tbuckley/cabot-search huggingface dataset:
Understanding the role of ethnic status in Intensive Care Unit (ICU) deaths among advanced cancer patients
Authors: E. D. Trice, E. Paulk, M. E. Nilsson, A. A. Wright, T. Balboni, K. Viswanath, K. M. Emmons, H. Stieglitz, S. DeSanto-Madeya, H. G. Prigerson
Journal: Journal of Clinical Oncology (2008)

6506 Background: Studies suggest Blacks receive less aggressive, curative care for cancer but more aggressive care at end of life (EOL). This study investigated possible socio-cultural mediators (e.g. patient preference) of the relationship between ethnic status and aggressive care at EOL, defined as risk of death in the ICU, among advanced cancer patients. Methods: Location of death was established for 292 self-reported, Black (N=61) or White (N=231), Stage IV cancer patients interviewed at baseline as part of the prospective, multi-institutional Coping with Cancer study. We tested for mediators of the relationship between ICU death and ethnicity, controlling for possible confounding factors (e.g. socioeconomic status). Results: Blacks were more likely to die in the ICU than Whites (odds ratio, OR=4.40; 95% confidence interval, CI 1.81–10.72). Age, but no other sociodemographic factor (e.g. education), proved a confounder, reducing the ethnicity odds ratio to 3.65 (CI 1.47–9.08). Full mediators included religiousness/spirituality (OR=2.38, CI 0.69–8.31) and patient preference for a care plan emphasizing life extension despite pain or discomfort (OR=2.30, CI 0.78–6.77), with the latter being the only significant variable in the final model (OR 1.48, CI 0.31–7.15). Other factors investigated, but not found to be significant, included health, mental health status, social support, doctor-patient relationship and communication, terminal illness acknowledgement, and advance care planning (e.g. do-not-resuscitate orders). Conclusions: The increased risk of ICU death among Black advanced cancer patients compared to Whites was mediated by a disproportionate preference for care that focused on life extension among Blacks. Future studies should investigate whether this is an informed preference and therefore a true ethnic difference in values. Other prevailing hypotheses (e.g. trust) were not supported by this study. No significant financial relationships to disclose.
Increase in bone scan index during abiraterone treatment in relation to reduced survival in mCRPC patients.
Authors: Mariana Reza, Anders Bjartell, Mattias Ohlsson, Lars Edenbrandt, Elin Tragardh
Journal: Journal of Clinical Oncology (2014)

244 Background: Abiraterone acetate (AA) is one of several new treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). It has showed to prolong survival in patients who had disease progression after chemotherapy. An objective biomarker that is associated with improvement in survival would be of value in the management of patients under AA treatment, for example in decisions to continue or change treatment. Bone Scan Index (BSI) is a measurement that reflects the tumor burden in bone as a percent of the total skeletal mass. The purpose of this study was to evaluate BSI as a response biomarker in mCRPC patients on treatment with AA. Methods: We retrospectively studied a consecutive series of 28 mCRPC patients who received AA following disease progression after chemotherapy. All patients had undergone whole-body bone scan before and during AA treatment. Baseline and follow-up BSI data was obtained using the automated quantification software EXINI Bone bsi (EXINI Diagnostics AB, Sweden). Data on prostate-specific antigen (PSA) and survival were collected from the medical records. Cox proportional-hazards regression models and Kaplan-Meier estimates of the survival function were used to investigate the association between changes in BSI and PSA from baseline to follow-up and survival. Discrimination between prognostic variables was assessed using the concordance index (C-index). Results: Patients with an increase in BSI of at least 0.2 (n=15) had a worse one-year survival (36%) than those with improvement or stable disease (BSI change &lt;0.2) (96%) (p&lt; 0.006). Both follow-up BSI and the BSI change from baseline to follow-up showed higher C-index (0.80) than the corresponding PSA values (0.73 and 0.75). Conclusions: Increase in BSI is significantly associated with reduced survival in mCRPC patients under AA treatment following disease progression after chemotherapy. Calculation of BSI could be a valuable tool for treatment response evaluation as a complement to the traditional methods. [Table: see text]
Feasibility of multimodal molecular characterization of the androgen receptor (AR) in circulating tumor cells (CTCs) from patients with castrate-resistant prostate cancer (CRPC).
Authors: David James VanderWeele, Masis Isikbay, Edwin Reyes, Ryan Duggan, Alicia J. Wyche, Walter Michael Stadler, Donald Vander Griend, Russell Zelig Szmulewitz
Journal: Journal of Clinical Oncology (2014)

133 Background: Despite the wealth of agents targeting the androgen receptor (AR) signaling pathway in castrate-resistant prostate cancer (CRPC), emergence of resistance is common. Mechanisms for resistance are diverse and likely include quantitative alterations in AR as well as alterations in nuclear localization. Clinical interrogation of such events is challenged by difficulties in biopsying metastatic sites and limitations in available circulating tumor cell (CTC) platforms. We set out to explore different methodologies of AR interrogation within CTCs. Methods: CTCs and cultured prostate cancer cells were isolated from nucleated blood cells using fluorescence associated cell sorting (FACS) targeting the Epithelial Cell Adhesion Molecule (EpCAM) with CD45 negative selection. In addition to standard immunofluorescence imaging, ImageStreamX spectral flow analysis was used to analyze AR protein expression and nuclear localization. Targeted DNA sequencing and TaqMan copy number evaluation were used for downstream analysis of AR alterations. Patients with highly refractory disease were enrolled for these assay development studies. Results: Thirteen of 15 (87%) patients in an initial feasibility cohort had CTCs isolated for downstream evaluation. Targeted DNA sequencing of as few as 10 C4-2 cells isolated from nucleated blood cells confirmed specificity for prostate cells by identifying a known AR mutation. TaqMan copy number evaluation revealed AR amplification in two out of four evaluable patients. Fluorescence microscopy demonstrated feasibility of AR staining, with 10 of 10 patients exhibiting AR staining above negative control and 50% staining above that of AR+ LAPC4 cells. Though the numeric variability in AR expression using ImageJ software was high, AR protein interrogation with ImageStreamX allowed for more precise evaluation of nuclear localization of the AR revealing that in CRPC patients there can be distinct CTC populations with respect to AR localization. Conclusions: Identifying mechanisms of AR derangement is crucial for the precision management of advanced prostate cancer. CTCs are a promising way to evaluate molecular characteristics of AR in patients with late stage disease.
Preoperative angiogenesis and clotting/fibrinolysis circulating factors correlate with tumor stage, p21 and c-myc in colorectal cancer
Authors: I. Gil-Bazo, J. Rodríguez, V. Catalán, A. Alonso, J. de la Cámara, S. de la Cruz, S. Viteri, J. J. Sola, J. L. Hernández-Lizoáin, J. García-Foncillas
Journal: Journal of Clinical Oncology (2005)

3699 Background: Activation of clotting and fibrinolysis systems occurs during tumor angiogenesis. Due to this process, increased circulating vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), plasmingen activator inhibitor 1 (PAI-1), D-dimer (DD) and fibrinogen levels are observed, showing endothelial proliferation and fibrin clots formation and degradation. In addition, all these factors may correlate with cancer stage and molecular findings related to prognosis. The aim of this study was to correlate VEGF, vWf, PAI-1, DD and fibrinogen levels in stages I to III colorectal cancer (CRC) patients undergoing curative surgery with tumor stage (T and N), and over-expression of p21, p53, Ki67 and c-myc. Methods: 32 CRC patients, stages I to III, were enrolled in the study. Blood samples were taken the day before surgery and stored until further processing. Serum VEGF and plasma vWf, DD and fibrinogen were measured using commercial ELISA kits. Tumor specimens were collected, analyzed and stained using immunohistochemistry assays, immediately after resection. Linear polynomial contrast ANOVA, U-Mann-Whitney and Spearman tests were use for the statistical analysis. Results: Higher VEGF, PAI-1 and fibrinogen levels showed a significant positive trend with tumor stage (p<0.05). A positive correlation was also observed between higher VEGF and fibrinogen levels and a deeper wall infiltration (r=0.5, p=0.007 and r=0.4, p=0.01). In addition, vWf and p21 (p=0.03) and DD and c-myc (p=0.004) were positively associated. Conclusions: CRC patients presenting increased preoperative VEGF and fibrinogen circulating rates may show a deeper wall infiltration, a higher tumor stage and a subsequent poorer prognosis. PAI-1 levels may also be related with tumor stage. vWf and DD increased plasma concentrations may be closely correlated with molecular markers such as p21 and c-myc respectively. Further studies are needed to asses the implication of these findings on new adjuvant chemotherapy indications. (Supported by a grant from Gobierno de Navarra. Ref. 19/2003) No significant financial relationships to disclose.
Multicytokine and Polyfunctional CMV-Specific T Cells Are Associated with Stem Cell Transplant Donor CMV Serostatus.
Authors: Wendi Zhou, Jeffrey Longmate, Joycelynne Palmer, Simon F. Lacey, Ghislaine A. Hawkins, Ricardo Spielberger, Stephen J. Forman, John A. Zaia, Don J. Diamond
Journal: Blood (2007)
Are the cardiovascular side effects of bevacizumab caused by autonomic nervous system toxicity?
Authors: Zardasht Oqab, William McIntyre, Nazik Hammad, James Joseph Biagi, Geoffrey Seaborn, Wilma Hopman, Raveen Pal, Christopher Simpson, Adrian Baranchuk
Journal: Journal of Clinical Oncology (2014)

429 Background: Bevacizumab, a monoclonal antibody that inhibits the activity of vascular endothelial growth factor, has demonstrated activity against several malignancies. Reported adverse effects include hypertension, endothelial dysfunction, and heart failure. Animal models have suggested ANS toxicity as the mechanism. This pilot study investigates the effects of bevacizumab on short and long-term ANS function using a pre-post intervention design protocol. We report on the acute effects herein. Methods: Patients were recruited among those starting bevacizumab for colon cancer. A 10-minute ECG was recorded prior to, during, and following a first dose and analysed for heart rate variability (HRV), a marker of ANS dysfunction. The HRV values were compared using paired t-tests and repeated measures ANOVA. Plasma hormones were drawn before and after infusion and compared using paired t-tests. Results: Nine patients without a cardiac history were tested. Mean age was 63 years and 5 were male. All were in sinus rhythm with normal systolic function by echo. The Table reports changes in HRV indices and plasma hormones. Conclusions: Acute administration of bevacizumab produced a statistically significant decrease in plasma aldosterone and was associated with a trend towards decreases in plasma norepinephrine and the low/high frequency domain ratio of HRV. These changes may be signs of an early ANS imbalance. Both a larger patient series and longer follow-up are planned to characterize the effects of bevacizumab on the ANS. [Table: see text]
Erlotinib and patterns of pharmacogenomic (PGx) testing.
Authors: Jonas A. De Souza, Patrick P. Gleason, Catherine I. Starner, Yang P. Qiu
Journal: Journal of Clinical Oncology (2012)

182 Background: Erlotinib is an oral oncology drug that costs approximately $5,000 per month. Both the NCCN Guidelines (since March 2011) and ASCO (since April 2011) recommend PGx testing for tumor epidermal growth factor receptor (EGFR) mutation in patients with advanced non-small cell lung cancer prior to erlotinib use in the first line setting. Insight into early utilization patterns of PGx testing is crucial as new reimbursement methods, care models and evidence-based clinical pathways are developed. Methods: Using integrated medical and pharmaceutical data from four Blue Cross Blue Shield plans, we retrospectively identified members who received erlotinib between 01/2011 and 06/2011 and identified the date of the first erlotinib claim (index date). A new erlotinib user was defined as having no erlotinib claims filed in the prior 180 days. Among members who received erlotinib, medical claims were queried for the presence of ICD-9 codes for malignant neoplasm of trachea, bronchus and lung and for any current procedure terminology (CPT) code indicating PGx testing and other chemotherapy in the prior 24-month period and 1-month post the index date. Total paid amounts from all PGx test codes were obtained. The closest PGx testing date to the index date was used to calculate days between PGx testing and index date. Further analyses examining lines of therapy, monthly patterns of erlotinib usage and PGx testing pre- and post-guidelines recommendations, as well as a description of differences in utilized PGx CPT codes per individual patient, were performed. Results: Among 3,357,936 members insured, 125 (40 per million) received erlotinib, and 102 (81.6%) of those patients had a lung cancer diagnosis. Sixty (48%) were new erlotinib users, and 47 had a diagnosis of lung cancer. Of these, 36 (76.5%) had a PGx CPT code claim. The time between the PGx test and erlotinib start ranged from 4 days to 22 months. A total of $30,391 was spent on all PGx testing with an average of $844 per member tested. Conclusions: In a privately insured cohort of members who newly initiated erlotinib for lung cancer, 23.5% had no prior PGx testing. There is an opportunity for consensus guidelines, care management programs and a single PGx CPT code to possibly reduce variation regarding PGx testing patterns.
Who receives chemotherapy: An analysis of stage IV prostate cancer (PCa) patients in SEER-Medicare.
Authors: M. Grabner, E. Onukwugha, C. D. Mullins, B. S. Seal, A. Hussain
Journal: Journal of Clinical Oncology (2010)

4655 Background: Disparities in access to health care across demographic groups have been widely documented for primary therapies of PCa and among patients (pts) with early-stage PCa. Less is known about disparities in chemotherapy receipt among pts with advanced disease. The objective of this study was to investigate potential age disparities in chemotherapy treatment (ctx) and receipt of newer therapies such as docetaxel for Stage IV PCa pts using a large observational dataset. Methods: We analyzed pts aged 66 or older from the linked Surveillance, Epidemiology, and End Results and Medicare (SEER-Medicare) database. Pts were diagnosed with PCa between 2000 and 2005 and were followed until death or the end of the study period (December 31, 2007). We restricted the cohort to those with incident Stage IV disease (according to the AJCC-TNM classification). We calculated associations between demographic characteristics and the likelihood of receiving ctx using multivariable logistic regressions with monthly data. Outcomes of interest included “receipt of any ctx” as well as “receipt of docetaxel.” Results: Application of the inclusion/exclusion criteria resulted in 6,638 Stage IV PCa pts; among these 71% (N=4,724) were metastatic (M1) and 74% (N=4,905) received androgen deprivation therapy (ADT). The proportions of 66-74, 75-84, and 85+ year olds were 42, 41, and 17%, respectively. Nineteen % (N=1,252) received any ctx. Pts who were married, on ADT, had radiation treatment, saw a medical oncologist, had fewer comorbidities, or with M1 disease were more likely to receive any kind of ctx. The use of ctx decreased markedly with age ≥ 75 years, both in the full sample and the M1 subsample. Of those who received any ctx, 63% (N=788) were treated with docetaxel (including combination treatments). Younger patients were more likely to receive docetaxel following adjustments for confounding factors. Conclusions: We used the SEER-Medicare dataset to study demographic disparities in ctx among Stage IV PCa pts. We find evidence for differences in treatment by age and other patient characteristics. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis Amgen, Bayer, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Lilly, Merck, Novartis, Pfizer, sanofi-aventis sanofi-aventis Pfizer, sanofi-aventis GlaxoSmithKline, Novartis, Pfizer, sanofi-aventis
The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal carcinomatosis (PC) of appendiceal origin (AO).
Authors: Armando Sardi, Vladimir Milovanov, Michelle Sittig, Vadim Gushchin
Journal: Journal of Clinical Oncology (2016)

707 Background: Peritoneal carcinomatosis of mucinous appendiceal tumor origin is a rare condition which has poor prognosis if treated with limited surgery or systemic chemotherapy. Several publications show that CRS/HIPEC gives a significant survival benefit for patients with PC of AO. However, many patients do not get appropriate treatment. We show data from our 17-year experience using CRS/HIPEC in PC of AO. Methods: Retrospective analysis of a prospective database of 251 patients with PC of AO was performed. Peritoneal cancer index (PCI), completeness of cytoreduction (CC), lymph node (LN) status, and histopathology data was collected. The impact of each variable evaluated by Hazard ratio analysis. Overall survival (OS) estimated by Kaplan-Meier curves. Results: Mean age 53 years (range 23-81). 251 patients underwent 290 CRS/HIPEC procedures. 31 patients had 2, and 4 patients had 3 CRS/HIPEC. A total of 149 patients (59%) had peritoneal mucinous carcinomatosis (PMCA) and 102 (41%) had disseminated peritoneal adenomucinosis (DPAM) (Ronnett classification). Mean follow-up 4.8 years with a median of 4.7 years. Complete cytoreduction was achieved in 84% (89% DPAM, 80% PMCA; p = 0.047). Mean length of surgery 11.3 hours, mean hospital stay 14 days. No in-hospital or 30-day mortality. 73% had PCI &gt; 20 (78% DPAM; 68% PMCA). LN metastasis in 42% with PMCA. OS from date of HIPEC was 93%, 86%, 81% in DPAM and 90%, 60%, 44% in PMCA for 1, 3, and 5 years, respectively. With CC, the 5-year OS was 84% in DPAM and 49% in PMCA. All PMCA patients with incomplete cytoreduction (n = 30) had PCI ≥ 20 (p &lt; 0.001). Hazard ratios were 2.5 (95% confidence interval [95% CI] 1.3-4.5), 3.1 (95% CI 2.0-4.9), 3.6 (95% CI 2.1-6.2), for PCI &lt; 20, complete cytoreduction, and histopathology (DPAM vs. PMCA), respectively. Hazard ratio (for LN status in patients with PMCA was 3.0 (95% CI 1.8-5.1). Conclusions: Meaningful survival could be achieved in PC of AO even with extensive peritoneal disease (PCI &gt; 20). We consider CRS/HIPEC a standard of care for these patients. CRS/HIPEC should be provided in specialized centers by trained surgeons where complete cytoreduction could be frequently accomplished.
Updated results of a randomized phase II trial for neoadjuvant versus adjuvant docetaxel/cisplatin chemotherapy in patients with locally advanced gastric cancer.
Authors: Young Woo Kim, Keun Won Ryu, Il Ju Choi, Myeong-Cherl Kook, Young Iee Park, Hark K. Kim
Journal: Journal of Clinical Oncology (2014)

111 Background: Recent phase III trials proved the role of adjuvant chemotherapy in patients with gastric cancer after D2 resection, but the optimal treatment sequence remains to be determined. Here we report long-term follow up results for the randomized phase II trial comparing between neoadjuvant and adjuvant docetaxel/cisplatin (DC) chemotherapy in patients with locally advanced gastric cancer (LAGC). Methods: Patients with LAGC (stage IIIA-IV) were stratified by Japanese staging system and randomized to either neoadjuvant or adjuvant weekly DC chemotherapy in the National Cancer Center of Korea from 2003 to 2005. FDG-PET/CT screening was employed to exclude patients with metastasis. Patients randomized to neoadjuvant arm received 3 cycles of DC regimen (docetaxel 36 mg/m 2 and cisplatin 40 mg/m 2 on days 1 and 8 every 3 weeks), followed by surgery (D2 dissection). In adjuvant arm, patients underwent surgery, followed by 3 cycles of the same DC chemotherapy regimen. Results: Neoadjuvant arm (n=43) demonstrated higher R0 resection rate than adjuvant arm (n=44) [81% v 73%], but the difference was not statistically significant. At a median follow-up for suriving patients of 7.2 years, there were no significant differences in OS and PFS between the two arms [Log rank P=0.93 and P=0.89, respectively]. Conclusions: The timing of perioperative DC chemotherapy does not affect the overall survival of patients with LAGC.
A systematic literature review of the impact of 5-HT<sub>3</sub>RA use on health care utilization in patients with chemotherapy-induced nausea and vomiting in the United States.
Authors: Michael S. Broder, Claudio Faria, Annette Powers, Jehangeer Sunderji, Dasha Cherepanov
Journal: Journal of Clinical Oncology (2013)

269 Background: Uncontrolled chemotherapy-induced nausea and vomiting (CINV) can lead to nutrient depletion, diminished function, disruption of chemotherapy, and increased costs. Standard antiemetic therapy includes 5-HT 3 RAs for CINV prophylaxis, with palonosetron recommended in National Comprehensive Cancer Network (NCCN), Multinational Association of Supportive Care in Cancer (MASCC), and ASCO guidelines as the preferred 5-HT 3 RA for CINV prophylaxis with MEC. There is evidence that using 5-HT 3 RAs can reduce costs but no comprehensive review of the evidence is available. Methods: We searched MEDLINE, National Institute for Health Research (NIHR), Centre for Reviews and Dissemination (CRD databases, 4 conferences (Academy of Managed Care Pharmacy, ASCO, International Society for Pharmacoeconomics and Outcomes Research, MASCC), and bibliographies of included articles. We queried Medical Subject Headings (MeSH) and key terms: “ondansetron,” “granisetron,” “palonosetron,” “dolasetron mesylate,” “costs,” “cost analysis,” and “economics.” Included records reported data on cost/utilization (rescue medication, outpatient/inpatient services) related to 5-HT 3 RA use for CINV in English, in human subjects, and published after 1997. Results: Of the 433 identified records, the 16 reporting utilization in the US were reviewed (excluded: 29 duplicates, 388 off-topic records). Studies varied significantly in designs, patients, 5-HT 3 RA regimens, and definition of outcomes. Twelve studies reported rescue medication use for CINV in patients using different 5-HT 3 RAs. In 5 studies, fewer patients treated with palonosetron required rescue medication versus ondansetron users (56% vs. 61%, 28% vs. 83%, 14% vs. 24%, 8% vs. 11%, 6% vs. 11%); 2 studies found palonosetron users had fewer outpatient services versus ondansetron users (5% vs. 10%, 8% vs. 10%). Four studies, with a variety of patients and outcomes, reported fewer patients treated with palonosetron versus ondansetron or other 5-HT 3 RAs used inpatient care (e.g., 0.2% vs. 0.4%, 16% vs. 23%, 7% vs. 10%, 0% vs. 5%), while 2 studies reported similar use (1% vs. 1%, 0% vs. 0%). Conclusions: CINV prophylaxis with palonosetron is generally associated with lower use of rescue medications, outpatient and inpatient services compared to ondansetron or other 5-HT 3 RAs. Use of palonosetron as a standard treatment may lead to reduced utilization of rescue medications and healthcare services for CINV and subsequent cost savings.