tbuckley/cabot-search huggingface dataset:
Whole genome scanning strongly predicts clinical outcome in differently treated subgroups of patients with lymph-node negative breast cancer
Authors: J. Climent, P. Dimitrov, J. Fridlyand, J. Palacios, J. Garcia-Conde, D. Albertson, D. Pinkel, A. Lluch, J. A. Martinez-Climent
Journal: Journal of Clinical Oncology (2005)

9519 Background: Despite recent consensus on the eligibility of adjuvant systemic therapy based on clinical and histological criteria, one fourth of patients with lymph-node negative breast cancer (NNBC) will have recurrence and succumb of the disease. Gene expression profile of breast tumors may represent a powerful predictor of survival, but these systems are not applicable yet to the clinical setting. We examined the feasibility of developing a genomic predictor of the length of survival of patients with NNBC using assembled arrays for scanning the genome for DNA copy number changes. Methods: Whole-genome comparative genomic hybridization to microarrays (array CGH) was performed on 185 biopsy specimens obtained at diagnosis from NNBC patients treated in a single institution. Median follow-up time was 82 months (range, 11- 218). After surgery, 90 received anthracyclin-based chemotherapy (AC) whereas 95 did not receive adjuvant chemotherapy (NT). To correlate genomic data with clinical features and outcome, statistical analyses were performed using Cox proportional hazard models; the maxT procedure adjustment from multtest Bootstrap package was applied. Results: Analysis of NNBC genomes revealed a common signature composed of gain/amplification of 1q31-q41, 8q21-q24, 17q12-q21 and 20q12-q13, and loss of 8p21-p23, 11q21-q24, 16q21-q23 and 17p13. Specific gains or losses were associated with hormonal receptor expression. The distribution of genomic alterations was similar in the two treatment cohorts (AC group vs. NT group). In the AC group, none of the abnormal BAC clones correlated with disease-free survival (DFS). However, in the NT group, 29 BAC clones showing deletion and corresponding to only two different regions, 8p21-p23 and 11q21-q24, were strongly associated with relapse (DFS, 29% vs. 89%; p< 0,0001). Conclusions: DNA genomic profiling of tumor cells may predict outcome in differently treated subgroups of NNBC patients. Array CGH analysis of a limited set of BAC clones covering 8p21–23 and 11q21-q24 may select candidates for receiving anthracyclin-based chemotherapy despite other clinical and histological features No significant financial relationships to disclose.
Trends in chemotherapy-related treatment of advanced-stage colorectal (CRC) cancer.
Authors: Cathy Bradley, K. Robin Yabroff, Joan L. Warren, Neetu Chawla, Christopher Zeruto, Elizabeth B. Lamont
Journal: Journal of Clinical Oncology (2013)

258 Background: New drugs and technology are primary drivers of health care costs, but their marginal benefit is questionable, particularly in patients with incurable cancer. We examined trends in population-based treatment following diagnosis for metastatic colon and rectal cancer in elderly adults. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) – Medicare linked database to identify persons aged 65 and older diagnosed with distant stage colon (N=16,086) and rectal cancer (N=4,003) between 2000 and 2009. For each year, we report the percent of patients who received cancer directed surgery, chemotherapy, antiemetics/premedications related to the chemotherapy, and hematopoietic growth factors, and the mean cost of care. All estimates are adjusted for patient characteristics, SEER region, survival, and year of diagnosis. Results: The percent of patients who had cancer directed surgery declined 12 and 11 percentage points for colon and rectal cancer patients, respectively. The percent of patients who received chemotherapy increased from 41% to 46% for colon patients and from 52% to 57% for rectal patients. Chemotherapy treatment intensified from 2000 to 2009, with longer duration in chemotherapy and more agents given. Over a third of colon and rectal cancer patients received three or more agents in 2009, often including oxaliplatin and/or bevacizumab. The percent of patients who received hematopoietic growth factors rose appreciably from 4% to 19% for colon patients and from 6% to 21% for rectal patients. Antiemetics/premedication use increased approximately 20 percentage points for all patients. Total costs of care rose from a mean of $61,171 to $74,567 per colon patient and from $68,213 to $82,031 per rectal patient. The percentage of costs due to hospitalizations declined for colon (56% to 47%) and rectal (47% to 40%) cancer patients. Conclusions: The use and intensity of chemotherapy, along with cost of care, for patients with advanced cancer increased markedly from 2000 to 2009. The inclusion of newer more expensive agents shifted the bulk of treatment costs from hospitalizations to the outpatient setting. The value of these treatments for advanced stage elderly patients is unknown.
Quality of life with malignant bowel obstruction: provider assessed health state utilities
Authors: S. L. Wong, D. Wong, E. B. Elkin
Journal: Journal of Clinical Oncology (2005)

8260 Background: Bowel obstruction in patients with advanced malignancy represents a difficult management issue. The optimal role of surgery for malignant bowel obstruction (MBO) remains undefined, and data on quality of life (QOL) are sparse. Health state utilities are a quantitative measure of preferences and represent the relative QOL for potential health states. The purpose of this study was to assess the feasibility of eliciting rating scale (RS) values and standard gamble (SG) utilities for health states associated with MBO. Methods: A paper-based SG was developed to assess the health-related QOL associated with MBO. Five representative scenarios were presented, describing various levels of abdominal pain, nausea, and fatigue; effects on diet and bowel function; restriction on daily activities; relief of symptoms; and other treatment-related outcomes (i.e., surgical complications). Respondents were asked to rank the scenarios from best to worse, to rate each scenario from 0 (worst health condition imaginable) to 100 (best health condition imaginable), and to perform the SG exercise. In all cases there was a diagnosis of advanced malignancy, although the patient’s prognosis was not specified. Results: Ten health care professionals participated in this pilot study. Respondents varied in their rankings of the five clinical scenarios, but all identified the same scenario as the best one, and 9 identified the same scenario as the worst one. The best scenario had an average RS value of 81 and average SG utility of 0.98. The scenario identified as the worst by the majority of respondents had an average RS value of 29, and an average SG utility of 0.63. For intermediate scenarios, RS values varied from 56 to 67, and SG utilities varied from 0.86 to 0.91. Seven of the 10 respondents gave RS values and SG utilities that were consistent with their explicit rank ordering of the scenarios. Conclusions: Utility assessment by health care providers of MBO-related health states using SG is feasible. Development of QOL measures in the treatment of MBO can inform decision-analytic models of MBO treatment strategies and lead to the improvement of the decision-making process for patients. No significant financial relationships to disclose.
Are patients with colonoscopy also more likely to undergo other cancer screening? A population-based analysis.
Authors: Gregory Cooper, Tzuyung Doug Kou
Journal: Journal of Clinical Oncology (2014)

401 Background: Colonoscopy use in the United States has been increasing but remains short of target rates, especially among minorities and lower SES; these same groups are also less likely to receive breast and prostate cancer screening. However, at a population level, it is not known whether disparities are accounted for by the same individuals. Methods: Using a 5% national random sample of fee-for-service Medicare beneficiaries, we identified patients ≥ 70 years in 2009. Medicare claims from 2004-2008 were used to identify receipt of prior colonoscopy and exclude previous cancer, and claims from 2009-10 were used to identify receipt of colonoscopy, mammography in women and PSA testing in men. Differences in mammography and PSA were compared between four groups: no prior colonoscopy (2004-8)/no colonoscopy in follow up (2009-10) (group 1), no prior colonoscopy/colonoscopy in follow up (group 2), prior colonoscopy/no colonoscopy in follow up (group 3), and prior colonoscopy/colonoscopy in follow-up (group 4). Differences were also evaluated in a multivariate logistic regression model that adjusted for SES and physician supply at the level of the hospital referral region (HRR). Results: 717,334 beneficiaries (453,945 women and 263,389 men) were included in the study. During 2009-2010, the frequency of mammography was 38.0%, PSA was 41.7% and colonoscopy was 16.1%. All three procedures were less frequently performed in patients who were older, nonwhite, and with higher comorbidity scores. The presence of additional cancer risk factors was also associated with screening. Screening receipt according to colonoscopy status is shown in the Table. Conclusions: In this population-based analysis, we found that individuals with repeat colonoscopy were also more likely to undergo other screening procedures, including mammography and PSA. The findings may be accounted for by patient factors as well as physician practice patterns. [Table: see text]
A new approach to delay the development of resistance to docetaxel in the treatment of castration-refractory prostate cancer.
Authors: S. Filleur, S. R. Sennoune, J. C. Lees, J. Hirsch, L. Bermudez, R. Martinez-Zaguilan, T. Nelius
Journal: Journal of Clinical Oncology (2011)

e15177 Background: Resistance to docetaxel is a common problem in the treatment of castration-refractory prostate cancer (CPRC). Pigment epithelium-derived factor (PEDF) is antiangiogenic. We have shown that: (a) PEDF is down-regulated in prostate cancer; and (b) over-expression of PEDF in CRPC cells decreased tumor growth in vivo. Since both increase in interleukin-8 (IL8) production and, plasma membrane Vacuolar H+-ATPases(pmV-ATPases) have been involved in the resistance of cancer cells to chemotherapeutic drugs, we hypothesize that PEDF enhances docetaxel cytotoxicity by modulating IL8 and pmV-ATPases in prostate cancer cells. Methods: CRPC cells (PC3/DU145) were treated with 0-100 nM PEDF alone or in combination with 0-100 nM docetaxel. IL8 was measured in cell conditioned media by ELISA. mRNA levels of the a isoforms that target V-ATPase to the cell surface were investigated by qPCR. pmV-ATPase activity was measured on isolated plasma membranes. To evaluate PEDF anti-tumor properties, we used human CRPC LNCaP-derivative CL1 and LNCaP cell lines that stably express the fluorescent DsRed Express protein in combination with PEDF. Results: We found that PEDF inhibits the proliferation of all CPRC cells tested in vitro associated with a decrease in IL8 production in PC3 and DU145 cells. The effect of PEDF on growth was prominent in PC3 and DU145 cells under PEDF/docetaxel combined treatment. The mRNA levels of the a isoforms of pmV-ATPase were decreased when PEDF is expressed. PEDF expression in vivo decreases by 70% the development of subcutaneous CL1 tumors in immuno-compromised mice. We injected CL1 cells (pre-mixed with 50 nM human recombinant PEDF) into the left lobe of mice dorsal prostate. We found that all control animals die within 61 days after surgery. Importantly, 50% of PEDF-pretreated animals were still alive. Conclusions: These data indicate that inhibition of V-ATPases and over-expression of PEDF are promising new targets to enhance the cytotoxicity of docetaxel drug. Understanding the consequences of V-ATPase inhibition or PEDF over-expression in human prostate cancer cells will contribute significantly to our understanding of prostate cancer progression and treatment.
Relationship of aberrant glycosylation of n-glycan on immunoglobulins with survival of patients with renal cell carcinoma.
Authors: Shingo Hatakeyama, Maho Amano, Takuya Koie, Yuki Tobisawa, Tohru Yoneyama, Kazuyuki Mori, Norihiko Tsuchiya, Tomonori Habuchi, Shin-Ichiro Nishimura, Chikara Ohyama
Journal: Journal of Clinical Oncology (2013)

438 Background: Biomarkers for early detection and prediction of patient survival for renal cell carcinoma (RCC) have not yet been established. We have developed a novel glycoblotting method that allows high-throughput, comprehensive, and quantitative glycan analysis of whole human serum. We examined the relationship between serum N-glycan profiling and survival of the patient with RCC. Furthermore, we attempted to identify carrier protein to which the responsible N-glycan attached. Methods: We performed a comprehensive N-glycan structural analysis of sera from 64 patients with RCC using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The intensity of the N-glycans was then analyzed with the help of the logistic regression analysis and a receiver operating characteristic curve to select N-glycans which associated with patient survival in RCC. The candidate N-glycans which had statistically significant relationship in overall survival were evaluated their independency using Cox-regression model to elucidate its superiority comparing to other conventional biomarkers of RCC. Then, we recovered the responsible N-glycan together with its carrier protein by sialobloting method to identify the carrier protein. Results: We identified 56 kinds of N-glycans in sera from RCC patients. The intensity of peak 19 was significantly higher, and the intensity of peak 49 was significantly lower in the patients who survived longer. Multivariate analysis revealed that peaks 19 and 49 were independent predictors of overall survival as well as conventional risk factors. Protein analysis for the carrier protein revealed that the aberrant N-glycan was harbored by IgA1 or IgG4. Conclusions: Aberrant glycosylation of N-glycan on IgA1 or IgG4 may serve as novel biomarkers for RCC. Further validation study is warranted.
Population-based standardized symptom screening: Cancer Care Ontario’s Edmonton Symptom Assessment System and performance status initiatives.
Authors: Sean Molloy, Jose Pereira, Esther Green, Deborah Jane Dudgeon, Doris Howell, Monika K. Krzyzanowska, Wenonah Mahase, Reena Tabing, Sara Urowitz, Laura Macdougall
Journal: Journal of Clinical Oncology (2014)

56 Background: The goal of the collaborative is to improve the quality and consistency of physical and emotional symptom management across the cancer journey. Objectives are: (a) promote the adoption of electronic symptom assessment using a standardized tool and (b) increase the clinical use of evidence based guidelines to effectively manage patient identified symptoms. Methods: The actions taken for this initiative are to manage cancer symptoms through a patient reported measurement tool; improve the quality of symptom management through the uptake of symptom management guides and algorithms for care; and drive improvement through the adoption of an electronic symptom assessment platform The following aims were established for this work: (1) Aim for symptom screening and assessment (70% of ambulatory cancer clinic patients are screened for symptom severity using ESAS at least once/month) (2) aim for symptom management (evidence from chart audits show intervention as per evidence based guidelines for patients reported symptom scores) (3) aim for patient satisfaction (90% of target population indicates that their health care team took their scores into consideration when developing a care plan) and (4) aim for evidence of use (90% of patients state that their doctor or nurse spoke with them about their symptom screen). Results: 60% of cancer patients are screened each month representing over 28,000 people. Six of fourteen cancer regions are above the provincial target of 70%, with some close to 90%. 92% of patients felt ESAS was important to complete to help health care providers know how they are feeling. Conclusions: Cancer Care Ontario has been able to drive improvements in symptom management through the implementation of system wide electronic symptom assessment. For other jurisdictions interested in adopting this approach, the following areas are critical for success. (a.) Leadership at all levels of the system; (b.) clinical tools at the point of care; (c) engagement of patients in the design of care; (d) communications support to spread information to all stakeholders; and (e) using to data to drive performance improvement and accountability.
Molecular and clinical subgroup analyses from a phase III trial comparing gefitinib with docetaxel in previously treated non-small cell lung cancer (INTEREST)
Authors: J. Douillard, V. Hirsh, T. S. Mok, M. A. Socinski, C. Watkins, E. Lowe, A. Armour, E. S. Kim
Journal: Journal of Clinical Oncology (2008)

8001 Background: In INTEREST, gefitinib demonstrated non-inferior overall survival (OS), more favorable tolerability and improved QoL vs docetaxel in advanced pretreated NSCLC. We examined potential clinical and biomarker correlations with efficacy. Methods: Pre-defined clinical subgroups included histology, performance status, prior platinum and paclitaxel therapy, number of prior regimens, smoking history, gender, and ethnicity. Tumor tissues were evaluated by FISH, IHC, direct-gene sequencing and PCR for EGFR gene-copy number, EGFR protein expression, EGFR and K-Ras gene mutation, respectively. The OS effect was compared between subgroups using treatment-by-covariate interaction tests. OS and progression-free survival (PFS) were compared between treatments within subgroups using Cox proportional hazards models and objective response rate (ORR) using logistic regression models. Results: OS results were consistent in all clinical subgroups except for the number of prior regimens (interaction test P=0.03, 1 prior regimen HR 0.96, 95% CI, 0.85- 1.08: P=0.50, 2 prior regimens HR 1.39, 95% CI, 1.03–1.87; P=0.03). Subgroups such as never smokers, Asian ethnicity, adenocarcinoma and females had longer survival than the overall population, but equally long survival on both treatments. PFS and ORR results were generally consistent across subgroups. Of 1466 pts randomized, 453 had tissue samples evaluable for ≥1 biomarker. Exploratory analysis showed no difference in OS between treatments for any biomarker. OS was equally longer with both treatments in EGFR mutation positive pts (M+ n=44) than EGFR mutation negative pts (M- n=253) (M+, 14.2m and 16.6m; M-, 6.4m and 6.0m for gefitinib and docetaxel, respectively). PFS was longer with gefitinib than docetaxel in M+ pts (n=38 HR 0.16, 95% CI, 0.05–0.49; P=0.001) and ORR was higher with gefitinib in EGFR FISH + (13% vs 7%; P=0.04) and M+ pts (42% vs 21%; P=0.04). Conclusions: Gefitinib survival effect was not restricted to certain subgroups. Some subgroups had equally better outcomes compared to the overall population on both treatments. No clinical factors or biomarker appeared to be predictive of a greater gefitinib survival effect over docetaxel. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca, sanofi-aventis AstraZeneca AstraZeneca, Eli Lilly, Merck, Pfizer, Roche, sanofi-aventis AstraZeneca, Lineberger Comprehensive Cancer Center
Relationship of bone scan index and progression-free survival after docetaxel treatment for CRPC patients with bone metastases.
Authors: Atsushi Mizokami, Kouji Izumi, Satoru Ueno, Yoshifumi Kadono, Hiroshi Wakabayashi, Kenichi Nakajima, Mikio Namiki
Journal: Journal of Clinical Oncology (2014)

280 Background: A computer-aided diagnosis system for bone scintigraphy using semiquantitative index [Bone Scan Index (BSI)] has been used to measure the tumor burden of bone metastases. We examined relationships of BSI, bone turnover marker, and prostate-specific antigen (PSA)-progression free survival (PFS) after docetaxel-treatment for castration resistant prostate cancer (CRPC) with bone metastasis. Methods: Sixteen CRPC patients with bone metastases (median age 72, range 52 to 82) were treated with docetaxel. We evaluated bone metastasis by bone scintigraphy before or around six months after docetaxel-treatment retrospectively. BSI was automatically calculated by BONENAVI software version 1 (FUJIFILM RI Pharma, Co. Ltd., Tokyo, Japan; Exini Bone, Exini Diagnostics, Sweden). Serum PSA, bone alkaline phosphatase (BAP), carboxyterminal telopeptide of type I collagen (I-CTP) were examined every months. PSA-PFS was evaluated after docetaxel-treatment and compared with baseline of BSI, BAP, I-CTP, and change of these value after treatment. Overall survival (OS) was also evaluated by these markers. The rate of patients with PFS and OS was estimated by the Kaplan-Meier method. Results: Baseline of BSI, the serum BAP, and I-CTP before docetaxel-treatment did not affect PFS. The change of BAP and I-CTP by the docetaxel-treatment also did not affect PFS. Only the change of BSI affected PFS and the median PFS of CRPC patients with increased BSI and decreased BSI was 5.5 months and 10 months, respectively (p=0.026). Although OS showed a longer tendency in CRPC patients with decreased BSI than with increased BSI, there was not the significant difference (p=0.12). Conclusions: The change of BSI affected PFS in CRPC patients with bone metastases. Bone scan and its evaluation with BONENAVI was effective to monitor the clinical course during chemotherapy.
Nephrectomy status, race, and overall survival in patients with metastatic renal cell carcinoma.
Authors: Dale Kesley Robertson, Chao Zhang, Yuan Liu, Theresa Wicklin Gillespie, Omer Kucuk, Bradley Curtis Carthon, Viraj A. Master, Muta Issa, John Petros, Wayne B. Harris
Journal: Journal of Clinical Oncology (2016)

529 Background: In most settings median overall survival (OS) is longer for non-Hispanic whites relative to non-Hispanic blacks with metastatic renal cell carcinoma (mRCC). However, absence of nephrectomy has been a predictor of shorter OS for both groups. The primary objectives of this study were to define the reasons why patients with mRCC do not undergo nephrectomy and to correlate absolute contraindications to surgery with race and OS. Methods: Retrospective chart reviews of patients treated with targeted therapy for mRCC were conducted at the Winship Cancer Institute of Emory University and the AVAMC after obtaining institutional authorizations. Reasons for not undergoing nephrectomy were categorized as absolute, relative or no contraindication to nephrectomy. Descriptive statistics were employed along with Kaplan-Meier survival analysis. Results: See Table. The median OS (months) by nephrectomy status was 15.9 (6.8 – 24.7) vs. 41.8 (25.6 – 49.4), p value 0.0003, for patients at Emory with no nephrectomy vs. nephrectomy, respectively. The corresponding AVAMC values were 15.5 (8.5 – 29.5) vs. 45.2 (30.3 – 100.9), p value 0.0002. Conclusions: The number of patients with absolute contraindications to nephrectomy varied widely by race and institution, yet absence of nephrectomy was the predominant predictor of shorter OS in both settings. [Table: see text]