bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC): Continuation of anti-EGFR therapy while switching chemotherapy regimen.
Authors: Vladimirova Liubov Yu , Abramova Natalya A , Kit Oleg Ivanovich 
Published: February 2017

744 Background: The purpose of the study was to assess the effeciency and safety of continuing of EGFR-inhibition while switching the chemotherapy (CT) from FOLFOX+Cetuximab (C) as the 1st-line to FOLFIRI+С as the 2nd-line treatment for pts with RAS wt mCRC. Methods: Pts with RAS wt mCRC were enrolled to the pilot study according to inclusion criteria: ECOG≤2, normal bone marrow, liver and kidney functions, no brain metastases, measurable metastatic lesions. The therapy included: the 1st-line with FOLFOX-6+C until progression, then FOLFIRI+C as the 2nd-line therapy. The treatment continued until progression or unacceptable toxicity. Response rate (RR), PFS after the 1st and the 2ndlines of treatment as well as toxicity were evaluated. Results: 20 pts (11 men, 9 women), 38-58 years old, mean age 48.3±1.3 years, were recruited. All pts had multiple visceral metastases: to the liver –30.0%(6), lungs and pleura – 20.0%(4), liver and lungs – 50.0%(10), including the bone metastases – 15.0%(3). The RR was 85.0 %(17), including PR - 4(20.0%) and SD - 13(65.5%). Median PFS after the 1st-line therapy was 12.3±2.6 months, median PFS after the 2nd-line therapy - 6.5±2.8 months. Median OS was not reached yet. Adverse events included: neutropenia Gd2 – 30.0%(6), Gd3 – 20.0%(4), anemia Gd2 – 10.0%(2), stomatitis Gd2-3 – 20.0%(4), diarrhea Gd2 - 55.0%(11), thrombophlebitis – 10.0%(2). C-associated dermatologic toxicity: acneiform rash Gd2-3 – 85.0%(17), skin itching Gd2 - 30.0%(6), panaritium Gd1-2 -30.0%(6), blepharitis Gd1-2 – 10.0%(2), hypertrichosis – 20.0%(4). Conclusions: Continuing EGFR-inhibition with C while switching CT regimens beyond progression provided significant tumor control and was not accompanied by unacceptable toxicity. This strategy deserves futher evaluation in randomized studies in EGFR-dependent mCRC pts.
Pembrolizumab (MK-3475) for previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase II KEYNOTE-180 study.
Authors: Shah Manish A. , Bennouna Jaafar , Shen Lin , Enzinger Peter C. , Li Qiao , Csiki Ildiko , Koshiji Minori , Doi Toshihiko 
Published: February 2017

TPS189 Background: PD-L1 is frequently overexpressed in esophageal cancer. Pembrolizumab is a humanized monoclonal antibody that targets the PD-1 receptor and blocks interaction with PD-L1 and PD-L2. In the multicohort, phase Ib KEYNOTE-028 trial, pembrolizumab showed manageable toxicity, a 30.4% ORR, and median duration of response of 40 wk in 23 patients (pts) with PD-L1+ advanced esophageal cancer. The single-arm, multicenter phase II KEYNOTE-180 trial is designed to further evaluate pembrolizumab as a monotherapy in pts with previously treated advanced/metastatic esophageal cancer. Methods: Key eligibility criteria include age ≥ 18 y, advanced/metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type I adenocarcinoma of the esophagogastric junction (EGJ), measurable disease, documented progression during or after 2 prior lines of therapy, ECOG PS 0-1, no active autoimmune disease or brain metastases, and provision of a tumor sample for retrospective biomarker analysis. Pts with metastatic Siewert type I EGJ adenocarcinoma must have known HER2 status and, if HER2+, must have documented progression on treatment containing trastuzumab. Eligible pts will receive pembrolizumab 200 mg Q3W for 35 cycles (~2 y) or until progression, unacceptable toxicity, or investigator or pt decision. Response will be assessed every 9 wk per RECIST v1.1 and RECIST adapted for immunotherapy response patterns. Treatment may be discontinued for pts who have a CR, and eligible pts may continue treatment beyond initial RECIST-defined progression. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs) and graded per NCI CTCAE v4.0. Pts will be followed for survival every 9 wk. The primary efficacy end point is ORR per RECIST v1.1 by central review. Secondary end points include PFS, OS, and duration of response. Exploratory analyses include evaluation of immune-related gene expression profiles and PD-L1 expression status as predictors of pembrolizumab efficacy. Enrollment in KEYNOTE-180 is expected to begin in October 2015 and will continue until approximately 100 pts are enrolled.
Phase 1/2a study of double immune suppression blockade by combining a CSF1R inhibitor (pexidartinib/PLX3397) with an anti PD-1 antibody (pembrolizumab) to treat advanced melanoma and other solid tumors.
Authors: Wainberg Zev A. , Eisenberg Peter D. , Sachdev Jasgit C. , Weise Amy M. , Kaufman David Ross , Hutchinson Marguerite , Tong Sandra , Aromin Ireene , Hu-Lieskovan Siwen , Patnaik Amita 
Published: February 2017

TPS465 Background: Tumor-associated macrophages (TAMs) support tumor growth and cause tumor resistance to chemotherapy and radiation therapy; myeloid-derived suppressor cells (MDSCs) suppress anti-tumor immunity and cause resistance to PD-1 inhibition. TAMs and MDSCs are both regulated by colony stimulating factor 1 (CSF1). Pexidartinib is a small molecule inhibitor of CSF1 receptor, CSF1R. The normal function of PD-1, expressed on the cell surface of activated T-cells, is to suppress excessive immune responses, eg, autoimmune reactions. Tumors utilize PD-1 signaling to downregulate immune-mediated elimination. Pembrolizumab is a potent, highly selective humanized monoclonal antibody that blocks interactions between PD-1 and its ligands, PD-L1 and PD-L2. We present the study design for a Phase 1/2a clinical trial assessing safety, efficacy, pharmacokinetics, and pharmacodynamics of the combination of pexidartinib and pembrolizumab in advanced solid tumors (NCT02452424). Methods: In Part 1 of this open-label, uncontrolled trial, patients with advanced solid tumors will receive pembrolizumab (200 mg IV q 3 weeks) and escalating daily oral doses of pexidartinib to establish the safety and tolerability of the combination and a recommended phase 2 dose (RP2D). In Part 2, the combination RP2D will be studied in an expanded panel of solid tumor cohorts in up to 475 patients, to assess safety and preliminary efficacy. The panel will include GI malignancies for which preclinical data support this combination, including gastric and gastro-esophageal adenocarcinoma, pancreatic cancer, cholangiocarcinoma, and GI stromal tumors. Overall response rate (RECISTv1.1) and progression free survival will be evaluated. Exploratory endpoints include novel biomarkers of clinical activity and drug mechanisms of action. A truncated sequential probability ratio test will be employed in each tumor cohort to allow early decision-making for futility or success. The results will support further development of the pexidartinib/pembrolizumab combination in the solid tumors that respond to treatment in this study. Clinical trial information: NCT02452424.
A phase I safety and pharmacokinetic (PK) study of nab-paclitaxel (nab-P) plus gemcitabine (Gem) for patients (pts) with advanced pancreatic cancer (APC) who have cholestatic hyperbilirubinemia (CH) secondary to bile duct obstruction.
Authors: Riess Hanno , Kunzmann Volker , Philip Philip Agop , Seufferlein Thomas , McGovern Desmond Micahel Thomas , Chen Peng , Romano Alfredo , Ramanathan Ramesh K. 
Published: February 2017

TPS474 Background: In pts with APC, the distal common bile duct is frequently obstructed, which can lead to elevated bilirubin levels. Normalization of bilirubin by stenting can take weeks, so treatment options that could be initiated in pts with elevated bilirubin are desirable. In a phase III trial of pts with metastatic PC, nab-P + Gem demonstrated superior efficacy vs Gem alone for all endpoints, including overall survival (OS; median, 8.7 vs 6.6 months; hazard ratio, 0.72; P < 0.001). This study will be the first to analyze safety and PK profiles of nab-P + Gem in pts with APC and CH secondary to bile duct obstruction. Methods: Treatment-naive pts (≈ 12 to 40) with APC, Karnofsky performance status ≥ 70, and CH due to bile duct obstruction are eligible. Pts with a biliary stent must have 2 stable (within 20% of each other) bilirubin readings within 48 to 72 hours of each other taken between 5 and 21 days after stenting. Exclusion criteria consist of brain metastases, any other active malignancy, infection requiring systemic therapy, a history of myocardial infarction, or current use of medications known to be strong inducers of CYP3A4 and CYP2C8. Pts will enter 1 of 2 cohorts based on bilirubin level: cohort 1, > 1.5 to 3 × upper limit of normal (ULN), or cohort 2, > 3 to 5 × ULN. Cohort 2 will proceed only after review of safety and PK data from cohort 1 by a safety monitoring committee (SMC) and a decision has been made to proceed. The starting doses are nab-P 100 mg/m2 and Gem 800 mg/m2 for cohort 1 and nab-P 75 mg/m2 and Gem 600 mg/m2 for cohort 2. Treatment will be administered on days 1, 8, and 15 of each 28-day cycle. Doses in each cohort will be modified according to tolerability as determined by the SMC. The primary endpoints are determination of maximum tolerated dose for each cohort and PK profile. Secondary endpoints include investigator-assessed objective response rate, progression-free survival, OS, PK profile of Gem, and safety. The exploratory endpoint is change in serum CA19-9 level from baseline. Enrollment is ongoing. ClinicalTrials.gov: NCT02267707. Clinical trial information: NCT02267707.
nab-paclitaxel (nab-P) + nivolumab (Nivo) ± gemcitabine (Gem) in patients (pts) with advanced pancreatic cancer (PC).
Authors: Firdaus Irfan , Waterhouse David Michael , Gutierrez Martin , Wainberg Zev A. , George Ben , Kelly Karen , Bekaii-Saab Tanios S. , Carrizosa Daniel R. , Soliman Hatem Hussein , Fraser Cindy Duval , Ko Amy , Pierce Daniel W , Manax Victoria G. , Stergiopoulos Sotirios G. , Hochster Howard S. 
Published: February 2017

TPS475 Background: Nivo, an antibody against PD-1, is approved for unresectable or metastatic melanoma and metastatic squamous non-small cell lung cancer (NSCLC) after initial standard therapies. nab-P does not require immunosuppressive steroid premedication and is approved for treatment of metastatic breast cancer (MBC) after initial chemotherapy (CT) including an anthracycline, and for advanced NSCLC (+ carboplatin), and metastatic PC (+ Gem). This 6-arm, multicenter phase I trial will evaluate the safety of Nivo with nab-P— based therapy in MBC, advanced NSCLC, and advanced PC. The study design for the pancreatic portion (arm A: nab-P + Nivo; arm B: nab-P + Gem + Nivo) is described below. Methods: This 2-part study will identify dose-limiting toxicities (DLTs) in Part 1 and assess safety and explore antitumor activity in Parts 1 and 2 (Table). If Arm A, Part 1, is deemed safe (≤ 1 DLT in up to 6 pts), then Arm B, Part 1, will initiate enrollment. Regimens in Part 1 may be expanded in Part 2. Enrollment in Arm A, Part 1, is ongoing. ClinicalTrials.gov: NCT02309177. Clinical trial information: NCT02309177. [Table: see text]
Using technology to improve quality metric adherence.
Authors: Jacobsen Paul B. , Gaguski Michele , Thomas Kathryn A , Hathaway Amanda , Halilova Karina I. , Stricker Carrie Tompkins , Hammelef Karen , Panzer SarahLena , Blayney Douglas W. , Rocque Gabrielle Betty 
Published: February 2017

257 Background: Many barriers to adherence to quality standards exist, including patient, provider, and system barriers to delivery and documentation of timely, evidence-based care. Gaps in clinician knowledge about care standards likely contribute to non-adherence. Methods: Prior to an intervention study, providers completed a questionnaire assessing their knowledge of and ability to influence institutional attainment of specific QOPI metrics. Providers’ ability to influence meeting each of 9 QOPI metrics was measured on a 1-4 scale from “not at all” to “significantly” able to influence. Providers also identified barriers to meeting each metric. Results: 28 providers completed surveys; 43% from a university based cancer center and 57% from a community based cancer center. Respondents include oncology MDs (43%), NPs (7%) and RNs (46%). Perceived ability to influence 9 quality metrics are detailed in the Table below. Providers felt the least able to influence metrics related to fertility preservation with 32% reporting no influence. 21% credited ‘lack of visibility into current data’ to be a main barrier. Providers reported limited ability to address emotional well-being with 36% reporting a ‘lack time to assess/manage’. Providers felt most able to influence physical symptoms such as pain. Conclusions: The most frequently cited barriers to meeting study-specific quality metrics included lack of a) current knowledge/latest evidence and, b) time to assess/manage. Employing methods to address these barriers may improve quality care. In part 2 of this study providers engage with the Carevive Care Planning System, designed to address these barriers by assessing patient needs at the point of care and providing evidence-based recommendations for treatment. [Table: see text]
The influence of treatment facility volume on the mortality of multiple myeloma patients.
Authors: Go Ronald S. , Bartley Adam C , Crowson Cynthia S , Shah Nilay D. , Habermann Elizabeth B. , Holton Sara , Holmes David R 
Published: February 2017

284 Background: MM is an uncommon cancer with annual incidence of only 27,000 cases in the US. Our study determined the extent to which the number of MM patients treated annually in a treatment facility affected all-cause mortality. Methods: We used the National Cancer Data Base (NCDB) to identify adult patients with MM diagnosed from 2003-2011. NCDB is sourced from over 1,500 Commission on Cancer-accredited cancer registries representing 70% of cancer cases in the US. We classified treatment facilities by quartiles based on facility volume (mean patients/year): Quartile 1 (Q1: < 3.6), Quartile 2 (Q2: 3.6-6.1), Quartile 3 (Q3: 6.1-10.3) and Quartile 4 (Q4: > 10.3). We used hot deck imputation to account for missing data, Cox regression to analyze the association between facility volume and time-to-death, and random intercepts to adjust for multiple patients per facility. Results: There were 94,722 MM patients cared for at 1,333 facilities. Most patients (73.5%) were diagnosed and treated in the same facility. The median age at diagnosis was 67 years and 54.7% were males. The median annual facility volume was 6.1 patients/year (IQR: 3.6-10.3; range: 0.2-109.9). The distribution of patients according to facility volume was Q1 (5.2%), Q2 (12.6%), Q3 (21.9%) and Q4 (60.3%). The unadjusted median overall survival by facility volume was: Q1: 26.9 months, Q2: 29.1 months, Q3: 31.9 months and Q4: 49.1 months. After multivariable analysis adjusting for demographic (sex, age, race, ethnicity), socioeconomic (income, education, insurance type), geographic (area of residence, treatment facility location), co-morbidity (Charlson-Deyo score), and disease-specific (year of diagnosis) factors, we show that facility volume remains an independent predictor of all-cause mortality. Compared to patients treated at Q4 facilities, patients treated at lower quartile facilities had a higher risk of death (Q3 HR: 1.16 [95% CI, 1.12-1.20]; Q2: 1.21 [1.17-1.26]; Q1: 1.27 [1.22-1.34]). We observed an inverse volume-outcome relationship up to an annual facility volume of approximately 60 patients. Conclusions: MM patients treated at higher volume facilities had lower risk of mortality compared to those treated at lower volume facilities.
RO-ILS: Radiation Oncology Incident Learning System data trends 2014-2015.
Authors: Hoopes David J. , Ford Eric C. , Eads Nadine L. , Kapetanovic Ksenija , Tomlinson Cindy 
Published: February 2017

59 Background: Incident learning is one of the most effective ways to improve quality care. To facilitate patient safety improvement at a national level, American Society for Radiation Oncology (ASTRO) and American Association of Physicists in Medicine (AAPM) launched RO-ILS: Radiation Oncology Incident Learning System in June 2014. RO-ILS mission is to facilitate safer and higher quality care through a shared learning environment that is secure and non-punitive. Methods: To ensure the security and protection of data, ASTRO contracted with Clarity PSO, a federally-certified patient safety organization that operates under the auspices of the Patient Safety and Quality Improvement Act of 2005. Radiation oncology practices sign a no-fee contract with Clarity PSO to participate in RO-ILS and then enter safety data into a customized web-based portal. Submitted data are analyzed and interpreted by the Radiation Oncology Healthcare Advisory Council (RO-HAC), a multi-professional team. Practices receive aggregate quarterly reports and institutional reports when substantial data are submitted. Results: During the first year, 61 US practices (123) facilities signed contracts. 42 practices entered 1259 events and 619 of these events (49%) were submitted to the national database. Types of events included: 242 (39%) incidents that reached the patient with or without harm; 206 (33%) near-misses; and 171 (28%) unsafe conditions. RO-HAC identified risk-prone processes including ineffective communication, compressed timelines to start treatment, changes to treatment during the course of therapy and junior practitioners’ errors not remedied by experienced staff. Conclusions: Data suggests that quality assurance processes were effective in catching errors; however, continued work needs to address the origin of these errors and suggest robust solutions. To facilitate improved communication, effective protocols and software enhancements are recommended to alert staff to changes in patients’ management. Policies and procedures on patient hand-offs, emergency cases and oversight of junior staff will help error mitigation. While in its infancy, RO-ILS provides useful data and will serve to improve the quality and safety of radiotherapy.
Understanding the patient experience with soft tissue sarcoma: A systematic review of the literature.
Authors: Hess Lisa M. , Winnette Randall , Nicol Steven , Tai Datchen Fritz , Copley-Merriman Kati 
Published: February 2017

61 Background: Soft tissue sarcomas (STS) are a heterogenous group of rare tumors that involve the connective tissue in the body. As with many rare tumors, little is known about the impact of STS on patient well-being. The objective of this review was to understand patient experience and quality of life (QOL) following diagnosis of STS. Methods: This was a systematic review of English language articles published between 2005-2015 in PubMed/Medline, Embase, PsychINFO, and Evidence-Based Medicine. The review included recent conference proceedings and resources from advocacy websites. Articles were considered relevant if they included adult STS patient reported outcomes (PROs) or details on patient experience. Results: Of the 3,430 articles identified, 20 were eligible for inclusion. Of these, 14 were clinical studies that included PRO measures, 1 summarized PRO measures used in STS studies, and 5 described the STS patient experience. Patients with STS report a variety of concerns including emotional well-being (e.g. anxiety, depression), body image, functional deficit following surgery, and practical considerations such as obtaining child care and ability to work. Reports of patient experience vary widely given the heterogeneity of STS and individualized treatment. In clinical studies that used PROs, the European Organization for Research and Treatment of Cancer QOL Questionnaire Core 30 (EORTC QLQ-C30) was the most commonly used cancer-specific measure (N = 5) followed by the Functional Assessment of Cancer Therapy–General (N = 2). The generic EQ-5D was used in 5 publications but was limited to the visual analog scale portion of the measure in two of these studies. Similar to other cancers, STS patients report lower QOL when compared to the general population. Conclusions: Few studies have published either qualitative or quantitative data on the patient experience with STS. While STS has a measurable impact on QOL, there is a lack of detailed information in the published literature. Although PROs are often used in clinical studies of STS, they are not STS-specific tools and may not capture the unique needs of this population. There is a need for qualitative research to better understand the patient perspective of STS.
What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis
Authors: Ribassin-Majed Laureen , Marguet Sophie , Lee Anne W.M. , Ng Wai Tong , Ma Jun , Chan Anthony T.C. , Huang Pei-Yu , Zhu Guopei , Chua Daniel T.T. , Chen Yong , Mai Hai-Qiang , Kwong Dora L.W. , Cheah Shie-Lee , Moon James , Tung Yuk , Chi Kwan-Hwa , Fountzilas George , Bourhis Jean , Pignon Jean Pierre , Blanchard Pierre ,   on behalf of the Meta-Analysis of Chemotherapy in Nasopharyngeal Collaborative Group
Published: February 2017

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.