tbuckley/cabot-search huggingface dataset:
Totally implantable venous access device use in pancreatic cancer: A national analysis.
Authors: Lindsay A. Bliss, Catherine J. Yang, Rebecca A. Miksad, Nicholas E. Tawa, Elan R. Witkowski, Sing Chau Ng, Jonathan F. Critchlow, Jennifer F. Tseng
Journal: Journal of Clinical Oncology (2014)

e15188 Background: Totally implantable venous access devices (ports) can be used in pancreatic cancer treatment. Long-term device placement facilitates agent infusion and reduces discomfort from repeated intravenous (IV) catheterization but can be associated with complications. This study examined US port placement, utilization, and removal patterns. Methods: Retrospective review of Surveillance, Epidemiology, and End Results Program-Medicare (SEER-Medicare) patients with pancreatic cancer 2000-2007. Patients ≥65 years at diagnosis with placement of ports identified based on procedure codes. Post-placement short-term (≤30 days) and long-term (>30 days) complications, IV chemotherapy administration, and device removal timing were identified. Patient characteristics collected included age, sex, marital status, neighborhood socioeconomic status, region, stage, resection status, Charlson comorbidity score, and survival time. Chi-squared and Cochran-Armitage trend tests used for statistical analyses. Results: Of 19,315 patients, 21.4% (1,379) of resectable patients and 18.9% (2,163) of unresectable patients underwent port placement (p<0.0001). Patients undergoing port placement increased from 13.4% in 2000 to 25.8% in 2007 (p<0.0001). Port placement varied from 17.7% in Stage IV to 25.1% in Stage III patients. 88.0% of patients with ports received IV chemotherapy compared to 36.1% without ports (p<0.0001). Of those receiving IV chemotherapy, 36.7% underwent port placement. Short-term and long-term device-specific complication rates were 20.7% and 39.1%, respectively. Common short-term complications were sepsis (8.6%), thromboembolism (6.2%), and pneumothorax (2.4%). 11.2% of all patients, 17.5% with complications and 4.9% without, underwent port removal. Conclusions: Port placement is documented in 1/5 of pancreatic cancer patients and is associated with short-term and long-term complications. Once placed, device utilization is high; most patients die without port removal. Risks of complications and treatment goals must be weighed against likelihood of device use when identifying pancreatic cancer patients who would benefit from ports.
The combination of gallium nitrate, rituximab and dexamethasone is effective and safe as a salvage regimen for diffuse large B-cell lymphoma
Authors: S. E. Smith, A. Toor, J. Klein, T. Rodriguez, P. J. Stiff
Journal: Journal of Clinical Oncology (2006)

17510 Background: More than 56,000 new cases of non-Hodgkin’s lymphoma (NHL) will be diagnosed this year in the United States. As our aging patient population develops worsening performance status and co-morbidities, it seems appropriate to develop effective lymphoma treatments, which have fewer toxicities and lower costs for administration. One approach is to combine non-myelosuppressive therapies. One non-myelosuppressive agent, which has efficacy in lymphoma, is gallium nitrate. Investigation of gallium nitrate for cancer treatment dates back to the 1970’s and it has been shown to inhibit ribonucleotide reductase and bind transferrin and potentially complex with transferrin and/or transferrin receptor, which is highly expressed in intermediate and aggressive histology lymphomas. It appears that the binding of the transferrin receptor on the lymphocyte as well as its inhibition of ribonucleotide reductase, eventually impairs iron metabolism, which is a necessary component of the intracellular cytochrome systems/mitochondrial function and ultimately oxidative phosphorylation. Methods: The current study is a phase II clinical trial investigating the combination of gallium nitrate, rituximab and dexamethasone (GaRD) for relapsed or refractory DLBCL, MCL or transformed follicular lymphomas. The gallium nitrate is given at 200mg/m 2 CIV days 1–7, rituximab 375mg/m 2 IVPB day 1 and dexamethasone 40 mg po days 1–4. Eligible patients must have proven relapsed or refractory disease and have a SWOG PS ≤3. Patients may have failed prior ASCT or allogeneic SCT. The accrual goal was 37 patients however the study was stopped after 22 patients were accrued as the primary endpoint was reached after the initial interim analysis. Results: ORR 12/22 (55%); CR/CRu 6/22(27%); PR 6/22(27%); SD 3/22 (14%); and PD 7/22 (32%). Most of these patients were refractory to prior salvage regimens 15/22 (68%), including ESHAP, DHAP or high-dose cyclophosphamide. No patients developed grade 3 or 4 toxicities, with the exception of grade 4 lymphopenia. Conclusions: Gallium nitrate, rituximab and dexamethasone (GaRD) appears to be an effective and non-toxic salvage regimen for patients with relapsed DLBCL [Table: see text]
TRAINING TRENDS AND INJURY INCIDENCES AMONG IRISH DISTANCE RUNNERS
Authors: Colin Griffin, Brendan Egan, Catherine Blake, Peter Horgan
Journal: British Journal of Sports Medicine (2017)

Background To date, research investigating the training habits and practice of resistance training among elite distance runners as well as training factors relating to injury, has been sparse. Objective To investigate the typical training of Irish distance runners and self-reported injury incidences over a previous two year period. Design Mixed methods. Setting Irish elite distance runners completed a questionnaire using Google Forms. Participants Opportunistic sampling (n=109, n=78 male and n=31 female respondents) from age 18+ who compete from 800 m up to the Marathon, from national competitive to international level of performance. Interventions The independent variables included demographic profile, typical weekly running training volume and practice of resistance training. Main Outcome Measurements A multi-stage data analysis process using SPSS, data coding and Chi square analysis. A p-value of &lt;0.05 was used to determine statistical significance between variables and sub-groups. Results More than half the respondents (53.2%) run less than 60 miles per week and 11% run more than 80 miles per week. Eighty-eight per cent of athletes include resistance training. Weight training (36.5% complete two sessions per week), plyometric training (35.4% complete one session per week), core training (47.9% complete two sessions per week) and hill training (60.4% complete one session per week) were the most common resistance training methods employed. In the previous two years, 60.5% of athletes experienced a running-related injury. The knee (24.2%) was the most common injury site and 25.8% of athletes experienced a bone stress injury. Conclusions Irish distance runners train at lower weekly running volumes than previously reported for world-class elite athletes, but include resistance training methods that are typically employed to improve running economy and performance. No significant relationships were found between training trends, demographic profile and injury incidences. Future prospective studies should examine the periodisation of training loads and resistance training across a season.
Quality-of-life (QOL) assessment in patients (pts) with metastatic melanoma receiving vemurafenib (V) and cobimetinib (C).
Authors: Brigitte Dréno, Karen Bartley, Paolo Antonio Ascierto, Victoria Atkinson, Gabriella Liszkay, Michele Maio, Mario Mandalà, Lev V. Demidov, Daniil Stroyakovskiy, Luc Thomas, Luis De La Cruz-Merino, Caroline Dutriaux, Claus Garbe, Ilsung Chang, Stephen Paul Hack, James M. G. Larkin, Grant A. McArthur, Antoni Ribas
Journal: Journal of Clinical Oncology (2015)

9021 Background: The phase 3 coBRIM study showed significant improvement in progression-free survival in pts with metastatic melanoma on V + C compared with those on V and placebo (P) (HR, 0.51; 95% CI, 0.39-0.68, P< 0.001 (Larkin et al. N Engl J Med 2014;371:1867-1876). We report the evaluation of health-related QOL in coBRIM for V + C versus V + P, as measured by the European Organization for Research and Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). Methods: The EORTC QLQ-C30 was evaluated in pts with baseline (BL) and ≥ 1 post-BL assessment. Assessments were conducted on Days (D) 1 and 15 in cycles (C) 1 and 2 (each C = 28 days), and every other cycle thereafter until pt withdrawal or end of study. The analysis includes assessments up to C8D1. Each domain score, assessing global health status and QOL, and symptom scales were examined at BL and for each time point (change from BL) by treatment arm descriptively; formal statistical comparisons were not conducted. Clinically meaningful (CM) change was defined as a ≥ 10-point increase or decrease from BL. Results: The completion rate at BL for both treatment arms was 96.7% and was consistently high ( ≥ 88%). Across all functioning domains (cognitive, emotional, social, role, and physical) and symptoms (appetite loss, constipation, nausea and vomiting, dyspnea, pain, and fatigue), pts in the V + C arm reported better scores at 1 or more post-BL time points evaluated versus those in the V + P arm, but mean score change did not reach CM criteria. However, pts in the V + C arm experienced a CM or marginal improvement in insomnia (C2D15, C4D1, C6D1, C8D11), while no V + P pts showed CM change from BL in insomnia. The V + C arm experienced CM worsening of diarrhea from BL only at C1D15 and C2D15; no CM change from BL for diarrhea was observed in the V + P arm. Responder analysis showed that a higher percentage of pts in the V + C arm had CM score improvements from BL for all EORTC domains; the greatest differences were observed in insomnia (16%), social functioning (11%), fatigue (9%), and pain (7%). Conclusions: In pts with metastatic melanoma, V + C provided superior efficacy compared with V +P and symptom improvement for insomnia, social functioning, fatigue, and pain with similar QOL. Clinical trial information: NCT01689519.
The prognostic utility of hemoglobin and lymphocytopenia in bladder-sparing therapy.
Authors: Michael Drumm, Hannah Johnson Roberts, William U. Shipley, Andrzej Niemierko, Niall M. Heney, Donald S. Kaufman, Anthony L. Zietman, Jason A. Efstathiou
Journal: Journal of Clinical Oncology (2017)

370 Background: Many patients with bladder cancer are found to have laboratory derrangements such as anemia and lymphocytopenia prior to treatment, though their prognostic value is unknown. We examined pretreatment lab values and clinical outcomes in patients with muscle-invasive bladder cancer (MIBC) who underwent bladder sparing trimodality therapy (TMT). Methods: We performed a retrospective analysis of 181 patients with T2-T4a bladder cancer who underwent TMT between 2001 and 2013. Pretreatment absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR), and hemoglobin (Hgb) values were collected, and cut-off values were established to be 1.5*10^9/L, 3.12, and 12 g/dl, respectively. Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared with Kaplan Meier survival probabilities and univariate and multivariate Cox regression analysis, controlling for gender, age, completeness of TURBT, response to TMT, cystectomy, clinical T stage, and hydronephrosis. Results: Median follow-up was 47 months. On univariate analysis, patients with a low pretreatment lymphocyte count had poorer OS (p = 0.03) than patients with a higher pretreatment lymphocyte count (5 year OS rates: 54% and 71%, respectively). Patients with pretreatment anemia had poorer OS (p = 0.001) and DSS (p &lt; 0.001) than patients with a higher pretreatment hemoglobin count, (5 year OS rates: 39% and 65%; 5 year DSS rates: 39% and 72%, respectively). On multivariate analysis, pretreatment anemia was significantly associated with poorer OS (HR 2.58, 95% CI 1.36–4.90) and DSS (HR 3.23, 95% CI 1.62–6.43), whereas complete response to TMT was significantly associated with improved OS (HR 0.24, 95% CI 0.13–0.43) and DSS (HR 0.29, 95% CI 0.14–0.59). Complete response to TMT was significantly associated with improved DFS (HR 0.36, 95% CI 0.21–0.61), and a higher clinical T stage was associated with poorer DFS (HR 2.38, 95% CI 1.19–4.75). Conclusions: When adjusting for clinical factors, pretreatment anemia remained an independent predictor of overall and disease-specific survival following TMT. Further prospective validation of lab values and clinical outcomes in MIBC are needed.
Efficacy of the PARP inhibitor (PI) ABT-888 (veliparib [vel]) either with carboplatin (carb) or as a single agent followed by post-progression therapy in combination with carb in patients (pts) with <i>BRCA1</i>- or <i>BRCA2</i>- (<i>BRCA</i>)-associated metastatic breast cancer (MBC).
Authors: George Somlo, Paul Henry Frankel, Thehang H. Luu, Cynthia X. Ma, Banu Arun, Agustin A. Garcia, Tessa Cigler, Leah Cream, Harold A. Harvey, Joseph A. Sparano, Rita Nanda, Helen K. Chew, Timothy Jerome Moynihan, Linda T. Vahdat, Matthew P. Goetz, Arti Hurria, Joanne E. Mortimer, David R. Gandara, Alice P. Chen, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2015)

520 Background: Based on the concept of synthetic lethality combining platinum agents and PIs should benefit patients (pts) with BRCA-associated MBC. We report mature outcomes with vel alone, or with carb. Methods: Pts with germline BRCA-associated MBC, ECOG performance status of ≤ 2, without prior PI treatment were included. In phase I the maximum tolerated dose (MTD) of carb (AUC of 5) IV every 21 days, and vel 150 mg BID were defined. In phase II, pts received vel 400 mg BID and upon progression, carb and vel at the MTD. Results: Between 6/2010 and 4/2014, 72 evaluable pts (28 in phase I, 44 in phase II) with BRCA1 (34 patients) or BRCA2 (37 patients) mutations (1 pt had both) and with MBC were enrolled. The median age was 44-years (range; 28-68); 49% of pts had hormone receptor + MBC. Pts received a median of 1 (0 – 5) prior chemo-regimen for MBC. Response rate (RR) for the 28 pts in phase I was 50% [CR rate 18%] and 2 pts remain in CR at 43+ and 34+ cycles, both are on vel maintenance, alone; median progression-free survival (PFS) was 8.5 mos (95% CI 7.3-10.1), and median TTF was 8.3 mos (6.9-9.5). For 44 phase II pts treated with vel, the median PFS was 5.2 months (4.0-6.4) and including their cross-over carb/vel treatment the cumulative TTF was 6.7 months (4.6-8.5); 13/44 (30%) responded to vel; 2 pts are still on vel (1 with a PR at 14 cycles, 1 with a CR at 25 cycles); 1 pt converted to PR after cross-over to carb/vel. OS was 18.8 months (95% CI 15.0-26.3) for the 28 pts treated with the combination of carbo/vel, and 12.6 months (95% CI 11.7-NR) for the 44 pts treated with vel followed by carbo/vel (p < 0.1). In phase I, dose delay or adjustment was needed in 1/3 of the pts treated at the MTD within the first 3 cycles due to cytopenias. In phase II, 8/44 (18%) required dose adjustment on single agent vel, and 5 pts required dose adjustment after cross-over to carb/vel. Conclusions: The trend for longer TTF with the carb/vel combination first vs. vel followed by carb/vel, combined with the improved time OS suggest that carb/vel followed by vel maintenance deserves further testing in a randomized prospective trial. Clinical trial information: NCT01149083.
Cost effectiveness analysis of the addition of bevacizumab in high risk of relapse ovarian cancer patients in Canada.
Authors: Iker Martin Nunez, Elaine J. Wright, Lori Yin, Joshua Ray, Michael Fung-Kee-Fung, Prafull Ghatage
Journal: Journal of Clinical Oncology (2015)

e16580 Background: On an ICON7 RCT subgroup, Oza et al. reported frontline ovarian cancer patients with a high risk of relapse (stage III suboptimal debulking, stage III unresectable or stage IV disease), benefited from the addition of bevacizumab (7.5mg/kg) to chemo (carboplatin and paclitaxel), compared to chemo alone. The objective of this study is to investigate the cost effectiveness of adding bevacizumab as a treatment of frontline high risk of relapse ovarian cancer from a Canadian publicly funded perspective. Methods: A Markov model was used to estimate the CE with long-term PFS and OS from the ICON7 high risk of relapse subgroup predicted by log logistic time-to-event functions over a time horizon of 10 years. Canadian PFS health state utility values were obtained from the ICON7 high risk patient population EQ5D questionnaires. Canadian post progression utility values were consistent with other gynecological cancers. Cost inputs such as standard health state resource use, management of adverse events and drug costs were informed from public sources. An annual 5% efficacy and cost discount rate was applied. PSA as well as one-way sensitivity analyses were conducted. Results: ICON7 high-risk patients receiving bevacizumab plus chemo had a mean LY gain of 5.8mths compared to chemo, a mean QALY gain of 4.5mths, an ICER of $74,084CAD per LY gained and $96,261CAD per QALY gained. 55% of PSA simulations resulted in ICERs below $100,000CAD. Conclusions: Although no formal HTA willingness-to-pay threshold exists in Canada, $100,000CAD has often been used in oncology. At this threshold, and based on evidence from a subgroup of patients from the ICON RCT, bevacizumab in addition to chemo is potentially a cost-effective alternative for frontline ovarian cancer high risk of relapse patients (stage III suboptimal debulking, stage III unresectable or stage IV). Clinical trial information: NCT00483782.
Prognostic value of PET/CT scans on early chemo-cycle in diffuse large B-cell lymphoma: Prospective study.
Authors: He Huang, Jia Tian Lin, Cheng-cheng Guo, Dr.Prem Raj Shrestha, Tingzhi Liu, Ying Tian, Chao Yong Liang, Xue Ying Li, Mengping Zhang, Huang Ming Hong, Tongyu Lin
Journal: Journal of Clinical Oncology (2013)

8573 Background: To evaluate the prognostic value of positron emission tomography/computed tomography (PET/CT) scan on early chemo-cycle in newly-diagnosed diffuse large B cell lymphoma (DLBCL) patients. Also to distinguish the variation in outcome of early-responder (ER), late-responder (LR) and non-responder (NR). Methods: Newly diagnosed 149 DLBCL patients were treated with R-CHOP regimen for 2-8 cycles (mean: 5.49 cycles) in our center (Feb 2008–Jan 2013). The median age at diagnosis was 47 years (range, 17-80 years); 78 males (52.35%) and 71 females (47.65%); 63 stage I-II (42.3%) and 86 stage III-IV (57.7%); 45 B symptoms (30.2%); 90 IPI 1-2 scores (60.4%) and 59 IPI 3-5 scores (39.6%). All the patients with bulky disease, extranodal invasions and residual disease underwent baseline PET/CT scan and repeated after every 2 chemo-cycles. Results: After 2 subsequent cycles, the PET/CT evaluation showed complete remission (CR) in 82/149 (early-responder, 55.03%), and non-CR in 67/149 (44.97%) patients. Among 67 non-CR patients, 39 achieved CR (late-responder), 21 partial remission (PR), 3 stable disease (SD) and 4 progressive diseases (PD) (non-responder). After a follow-up of median 618 days (range 45-1816 days), the 1st and 2nd year progression-free survival (PFS) rate in NR were significantly different from ER (61.3% vs 92.6% , 52.5% vs 86.6%, p &lt; 0.001) and LR (61.3% vs 91.6%, 52.5% vs 75.9%, p=0.023), and no significant differences were found between ER and LR (p=0.329). The 1st and 2nd year overall survival (OS) were 98.5%, 91.9% in ER; 97.3%, 97.3% in LR and 89.8%, 60.0% in NR respectively with significant differences between NR and ER (p=0.005), between NR and LR (p=0.008), but there was no statistically significant difference between ER and LR (p=0.558). The 1st and 2nd year disease free survival (DFS) rate did not differ between ER and LR (92.6% vs 84.6%, 86.9% vs 76.7%, p=0.250). Conclusions: The PET/CT findings in early chemo-cycle response might predict PFS advantage, but the difference of DFS and OS between ER and LR were not so obvious, and NR showed poor prognosis according to our current data. Clinical trial information: CTR-TRC-11001687.
Efficacy of high-dose adjuvant interferon therapy in high-risk melanoma harboring gene mutations.
Authors: Xuan Wang, Li Li Mao, Lu Si, Zhihong Chi, Chuanliang Cui, Xi Nan Sheng, BIN LIAN, Bixia Tang, Xieqiao Yan, Jun Guo
Journal: Journal of Clinical Oncology (2015)

9047 Background: BRAF/NRAS mutations are predictors of poor prognosis in melanoma. High-dose interferon (HDI) is the only drug approved by FDA as adjuvant therapy in high risk resected melanomas. However, efficacy of HDI in high-risk melanomas harboring BRAF/NRAS mutations has not been evaluated systemically. This study aimed to clarify whether there is beneficial effect of HDI in these patients. Methods: Melanoma patients, after melanoma resection, with BRAF mutation (Exon 15) or NRAS mutation (Exon 2) in melanoma of high risk (Stage IIB to Stage IIIC) were enrolled in this study. Patients were randomized (ratio of 2:1) into 1-year adjuvant HDI therapy group (n = 88) and observation group (n = 52). The endpoint was disease-free survival (DFS). The median follow-up is 16 months till Dec. 2014. Somatic mutations were detected by DNA sequencing. All the statistical analyses were performed using SPSS 16.0 software. Results: The proportion of stage IIB/IIC and III disease were 55.0% and 45.0%, respectively. 53.6% patients were acral melanomas. Primary ulceration was found in 52.9% lesions. Of the 140 patients, 108 cases harbored BRAF mutation, and 32 cases with NRAS mutations. At the end of follow-up, 55% patients had metastatic or local recurrence. The overall median DFS was 19.0 months. DFS in HDI group was significantly longer than observation group (21.0 months vs. 10.0 months, p = 0.002). DFS of HDI vs. observation group were 19.0 vs. 9.0 months (p = 0.021) in BRAF-mutated patients. But stratified analysis did not show significantly DFS improvement of HDI in acral or stage IIB/IIC subgroups in BRAF-mutated patients. NRAS-mutated patients did not get significantly benefit from HDI therapy (DFS: 24.0 months vs. 20.0 months, p = 0.21). Stratified analysis did not show significantly different in DFS between two groups either in different stages (stage IIB/IIC vs. III) or in different subtypes (Non-CSD/CSD vs. acral). Conclusions: In the BRAF-mutated high-risk melanoma, HDI may provide beneficial effect in the resected patients. However, more powerful adjuvant therapy should be explored for NRAS-mutated melanoma patients.