tbuckley/cabot-search huggingface dataset:
Patient preferences for research access to administrative data in Ontario.
Authors: Chenchen Tian, Catherine Brown, Andrea Perez Cosio, Yvonne Leung, Alisa Lagrotteria, Mindy Liang, Gursharan Gill, Lauren Wong, Kendra Sinnesael, Cheryl Noronha, Stephanie Willing, Erin N Bell, Ashlee Vennettilli, Jackie Edwards, Joseph L. Pater, Doris Howell, Zahra Kassam, Geoffrey Liu, Annette E. Hay
Journal: Journal of Clinical Oncology (2016)

144 Background: Clinical trials collect outcome data until the trial ends. Subsequent health data is often available in government or health care administrative databases, yet this information is often not made available to researchers. We assessed patient preferences of long-term linkage of such administrative databases to clinical trials databases. Methods: A self-reported questionnaire was administered to outpatients in clinics of academic and community cancer centres. Cancer patients were presented with a hypothetical scenario of a clinical trial and asked about their willingness to allow confidential research access to their personal health information contained in administrative databases. Results: Of 524 patients, 54% were females, median age was 60 (range 19–93), 81% were Caucasian, and 61% had post-secondary education. Of cancer sites, 20% had breast cancer, 17% GI, 14% GU, 13% hematology, 12% thoracic, 12% head/neck and 11% gynecologic cancers. One-third (33%) had participated in a clinical trial. An overwhelming 93% allowed confidential access to health information in administrative databases (59% always, 34% depending on circumstances) including access to initials and birth dates, to be used to match information across databases (70% always, 23% depending on circumstances). Only 3% were unwilling to release their information under any circumstances. When asked about other identifiable information, such as name and address, more than 74% allowed the secure storage of this information at the central study coordinating center. In a new cohort of 103 patients, 84% preferred long-term data to be continually available to researchers after the clinical trial has ended; only 9% did not want this option. Results were similar across all sociodemographic subgroups studied including patients who had prior participation in clinical trials, although older patients were even more likely to allow access than younger patients (p = 0.02). Conclusions: The vast majority of patients were willing to have their long-term outcome data collected through government and health care administrative databases made available to clinical trial researchers, to improve our understanding of long-term outcomes of trial procedures and drugs.
Predicting response to platinum chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) using a genomic signature for “BRCAness”: A phase II clinical trial of satraplatin in men with mCRPC who have progressed on docetaxel.
Authors: S. M. Seng, M. D. Galsky, C. Tsao, J. Li, P. G. Febbo, W. K. Oh
Journal: Journal of Clinical Oncology (2011)

TPS191 Background: The BRCA genes preserve genomic integrity during double stranded DNA breaks via homologous recombination. Patients with germline BRCA mutations must utilize alternative repair pathways that are more error prone. Pre-clinical and early clinical studies have demonstrated that BRCA deficient tumors are particularly sensitive to platinum chemotherapy as they are unable to repair the DNA injury induced by platinum compounds, leading to cell death. Germline BRCA mutations are rare in solid cancers. However, 25% of patients with sporadic cancers acquire genetic changes in the BRCA genes conferring a phenotype similar to patients with germline mutations. Platinum compounds may have a greater role in these patients with sporadic cancers and “BRCAness.” Satraplatin, is a fourth generation oral platinum active in cisplatin resistant tumors and associated with an increase in progression free survival in men with metastatic castration resistant prostate cancer. No study has evaluated the clinico-pathologic correlates of “BRCAness” in prostate cancer or utilized a genomic approach to pre-identify patients that would benefit from platinum chemotherapy. Methods: We have initiated a phase II clinical trial of satraplatin in men with metastatic CRPC who have progressed on docetaxel therapy. All men ≥ age 18 with radiographic evidence of metastatic disease amenable to image-guided biopsy will be eligible for trial participation. All patients will undergo a pre-study biopsy of a metastatic lesion and receive Satraplatin 80 mg/m2 orally on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily. We are concurrently developing a prostate cancer genetic signature for BRCAness derived from genomic profiles of BRCA1/2 breast cancers and standard estrogen-receptor (+) breast cancers. This signature will be applied to a large dataset of primary localized prostate cancers and later validated in an independent dataset of trial participants. We will be evaluating the efficacy of satraplatin in relationship to the BRCAness signature status. One of thirty patients has been enrolled.
Evaluation of obstructive jaundice as a poor prognostic factor after curative resection of advanced gallbladder cancer.
Authors: Y. Nasu, S. Kondo, S. Hirano, E. Tanaka, T. Tsuchikawa, J. Matsumoto, K. Kato
Journal: Journal of Clinical Oncology (2011)

340 Background: Gallbladder cancer (GBC) is one of the most common malignancies of the biliary tract. Because of the lack of specific presentations, this condition is frequently diagnosed only at an advanced stage. Obstructive jaundice is generally regarded as an indicator of far advanced disease, unresectability, and poor prognosis. The aim of this study was to evaluate clinicopathological factors, especially jaundice, influencing outcome after radical resection of gallbladder cancer, in order to identify the patients benefiting from radical surgery. Methods: Seventy-five patients with GBC underwent surgical resection between 1998 and 2008. A retrospective analysis was conducted on sixty-four patients with UICC T2 or more tumors. Clinicopathologic features, extents of resection, and survival rates were investigated retrospectively. Obstructive jaundice was defined that serum T-bil level was more than 2.0 mg/ml. Patients with jaundice underwent ENBD or PTBD and curative resection was performed when serum T-Bil level decreased below 2.0 mg/ml. Right after laparotomy, para-aortic lymphadenectomy and frozen section pathology were performed to convert a radical resection to a palliative procedure when a para-aortic lymph node was positive. Results: The three and five-year disease-specific survival rates were 47% and 41%, respectively. Nine patients survived for more than five years.Univariate analysis showed that blood loss during operation, hepatic invasion, portal vein invasion, N category, M category after postoperative pathological examination and residual tumor were significant prognostic factors (p&lt;0.05), but multivariate analysis showed that M category only was independent prognostic factor (p&lt;0.05). Five-year disease-specific survival rates for patients with (n=37) and without (n=27) obstructive jaundice were 47% and 35%, respectively (p=0.69). Conclusions: Obstructive jaundice had no impact on postoperative survival as long as metastatic disease was exclueded and adequate resection of the hepatic hilum was performed. Aggressive surgery might bring long-term survival in selected patients even with obstructive jaundice by advanced gallbladder cancer. No significant financial relationships to disclose.
Changes in neutrophil-to-lympocyte and platelet-to-lymphocyte ratios to predict survival and pathologic complete response in esophageal cancer patients who receive trimodality therapy.
Authors: Jalal Hyder, Drexell Boggs, Andrew Hanna, Mohan Suntharalingam, Michael David Chuong
Journal: Journal of Clinical Oncology (2015)

170 Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multi-modality therapy, the effect of each specific therapy on the NLR and PLR is not well understood. We therefore evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods: We performed a retrospective analysis of non-metastatic patients with esophageal cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained the following time points (TP): 1) at diagnosis before CRT, 2) after CRT prior to surgery, and 3) after surgery. We also evaluated change in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: 83 patients with stage II-IV esophageal cancer and median age 60 years were included. Median follow up was 29.3 months. Median dose of 50.4 Gy (50.4-59.4) in 28 fractions (28-33) was used. Median NLR and PLR at the each TP: 1) 3.3 and 157.2, 2) 12 and 645, and 11.5 and 391.7, respectively. On multivariate analysis, inferior OS was associated with PLR ≥250 at TP 3 (p=.03), PLR decrease ≥609.2 from TP 2-3 (p=.02), and PLR ratio (TP 1/TP3) ≥1.08 (p=.03). Inferior progression free survival (PFS) was associated with NLR at TP 2 ≥36 (p=.0008), NLR increase ≥28.3 from TP 1-2 (p=.0005), PLR increase from TP 1-3 ≥19 (p=.01), and PLR ratio (TP 2/TP 3) ≥0.34 (p=0.1). Pathologic complete response (pCR) was less likely for adenocarcinoma histology (p=.03), NLR at TP 2 ≥10.6 (p=.04), and NLR increase from TP 1 to TP 2 ≥4.6 (p=.03). Conclusions: This is the first study to demonstrate that changes in NLR and PLR throughout trimodality therapy for esophageal cancer correlate with OS, PFS, and pCR. Further evaluation is warranted to better define which of the identified cut-off values are most clinically significant.
A phase II study of biweekly gemcitabine at fixed dose rate infusion plus S1 as first-line chemotherapy in patients with locally advanced or metastatic pancreatic cancer.
Authors: Xj Xiang, L Zhang, Jh Li, Zy Zhan, M Feng, J Chen, JP Xiong
Journal: Journal of Clinical Oncology (2016)

357 Background: The combination regimen of gemcitabine plus S1 (GS) as first-line chemotherapy has shown good efficacy in advanced pancreatic cancer. However, it is inconvenient to deliver gemcitabine on days 1 and 8 within one treatment cycle. In addition, previous studies have demonstrated that the gemcitabine administration by fixed dose rate infusion of 10 mg/m 2 /min should maximize the rate of intracellular accumulation of gemcitabine triphosphate and might improve clinical efficacy. The aim of this study was to evaluate the efficacy and safety of biweekly gemcitabine at fixed dose rate infusion combined with S1 (FGS) in chemonaive patients with locally advanced or metastatic pancreatic cancer. Methods: Forty-three eligible patients with locally advanced or metastatic pancreatic cancer received gemcitabine at a fixed dose of 10 mg/m 2 /min intravenously over a 2-h period on day 1, together with oral S1 40mg/m 2 twice daily on days 1 to 10, every 2 weeks. Tumor assessment was performed for every 3 cycles of chemotherapy. Results: All patients were evaluable for toxicity and 42 patients for efficacy. The overall response rate was 35.7% with 1 complete response, 14 partial responses, 17 stable diseases, and 10 progressions. Median time to progression was 5.9 months and median overall survival was 9.6 months. The main grade 3/4 toxicities included neutropenia (30.2%), thrombocytopenia (6.9%), anemia (2.3%), nausea (4.6%), diarrhea (2.3%). Conclusions: The biweekly FGS regimen is active, well tolerated and conveniently delivered as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.
A phase III study of cetuximab (CET) plus either brivanib alaninate (BRIV) versus placebo in patients with chemotherapy-refractory KRAS wild-type (WT) advanced colorectal cancer (aCRC): The NCIC CTG/AGITG CO.20 trial.
Authors: J. D. Shapiro, L. L. Siu, J. R. Zalcberg, M. J. Moore, J. Ringash, N. Mittmann, J. Simes, C. J. O'Callaghan, D. Tu, I. B. Walters, N. Magoski, P. Smith, D. Nomikos, L. Zhu, M. Savoie, S. Virk, F. El-Tahche, R. Gill, T. J. Price, D. J. Jonker
Journal: Journal of Clinical Oncology (2011)

TPS163 Background: While anti-EGFR monoclonal antibody, CET, improves survival in KRAS WT chemotherapy refractory aCRC, dual biologic strategies may overcome observed resistance to therapy. BRIV is a tyrosine kinase inhibitor of the vascular endothelial and fibroblast growth factor receptors (VEGFR/FGFR). This study is designed to assess the added benefit of combining brivanib with cetuximab. Methods: Stratified by centre and ECOG performance status (PS), patients were randomized 1:1 to receive CET + BRIV vs CET + placebo. Primary endpoint is overall survival (OS), estimated to be 9.7 months for the CET+placebo arm. With a 1-sided alpha of 2.5% and 90% power, 527 deaths are required to detect a 3.2 months difference (a hazard ratio of 0.75) in median OS, after accounting for one interim analysis at 50% events. Final analysis will be conducted after at least 536 deaths have been recorded in patients with KRAS WT tumours. Secondary endpoints include PFS, ORR, QOL, Health Utilities, economic evaluation and safety. Analyses with stratified Cox proportional hazards model will also be completed. Intervention: Both study arms receive iv CET 400mg/m2 d1 then 250mg/m2 weekly. In addition patients receive BRIV 800mg po daily or matched placebo. Eligibility: Patients must have aCRC with measurable or evaluable disease, ECOG PS 0-2, and received a prior fluoropyrimidine and failed irinotecan and oxaliplatin, or have documented unsuitability for these treatments. One prior regimen including a VEGF inhibitor was permitted. Four months post-activation the trial was amended June 2008 to include only KRAS WT status patients. Patients with uncontrolled hypertension or thrombosis within 6 months were excluded. Correlative studies: Pre-specified molecular analyses include FGF-2, Collagen IV, amphiregulin,epiregulin and BRAF. Trial status: Accrual will be completed in early Feb 2011. Interim analysis was conducted by the DSMC in November 2010 and suggested that the trial continue as planned. Clinicaltrials.gov registry: NCT00640471.
Recurrence risk perception and quality of life after treatment of breast cancer.
Authors: Sarah T. Hawley, Nancy K. Janz, Reshma Jagsi, Kent A. Griffith, Christopher Ryan Friese, Allison W. Kurian, Monica Morrow, Lauren P. Wallner, Steven J. Katz
Journal: Journal of Clinical Oncology (2016)

175 Background: Many breast cancer patients overestimate their risk of distant recurrence after treatment. We explored risk perception in a large, diverse population of breast cancer patients with favorable prognosis and assessed associations between overestimation and quality of life (QoL). Methods: As part of the iCanCare Study, we surveyed a weighted random sample of newly diagnosed patients with early-stage breast cancer treated in 2013-14, identified through the population-based SEER registries of Los Angeles &amp; Georgia about 3 months after surgical treatment (N = 2632, RR = 70%). Actual 10-year risk of distant recurrence after treatment was determined for women with DCIS (N = 502), and with low risk invasive (LRI: N = 520, Stg 1A, ER+HER2-, Gr 1-2). Women reported perceptions of their risk numerically between 0 – 100%, with values &gt; 10% for DCIS and &gt; 20% for LRI considered substantial overestimates. We assessed which patient and treatment factors were correlated with overestimation and report the bivariable associations between overestimation and the QoL measures of worry, distress, &amp; PROMIS physical and mental health. Results: One third (36%) of DCIS and 25% of women with LRI breast cancer substantially overestimated their risk of distant recurrence. Overestimation of risk was significantly associated with lower education (p = 0.02), and marginally with lower acculturation (p = 0.08). DCIS patients were more likely to overestimate risk of distant recurrence than LRI patients (OR = 2.0, 95% CI: 1.4-2.7). Women who overestimated risk in both groups reported more worry about recurrence; 49% vs. 16% DCIS, p &lt; 0.001 and 54% vs. 24% LRI, p &lt; 0.001. These women more often had higher distress (0-10 scores, mean of 3.5 vs. 2.5 DCIS p &lt; 0.001, and 3.9 vs. 2.2 for LRI, p &lt; 0.0001) and had poor PROMIS physical (21% vs. 14% DCIS, p &lt; 0.001; 34% vs. 16% LRI, p &lt; 0.001) and mental health (13% vs. 11% DCIS, not significant; 21% vs. 7% LRI, p &lt; 0.001) scores. Conclusions: Marked overestimation of risk after treatment was common, particularly among women with very low risk (DCIS). The strong association between risk overestimates and lower QoL suggests the need to address women’s perception of risk of distant recurrence after treatment of breast cancer. Funding: P01CA163233
Avenues to integrate and improve care: Surgeon attitudes toward end-of-life care.
Authors: Jonathan Bergman, Karl A. Lorenz, Charles D. Scales, Gery Ryan, Christopher Saigal, Carol J. Bennett, Mark S. Litwin
Journal: Journal of Clinical Oncology (2012)

16 Background: To examine urology trainees’ views about the quality and current practices of end-of-life care, and to explore strategies for improving integration and quality of care. Methods: We conducted semi-structured interviews with 20 urology trainees from four institutions in different regions of the United States. Stage of training ranged from intern to senior urologic oncology fellow; all were clinically active at busy academic institutions caring for many patients with advanced malignancies. Open-ended questions allowed participants to express themselves independently, and follow-up discussions explored their perception of current end-of-life practices, as well as avenues for future integration and improvement. We analyzed transcripts using a multi-stage, cutting-and-sorting technique in an inductive approach based on grounded theory analysis. Results: Clinicians unanimously agreed that their patients do not currently receive ideal care and were unanimously interested in joining a team geared towards improving care at the end-of-life. They expressed a preference for a multidisciplinary team, although the precise role each wanted to play within the team varied. Better identification of depression, pain, and patient-centered goals to allow value-congruent care were high in priorities for improvement. Trainees sited the lack of an educational curriculum on end-of-life care as a barrier to improving care, and expressed a desire for formal education on this topic. Conclusions: Urology trainees do not think that current care at the end-of-life is ideal for patients, and are interested in participating as part of a multidisciplinary team to better care for these individuals. There was a unanimous consensus that end-of-life care should be formally taught to all intern and resident physicians, and care at the end-of-life must be integrated to pursue value-congruent care for each patient. In response to the information gathered, we built a web-based, interactive, self-directed learning module emphasizing high-quality end-of-life care, issues to address with patients during clinic visits, and integration of end-of-life care. We have also integrated palliative care into the team caring for our patients with advanced disease.
The effect of darbepoetin alfa on patient-reported fatigue in cancer patients: Results from three phase III clinical trials
Authors: D. Revicki, D. Stull, H. Viswanathan, D. Tomita, M. E. Rader, D. Fairclough
Journal: Journal of Clinical Oncology (2008)

9616 Background: Cancer patients (pts) often develop chemotherapy-induced anemia (CIA), resulting in an increased risk for transfusions and fatigue. Darbepoetin alfa (DA) reduces transfusions in CIA pts. However, the impact of DA on fatigue has been difficult to examine in placebo-controlled trials due to the indirect mediating effect of hemoglobin (Hb) and the confounding effect of transfusions. This analysis examined the effects of DA on fatigue in cancer pts using latent growth modeling (LGM), which allows for simultaneous examination of direct and indirect effects incorporating data from all time points. Methods: Data from 3 placebo-controlled trials of DA in cancer pts with lung (2 trials; n=596 and 314) and lymphoproliferative malignancies (1 trial; n=349) were analyzed separately to study the effect of DA on fatigue in each trial. Fatigue was measured using the FACT-Fatigue (FACT-F). The direct and indirect effect of DA on fatigue was analyzed using multiple regression and LGM, while controlling for transfusions and baseline health status. Results: Pts receiving DA had higher Hb levels (lung: β=0.54 to 0.58, p<0.05; lymphoproliferative: β=0.44, p<0.05) compared with pts on placebo, controlling for transfusions. Pts with higher Hb levels during the trial also had less fatigue (lung: β=0.30 to 0.31, p<0.05; lymphoproliferative: β=0.49, p<0.05). The total standardized effect of DA on fatigue, calculated by multiplying the effect of DA on Hb by the effect of Hb on fatigue, ranged from 0.54*0.31=0.17 (lung cancer) to 0.44*0.49=0.22 (lymphoproliferative disease). In lung cancer pts, the mean change in FACT-F using LGM was 2.3 and 2.9 points, which approached the minimally important difference (MID) of 3 points for the FACT-F. The mean change in FACT-F was 3.5 points for pts with lymphoproliferative disease receiving DA, which is greater than this MID. Conclusions: When controlling for transfusions and baseline health status, DA was found to have an indirect effect on fatigue mediated by Hb increase in pts with lung and lymphoproliferative malignancies. Results suggest that analyses that incorporate the mechanism of DA action may better quantify the benefits of DA on pt-reported fatigue and the mediating effect of Hb increase on fatigue improvement. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc. Amgen Inc. Amgen Inc. Amgen Inc.
Correlation of pain and depression with tumor extent in patients with resected pancreas cancer.
Authors: B. I. Carr, L. Pujol, C. Yeo
Journal: Journal of Clinical Oncology (2010)

e14616 Background: Psychological tools have been used to assess pain and depression in various cancers and their impact on patient quality of life (Qol). Little is known about such factors in pancreas cancer, especially the correlations of QoL with pathologically-proven disease tumor extent. Methods: We prospectively examined QoL using Fact-Hep and CES-D scores in patients with resected pancreas cancer and correlated scores at presentation with baseline tumor extent. Results: 113 patients were evaluated. There were 63% males and 37% females. Pain was a presenting symptom in 38% in each gender and jaundice was the presenting symptom in 10% of females and 14% of males. Patients with Pain or No Pain at presentation were compared. Patients with pain had more metastases than patients without pain (52% vs. 27%). An ANOVA found higher CEA and depression scores (CES-D) and lower Physical and Functional well-being (FACT-HEP) for patients with pain than those without pain. No differences were found between groups for serum bilirubin or CA19-9 levels, social or emotional well-being FACT-HEP sub-scales. Patients who had the worst depression scores (CESD ≥ 26, worst 33%) were compared with all others. 36% of them had tumors ≥ 2 cm and 33% 2 cm; 43% had vascular invasion vs. 26% without; 42% had neural invasion vs. 25% without and 36% had local invasion (fat) vs. 25% without. Conclusions: This study in pancreas cancer patients shows a correlation of psychological dimensions with proven invasiveness of tumors, relating depression to both pain and tumor extent. No significant financial relationships to disclose.