tbuckley/cabot-search huggingface dataset:
Sequence dependence of MEK inhibitor AZD6244 combined with gemcitabine for treatment of biliary cancer.
Authors: Junyao Xu, Jennifer J. Knox, Emin Ibrahimov, Eric Xueyu Chen, Stefano Serra, Ming Sound Tsao, Pinjiang Cao, Douglass Vines, David E Green, Mairead Geraldine McNamara, David W Hedley
Journal: Journal of Clinical Oncology (2013)

196 Background: MEK inhibition has clinical activity against biliary tract cancers, and might therefore be successfully combined with gemcitabine; one of the most active chemotherapy agents for these cancers. As gemcitabine is active in S-phase, and the ERK pathway has a major role driving cell cycle progression, concurrent use of a MEK inhibitor could potentially antagonize the effect of gemcitabine. We therefore tested the sequence dependence of the combination of gemcitabine and the MEK inhibitor AZD6244 in vitro and in vivo. Methods: Two biliary tract cancer cell lines and 4 xenografts established from patients were used in this study. In vitro, cell cycle effects of AZD6244 and their impact on gemcitabine sensitivity were detected by Flow cytometry, EdU uptake assay, MTS assay and Clonogenic survival assay. In vivo, tumor-bearing SCID mice were treated for 48hr with AZD6244 and then monitored for 48hr off treatment. Plasma and tumor drug levels were assessed by LC-MS. The time course for recovery of ERK signaling, cell cycle distribution and cell proliferation were measured by Immunofluorescence staining, Flow cytometry, EdU uptake assay and 18 F-FLT PET imaging. Based on these results, two different treatment schedules combining AZD6244 with gemcitabine were tested in four different biliary tract cancer models. Results: DNA synthesis was suppressed during treatment with AZD6244, and re-entry into S-phase was delayed by 15hr in vitro and 48hr post-treatment in vivo. Concurrent treatment showed antagonistic effect (IC50=2.02±0.91uM) compared to gemcitabine alone (IC50=0.09±0.04uM) whereas when gemcitabine treatment was delayed for 24 hr after AZD6244 removal, enhanced cytotoxic effect was observed (IC50=0.051± 0.012uM). Consistantly, strong schedule dependence was seen in all four biliary cancer models tested: combined treatment with AZD6244 plus gemcitabine exerts enhanced antitumor effect when gemcitabine is given following a 48hr interruption in AZD6244 dosing, rather than concurrently. Conclusions: The combination of AZD6244 plus gemcitabine is highly schedule dependent, and predicted to be more effective in the clinic using sequential rather than simultaneous dosing protocols.
Results from a phase II, open-label, randomized study (SIGN) comparing gefitinib with docetaxel as second-line therapy in patients with advanced (stage IIIb or IV) non-small-cell lung cancer
Authors: T. Cufer, E. Vrdoljak
Journal: Journal of Clinical Oncology (2005)

7035 Background: Gefitinib (IRESSA) and docetaxel are both approved for the treatment of pretreated patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC); this international multicenter study provides randomized data on gefitinib monotherapy versus docetaxel. Methods: Patients were randomized to receive gefitinib (250 mg/day orally) or docetaxel (75 mg/m2 intravenously 3-weekly). The primary objective was to estimate the symptom improvement rate by assessing disease-related symptoms. Secondary objectives were quality of life, objective response rate (ORR), disease control rate (DCR), progression-free and overall survival. Results: Demographics were comparable in the gefitinib (n=65) and docetaxel (n=69) arms: most patients were male (68% and 70%, respectively) and had performance status 0–1 (73% and 71%, respectively). Gefitinib and docetaxel had comparable ORRs of 15.2% (7/46 evaluable patients) and 12.7% (7/55 evaluable patients), respectively, with the DCRs being 82.6% (38/46 evaluable patients) and 63.6% (35/55 evaluable patients), respectively. Gefitinib was better tolerated than docetaxel: fewer patients had drug-related adverse events (AEs) [42% vs 67%], withdrew due to toxicity (3% vs 10%), or died due to drug-related AEs (0% vs 4%). Conclusions: These preliminary data suggest that in patients with NSCLC, gefitinib is likely to be comparable to docetaxel in terms of ORR and DCR, but better tolerated. Analyses for progression-free and overall survival, symptom improvement, and quality of life are not yet completed but will be presented. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca
Prior Rituximab Exposure Does Not Appear to Affect Time to Treatment Failure After Radioimmunotherapy
Authors: Brian L. Burnette, Gregory Wiseman, Thomas M. Habermann, Stephen M. Ansell, Luis F. Porrata, David James Inwards, Patrick B. Johnston, Ivana Micallef, William R Macon, Thomas E. Witzig, Grzegorz S. Nowakowski
Journal: Blood (2011)
Cancer care transparency: Trying to move the dial in California.
Authors: Stephanie Teleki
Journal: Journal of Clinical Oncology (2014)

256 Background: Each year in California, about 150,000 patients (more than 16 each hour) are diagnosed with cancer. Yet there is little useful information about the quality of cancer care to help patients, providers and payers make decisions about care. Methods: In 2012, the California HealthCare Foundation, an Oakland-based independent nonprofit philanthropy, launched an initiative focused on improving cancer care quality measurement and public reporting in the State. Since then, the Foundation has funded a number of projects aimed at filling information gaps; 2014 highlights include: (1) development of a Consumer Assessment of Healthcare Providers and Systems (CAHPS) patient experience of cancer care survey (with NCI and AHRQ). CHCF is now funding 6 community oncology test sites in California; (2) analytic work to measure and report the number of cancer procedures performed by hospitals using State discharge data, for procedures where there is an established volume-outcome link; public reporting by hospital expected by early 2015 (with Stanford University); (3) a feasibility study of measuring cancer care quality at the medical group level in California using claims data combined with California Cancer Registry data (with Integrated Healthcare Association); (4) a report on cancer care spending in California, publication expected Winter 2014 (with Dana Farber); (5) a workgroup of State and national thought leaders to contemplate and articulate the challenges and opportunities of leveraging the California Cancer Registry for quality measurement and public reporting; Sacramento briefing to state legislators in Winter 2014 (with UCSF). Results: Significant challenges exist at the state level to provide information for improved decision-making about cancer care. Among them: access to data, especially cancer registry data that importantly includes detailed diagnostic information; lack of clinical outcome and patient experience measures; time needed to engage partners; and costs of carrying out quality measurement projects. Conclusions: This presentation will provide a 2014 update on efforts underway in California, focused especially on the challenges and opportunities at the state level for cancer quality measurement and public reporting.
The prevalence of human papillomavirus types 52 and 58 in uterine cervical lesions from Japanese women.
Authors: K. Takehara, T. Nishimura, J. Sakane, Y. Kawakami, T. Mizunoe, M. Nishiwaki, K. Taniyama
Journal: Journal of Clinical Oncology (2011)

1543 Background: In recent years, molecular biology has firmly established a causal relationship between persistent infection with high-risk human papillomavirus (HPV) genotypes and cervical cancer. While HPV 16 is the most prevalent type in the world, it has been reported that the frequency of other high-risk HPV types varies by region. We estimate the prevalence and genotypes of high-risk HPV focusing HPV 16, 18, 52, and 58, using liquid-base cytology (LBC) in Japan. Methods: ThinPrep LBC specimens were collected from Japanese women (n=11022), aged 14-98. After classifying cytodiagnosis by the Bethesda system 2001, specimens were analyzed for HPV DNA by the multiplex polymerase chain reaction method (PapiPlexTM), where 1195 specimens were positive for cervical smear except adenomatous lesions and 2068 samples were randomly selected from 9760 did not display abnormal cytological findings (NILM). Written informed consent was obtained from all patients. Results: Atypical squamous cells of undetermined significance (ASC-US) or severer cytological findings were found in 1195 (10.8%, 1195/11022) cervical smears. HPV genotypes were detected in 9.5% (194/2068) of NILM and 72.2% (841/1195) of ASC-US or more cervical lesions. In NILM, HPV genotypes and positive rates were HPV 52 (23.7%, 46/194), HPV 58 (17.0%, 133/194), HPV 16 (15.5%, 30/194), and HPV 18 (10.8%, 21/194). In positive cervical smears, HPV genotypes were HPV 52 at 26.6%, HPV 16 at 25.2%, HPV 58 at 21.8%, and HPV 18 at 7.1%. Most patients infected with HPV 16 were between 20-29 years old, decreasing with age thereafter. As for HPV 52 and 58, although the detection rate was high in 30- to 39-year-olds, it also was significant in 50s and 60s age groups. Conclusions: In Japan, as a cause of abnormal cervical cytology, HPV52 and 58 are detected frequently in addition to HPV 16. In older age groups, HPV 52 and 58 were higher than that observed for HPV 16. After widespread current HPV vaccination, we still must be aware of HPV 52 and 58 infections.
A randomized phase I/II study of everolimus, irinotecan, and cetuximab versus capecitabine and oxaliplatin in gemcitabine-resistant patients with pancreatic cancer.
Authors: Jon Kroll Bjerregaard, Morten Ladekarl, Katherina Podlekareva Farr, Lene Weber Vestermark, Helle Anita Jensen, Per Pfeiffer
Journal: Journal of Clinical Oncology (2014)

337 Background: Little evidence exists on 2 nd line therapy for gemcitabine resistant patients. The combination of oxaliplatin (Ox) and 5-FU has shown efficacy in small trials. We wanted to establish a tolerable dose of the combination of irinotecan, cetuximab and everolimus(ICE), and test it vs. the combination of capecitabine (Cap) and Ox in a randomized phase I/II setting. Methods: Patients were initially recruited in a 3+3 dose finding design with an expanded MDT cohort. After establishing MDT; patients were randomized between ICE (at MDT-1) and CapOx (Cap: 1250 mg/m 2 BID and Ox: 70 mg/m 2 q14d). Patients that progressed could cross-over to the other arm. (NCT01042028). Results: Between January 2010 and November 2012, 40 patients were recruited. Due to DLT toxicity (mainly mucositis) at dose level 1 of the phase I trial, the protocol was amended and patients were treated at dose level -1. Ten patients were safely treated at this dose. The final dose for everolimus was 2.5 mg q1d, for irinotecan 180 mg/m 2 q14d and 500 mg/m 2 q14d for cetuximab. At this dose level patients were randomized to either ICE or CapOx. Planned accrual was 90 patients, but due to the emergence of FOLFIRINOX and slow accrual, the study was terminated after randomization of 26 patients. One patient died before randomization. Median PFS for the ICE regime was 3.8 months (2.5-7.8), CapOx 3.5 (1.7-5.3) p=0.72. Median OS for ICE was 7.7 (4.5-11.8) and for CapOx 4.5 (2.2-7.4) p=0.04. Six patients crossed from CapOx to ICE, and 3 patients from ICE to CapOx upon progression. RR for ICE was 25% (5-57), CapOx 29% (8-58). Toxicity grade 3+ in the ICE regime was acne-like-rash (20%), fatigue (16%), infection (16%) and emboli (12%). CapOx was associated with grade 3+ neuropathy (21%), emboli (14%), pain (21%) and PPE (14%). Conclusions: The triple combination of ICE displayed similar PFS but significantly increased OS compared to CapOx. Both regimes displayed cancer activity with acceptable response rates. Toxicity was manageable. Due to early termination no solid conclusions can be drawn. Selected patients may benefit from dual-targeted therapy. Clinical trial information: NCT01042028.
Risk of venous thromboembolism (VTE) in breast cancer patients receiving erythropoietin for chemotherapy-induced anemia: A Tertiary Cancer Center experience from the University of Arkansas for Medical Sciences
Authors: H. Keshava Prasad, D. Nelsen, E. R. Siegel, G. Raval, S. Rajan, L. F. Hutchins
Journal: Journal of Clinical Oncology (2008)

20621 Background: ESAs have been associated with increased rates of death, myocardial infarction, strokes and thromboembolism in dialysis patients(pts) especially when targeted to higher hemoglobin(Hgb) levels. VTE and cancer progression have also been reported in cancer pts receiving ESAs with chemo- and/ or radiotherapy, with no clear correlation with Hgb levels. We conducted a retrospective cohort study of breast cancer pts to evaluate ESA-associated VTE risk, and to correlate it with the Hgb levels. Methods: Data were extracted from the electronic medical record database used at UAMS. We included breast cancer pts treated with chemotherapy between July 1, 2004 and July 1, 2007, and followed them until September 9, 2007 for ESA(Erythropoietin/Darbepoietin)exposure and VTE development. We excluded pts with past history of VTE. The association between ESA exposure and VTE was assessed using Cox regression with ESA exposure as a time- dependent covariate, and the results were reported as the hazard ratio (HR) along with associated chi-square statistic and p value. Results: 483 pts (482 female, 1 male) met the inclusion criteria. Median age(range) was 56 yrs (27–89). 75% were Caucasian, 22% African-American, and 3% of other ethnicity. 9 of the 483 pts (1.86%) developed a VTE [7 Deep Vein Thromboses (DVTs) and 2 pulmonary embolism (PE)]. 2 of 63 subjects (13%) exposed to ESAs developed VTE during the study period (1 DVT, 1 PE). 7 of 420 pts not exposed to ESA developed VTE(1 DVT, 1 PE). Comparisons of the Hgb in the various groups with or without VTE and, with or without ESA exposure showed no significant differences. Cox regression showed little evidence of increased risk with ESA use for either VTEs in general (HR=1.83; X21=0.57, P=0.45)or DVT in particular (HR=1.08; X21=0.005, P=0.94). Conclusions: The number of VTEs in the study patients was very small, much lower than previous reports. There was no evidence of increased risk from ESAs. Due to the rarity of VTE events, no firm conclusions can be drawn. However, the low incidence of VTEs in ESA- exposed pts may be reassuring in that, when used appropriately, ESA use is likely to be safe, and may reflect our conservative ESA usage. No significant financial relationships to disclose.
Racial and ethnic variation in baseline health-related quality of life scores prior to prostate cancer treatment.
Authors: Stephanie R. Reading, Kimberly R. Porter, Jeffrey M. Slezak, Gary W. Chien, Steven J. Jacobsen
Journal: Journal of Clinical Oncology (2016)

232 Background: To compare the racial and ethnic variations in baseline health-related quality of life (HRQOL) scores among men newly-diagnosed with prostate cancer prior to their prostate cancer treatment. Methods: Male members of the Kaiser Permanente of Southern California (KPSC) health plan, newly-diagnosed with prostate cancer, completed the five-domain specific Expanded Prostate Index Composite (EPIC-26) health-related quality of life (HRQOL) questionnaire between March 1, 2011 and August 31, 2013 (n=2,225). The five EPIC-26 domain scores (sexual, bowel, hormonal, urinary incontinence and urinary irritation) were compared across racial and ethnic subgroups and multiple logistic regression analyses were used to assess the association, adjusting for socio-demographic and clinical characteristics. Results: Within each racial and ethnic subgroup,higher baseline HRQOL scores were seen on the bowel, hormonal, urinary incontinence and urinary irritation domains (median score range: 87.5 – 100) as compared to the sexual domain (median score range: 49.3 – 62.5). Asian or Pacific Islander men were less likely to be above the sample median on the sexual (OR=0.51; 95% CI [0.36, 0.74]; p&lt;0.001) and urinary incontinence domains (OR=0.65; 95% CI [0.46, 0.92]; p=0.015) as compared to the non-Hispanic white men. No additional statistically significant differences (p&lt;0.05) were identified. Conclusions: These data suggest that few differences exist in baseline HRQOL scores across racial and ethnic subgroups among men newly-diagnosed with prostate cancer in an integrated health care organization. This finding provides important insight into the pre-treatment HRQOL status among these men with which to interpret HRQOL changes during and after prostate cancer treatment.
Treatment pattern and prognosis in Japanese patients with metastatic renal cell carcinoma (mRCC) with favorable or intermediate MSKCC risk factors in the era of molecular targeted therapy.
Authors: Nobuo Shinohara, Satoru Maruyama, Wataru Obara, Katsunori Tatsugami, Sei Naito, Tomomi Kamba, Seiji Naito
Journal: Journal of Clinical Oncology (2014)

532 Background: We investigated the prognosis of Japanese mRCC patients with favorable or intermediate MSKCC risk factors in the era of molecular targeted therapy Methods: Data on patients who started systemic therapies including cytokine and molecular targeted therapies at 18 hospitals between 2008 and 2010 was analyzed. Of these, 269 patients classified as favorable or intermediate prognosis according to MSKCC risk classification were the subject of this analysis. The endpoints of the present study were progression-free survival (PFS) and overall survival (OS). Relationships between PFS or OS and clinical variables were assessed using the Cox-proportional hazard model. Results: The median OS of all 268 patients was 38 month, and 3-year OS rate was 51% (95%CI 45-58). Regarding the first-line therapy, IFN-alfa (IFN), sunitinib (SU), sorafenib (SO), and others were administered in 89 (33%), 104 (39%), 40 (15%), and 35 (13%). There were more patients without nephrectomy and with multiple organ metastases in patients received SU or SO compared to patients received IFN. Median PFS (mPFS) and 1-year PFS rate in patients who received IFN, SU, and SO were 5 months and 38%, 12 months and 50%, and 11 months and 48% (p=0.556), respectively. Second-line therapy was performed in 69 patients of first IFN group (mPFS: 9 months), 67 of first SU group (mPFS: 7 months), and 24 of first SO group (mPFS: 3 months). Third-line therapy was performed in 47 patients of first IFN group (mPFS: 11months), 35 of first SU group (mPFS: 5 months) and 12 of first SO group (mPFS 3 months). Median OS in patients who received IFN, SU, and SO as first-line therapy were 45, 29 and 27 months (p=0.093), respectively. Multivariate analysis demonstrated that lower value of serum C-reactive protein and first IFN therapy were associated with more favorable OS (p&lt;0.05). Conclusions: In Japanese mRCC patients with favorable or intermediate MSKCC risk factors, first IFN therapy would still be appropriate even in the era of molecular targeted therapy. Furthermore, more potent sequential strategy after first molecular targeted therapy should be established for the improvement of OS.
Early surgical bypass versus endoscopic stent placement in pancreatic cancer.
Authors: Lindsay A. Bliss, Tara Kent, Ammara Watkins, Mariam Eskander, Susanna deGeus, Sing Chau Ng, Mark Callery, James Moser, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2015)

391 Background: Biliary obstruction frequently occurs in locally advanced or metastatic pancreatic cancer and is often managed by surgical biliary bypass or endoscopic stenting. We compared readmissions/reinterventions among pancreatic cancer patients undergoing bypass vs. stenting. Methods: Retrospective analysis of unresected pancreatic cancer patients in the Healthcare Cost and Utilization Project (HCUP) Florida State Inpatient Database and Florida State Ambulatory Surgery Database 2007-2011 using revisit variables. Patients with early surgical or endoscopic approach analyzed. Subsequent admissions and surgical, endoscopic or percutaneous interventions identified. Propensity score matching by approach. Univariate analysis of patient characteristics and outcomes before and after matching. Multivariate analysis of readmission and reintervention performed by logistic regression. Results: 1,823 and 342 underwent endoscopic treatment vs. early surgical bypass, respectively. After propensity score matching, 684 patients analyzed (table). 64.0% (219) of endoscopic and 70.5% (241) of surgical patients readmitted (p=0.07) and 15.2% (57) and 9.1% (31) underwent reintervention (p=0.01). Endoscopic patients had lower index median length of stay (6 vs 11 days, p&lt;0.01) and admission costs ($11,549 vs $23,215, p&lt;0.01). In multivariate analysis, surgical biliary bypass was predictive of readmission (OR 1.50; 95% CI 1.03-2.18), but initial procedure was not predictive of reintervention (p=0.20). Conclusions: Surgical biliary bypass is less commonly performed than endoscopic stenting. Among propensity score-matched patients, readmission rates are similar, though endoscopic patients require more subsequent interventions. Candidates for both techniques may experience fewer invasive procedures if offered initial surgical biliary bypass. [Table: see text]
Detecting and classifying circulating tumor cell subclasses from On-Q-ity microfluidic chips using a customized imaging platform.
Authors: Chunsheng Jiang, David Tims, Aladin Milutinovic, Oleg Gusyatin, Keith D. Merdek, Kam M. Sprott, Yi Dong, Michael Stocum, Walter P. Carney
Journal: Journal of Clinical Oncology (2012)

72 Background: Circulating tumor cells (CTCs) have clinical value in cancer diagnosis, prognosis, and treatment prediction. The On-Q-ity Microfluidic Chip (OnQchip ) with a gradient design has the advantage of dual size and affinity capture resulting in increased efficiency. Accurately detecting and classifying these rare captured cells in patient blood however is difficult. We present an imaging platform for accurate and reproducible CTC detection, where identified cells and fragments are further classified into several subclasses that may have separate prognostic utilities. Methods: Whole blood from advanced stage cancer patients and non-diseased controls was processed within 36 hours of collection. Blood was run on OnQchips coated with anti-EpCAM antibody. Captured CTCs and cellular fragments were identified by on-chip immunofluorescence. Chips were imaged at 5X magnification on a rapid automated platform. Cytokeratin positive (CK + ) events were identified and sorted via an advanced detection algorithm using a set of spatial and spectral features. Events were further validated and separated into subclasses by trained experts using 10X magnification. Results: Greater than 85% capture efficiency was repeatedly achieved in spiked blood with nearly 100% detection sensitivity and 3% false positive rate following automated sorting of CTC candidates. On a cohort of 27 prostate cancer patients and 33 normal subjects a median of 19 CK + events/7.5 ml blood were detected in cancer patients, compared to a median of only 6 in normals. ROC analysis yielded AUC values of 0.62 to 0.77 for separate subclasses of CTCs. An AUC of nearly 0.80 was achieved by combining two or more subclasses. Conclusions: Preliminary evaluation of this imaging platform shows efficient and reproducible CTC detection in spiked and patient samples. Enumeration using subclasses achieved high sensitivities and specificities in separating cancer patients from normals and therefore, makes this technology feasible for both research and clinical studies. Future clinical studies with large sample sizes will be performed to validate clinical significance of CTC subclasses.