tbuckley/cabot-search huggingface dataset:
A cluster randomized trial of a patient-centered communication intervention in advanced cancer: The Values and Options In Cancer Care (VOICE) study.
Authors: Joshua J Fenton, Richard L Kravitz, Paul Duberstein, Daniel J Tancredi, Guibo Xing, Ronald M. Epstein
Journal: Journal of Clinical Oncology (2016)

2 Background: Observational studies demonstrate links between patient-centered communication, prognosis discordance, quality of life (QoL) and aggressive treatments near the end of life, yet there are few randomized evaluations of communication interventions in advanced cancer. Methods: We completed a cluster randomized controlled trial in cancer clinics in Western NY and Northern CA with medical oncologists (n = 38 randomized to intervention or control) and their community-dwelling adult patients with advanced non-hematologic cancer (n = 265; 194 with enrolled caregivers). Interventions foroncologists (individualized communication training using Standardized Patient Instructors) and patients/caregivers (individualized coaching using question prompt lists) were directed towards enhancing patient engagement in consultations, oncologists’ response to emotions, and provision of balanced information about prognosis and treatment choices. Oncologists and patients randomized to control received no interventions. Primary outcome was a composite of 4 communication measures coded from audio-recorded oncologist visits shortly after patient coaching (intervention) or enrollment (control). Secondary outcomes included the patient-physician relationship, shared understanding of prognosis, QoL, and utilization of aggressive treatments and hospice in the last 30 days of life. Results: In fully-adjusted models, the intervention significantly improved mean composite communication scores [0.34, 95% CI (0.06, 0.62), p = 0.017]. Effects on secondary outcomes were not significant. Conclusions: Oncologist communication training combined with coaching for patients with advanced cancer and available caregivers promoted patient-centered communication. Nevertheless, we did not observe changes in QoL and utilization, suggesting that more intensive, psychologically-oriented or longitudinal interventions may be needed, along with support and incentives for clinicians to participate. Clinical trial information: NCT01485627.
COUGAR-02: A randomized phase III study of docetaxel versus active symptom control in advanced esophagogastric adenocarcinoma.
Authors: Hugo Ford, Andrea Marshall, Jonathan Wadsley, Fareeda Y. Coxon, Wasat Mansoor, John A. Bridgewater, Srinivasan Madhusudan, Stephen Falk, Gary William Middleton, Daniel Swinson, Ian Chau, Joyce Thompson, Jane M. Blazeby, David Cunningham, Paula Kareclas, Janet A. Dunn
Journal: Journal of Clinical Oncology (2013)

LBA4 Background: Survival in patients who relapse after first-line chemotherapy for advanced esophagogastric adenocarcinoma (OGC) is poor though recently randomized trials have suggested a small survival benefit for second-line chemotherapy with taxanes or irinotecan. There is very little data on quality of life or survival, particularly in patients who progress shortly after first-line therapy. Methods: COUGAR-02 was a multicenter open-label, randomized controlled phase III trial for patients with locally advanced or metastatic OGC of performance status (PS) 0-2 who had progressed within 6 months of previous platinum/fluoropyrimidine (PF) chemotherapy (CT). Patients were randomized (1:1) to receive either docetaxel 75mg/m 2 every 3 weeks for up to 6 cycles or active symptom control (ASC), which could include any treatment thought by the treating clinician to be appropriate for the management of symptoms including radiotherapy, steroids and supportive medications. The primary endpoint was overall survival. Secondary endpoints were response rate, toxicity, health related quality of life (HRQL) and healthcare resource use. Results: Between April 2008 and April 2012, 168 patients were recruited (84 patients in each arm). Median age was 65 years (range 28-84), 81% were male. PS at randomisation was 0 for 27%, 1 for 57% and 2 for 15%. Site of disease was stomach in 46%, esophagogastric junction in 34% and esophagus in 20%. 86% had metastatic disease. 43% progressed during previous CT, 28% progressed within 3 months of end of previous CT and 29% progressed between 3 and 6 months. 19 (23%) patients completed 6 CT cycles (median 3 cycles per patient). The main reasons for not completing treatment were progression and toxicity. Docetaxel significantly improved overall survival over ASC alone (median 5.2 months (95% CI 4.1-5.9 months) for docetaxel; 3.6 months (95% CI 3.3-4.4 months) for ASC, HR=0.67 (95% CI 0.49-0.92); p=0.01). 7% had a partial response and 46% had stable disease after CT. 21% on docetaxel had grade 4 toxicity. Conclusions: The addition of docetaxel to ASC significantly improved overall survival. Docetaxel can be considered a standard of care in this setting. Clinical trial information: 13366390.
Utilization of sexual health and pelvic floor physiotherapy services in Vancouver’s Prostate Cancer Supportive Care (PCSC) Program.
Authors: Celestia S. Higano, Christine Zarowski, Marcy Dayan, Phil Pollock, Stacy Elliott, Sarah Mahovlich, Monita Sundar, Larry Goldenberg
Journal: Journal of Clinical Oncology (2016)

163 Background: The Vancouver Prostate Centre established PCSC in January 2013 to provide education and clinical services to men with prostate cancer (pts) and their partners. The program includes a dedicated sexual health (SH) clinician and physiotherapist (PT) with expertise in male pelvic floor anatomy and physiology. Educational and clinical services are available to pts without charge. We examined the use of the SH and PT services in PCSC to better understand how the services are utilized. Methods: Pts who are pre-treatment or within 6 months of surgery or radiation are offered a group educational (ED) session regarding sexual rehabilitation with the option of visits to the SH clinic. Those who were &gt; 6 months from surgery or radiation were offered evaluation in the SH clinic. Pts who are about to undergo surgery or who have postoperative incontinence are offered attendance at a group ED session and/or 3 visits with the PT clinician. We gathered data from PCSC logs, clinic schedules, and patient records to assess utilization of SH and PT services. Results: SH and PT ED sessions and clinics (CLIN) were initiated in July and October 2013 respectively. Of 802 pts oriented to PCSC, 400 pts, median age 64 (42-92), participated in the SH module and 229, median age 66 (range 42-88) in the PT module. 90% of patients in each module had been treated with surgery; 10% were on ADT. Details of utilization of the ED and CLIN components by pts for both modules are shown in the table below. There was a total of 781 SH clinic visits: 141 pts had one visit, the remainder had a median of 3 visits (range 2-8). For PT, there were 334 visits, with a median of 2 (range 1-4) per pt. 37% of pts who were seen by SH were also seen by PT and 65% of those seen in PT were seen in SH. Conclusions: Sexual dysfunction and urinary incontinence can be significant problems, and often occur together. The PCSC Program offers both educational and clinical services to address these issues, and continues to modify its programs to best serve patient and partner needs at various time points after therapy. [Table: see text]
KIR Haplotype B Donors but Not KIR-Ligand Mismatch Result in a Reduced Risk of Relapse After Haploidentical Hematopoietic Stem Cell Transplantation Using Reduced Intensity Conditioning and a CD3/CD19 Depleted Graft.
Authors: Sebastian Michaelis, Markus Mezger, Martin Bornhauser, Rudolf Trenschel, Gernot Stuhler, Matthias Stelljes, Lutz P Mueller, Herrad Baurmann, Birgit Federmann, Lena Oevermann, Lothar Kanz, Rupert Handgretinger, Wolfgang A. Bethge
Journal: Blood (2012)
Analysis of molecular profiling of renal cell carcinoma: Identification of a 4-microRNA signature as a prognostic value in patients with stage I-II disease.
Authors: Daniel E. Castellano, Carlos A. Farfán, Gamez Angelo, Juan M. Sepúlveda, Guillermo De Velasco, Felipe Villacampa, Angel Tejido, Mario Dominguez, Federico de la Rosa, Juan A. Fresno
Journal: Journal of Clinical Oncology (2013)

395 Background: Renal-cell carcinoma (RCC) accounts for 3% of all cancers and produces over 12,000 deaths every year in the EE.UU. Currently, there is a need to identify stage I/II RCC patients with high risk of relapse following nephrectomy, given that these patients do not receive adjuvant treatment and ≈ 25% of them relapse. MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNA and playing an important role as regulators of gene expression during tumorigenesis. Our willing is to define a miRNA expression profile associated with a high risk of relapse in early RCC. Methods: We analyzed 113 pts. with RCC stage I-II of a local data-base who had undergone nephrectomy from 2000 to 2008. RNA was extracted from FFPE samples using RecoverAll (Ambion). RNA samples were hybridized to Human miRNA Microarray Release 14.0, 8x15K (Agilent Technologies. Data were normalized using Quantile Normalization. Only 396 miRNAs with detectable signal in at least 10% of the hybridized samples were considered for further analysis. Identification of miRNAs related with recurrence risk and subsequent developing and validation of miRNA expression-based prediction models of recurrence risk were performed in BRB-ArrayTools v4.2.1. Results: We identified a 4-miRNA expression signature that distinguishes early stage RCC patients with low and high recurrence risk (p value = 0.0013; HR = 4.68 [1.82-12.0]). Distant recurrence free survival rate at five years was 97.4 and 81.2 for the low and high recurrence risk groups respectively. High levels of miR-424 were related with a high recurrence risk (p = 0.023). Conclusions: The TNM staging system lacks accuracy to identify prognostic markers of survival in early RCC. Our results suggest that specific miRNAs are involved in the recurrence of early disease. We have found a miRNA expression signature that identifies patients with high risk of developing distant metastasis using the FFPE sample of primary tumors. High expression levels of miR-424 were related with a high recurrence risk. MiR-424 is a hypoxia induced miRNA whose expression has been related with HIF-1α and HIF-2α stabilization and angiogenesis induction.
The relationship between travel distance to cystectomy and likelihood of readmission.
Authors: Troy Sukhu, Jason Lomboy, Matthew Macey, Anne-Marie Meyer, Ke Meng, Matthew Edward Nielsen, Raj Pruthi, Eric Wallen, Michael Woods, Angela Smith
Journal: Journal of Clinical Oncology (2016)

462 Background: Population-based estimates of readmissions following cystectomy range from 25-43%. Recent studies have investigated the relationship between complications and other patient- and hospital-level factors; however, the relationship between distance traveled for surgery and risk of readmission remains unclear. We hypothesized that larger distances would increase the risk of readmission following surgery. Methods: Using a linked data resource combining NC Central Cancer Registry with administrative claims data from Medicare, Medicaid, and private insurance plans, we included adult patients undergoing radical cystectomy for bladder cancer from 2003-2008. Complications were carefully coded and grouped based on previously published standards: genitourinary, gastrointestinal, wound, infection, venous thromboembolism, and others. Travel distances were calculated by using straight-line distances between zip codes of the patient and cystectomy provider. Bivariable analyses were performed, and multivariable logistic regression was used to evaluate the association of travel distance to cystectomy with likelihood of readmission within 30 and 31-90 days. Results: Of 735 patients who underwent cystectomy, 171 (23%) were readmitted within 30 days, and n = 156 (21%) were readmitted between 31-90 days. Mean age was higher among those readmitted, but was statistically non-significant. No significant differences were noted based on race, stage, comorbidity status, or complication type. However, on bivariable analysis, distance to the cystectomy provider &gt; 30 miles was associated with a higher likelihood of readmission (p = 0.0009). On multivariable analysis, the only predictor of 30-day readmission was a longer travel distance to the cystectomy provider (OR 1.27, 95% CI: 1.05, 1.54). Results were also analyzed for 31-90 day readmissions, but no significant predictors were identified. Conclusions: Longer travel distance to a cystectomy provider is associated with higher 30-day readmission rates, suggesting that complications occurring during this time period may benefit from closer follow-up.
Use of P63 expression to define a lethal subset of muscle-invasive bladder cancers.
Authors: W. Choi, J. B. Shah, M. Tran, R. S. Svatek, L. Marquis, I. C. Lee, D. Yu, L. Adam, J. E. Bondaruk, S. Wen, Y. Shen, C. P. N. Dinney, B. Czerniak, D. J. McConkey, A. O. Siefker-Radtke
Journal: Journal of Clinical Oncology (2011)

4653 Background: Previous studies implicate p63 as an epithelial marker in epithelial-to-mesenchymal transition (EMT) and in the maintenance of epithelial stem cell compartments. While known to be downregulated in the transition from superficial to muscle-invasive bladder cancer (MIBC), the relationship between p63 expression and survival in MIBC is not clear. Methods: Using real-time PCR and whole genome expression profiling, we characterized p63 expression and several genes implicated in EMT in 15 human bladder cancer cell lines and 101 primary tumors. We correlated marker expression with stage, disease-specific (DSS), and overall survival (OS), and then validated these markers at the protein level by immunohistochemistry (IHC) in an independent set of tissue from 57 patients with MIBC. Results: Expression of epithelial markers E-cadherin and p63 correlated directly with one another and inversely with expression of mesenchymal markers Zeb-1, Zeb-2, and vimentin. EMT marker expression was associated with muscle invasion with non-MIBC expressing high levels of E-cadherin (p<0.0001) and p63 (p=0.01), and MIBC expressing high levels of mesenchymal markers (p<0.0001 for Zeb-1, Zeb-2, and vimentin). Interestingly, a subset of MIBC maintained high levels of E-cadherin and p63 expression. Patients with MIBC that retained p63 had a significantly worse OS (p=0.007) and DSS (p=0.004). In an independent validation set, p63 expression by IHC was restricted to the nucleus of tumor cells, with higher percent expression associated with adverse OS (p=0.03) and DSS (p=0.046). Using multivariate analysis, both p63 and MMP9, which has been previously associated with adverse outcome, remained independent predictors of survival (DSS p63: HR1.63, p=0.022; log-MMP9: HR 1.35, p = 0.003). Conclusions: Molecular markers of EMT are elevated in muscle-invasive bladder cancers; however, retention of the “epithelial” marker p63 in muscle-invasive tumors is associated with a worse outcome. MMP9 and p63 expression appeared independent in predicting adverse outcomes in MIBC. Mechanisms driving MIBC displaying an “epithelial” phenotype and the role of EMT in chemotherapy response and cancer metastases need to be more fully explored in future studies.
A phase II study of gefitinib versus vinorelbine or gemcitabine in chemotherapy-naïve elderly patients with advanced non-small cell lung cancer based on epidermal growth factor receptor mutation status.
Authors: S. Fujita, N. Katakami, K. Masago, H. Yoshioka, K. Tomii, T. Kaneda, M. Hirabayashi, T. Morizane, T. Mio
Journal: Journal of Clinical Oncology (2010)

7559 Background: Elderly patients are more vulnerable to toxicity from chemotherapy, possibly from progressive organ failure and comorbidities. Activating epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine kinase inhibitors (EGFR-TKI). We studied patients with advanced NSCLC where treatment was customized based on EGFR mutation status. Methods: We screened 57 chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, age 70 or older, and performance status 0 or 1, for EGFR exon19 codon 746-750 deletion and exon21 L858R mutation. The 22 patients with EGFR mutations received gefitinib (250 mg/day); 32 patients without mutations received vinorelbine (at 25 mg/m2 on days 1 and 8, every 21 days) or gemcitabine (at 1,000 mg/m2 on days 1 and 8, every 21 days). The primary endpoint was response rate. Results: Characteristics of the 54 eligible patients enrolled from July 2006 to April 2009 included median age of 80 years (range, 71-89 years); 20 men; 29 never smokers; and 37 with adenocarcinoma. Response was 45% in patients with EGFR mutations and 19% in patients without EGFR mutations. Median overall survival was 24.4 months in patients with EGFR mutations, while it is 18.9 months in patients without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction occurred in 23%; dermatitis, in 5%. In patients treated with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were neutropenia (47%; 4 had febrile neutropenia), anorexia (9%), anemia (6%), nausea (6%) and fatigue (6%). No treatment-related death occurred. Conclusions: Customized gefitinib in EGFR-mutant NSCLC patients resulted in a remarkable response to EGFR-TKI, consistent with previous reports. Treatment customization on the basis of EGFR mutation status deserves consideration, especially for elderly patients, who often cannot receive second-line chemotherapy due to poor organ function and comorbidities. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Japan K.K.
Budgetary impact of adding ziv-aflibercept to a United States health plan formulary as a post-oxaliplatin biologic option for patients with metastatic colorectal cancer (mCRC).
Authors: Keith Huff, Edward Drea, Daniel Hennessy, Stephen F. Thompson, Ravinder Dhawan
Journal: Journal of Clinical Oncology (2015)

765 Background: To assess the economic impact of the availability of ziv-aflibercept for patients with mCRC following disease progression after oxaliplatin, a user-adaptable budget impact model was developed for payers, based on use of 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) chemotherapy alone or combined with a biologic agent, including ziv-aflibercept. Methods: A Markov-like model simulated transition from progression-free survival (PFS) to progressive disease (PD) and death. Over the model time frame of 1 year, each 90-day cycle adjusted for the probability of patients experiencing PFS, PD or death. Treatment options were FOLFIRI alone or combined with a biologic agent, ziv-aflibercept, bevacizumab, cetuximab or panitumumab. April 2013 United States utilization rates were used as baseline, with biologic agent drug costs as per July 2014 Medicare Part B Drug Average Sales Price. PFS and overall survival were calculated from clinical trial data of biologic agents combined with chemotherapy. Adverse event cost calculations used documented incidence rates and published cost sources. Other costs were for biomarker testing, drug administration/monitoring and death/terminal care. Results: The estimated number of patients receiving FOLFIRI alone or with a biologic agent for mCRC was 57 per million-member health plan. Using April 2013 utilization rates (including ziv-aflibercept at 3.4%), estimated treatment costs were $5.259M, a per-member-per-month (PMPM) cost of $0.0438. Changes in utilization rates of biologic agents, including, for example, ziv-aflibercept at 20.1%, would decrease costs by 2.1% ($108,176) to $5.151M annually, a PMPM decrease of $0.009. The model suggests cost savings primarily due to lower unit costs for ziv-aflibercept and lower death-related costs, rather than decreased adverse event management. Conclusions: The model estimates a PMPM cost saving with increased utilization of biologics, including ziv-aflibercept. Sensitivity analysis of utilization rate changes supports these findings. Including further user-defined scenarios allows plan-specific modeling of budgetary impact.
The combination of sorafenib and everolimus in patients with solid tumors: Results of a phase I study.
Authors: L. Nogova, C. Mattonet, M. Scheffler, I. Papachristou, N. Muthen, M. Sos, U. T. Hacker, T. Elter, H. Backes, C. Kobe, K. Rhiem, P. Mallmann, U. Fuhr, R. Schnell, I. Katay, K. Toepelt, M. Reiser, N. Harbeck, M. Dietlein, J. Wolf
Journal: Journal of Clinical Oncology (2011)

e13613 Background: The combination of the multi-kinase inhibitor sorafenib (S) and the mTOR inhibitor everolimus (E) may increase anti-tumor efficacy by dual inhibition of key nodules of signaling pathways regulating angiogenesis and cellular proliferation. FDG-PET might be a suitable method for the assessment of pharmacodynamic activity of E. Methods: Patients with advanced solid tumors after failure of standard therapy were treated with E in a dose escalating schedule of 1x 2.5-10mg daily in combination with a fixed dose of 2x 400mg S daily. The primary objective was to determine the maximum tolerated dose (MTD) of the combination. Dose-limiting toxicity (DLT) was defined as any of the following toxicities occurring during the first 29 treatment days(DLT interval): hematological or non-hematological toxicity of CTC grade IV, any toxicity requiring hospitalization or any toxicity leading to delay of treatment for more than 2 weeks. In addition to pharmacokinetics, pharmacodynamic analyses using dynamic FDG-PET were performed on days 0, 5 and 14. Response after 8 weeks of treatment was assessed by CT. Results: Sixteen patients have been enrolled. The DLT was not reached according to protocol definition. However, at a dose level of 1x 10mg E daily and 2x 400mg S daily the following toxicities occurred in the non DLT interval: upper respiratory tract infection III°, treatment delay caused by leukopenia III° and thrombopenia III° and sudden cardiac death probably due to arrhythmia. Based on these observations the dose level of 1x 7.5mg E daily and 2x 400mg S daily was defined as MTD. Data analysis of patients treated on MTD is currently ongoing. Response after 8 weeks could be evaluated in 9 patients, showing progressive disease in one patient (pancreatic cancer) and stable disease in 8 patients (NSCLC, melanoma, CUP, ovarian, colorectal, vaginal and breast cancer). Conclusions: Combination of S and E is feasible for the treatment of patients with advanced solid tumors. The full analysis including pharmacodynamics and pharmakokinetics will be presented.