis. Better understanding of Nix in the context of a growing colon tumor is needed and could lead to development of more successful therapeutics. No significant financial relationships to disclose.
Analysis of adherence to chemotherapy regimens at an urban academic medical center
Authors: M. T. Nguyen, I. S. Yasin, L. R. Bressler, S. S. Shord, J. L. Villano
Journal: Journal of Clinical Oncology (2008)

17545 Background: Recently there has been emphasis placed on patients receiving chemotherapy at the recommended doses and time interval, to ensure optimal results. Our urban setting provides an opportunity to examine multiple variables that might impact adherence. Methods: We performed a retrospective analysis of adult patients diagnosed with a solid malignancy or lymphoma treated between September 2004 and 2006 at University of Illinois. Patients receiving oral anticancer agents were excluded. Demographic data and planned chemotherapy regimens were reviewed. The planned chemotherapy regimens were compared with actual administration. Adherence was determined by the frequency of dose delays, reasons for dose reductions and delays, and frequency of early termination of chemotherapy. These data were compared between Black and other minorities (B/OM) to Whites (W) and between the palliative and curative setting. Descriptive statistics were used to analyze the data. Results: Of the 350 patients treated during this time period,102 have been analyzed thus far (35M:67F, 80%B/OM:20% W, mean age 55.5 yrs). 85.3% had dose reductions, delays, and/or early termination of therapy. The most common reasons for dose reduction were adverse events and changes in organ function. Reasons for dose delays ≤ 7 days were commonly not documented while the most common reason for dose delays > 7 days was myelosuppression in both W and B/OM. Other causes for dose delays include adverse events, infection/fever, failed appointments, holidays, and vacations. The total frequency of non- adherence to chemotherapy was higher in W than B/OM (95% vs. 84%). The frequency of non-adherence was higher in the palliative setting than curative setting (93.6% vs. 78.2%). Conclusions: Dose reductions, delays, and/or early termination of therapy are common in patients receiving cancer chemotherapy at our institution, leading to high non-adherence rates even in the curative setting. No significant financial relationships to disclose.
Outcome of preoperative chemotherapy (POC) in locally advanced rectal cancer (LARC): Meta-analysis of randomized clinical trials (RCT)
Authors: E. Tamburini, D. Tassinari, M. Papi, G. Oliverio, S. Nicoletti, L. Gianni, B. Poggi, C. Possenti, F. Drudi, P. Fattori, A. Ravaioli
Journal: Journal of Clinical Oncology (2008)

4085 Background: Besides its large use in clinical practice, till now no definitive data exist supporting the efficacy of POC when combined with radiotherapy in improving the outcomes of LARC. Outcome of our work was supporting the use of POC in LARC, making a systematic review of literature with meta-analysis of RCT. Methods: A systematic review of literature from 1966 to September 2007 was independently performed by two authors (ET and DT). All the RCT comparing POC with total mesorectal excision ± neoadjuvant radiotherapy ± adjuvant radiochemotherapy were considered eligible and included into the analysis. Primary end point of our work was the 5-years overall survival (OS); Locale Relapse Risk Reduction (5LRRR), and pathologic complete remission rate (pCR) the secondary ones. A further sub-analysis of Sphincter-Sparing Surgery rate (SSS) was performed including uniquely the trials reporting the datum. Heterogeneity between the trials was assessed using the Mantel-Haenszel test, and the pooled Odds Ratios (ORs) were calculated using a random effects model and an alpha error<5%. Results: Eleven trials (4,515 patients) were considered eligible and included into the analysis. Heterogeneity between the trials was documented respectively in 5LRRR (p=0.027), pCR (p=0.038) and SSS (p=0.014), with a trend for OS (p=0.08). No differences between the groups were observed for 5OS (OR=1.151 p=0.169), while a significant improve in 5LRRR (OR=1.503 p=0.015) and pCR (OR=3.127 p<0.001) was observed in patients treated with POC. A trend in favour of POC (without reaching statistical significance) was observed in SSS (OR=1.253, p=0.079). Conclusions: Besides the heterogeneity between the trials, our data seem to confirm the role of POC in the treatment of LARC: its role seems to be mainly related with the local control of the disease, while no definitive data exist about overall survival. Further trials are probably needed to better define the role of POC in improving the outcomes of LARC; likewise a better definition of the meaning of pCR as a surrogate prognostic and predictive factor after surgery is probably needed to better understand the role of POC in the treatment of LARC. No significant financial relationships to disclose.
Prognostic and predictable value of COX2 expression in Russian women with stage I breast cancer.
Authors: Irina Vladimirovna Kolyadina, P. J. K. Kuppen, Cornelis J. H. Van De Velde, Irina Vladimirovna Poddubnaya, N.G. Dekker-Ensink, B. Prinse, G. Frank, A. Karseladze, D. Komov, C. Engles, V. Ermilova
Journal: Journal of Clinical Oncology (2014)

80 Background: Some previous studies found worse prognosis among cyclooxygenase-2 (COX2)-expressing breast cancers; we study prognostic and predictiable value of COX2 expression in breast cancer stage I. Methods: our study included Russian women with breast cancer stage I (n=315) treated in RCRC, RMAPE (1985-2009). A Tissue Micro Array (TMA) with triplicate 1 mm tumor tissue punches taken from tumor blocks was constructed in LUMC; sections were immunohistochemically stained for ER, PR, HER2-status, Ki67 (by standard morphological criteria); COX2-expression were evaluated as positive (&gt;median; 31/309 cases, 10%) or negative (≤median; 278/209 cases, 90%). Also the histological type, grade, age and adjuvant endocrine therapy were examined. We analyzed the clinic and morphological data of COX2-positive tumors, prognostic value for survival (relapses free- RFS, overall- OS and cancer specific- CSS) and predictable value for endocrine therapy. Results: COX2-positive tumor were associated with ductal histological type (p=0,018), PR-negative status (p=0,027) and high Ki67 (p&lt;0,0001), but not correlated (p&gt;0,05) with age, grade, ER, HER2 status or biological subtype. In women with ER-negative tumors (104 patients, 34,1%) COX2-expression did not associate with worse survival (p&gt;0,05). In contrast to this, in patients with ER-positive tumors (201 women, 65,9%) COX2-expression strongly correlated with worse RFS in univariate (HR 2,829, 95% CI 1,366-5,860, p=0,005) and multivariate analyses (HR=2,972, 95% CI 1,190-7,423, p=0,02). The same value of COX2-expression in women with ER-positive tumors was found for CSS (univariate: HR 3,421, 95% CI 1,436-8,149, p=0,005; multivariate: HR 4,260, 95% CI 1,344-13,504, p=0,014), but not for OS (p&gt;0,05). In women who did not receive adjuvant endocrine therapy (145 patients, 46%) COX2 expression did not have any prognostic value for RFS, OS and CSS (p&gt;0,05) but in patients that used adjuvant endocrine therapy (170 women, 54%) COX2-expression strongly associated with worse cancer-specific survival (HR 5,614 95% CI 1,165-27,059, p=0,032), but not with RFS and OS (p&gt;0,05). Conclusions: COX2 expression plays a role in hormonal pathways and sensitivity for endocrine therapy.
Cardioprotective effect of telmisartan in cancer patients treated with epirubicin
Authors: G. Mantovani, G. Mercuro, M. Dessì, C. Madeddu, R. Serpe, E. Massa, C. Cadeddu, A. Piras
Journal: Journal of Clinical Oncology (2009)

e20671 Background: We previously showed on 31 cancer patients (pts) that early cardiac abnormalities occurred at epirubicin (EPI) doses of 200 mg/m 2 and persisted throughout subsequent EPI doses and even up to 18 months. Early contractility impairment, i.e. Strain rate (SR) reduction was detected by tissue doppler imaging (TDI) associated with high levels of inflammatory/oxidative stress markers. Renin-angiotensin system activation has been suggested to play an important role in the pathogenesis of Anthracycline-induced cardiotoxicity. Methods: A phase II placebo-controlled study was designed to investigate the possible role of telmisartan (an antagonist of angiotensine II type I receptor) in preventing both early preclinical and late myocardial damage induced by EPI. The correlation with changes of biochemical/inflammatory markers was also assessed. Planned sample size was 100 pts (50 pts per arm). Inclusion criteria: 18–70 y, histologically confirmed cancer, previously untreated and candidates for an EPI-based regimen; LVEF ≥55%; ECOG PS 0–2, no history of cardiac disease and previous mediastinal irradiation. Eligible pts were randomized to receive telmisartan 40 mg (1 tablet)/day or placebo starting 1 week before EPI until 6 months after the end of EPI administration. TDI as well as inflammatory/oxidative stress markers were assessed at baseline, 24 hours and 7 days at EPI doses of 100, 200, 300, and 400 mg/m 2 . Results: At December 2008 we enrolled 27 pts (M/F: 7/20, mean±SD age 58±14 years): 14 telmisartan and 13 placebo. 15 pts completed EPI treatment (8 telmisartan and 7 placebo). A significant reduction of SR peak was observed at 200mg/m2 of EPI in the placebo arm. Viceversa no significant TDI changes occurred in the treatment arm. Proinflammatory cytokines did not change in both arms whilst reactive oxygen species increased significantly in the placebo arm. Conclusions: The study is in progress. No significant financial relationships to disclose.
Capecitabine plus oxaliplatin (XELOX) followed by capecitabine plus irinotecan (XELIRI) in a sequential schedule in first-line metastatic colorectal cancer (MCRC): a phase II multicenter study
Authors: J. Cassinello, J. V. Álvarez, M. J. García-López, E. Pujol, A. Colmenarejo, F. De Segovia, F. Marcos, E. Filipovich, I. García Castro, A. Arcediano
Journal: Journal of Clinical Oncology (2006)

13516 Background: In phase II trials, XELOX and XELIRI were highly active and well tolerated in first-line MCRC. The aim of this study is to explore the efficacy and safety of XELOX followed by XELIRI as first-line treatment in MCRC. Specifically, we wanted to evaluate the impact of sequential scheduling on the dose-limiting neurotoxicity associated with oxaliplatin accumulation. Methods: Eligible patients (pts) had histologically or cytologically confirmed MCRC, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic function. Prior chemotherapy for MCRC was not allowed. Pts received 4 cycles of XELOX (capecitabine 1000mg/m 2 orally bid d1–14 + oxaliplatin 130mg/m 2 i.v. d1, q3w) followed by 4 cycles of XELIRI (capecitabine 1000mg/m 2 bid d1–14 + irinotecan 240mg/m 2 i.v. d1, q3w). This sequential schedule was repeated until unacceptable toxicity or disease progression. Results: Of the 35 pts analized to date: M/F (69%/31%); median age 68 years (range 41–78); ECOG PS 0–1 (94%); surgery (77%) and adjuvant chemotherapy (31%). 240 cycles (median 6, range 1–16) have been administered. 35 pts received XELOX (123 cycles, median 4), and 21 pts received XELIRI (83 cycles, median 4) in the first sequential schedule. In the second sequential schedule 6 pts received XELOX (22 cycles, median 4) and 4 pts received XELIRI (12 cycles, median 3.5). Median relative dose intensity was 88% for XEL, 96% for OX and 92% for IRI. In 27 efficacy evaluable pts, the ORR was 48% (95% CI, 29–67%). Eight pts were not evaluable due to adverse events (n=6), ongoing treatment (n=1) and lost of follow up (n=1). Conclusions: This sequential schedule is active and well tolerated in first-line MCRC. The improvement/recovery of the oxaliplatin-related neurotoxicity during the XELIRI phase is also promising and allows the re-treatment with oxapliplatin in the next sequence without accumulating neurotoxicity. Final results will be presented at the meeting. [Table: see text] No significant financial relationships to disclose.