tbuckley/cabot-search huggingface dataset:
Attenuated dose of gemcitabine with cisplatin in patients (pts) with unresectable or metastatic biliary tract cancer (ABC): Results of single Thai institution.
Authors: Chaiyut Charoentum, Arnon Chotirosniramit, Taned Chitapanarux, Chusak Sirivanichai, Nirush Lertprasertsuke, Busyamas Chewaskulyong, Sumitra Thongprasert
Journal: Journal of Clinical Oncology (2013)

265 Background: Combination of gemcitabine/cisplatin becomes a recent standard regimen for pts with advanced (ABC). We previously reported the encouraging activity of gemcitabine (1250 mg/m 2 ) with cisplatin and reported grade 3/4 toxicities of anemia and neutropenia in 33% and 22% respectively. (Charoentum et al. World J Gastroenterol 2007.). This study examines the toxicity and activity of attenuated dose gemcitabine (1000 mg/m 2 ) with cisplatin in Thai pts with ABC. Methods: Chemotherapy-naive patients with histological/cytological proven ABC, aged &gt; 18 years, ECOG 0-2 and adequate organs function were treated with gemcitabine (1000 mg/m 2 in a 30-min infusion D1, 8 q 21 d) followed by cisplatin (75 mg/m 2 D1) for maximum 6 cycles. Results: From November 2007 to June 2012, 37 patients were evaluated. Median age was 56 yrs (range 34 - 66), 54% were male, 76% were metastatic disease and 97% were ECOG PS 0/1. The median number of cycle was 4 (range 3-6). Among the 34 pts with measurable disease, there were 11 PR, 15 SD and 8 PD (response rate 32%). The most common hematologic toxicity of interests was gr 3 anemia in 11% and gr 4 neutropenia in 6%. Non-hematologic toxicity was generally mild. No cases of febrile neutropenia or treatment-related death were observed. The median progression free survival was 6 months (range 3-13). Conclusions: Treatment with attenuated dose of gemcitabine in combination with cisplatin in this study appears more tolerable than our previous reports in Thai pts with advanced ABC. The efficacy of both regimen appears similar.
Efficacy of early and delayed radiation in a prostatectomy cohort adjusted for genomic and clinical risk.
Authors: Robert Den, Kasra Yousefi, Bruce J. Trock, Elai Davicioni, Jeffrey J. Tosoian, Darby J. S. Thompson, Voleak Choeurng, Zaid Haddad, Phuoc T. Tran, Edouard John Trabulsi, Leonard G. Gomella, Costas D. Lallas, Firas Abdollah, Felix Yi-Chung Feng, Adam Dicker, Stephen J. Freedland, Jeffrey Karnes, Edward M. Schaeffer, Ashley Ross
Journal: Journal of Clinical Oncology (2016)

12 Background: In 3 published randomized trials, adjuvant radiation therapy (ART) for prostate cancer (PCa) resulted in improved progression free survival. However, the impact on metastases and overall survival is unclear. To date, there have been no published prospective trials examining the impact of salvage radiation therapy (SRT) in this disease state. Hence, we conducted a retrospective, nonrandomized comparative study of ART, SRT, or no radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathologic features, APF). Methods: 422 PCa men treated at 4 institutions with RP and having APF were analyzed with a primary end point of clinical metastasis. ART (n = 111), early SRT (n = 70) and delayed SRT (n = 83) were defined by PSA levels of &lt; 0.2, 0.2 to 0.5, and ≥ 0.5 ng/mL, respectively, prior to RT initiation. Remaining 157 men who did not receive additional therapy prior to metastatic onset formed the no RT arm. Clinical-genomic risk was assessed by CAPRA-S and Decipher. Cox multivariable (MVA) model was used to evaluate the impact of treatment on outcome. Results: During study follow-up, 37 men developed metastasis with a median follow-up of 8 years. Both CAPRA-S and Decipher had independent predictive value on MVA for metastatic outcome (both p &lt; 0.05). On MVA adjusting for clinical-genomic risk, delayed SRT and no RT had an HR of 4.31 (95%CI, 1.20-15.47) and 5.42 (95% CI, 1.59-18.44) for metastasis compared to ART. No significance difference was observed between early SRT and ART (p = 0.28). Men with low to intermediate CAPRA-S and low Decipher have a low rate of metastatic events regardless of treatment selection. In contrast, men with high CAPRA-S and Decipher benefit from ART, however the cumulative incidence of metastasis remains high. Conclusions: The decision as to the timing and need for additional local therapy following RP is nuanced and requires providers and men to balance risks of morbidity with improved oncologic outcomes. This analysis provides the most robust and accurate quantification of risk for these men. Post-RP treatment can be safely avoided for men who are low risk by clinical-genomic risk, whereas those at high risk should favor enrollment in clinical trials.
Late Onset, Acute Severe Neutropenia in Patients Treated with Rituximab for B-Cell Lymphoproliferation.
Authors: Philippe Solal-Celigny, F. Morschhauser, O. Tournilhac, C. Foussard, O. Fitoussi, A. Lillo-Le Louet, P. Brice, T. Lamy, H. Tilly, E. Gyan, Ph. Agape, E. Suc, A. Saad, A. Devidas, M. Blanc, A. Le Rol, P. Galanaud, J. Y. Muller, E. Voog
Journal: Blood (2004)
Symptom burden to predict health care utilization in hospitalized patients with incurable cancer.
Authors: Ryan David Nipp, Areej El-Jawahri, Samantha M.C. Moran, Sara D'Arpino, Connor Johnson, Daniel E. Lage, Risa Wong, Yian Xiao, Harry VanDusen, William F. Pirl, Lara Traeger, Inga Tolin Lennes, Barbara J. Cashavelly, Holly S. Martinson, Vicki A. Jackson, Joseph A. Greer, David P. Ryan, Ephraim P. Hochberg, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2016)

98 Background: Patients with incurable cancer are often hospitalized and have frequent readmissions after discharge. Considering the high physical and psychological symptom burden in this population, we sought to investigate symptoms as predictors of hospital length of stay (LOS) and time to first unplanned readmission. Methods: We consecutively enrolled incurable cancer patients with unplanned hospital admissions from 9/2014-4/2016. Within the first 5 days of admission, we assessed physical (Edmonton Symptom Assessment System [ESAS]; scored 0-10) and mood symptoms (Patient Health Questionnaire 4 [PHQ-4]; scored categorically). We created summated ESAS total and physical symptom variables. To identify predictors of LOS we used linear regression and for time to readmission we used Cox regression, with all models adjusted for age, sex, marital status, comorbidity, education, cancer type and time since incurable diagnosis. Results: We enrolled 1,000 of 1,227 (81%) eligible patients (mean age = 63.4; 50% female; 66% married). Gastrointestinal (33%) and lung (18%) cancers were the most common. Mean hospital LOS was 6.2 days and 30-day readmission rate was 25%. Over half of patients reported moderate/severe fatigue, drowsiness, lack of appetite, pain and poor well-being. Over one-fourth screened positive for PHQ depression and anxiety. All physical and mood symptoms individually predicted for longer LOS. Pain, nausea, poor well-being, ESAS total, ESAS physical and PHQ anxiety predicted for shorter time to readmission. Conclusions: Hospitalized patients with incurable cancer experience a high symptom burden, which correlates with their health care utilization. Both physical and psychological symptoms predict for longer hospital LOS and shorter time to readmission. These findings can inform interventions targeting patients’ symptoms during hospital admissions in an effort to improve health care delivery and utilization. [Table: see text]
Piroxicam promotes apoptosis and has a twofold effect on colon tumorigenesis in Mlh1/Apc mouse
Authors: E. Palmerini, M. Risio, G. Biasco, K. Yang, R. Hakim, M. Lipkin
Journal: Journal of Clinical Oncology (2005)

1026 Background: Increase amount of cyclooxygenase 2 (COX-2) is commonly found in malignant and premalignant lesions and overexpression of COX-2 is associated with both human and animal colon cancer. It has recently become evident that nonsteroidal anti-inflammatory drugs (NSAIDs) such as piroxicam, which inhibits the constitutive (COX-1) and inducible (COX-2) isoforms, represent a potential class of cancer chemopreventive agents. The mechanism of action of piroxicam on gastrointestinal cancer has not been determined. The present study examines the effect of piroxicam on Mlh1/APC 1638N mice, a preclinical model of intestinal cancer. Methods: Mice were fed orally once daily for 9 weeks with either AIN-76 diet or the same diet supplemented with piroxicam (60 ppm). Upon completion of treatment, the number and location of intestinal tumors was determined. Additional variables examined were the mean number of apoptotic cells in each crypt in the cecum and in the small intestine. Results: Administration of piroxicam to Mlh1/Apc mice produced an 82% decrease of the mean number of tumor per mouse in the small intestine (0.09 vs 0.5 respectively, p<0.05) and an increase in the cecum (1.18 vs 0.1, p<0.01) compared to vehicle-treated mice. The number of apoptotic positive cells/crypt was increased in the small intestine (0.21 versus 0.87, p<0.05) but also in the cecum (0.35 versus 0.84, p < 0.001). In small intestine, however, apoptosis was mostly triggered at the base of the crypt, the area considered to harbour the stem cells, whilst a whole length crypt apoptotic activation was found in the cecum. Conclusions: Piroxicam was able to induce apoptosis in intestinal mucosa, to reduce tumor number in the small intestine, and to increase tumorigenesis in the cecum when administered to Mlh1/Apc mice. Differences in the intramucosa distribution of the piroxicam-induced apoptosis between the two locations could be responsible for differences in tumor response. The findings in the present study call in to question the utility of piroxicam as a stand-alone chemopreventive agent. No significant financial relationships to disclose.
Immediate impact of the FOLFIRINOX phase III data reported at the 2010 ASCO Annual Meeting on prescribing plans of American oncology physicians for patients with metastatic pancreas cancer (MPC).
Authors: J. C. Bendell, S. Britton, M. R. Green, J. Willey, K. E. Lemke, J. Marshall
Journal: Journal of Clinical Oncology (2011)

286 Background: Since 2005 we at Xcenda, LLC have studied prescribing plans of American medical oncologists for first-line therapy in patients with MPC. In 2008 we reported the steady growth of prescribing plans for the gemcitabine-erlotinib (GE) combination from 23% in late 2005 to 46% in 2007. In 2007, gemcitabine (G) alone was the second most common regimen planned (27%) (Green MR. Proc GI ASCO 2008). No cytotoxic doublet consistently garnered &gt;10% prescribing share in this clinical setting. At ASCO 2010 Conroy et al. (J Clin Oncol. 2010;28(15s): Abstract 4010) reported a survival advantage for the FOLFIRINOX regimen compared to package insert dose and schedule of G alone as first-line therapy in patients with MPC and excellent PS (0-1). Methods: Between 7/31 and 8/28/2010 we again used our extensively tested, live research vehicle, NMCR Challenging Cases, to assess current prescribing plans of over 370 American medical oncologists for first-line therapy in a patient with metastatic pancreas cancer and either PS 1 or PS 2. Results: The FOLFIRINOX data have produced an immediate change in the distribution of planned first-line prescribing with 18% share for the PS 1 scenario, largely substituted for previous use of GE for this setting (Table). In PS 2, plans for FOLFIRINOX are minimal with G alone followed by GE as the dominant selections. Conclusions: The recently reported phase III FOLFIRINOX data are impacting first-line prescribing plans for patients with MPC. We will continue to quantitate physician-prescribing plans to more fully understand the additional impact the FOLFIRINOX data may have on overall chemotherapy management of these patients. [Table: see text] [Table: see text]
Efficacy and safety of nintedanib versus sorafenib in Asian patients with advanced hepatocellular carcinoma (HCC): A randomized phase II trial.
Authors: Ann-Lii Cheng, Chia-Jui Yen, Tae-You Kim, Yin-Hsun Feng, Yee Chao, Deng-Yn Lin, Arsene-Bienvenu Loembe, Julia Hocke, Caren Choi, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2015)

339 Background: Nintedanib (N) is an oral, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This randomized, multicenter, open-label, Phase II study (NCT00987935; 1199.39) evaluated the efficacy and safety of N versus sorafenib (S) in Asian patients with advanced HCC. Preliminary analysis showed similar time to progression (TTP) by independent central review (ICR). Methods: Asian patients with unresectable advanced HCC, Child–Pugh score 5–6, ECOG-PS ≤2, and alanine/aspartate aminotransferase (ALT/AST) ≤2× upper limit of normal were enrolled. Patients were randomized 2:1 to N 200 mg bid or S 400 mg bid continuously in 28-day cycles, until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. Primary endpoint was TTP by ICR (RECIST 1.0) and secondary endpoints were overall survival (OS) and investigator-assessed (IA) TTP. Results: Patients (N=95) were randomized to receive N (n=63) or S (n=32); arms were balanced except for macroscopic vascular invasion (48% vs 31%). At the final cutoff date (16 Jul 14), 88% of patients had a TTP event, and 86% had an OS event; 1 patient was on treatment beyond PD. N and S had comparable IA TTP (median 2.8 vs 3.0 months; HR 1.39 [95% CI: 0.87–2.23]) and OS (median 10.2 vs 10.7 months; HR 0.94 [95% CI: 0.59–1.49]). ICR TTP data are pending. All but 1 patient reported an AE (CTCAE 3.0). More S-treated patients had Grade ≥3 AEs (56% vs 84%), serious AEs (46% vs 56%), and AEs leading to dose reduction (19% vs 59%) and drug discontinuation (24% vs 34%). Class-specific AEs of tyrosine kinase inhibitors in &gt;15% of S-treated patients were hypertension, hand-foot skin reaction, and thrombocytopenia; only anemia was higher with N. AEs previously observed and higher with N were vomiting and nausea; ALT/AST increases and diarrhea were higher with S. Rash was reported in &gt;15% of patients only with S. Conclusions: N shows similar efficacy to S for TTP and OS. N was better tolerated than S and AEs were generally manageable. Further studies of N in Asian patients with advanced HCC are warranted. Clinical trial information: NCT00987935.
Moving toward patient-based funding through quality-based procedures (QBPs) for GI endoscopy and colposcopy.
Authors: Nabeela Ratansi, Aimee Langan, Irene Blais, Erin Svara, Karla Houser, Bronwen McCurdy, Jessica Moffatt, Lori Elliott
Journal: Journal of Clinical Oncology (2014)

43 Background: As part of the Ministry’s Health System Funding Reform initiative, Cancer Care Ontario is tasked to develop and implement Quality-Based Procedures (QBPs) for programs such as GI Endoscopy and Colposcopy. QBPs are clusters of patients with clinically related diagnoses or treatments that have been identified by an evidence-based framework as providing opportunity for improving quality outcomes and reducing costs. As stated by the Ministry, the goal is to reimburse providers for the types and numbers of patients treated, using evidence-informed rates associated with the quality of care delivered. Methods: QBPs are multiyear and have four key deliverables: Clinical: developing clinical best practices. Funding: tying best practices to pricing. Capacity Planning: understanding procedure types/volumes for capacity management. Monitoring/Evaluation: measuring the QBP’s impact. Developing the QBPs has involved: Creating Clinical Expert Advisory Groups (CEAG) of clinicians who are recognized for their knowledge and expertise. Tasking the CEAG to define quality and develop best practices informed by literature reviews, jurisdictional scans, and guidelines. Documenting these standards and clinical pathways in a clinical handbook, providing information on the practices that should be implemented to ensure consistent care delivery. The development of best practices is imperative to the foundation of the QBP and spans multiple years. Once best practice development is complete, it will be tied to pricing, where the procedure will be micro-costed based on workload, equipment, supplies, and other administrative costs. Results: The QBPs continue to evolve and aim to: Reduce practice variation. Improve patient outcomes. Improve system accountability. Improve cost-effectiveness of services. Effectiveness will be measured through a performance management framework, including an integrated QBP scorecard measuring appropriateness, access, and efficiency. Conclusions: The underpinning for moving towards an evidence-based, patient-based funding model involves defining quality standards and clincal best practices, and applying these guidelines to determine the cost of quality care.
Contemporary use of radium-223 (Ra-223) in men with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC): Feasibility and safety.
Authors: Hamid Emamekhoo, Rajasree Pia Chowdry, Paul Elson, Elisa M. Ledet, Allison Martin, Patrick Cotogno, Jennifer Beach, Allie E. Steinberger, Kimberly D Allman, Michael Stolten, Jorge A. Garcia, Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

210 Background: Ra-223 is an α-emitter that binds to the newly formed bone matrix and targets osteoblastic metastatic lesions. Treatment with Ra-223 delays symptomatic skeletal-related events (SREs) and improves overall survival (OS) in men with mCRPC. Concerns about the efficacy and safety of Ra-223 in the pre-chemotherapy space, given alone or in combination with Abiraterone Acetate (AA) or enzalutamide (ENZ), have been raised. Methods: To determine the feasibility, efficacy and safety profile of Ra-223 given alone or in combination with AA or ENZ to men with docetaxel-naïve mCRPC a retrospective study was conducted. PSA decline, rPFS and safety data for patients (pts) treated at Cleveland Clinic (CC) and Tulane University (TU) were analyzed. Results: Fifty-one (27 CC and 24 TU) chemo-naïve mCRPC pts with bone metastases were identified. The median age was 63 (46-87). Testosterone suppression was maintained during treatment. Pre-treatment alkaline phosphatase (ALP) was elevated in 16 pts (33%). In addition to bone, 24 pts (47%) had soft-tissue metastases. While 23 pts received Ra-223 alone, 22 pts (43%) received concomitant AA or ENZ therapy. To date, the median number of Ra-223 cycles received is 5 (1-6) with 39% of pts (20/51) receiving all 6 cycles. PSA declines &gt;30% were observed in 31% of pts. All but one pt had at least some decline in ALP. ALP decline &gt;30% was observed in 68% of pts. Reasons for treatment discontinuation included; completion of 6 cycles 39% (20/51); PD 35% (18/51); AEs 8% (4/51) and pt choice 4% (2/51). Grade (G) 3/4 AEs were observed in 4 pts; G3 anemia (n=3) and G4 thrombocytopenia (n=1). The vast majority of pts had PSA progression (81%) and 42% of pts have died. Estimated median time to PSA progression and OS are 3.9 (95% C.I. 1.84-4.82) and 11.0 months (95% C.I. 7.5-16.4), respectively. Pts with normal baseline hemoglobin levels and those who received concomitant AA tended to have better PSA progression-free and OS (p&lt;.06). Conclusions: Treatment with Ra-223 in combination with AA or ENZ in chemo-naïve mCRPC pts is feasible with no new safety signals of concern. Further evaluation of the combination of AA or ENZ with Ra-223 in this setting is warranted.
Integration of palliative care for patients with solid tumors on phase I clinical trials.
Authors: Betty R. Ferrell, Vincent M. Chung, Marianna Koczywas, Anna Cathy Williams, Arti Hurria, Tami R. Borneman, Rhonda Cooper, Louise Knight, Patricia Fischer, Denise Gallagher, Thomas J. Smith
Journal: Journal of Clinical Oncology (2016)

138 Background: Cancer patients receiving Phase I clinical trials are a population with advanced disease, high symptom burden, and with multiple QOL concerns including use of advance directives. Methods: An NCI funded R01 is currently in progress (2014-2019) as a randomized clinical trial to test a palliative care intervention (PCI) in this population. The PCI includes comprehensive patient assessment, goals of care communication, interdisciplinary care planning and patient teaching. Aims and hypotheses test the impact of the PCI on symptoms, QOL, resource use, spirituality and distress. Outcomes for the study (N = 400) will be conducted at the conclusion of the RCT. This paper reports preliminary baseline data of the first 100 subjects accrued. Results: Subjects mean age was 59 years and 59% were female, similar to prior trials. Forty eight percent (48%) were ethnic minorities, higher than prior trials (3% non-white, Finlay E, 2014; 9%, Parsons JA, et al. PLoS One 2012) with colon (22%) and lung (21%) cancers as dominant. Patients had a mean of 2 comorbidities (range 0-8) and 40% of the patients are &gt; 65 years of age. The most common symptoms reported by PRO-CTCAE (1 = least to 5 = most concern) were sexuality (4.2), fatigue (2.9), pain (2.6) and anxiety (2.5). Psychological Distress Thermometer, (0 - least to 10 = most distress) mean score was 4. FACIT spiritual concerns (1 = least to 5 = most concerning) identified greatest concerns of illness strengthening faith (2.0), strength from faith (2.0) and sense of harmony (2.6). There was limited use of supportive care services, PC consultation, or advanced directives. Conclusions: The population of Phase I trial patients is an important group for palliative care integration with major unmet needs in symptom management and advance care planning.
Thirty-day all-cause readmission rate at a cancer center as a quality of care measure.
Authors: Ronald Stewart Walters, Lisa M. Kidin, Joyce Roquemore, Victoria S. Jordan, Douglas Browning
Journal: Journal of Clinical Oncology (2012)

247 Background: Recently, a 30-day all-cause readmission rate has been proposed as a measure of quality of care. Readmissions are assumed to reflect failure by the discharging physician, hospital, or post acute care. These rates are generally easily calculated from available administrative data, and classifiable as "related to the previous discharge diagnosis" or not. Present on admission modifiers may enhance classification and assignment to "preventable" or "non-preventable," "expected or non-expected." This methodology is not generally applicable to the oncology population. The experience with one major cancer center is presented as an example of the limitations of such an approach. Methods: We analyzed 52,097 oncology admissions in an all-payer population that occurred between January 2010 and January 2012. Results: A mean of 32.5% (n=16,918) were readmitted within 30 days, compared to a "peer" group in the database of the University Health Consortium, median of 15%. The attached graph demonstrates the stability of this proportion. Leukemia, lymphoma, stem cell patients (46%), all patients with intense medical needs and frequent readmissions, n=7,635, were the largest subgroup. 42% (n=7,099) were readmissions for chemotherapy or immunotherapy, both planned and expected, and 11% (n=1,803) due to neutropenic fever, pneumonia, or sepsis, all common in this population and neither unexpected nor usually preventable. The most preventable, unexpected, and unplanned readmissions were for postoperative infection, dehydration, and urinary tract infection, accounting for 3.6% (n=609). Thus, the majority of readmissions were planned, expected, or not preventable. Conclusions: In a cancer population at an academic cancer hospital, the majority of readmission are not only planned, but also expected for this population of patients and should not be construed as representative of a quality of care issue. Proper stratification and classification of readmissions is essential to the interpretation of such a measure.