bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunomodulatory switch maintenance therapy in metastatic colorectal carcinoma: The phase III IMPALA study.
Authors: Cunningham David , Scheithauer Werner , Zurlo Alfredo , Salazar Ramon , Ducreux Michel , Waddell Tom Samuel , Tournigand Christophe , Sobrero Alberto F. , Van Cutsem Eric , Arnold Dirk 
Published: February 2017

TPS785 Background: The Toll-like receptor 9 agonist MGN1703 was compared to placebo in 59 metastatic CRC (mCRC) patients with disease control after standard induction chemotherapy in the double-blind randomized phase 2 IMPACT study. MGN1703 showed a superior effect over placebo, with a hazard ratio (HR) for the primary endpoint “PFS on maintenance” of 0.55 (p = 0.041) by local assessment and 0.56 (p = 0.070) by independent radiological review. Exploratory PFS analyses identified patients with objective RECIST response, normalized CEA and presence of activated NKT cells at the end of induction treatment to benefit the most from MGN1703. The OS evaluation showed a HR of 0.40 (median 24.5 vs. 15.1 months) for patients with RECIST response after induction therapy. Furthermore, at time of IMPACT study closure, 4 MGN1703 patients were still without progressive disease and continued treatment in compassionate use. As of August 2015, 3 patients were still receiving MGN1703 treatment in excess of three years (47-55 months), with 2 objective responses ongoing over 46 months. Methods: The international, multicenter, open-label phase 3 IMPALA study is conducted in collaboration with the AIO, TTD and GERCOR cooperative groups. In IMPALA, mCRC patients having achieved an objective tumor response following any type of first line induction therapy are randomized to receive MGN1703 switch maintenance monotherapy in the experimental arm or local standard of care in the control arm. In case of relapse, patients will reintroduce induction treatment whenever feasible, with those in the experimental arm continuing to receive MGN1703 therapy in the weeks without infusional chemotherapy. The primary endpoint of the study will be OS. Secondary endpoints include PFS, response rates, safety, and QoL in selected centers. Induction treatment, CEA and activated NKT at baseline are stratification factors and will be prospectively assessed. All randomized patients take part in a comprehensive immune monitoring plan evaluating cytokines and chemokines in serum and the activation status of immune cell populations. Recruitment started in September 2014 and the study is expected to recruit 540 patients within 24 months in 8 European countries. Clinical trial information: NCT02077868.
The ORCHESTRA trial: A phase III trial of adding tumor debulking to systemic therapy versus systemic therapy alone in multi-organ metastatic colorectal cancer (mCRC).
Authors: Gootjes Elske C. , Buffart Tineke E , Tol M.P. , Burger J , Grunhagen Dirk J. , van der Stok Eric P , Meijerink Martijn R. , Ten Tije Albert J. , Meerten Esther Van , van de Ven Peter M , Nuyttens Joost , Haasbeek Cornelis J , Verhoef Cornelis , Verheul Henk M.W. 
Published: February 2017

TPS788 Background: In the current multidisciplinary approach of mCRC, local treatment of oligometastases is common practice. Results of large case series of selected patients treated with complete surgical resection of metastatic lesions suggest that this approach substantially improves survival rates to around 30-60%. Other techniques such as radiofrequency or microwave ablation (RFA, MWA), transarterial chemoembolization (TACE) or radiotherapy can also be applied in local treatment. Curative treatment options are generally not available for patients with extensive hepatic and/or extrahepatic mCRC. These patients primarily receive palliative systemic treatment consisting of combination chemotherapy as well as targeted agents. So far, reports on the benefit of local treatment for metastases in multi-organ mCRC have major limitations, including being small, non-randomized, single-center and retrospective. The benefit from local treatment of metastases for these patients should be established to allow for interruption of the standard systemic therapy and exposure to possible adverse events from local treatment. Methods: The ‘ORCHESTRA’ trial is a randomized multicenter clinical trial for patients with multi-organ mCRC, comparing the combination of chemotherapy and maximal tumor debulking versuschemotherapy alone (NCT01792934). We will examine the interplay of both efficacy and toxicity for the combination of systemic chemotherapy and locoregional therapy. Our study design incorporates systemic as well as local therapy in the experimental arm and combines local treatment modalities to pursue maximal tumor debulking. We aim to improve overall survival of patients with multi-organ mCRC by maximal tumor debulking after induction chemotherapy with at least six months. A total of 478 patients will be included to meet the primary endpoint (power 80%, type I error rate 5%). We define local treatments feasible when they can be performed within a 3-month time period to prevent extensive delay of systemic therapy. Currently, 60 patients are included in 22 participating Dutch hospitals. Clinical trial information: NCT01792934.
KEYNOTE-177: First-line, open-label, randomized, phase III study of pembrolizumab (MK-3475) versus investigator-choice chemotherapy for mismatch repair deficient or microsatellite instability-high metastatic colorectal carcinoma.
Authors: Diaz Luis A. , Le Dung T. , Yoshino Takayuki , Andre Thierry , Bendell Johanna C. , Zhang Yinghua , Lam Baohoang , Koshiji Minori , Jäger Dirk 
Published: February 2017

TPS789 Background: Mismatch repair deficient (dMMR) tumors are characterized by high mutational load and lymphocyte infiltration and may be good candidates for immune checkpoint blockade. Pembrolizumab is a monoclonal antibody against PD-1 that is designed to block its interaction with PD-L1 and PD-L2 and thus allow an antitumor immune response. In the KEYNOTE-016 proof-of-concept study, pembrolizumab showed promising antitumor activity against dMMR tumors in patients (pts) with treatment-refractory metastatic colorectal carcinoma (mCRC). KEYNOTE-177 is an international, randomized trial designed to evaluate the efficacy and safety of pembrolizumab compared with standard-of-care (SOC) chemotherapy in the first-line setting for dMMR or microsatellite instability-high (MSI-H) mCRC. Methods: Key eligibility criteria include age ≥ 18 y, confirmed MSI-H or dMMR mCRC, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for metastatic disease. Pts will be randomized 1:1 to receive either pembrolizumab 200 mg Q3W or investigator’s choice of SOC chemotherapy. Chemotherapy must be chosen prior to randomization; options include mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab. Treatment will continue until PD, unacceptable toxicity, pt/investigator decision, or completion of 35 cycles (pembrolizumab only). Response will be evaluated every 9 wk per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns. Eligible pts may continue pembrolizumab beyond initial RECIST-defined progression. Pts in the SOC arm who have PD and meet crossover criteria may be eligible to receive pembrolizumab for up to 17 treatment cycles. 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. PFS per RECIST v1.1 is the primary end point; OS and ORR are key secondary end points. Other end points include duration of response and health-related quality of life. Planned enrollment in KEYNOTE-177 is 270 pts.
Improving the treatment of patients with low-risk neutropenic fever: A quality improvement project at the Cleveland Clinic Taussig Cancer Institute (TCI).
Authors: Goodman Lindsey Martin , Lau Jessica , Gallagher Erika M. , Moeller Machelle , Best Carolyn , Stevenson James 
Published: February 2017

101 Background: NF is an oncologic emergency and has historically resulted in inpatient (inpt) management. The Multinational Association for Supportive Care in Cancer (MASCC) score can be used to identify NF pts at LR for complications who can be safely managed in the outpatient (outpt) setting. Despite established guidelines supporting outpt management of LRNF, provider awareness is low and inpt admission for intravenous antibiotics (abx) continues to be standard of care. Methods: A multidisciplinary team performed a QI project to improve management of LRNF (baseline cohort of LRNF pts treated from Jan - Mar 2014, N = 13). Inpt provider education began in the Q2 2014. Providers calculated MASCC scores for pts with non-leukemia hematologic malignancies and solid tumors at the time of admission. Data was collected in a prospectively maintained registry. Pts identified as LR by MASCC score were admitted under observation and placed on oral abx. If exclusion criteria and social barriers were not identified, discharge (dc) within 24 hrs of admission was planned. To ensure pt safety, close follow up included phone follow up within 48 hrs of dc and a provider visit within 72 hrs. Results: 52 pts were admitted to the TCI inpt oncology unit with NF from Oct 2014 - June 2015. 34 pts (65%) had LRNF (MASCC score, < 21). 9 pts (26%) were dc within 24 hrs. Only 2 LRNF pts had a culture proven infection – both Enterococcus UTIs. 3 pts required readmission for reasons other than scheduled inpt chemotherapy: 1 high risk pt for new symptoms and 2 LRNF pts (22%) dc within 24 hours for recurrent fever; neither had culture proven infection. Pts with LRNF had an average LOS of 3.3 days compared to 6.2 days in the historical cohort. There were no deaths due to NF in either cohort. Conclusions: Calculating a MASCC score at admission identifies pts who are potential candidates for outpt, oral abx therapy. This pilot study demonstrates that provider education followed by implementation of a system to ensure close follow up may result in earlier dc for LRNF pts without increasing risk of complications or readmission. Further follow up will occur Q3 2015 and data will be presented on changes in cost measures.
The Kaiser Permanente Breast Cancer Survivorship National Clinical Algorithm: Regional variation in implementation processes/strategies within an integrated health care system.
Authors: Lagana Michele , Hahn Erin Elizabeth , Schottinger Joanne E. , Kutner Susan E , Littlewood Mark B 
Published: February 2017

104 Background: Kaiser Permanente (KP) is an integrated healthcare system providing comprehensive services to over 10 million members. The KP Interregional Breast Care Leaders, a multidisciplinary clinician group, developed a comprehensive evidence/consensus-based algorithm for breast cancer survivors, the KP Breast Cancer Survivorship National Clinical Algorithm (BCSNCA). The BCSNCA is intended to reduce variation in medical and psychosocial surveillance and improve outcomes by providing guidance to locally implemented survivorship programs, ie, recommendations for surveillance, late effects management, and risk reduction. As a quality improvement project, we evaluated regional/ facility level implementation. Methods: Qualitative data on BCSNCA implementation was collected from key informant interviews with oncology providers for 20 sites in 6 regions: Georgia, Colorado, Hawaii, Southern (KPSC) and Northern California (KPNC), and Mid-Atlantic, and by attending BCSNCA meetings. Implementation activities were recorded, categorized, and compared to BCSNCA. Results: Facilities in 3 regions implemented discrete BCSNCA components: Northwest and Georgia facilities implemented dedicated survivorship clinics; a KPSC facility piloted a nurse navigator standardized psychosocial assessment; KPNC implemented local guidelines, similar to the BCSNCA. One region has not implemented; Georgia implemented all BCSNCA components. There is variation within each region. Implementation drivers include available resources, competing QI priorities/leadership preferences, and adaptability of extant programs. Conclusions: We found variation between and within regions. The BCSNCA content accommodates variation in implementation, guided by a complex set of factors, including resource availability, leadership preferences, and local organizational goals. Even in integrated systems, the need for locally driven guideline adaptation is critical. Next step: assessment of BCSNCA components on patient-level outcomes.
Recommendations for the delivery of focal tumor ablation services.
Authors: Hertz Sherrie , McKay Cassandra , Wang Jonathan , Baldassarre Fulvia , Wong Amanda , Langer Deanna , Kachura John , Dobranowski Julian 
Published: February 2017

106 Background: The objective of this work was to develop recommendations for the organization and delivery of focal tumor ablation services. New, minimally-invasive ablation technologies such as radiofrequency ablation (RFA), microwave ablation (MWA), and transcatheter arterial chemoembolization (TACE) offer treatment options for patients with a variety of cancers. These emerging therapies can improve patient care (minimize side-effects, offer more rapid recovery with comparable or enhanced outcomes) compared to traditional approaches. However, they are often resource intensive, necessitating a planned system-level approach to ensure appropriate access to high quality services while optimizing care and resource utilization. Methods: This work was led by an Advisory Committee with regional, clinical, administrative and patient representatives and was based on best available evidence, current practice in Ontario, Canada, and guidance from other jurisdictions and experts in the field. A variety of data sources (clinical, system, provider), consultation with external stakeholders and consensus building supported the final recommendations. Results: Thirteen recommendations were developed. Clinical criteria are detailed for RFA for liver, kidney and lung tumors and TACE for hepatocellular carcinoma. MWA is not recommended for lung, liver or kidney tumors. System recommendations include infrastructure (capital equipment, multidisciplinary management and case conference review), the importance of volume-related expertise, and oversight for funding and collaborative planning. Results were broadly disseminated through 12 stakeholder groups connecting with over 40,000 individuals. Conclusions: A systematic approach to understanding opportunities and challenges for focal tumor ablation therapies resulted in multi-level recommendations spanning clinical criteria through to quality oversight. These recommendations will support improvements in care delivery in daily practice and at the system level.
A prospective study of an inpatient febrile neutropenia clinical practice guideline in oncology patients.
Authors: Le Tri Minh , Thomas Tanya , Reuss Joshua , Degennaro Gina , Daniels Elizabeth , Li Jin , Smolkin Mark , Keng Michael Kenneth 
Published: February 2017

114 Background: Febrile neutropenia (FN) is a common complication in oncology patients and is associated with significant morbidity and mortality if untreated. Because of this, it is regarded as a medical emergency. FN treatment guidelines universally recommend the prompt initiation ( < 60 minutes) of intravenous antibiotic therapy. We hypothesized that a quality initiative project creating a new FN clinical practice guideline (CPG) would reduce the time to antibiotic administration (TTA) for inpatient oncology patients with FN. Methods: This prospective study compared patients diagnosed with an initial episode of FN (4/2015-8/2015) with historical controls (4/2013-8/2013) on an inpatient oncology floor at a tertiary care academic hospital. Interventions included the development of an institutional CPG which standardized the definition of FN, implementation of a new clinical workflow, creation of education sessions for LIP’s and RN’s, and creation of an electronic FN order set. The primary outcome was TTA, with target goal being < 60 minutes from the onset of fever. Secondary outcomes included time to antibiotic order, need for ICU care, and 30-day mortality. P-values were calculated using a chi-square test. Results: In total, 31 consecutive FN episodes were observed over the 5-month study period. The median TTA decreased from 112 minutes in 2013 to 37.5 minutes in 2015 (p < 0.001). 30/31 (97%) patients in the 2015 group had their antibiotics ordered within 60 minutes vs 14/22 (64%) in 2013 (p = 0.002). 26/31 (84%) patients in the 2015 group had antibiotics administered within 60 minutes vs 4/22 (18%) in 2013 (p < 0.001). There was no significant difference in need for ICU care (16% in 2015 vs 9% in 2013, p = NS) or 30-day mortality (6% in 2015 vs 5% in 2013, p = NS). Conclusions: The inpatient FN CPG is a significant quality improvement initiative that has shown significant improvements in TTA. We were able to demonstrate value by a significant decrease in median TTA compared to historical controls with a significantly increased percentage of patients having both antibiotics ordered and administered within 60 minutes. In our cohort of patients, no significant differences were noted in rates of ICU care or 30-day mortality.
Data collection for care pathways in the Cleveland Clinic Health System.
Authors: Glass Katherine , Cummings Chad W , Shapiro Marc A. , Urbanek Dennis , Bolwell Brian James 
Published: February 2017

115 Background: Care pathways are established methods of reducing healthcare costs and disparities in oncology care. To demonstrate their impact, health systems must measure and report data on care pathway adherence and outcomes in near real-time. Automating data abstraction across a health system for oncology is difficult due to the amount and detail of data required. Manual abstraction of data is considered slow and costly. Many consider Electronic Medical Record (EMR) integration of care pathways essential in order to successfully implement and assess. Methods: 7 medical oncology care pathways and 45 medical oncologists across the health system were selected for a pilot study to assess the feasibility of implementing care pathways throughout the enterprise. The pilot study also allowed for testing of data collection capabilities. Patients eligible for the care pathways were prospectively identified by manual review of physician calendars. A small number of data points were manually abstracted from the patient EMR at the time of identification. Endpoints of interest, such as hospitalization rates, chemotherapy administered, time to treatment, and costs of care were reconciled through pre-existing databases within pharmacy, research, and finance. Tumor registry data identified a retrospective cohort. Results: Over 1,000 patients were prospectively identified for the care pathway pilot between 1/1/2014 and 12/31/2014. The tumor registry identified 700 additional retrospective patients. The rapid analyses possible as a result of these efforts demonstrated physician adherence, improved patient outcomes, and significant cost savings. In one example, a care pathway for metastatic non-small cell lung cancer reduced charges by more than $98,000/patient by recommending patients receive one standardized chemotherapeutic regimen. Conclusions: Timely data collection for oncology care pathways is feasible and cost effective without EMR integration. Manual identification of patients combined with pre-existing data sources allowed for near-real time analysis of care pathways and provided valuable information about care pathway impact. Institutions can implement and assess care pathways with resources already available to them.
Exploring providers and survivors perceptions of dedicated cancer survivorship care clinics.
Authors: Palos Guadalupe R. , Wagner Richard W , Hebdon Megan , McComb Sara , Gilmore Katherine Ramsey , Chapman Patricia , Rodriguez Maria Alma 
Published: February 2017

117 Background: The complex physical and psychological sequelae faced by cancer survivors require methodical follow-up care. A growing body of evidence suggests clinics and providers dedicated to survivorship care is a promising approach for addressing these needs. Yet there is limited published data of survivors and providers' perceptions of dedicated survivorship care. This study’s objective was to ascertain the strengths and weaknesses of clinical services provided in survivorship clinics. Methods: This study used a mixed-methods approach with stratified purposive sampling in the breast, genitourinary, and head/neck survivorship clinics. Characteristics used for stratification included: disease site, staffing characteristics, and clinical infrastructure. Semi-structured interviews were conducted with survivors and stakeholders, i.e. providers and executive leaders. Staff trained in qualitative methods conducted the interviews. Standardized questions focused on: 1) overall impression of the experience, 2) perceptions of the survivorship care plan (SCP), and 3) recommendations for improving clinical services. A brief survey collected demographic and clinical data. De-identified interviews were audio-recorded, transcribed verbatim, and analyzed to confirm themes. Descriptive statistics were used to summarize all data. Results: A total of 52 participants (36 survivors and 16 stakeholders) were interviewed. Overlapping themes centered on value, continuity of care, and uncertainty about SCPs. Survivors often reported not being able to remember any details of the SCP. Providers felt “patients really like coming here…it’s not as stressful” while survivors reported finding value in receiving “coaching for having a better lifestyle”. Both groups discussed resistance to the survivorship transition process, particularly providers as illustrated in a statement that “they [survivors] are the best part of their day. Conclusions: Dedicated survivorship clinics were perceived as being valuable by both providers and survivors, despite challenges associated with services. Our findings suggest further work is warranted to better understand the nuances of survivorship care and clinics.