bluuebunny/crossref_metadata_2025_split huggingface dataset:
Community oncology care delivery staffing model.
Authors: Fryefield David C. , Kafora Roberta , Bradshaw-Hucko Lori , Tribble Chris , Jensen Terry , Chentnik Tom , Beveridge Roy 
Published: February 2017

87 Background: In 2010, the US Oncology Network’s Clinical Advisory Council (CAC), a practice-based clinical leadership team, reviewed the care delivery process at 5 pilot community oncology clinics to determine how licensed and unlicensed clinical resources were used. The Lean Six Sigma methodology, which employs statistical analysis within a structured approach to problem-solving, was used to understand the required clinical activities of the practices within 3 primary areas. The objective of this pilot was to ensure patients receive timely, effective treatment from qualified personal in a cost-efficient model. Methods: A team led by a certified Master Black Belt studied tasks performed by licensed vs. non-licensed staff in the areas of physician services, treatment services and triage services at each practice. Based on the findings, tasks were realigned to maintain quality of care but to deliver care more efficiently. Results: Care Delivery processes comprised 95 tasks at baseline vs. 80 tasks in the redefined model. Within physician services, changes to workflow included rooming and clinic support (vitals, cleaning, and patient comfort) to be provided by Medical Assistants (MAs) instead of RN. RN duties were changed to MA supervision and tasks that require licensure. Changes to triage services included use of RNs to coordinate care and MAs for phone call screening, centralized triage (non-patient facing), and normal lab follow-up. Increased clarity of tasks and re-assignment of responsibilities reduced RN work load by 17% or 16.6 hours/day based on 120 patient visits. Each pilot site realized an annualized labor savings in excess of $100,000. This prospective, patient volume-based Care Delivery Staffing Model was adopted by the CAC as Network standard after completion of the pilot. Conclusions: Using Lean Six Sigma methods, the care delivery process was successfully re-designed such that clinical staff were re-aligned to better utilize each resource’s core competencies. Implementation of this care delivery model resulted in improved cost effectiveness while maintaining quality of care and also enabled prospective staff planning so that costs can be kept competitive in the future.
Can equitable care eliminate colon cancer disparities?
Authors: Patel Manali I. , Ma Yifei , Rhoads Kim Felder 
Published: February 2017

91 Background: Previous studies suggest lack of insurance and variations in quality of care may drive disparities in colon cancer (CC), but equitable care may close these gaps. To clarify the role of equitable care on racial disparities, we compared CC survival in one of California’s largest Health Maintenance Organization (HMO) to survival in all other hospitals across the state. We hypothesized that disparities would be less pronounced in the HMO. Methods: All CC cases treated from 1996-2006 were identified in the California Cancer Registry linked to hospital discharge abstracts from the Office of Statewide Health Planning and Development. Enrollees in the state’s largest HMO were identified as such. Five year mortality was compared between HMO enrollees and all other patients using Cox proportional hazard models. Results: 62,184 CC records were included. 25% were HMO enrollees. The HMO treated a higher percent of black patients (9.2% versus 5.5%) and fewer Medicaid patients (2.1% versus 4.5%). There was no disparity in the HMO setting blacks as compared with whites (HR 0.90 95% CI 0.79-1.02); but black patients fared worse in the non-HMO settings (HR 1.15 95% CI 1.07-1.23). Conclusions: CC disparities are differentially distributed across California hospitals systems. Since there were no disparities in California’s large HMO, where care is typically protocol-driven, our findings suggest delivery of equitable care may eliminate disparities. These findings are consistent with other studies in the literature. Future research should assess the effect of emerging Accountable Care Organizations on the elimination of racial disparities in other cancers and diseases.
Improving detection of Lynch syndrome using a reflex immunohistochemistry algorithm for all patients with newly diagnosed colorectal cancer.
Authors: Pan Minggui , Hoodfar Elizabeth , Bergoffen JoAnn , Fulton Regan , Hofmeister Laura , Chavez Annette , Li Dan 
Published: February 2017

98 Background: Identifying patients with Lynch syndrome has profound impact on the clinical care of patients and their families. Previous guidelines based on family history alone have shown low sensitivity. In our medical center, the detection rate of Lynch syndrome was <1% among colorectal cancer cases. Methods: We have developed a system-based algorithm using centralized testing by immunohistochemistry (IHC) for four mismatched repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2) as a screening method for all newly diagnosed colorectal cancer patients, followed by step wise testing of BRAF mutation, MLH1 promoter hypermethylation, +/- microsatellite instability, and germline mutation. Results: From April 1, 2011, to July 11, 2012, we have screened 116 patients. IHC detected absent expression of at least one of the MMR proteins in 18 cases. Three cases showed missing expression of MSH2/MSH6 and the presence of a germline mutation in MSH6 was confirmed in two cases. The newest case is still being investigated for germline mutation. Of the remaining 15 cases, 10 showed the presence of BRAF V600E mutation, two showed hypermethylation of the MLH1 promoter, and one showed germline MLH1 mutation. Two cases showed no BRAF V600E mutation, no MLH1 promoter hypermethylation or germline gene mutation. Overall, of 116 cases, three cases have confirmed Lynch syndrome with the detection of a germline mutation, two cases most likely have Lynch syndrome but without any detectable germline mutation of MLH1 or PMS2 using the current detecting methods. Conclusions: Our system-based screening algorithm using reflex immunohistochemistry of four MMR proteins has resulted in excellent detection rate of approximately 4% to 5% (5 out of 116 cases), consistent with the expected Lynch syndrome prevalence rate in the population. This represents a marked improvement over our previous family history-based approach in Lynch syndrome screening.
Molecular predictors of outcome and response to bevacizumab (BEV) based on analysis of RTOG 0825, a phase III trial comparing chemoradiation (CRT) with and without BEV in patients with newly diagnosed glioblastoma (GBM).
Authors: Sulman Erik P. , Won Minhee , Blumenthal Deborah T. , Vogelbaum Michael A. , Colman Howard , Jenkins Robert B. , Chakravarti Arnab , Jeraj Robert , Brown Paul D. , Jaeckle Kurt A. , Schiff David , Dignam James , Atkins James Norman , Brachman David , Werner-Wasik Maria , Komaki Ritsuko , Gilbert Mark R. , Mehta Minesh P. , Aldape Kenneth D. 
Published: February 2017

LBA2010 Background: RTOG 0825 evaluated the addition of BEV to standard CRT in the treatment of GBM and included molecular stratification that assessed the degree of mesenchymal (MES) gene enrichment. We investigated the ability of the MES signature to predict response to BEV. Methods: Sufficient FFPE tissue for molecular analysis was available for 650 registered, eligible patients. TaqMan PCR was performed prospectively using the molecular stratifier on all patients and an expanded 43 member MES set on 234 cases. A subset of specimens was subjected to whole genome expression profiling (GEP). Predictive models were evaluated for their ability to predict survival (overall, OS, and progression-free, PFS) in the training cohort of the BEV arm after adjusting for prognostic factors and treatment arm. Unsupervised clustering of GEP data was used to identify molecular subsets and gene set enrichment analysis (GSEA) performed to evaluate for MES enrichment. Results: We observed a significant association between increasing MES signature and worse PFS and OS in the BEV arm (p=0.036 and p=0.032, respectively). Based on the association between high MES expression and poor outcome in the BEV arm, we sought to optimize a predictor using an expanded set of MES genes. Unbiased gene selection from a total of 43 genes followed by radial basis machine modeling identified a 10-gene predictor of outcome in the BEV arm (p<0.001/HR 4.04 for OS and p<0.001/HR 2.21 for PFS). To further support the association of MES enrichment and poor outcome in the BEV arm, we performed GEP. Unsupervised clustering identified a subtype of tumors with MES enrichment associated with the 10-gene predictor survival probability (p=0.0124, t-test). Ongoing studies will determine the extent to which this represents a predictive marker for BEV. Conclusions: We developed a 10-gene predictor specific to BEV treatment and suitable for FFPE that may serve to identify subsets of patients with newly diagnosed GBM who benefit from BEV. Supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and Brain SPORE P50 CA127001 from the NCI and Genentech. Clinical trial information: NCT00884741.
A phase III trial of personalized chemotherapy based on serum tumor marker decline in poor-prognosis germ-cell tumors: Results of GETUG 13.
Authors: Fizazi Karim , Pagliaro Lance C. , Flechon Aude , Mardiak Jozef , Geoffrois Lionnel , Kerbrat Pierre , Chevreau Christine , Delva Remy , Rolland Frederic , Theodore Christine , Roubaud Guilhem , Gravis Gwenaelle , Eymard Jean-Christophe , Malhaire Jean-pierre , Linassier Claude , Habibian Muriel , Journeau Florence , Logothetis Christopher , Culine Stephane , Laplanche Agnes 
Published: February 2017

LBA4500 Background: Poor-prognosis GCT (IGCCCG, J Clin Oncol 1997) remains a challenge with no improvement in the 50% survival demonstrated in phase III trials for 25 years. Day 21 serum tumor marker decline rate identified a subgroup of patients (pts) with a better outcome (J Clin Oncol 2004, 22: 3868-76). The hypothesis we tested in this study is that treatment allocation based on early tumor marker decline will improve the progression-free survival (PFS). Methods: Pts with IGCCCG poor-prognosis GCT were treated with a first cycle of BEP. AFP and hCG were assessed at day 18–21: 1) Pts with a favorable decline continued BEP for a total of 4 courses (Fav-BEP); 2) Pts with an unfavorable decline were randomized to receive either BEP (Unfav-BEP) or a dose-dense regimen (Unfav-dose-dense), consisting of paclitaxel-BEP plus day-10 oxaliplatin x 2 cycles, followed by 2 cycles of cisplatin, ifosfamide, and continuous infusion bleomycin (depending on lung function) + G-CSF. The primary endpoint was PFS (hypothesis: 20% difference, type 1 error: 5%, power 80%, 196 randomized pts needed). Results: 263 pts were enrolled and 254 were evaluable at day 21 (6 early deaths, 3 withdrawals): 51 pts (20%) had favorable tumor marker decline and 203 had unfavorable decline (randomized: 105 Unfav-dose-dense arm, 98 Unfav-BEP). The prognostic value of early tumor marker decline (Fav-BEP vs Unfav-BEP) was confirmed: 70% vs 48% for 3-year PFS (p=0.01), and 84% vs 65% for overall survival (OS) (p=0.02). The 3-year PFS was 59% in the Unfav-dose-dense arm vs 48% in the Unfav-BEP arm (p=0.05; HR: 0.66 [0.44-1.00]). 3-year OS was 73% and 65%, respectively. More ≥ grade 2 neurotoxicity (21% vs 4%) and more hematotoxicity occurred in the dose-dense arm, with no excess febrile neutropenia (17% each arm) or toxic deaths (1 each arm). Salvage high-dose chemotherapy + stem-cell transplant were required in 6% in the Unfav-dose-dense arm and 16% in the Unfav-BEP arm (p=0.01). Conclusions: An algorithm of individualized treatment intensification determined by the rate of early tumor marker decline reduces the risk of progression or death in men with poor-prognosis GCT. Clinical trial information: NCT00104676.
Randomized proteomic stratified phase III study of second-line erlotinib (E) versus chemotherapy (CT) in patients with inoperable non-small cell lung cancer (PROSE).
Authors: Lazzari Chiara , Novello Silvia , Barni Sandro , Aieta Michele , De Marinis Filippo , De Pas Tommaso , Grossi Francesco , Mencoboni Manlio , Bearz Alessandra , Floriani Irene , Torri Valter , Bulotta Alessandra , Grigorieva Julia , Roder Joanna , Doglioni Claudio , Roder Heinrich , Righi Luisella , Foti Silvia , Bachi Angela , Gregorc Vanesa 
Published: February 2017

LBA8005 Background: Second-line therapy for advanced NSCLC patients (pts) after progression on platinum-based regimens typically employs CT or E. Improved PFS in E-treated pts is associated with EGFR sensitizing mutations. However, a test for optimizing treatment in pts with wild-type or unknown EGFR mutation status or squamous histology is of clinical value. VeriStrat (VS) is a serum protein test that assigns "good" (VSG) or "poor" (VSP) classification and has demonstrated prognostic and predictive utility. PROSE is a multicenter prospective randomized biomarker validation trial, designed to evaluate the ability of VS to predict survival in second-line NSCLC pts treated with E or CT. It is the first completed prospective randomized biomarker validation trial following the MARVEL design (Freidlin et al. JNCI. 2010). Methods: 285 pts, stratified by ECOG-PS, smoking, and blinded pretreatment VS classification, were randomized 1:1 to receive E or CT at standard doses. Primary endpoint was overall survival (OS) and the primary hypothesis was significant interaction between VS status and treatment. Sample size was calculated based on an estimated 65%/35% VSG:VSP ratio and hazard ratio (HR) for interaction of 2.35, with a 2-sided α=0.05 and 90% power. Results: 285 pts were randomized and 263 (129 CT, 134 E) included in the per protocol primary analysis. 68% of pts in CT arm and 72% in E arm were classified as VSG. Analysis was performed at 226 events. The trial reached its primary objective of significant interaction between treatment and VeriStrat classification with an interaction p value of 0.037. Pts in the VSP group performed worse on E compared to CT (HR: 1.72, 95% CI: 1.08-2.74); there was no significant difference in OS between treatments in the VSG group (HR: 1.09, 95% CI:0.79-1.50). 194/198 pts with histologic diagnosis had tissue available for EGFR and KRAS mutations. Conclusions: The results suggest that VS status is predictive of differential OS benefit for E versus CT in second line setting, complementing the result from a retrospective analysis of NCIC BR.21 where the prognostic behavior of VS was established (Carbone et al. JTO. 2012). Clinical trial information: NCT00989690.
Phase III study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC).
Authors: Aapro Matti S. , Rossi Giorgia , Rizzi Giada , Palmas Marco , Grunberg Steven 
Published: February 2017

LBA9514 Background: Management of CINV has been refined over the past several decades and CINV can now be managed with targeted prophylactic medications aimed at inhibiting several molecular pathways involved in emesis. NEPA, a fixed-dose combination of netupitant (NETU), a new NK1 receptor antagonist (RA) and palonosetron (PALO), a pharmacologically distinct 5-HT3RA, targets these dual antiemetic pathways and has been shown to uniquely work synergistically in vitro. Methods: This was a multinational, randomized, double-blind, parallel group study assessing the efficacy and safety of a single oral dose of NEPA (NETU 300mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in 1,455 chemotherapy-naive patients (pts) receiving anthracycline-based chemotherapy (all pts received oral dexamethasone (DEX) 12 mg (NEPA) or 20 mg (PALO) on Day 1). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the delayed (25-120h) phase. Results: Treatment groups had comparable demographic characteristics with the majority of the population being female (98%) and white (80%), with a mean age of 54 yrs; 97% pts had breast cancer. NEPA showed superior CR rates compared to PALO during the delayed, acute, and overall phases. NEPA was also superior to PALO during the delayed/overall phases for complete protection, no emesis, and no significant nausea. Most frequently reported study drug-related adverse events (AEs) for NEPA included headache (3.3%) and constipation (2.1%). The majority of adverse events for NEPA-treated pts were mild/moderate and there were very few (0.7%) severe drug-related AEs. The type and frequency of AEs were comparable between NEPA and PALO. There was no evidence of any cardiac safety concerns for NEPA or PALO. Conclusions: NEPA, a novel single-day fixed-dose combination targeting dual antiemetic pathways, is superior to PALO (both associated with DEX) in preventing CINV in pts receiving MEC. Clinical trial information: NCT01339260. [Table: see text]
Quantitative gene expression by RT-PCR in the tubular, cribriform, mucinous, and papillary histologic subtypes of invasive breast cancer.
Authors: Tan Vivian , Yoshizawa Carl N. , Anderson Joseph Michael , Shak Steven , Baehner Frederick L. 
Published: February 2017

10 Background: ER+ special histologic breast cancer subtypes are prognostically significant. Here we report the special histologic subtypes of ER+ breast carcinoma and associated patterns of observed gene expression as measured by the 21 gene OncotypeDX assay. Methods: All tumors from 6/1/04-5/31/12 were included in analyses. Central path used WHO criteria. Ductal NOS (DC), tubular (TC), cribriform (CC), mucinous (MC) and papillary (PC) carcinomas were included. Quantitative expression of 16 cancer related genes was measured on a scale from 2 to 15 (relative to reference genes) where a 1 unit increment is associated with ~2-fold change in expression. Recurrence Score (RS) was calculated as published. Descriptive stats for the RS and individual genes [ER, PR, invasion gene group (IGG) and proliferation gene group (PGG)] were obtained. Comparisons of means were adjusted to control the overall error rate under any complete or partial null hypothesis. Results: DC accounted for 95.1%, TC 0.7% , CC 0.3%, MC 3.1% and PC 0.7% of 246,555 cases. For all types a wide continuous range of RS was noted. DC had the highest mean RS, followed in decreasing order by MC, TC, CC and PC. PC had the highest ER and PC and CC the highest PR. TC had the lowest ER. ER was not different between CC and MC but PR was. The proportion with ER+/PR- phenotype was different among the subtypes: TC (8.1%) and CC (7.1%) had the lowest incidence whereas MC (12.9%) and PC (10.3%) were more similar to DC (14.1%). TC had lowest PGG expression. MC and PC had lower IGG expression compared to other subtypes. Conclusions: The special subtypes had a wide continuous range of RS: DC had the highest mean RS, followed in decreasing order by MC, TC, CC and PC. PC had the highest ER and PC and CC the highest PR. TC had the lowest ER (may reflect submission bias). ER was not different between CC and MC but PR was. The proportion with ER+/PR- phenotype was different among the subtypes: TC and CC had the lowest incidence, MC and PC were more similar to DC. TC had the lowest PGG expression. MC and PC had lower IGG expression. [Table: see text]
Heart exposure in 100 consecutive, unselected patients treated with adjuvant 3D conformal radiotherapy for left-sided breast cancer.
Authors: Lonardi Federico , Gioga Gloria , Coeli Manuela , Campostrini Franco 
Published: February 2017

103 Background: Women treated with radiotherapy for left-sided breast cancer may have their heart exposed to doses ranging from 1 to 7 Gy on the average. This was confirmed by a recent study* focusing on the ischemic risk based on medical records dating back to 1950s. Modern 3D conformal radiotherapy (3D-CRT), however, may play a major role in heart-sparing irradiation. Methods: We reviewed the treatment planning records and dose-volume histograms of 100 consecutive, unselected patients (pts) affected with left-sided breast cancer who underwent adjuvant 3D-CRT after either quadrantectomy (90 pts) or mastectomy (10 pts) in our center during the year 2011. Median age was 52 (range 42-90). The whole breast (or chest wall) received 50 Gy / 25 fractions in 66 pts and 45 Gy / 18 fractions in 34. Boost to surgical bed (10 Gy / 4-5 fractions) was delivered by photons in 10 pts. Median number of tangential fields was 2 (range 2-4). All treatments were performed in the supine position. Results: The average of the median doses to the whole heart was 2.89 Gy (range 0.8 to 13.05). Median doses were: 1.15 to 1.99 Gy in 21 pts; 2.01 to 3.00 Gy in 32 pts; 3.06 to 3.98 Gy in 16 pts; 4.16 to 4.83 Gy in 13 pts. Median dose only exceeded 5 Gy in 17 pts. One pt received less than 1 Gy and one pt more than 13 Gy. Median volumes (mV) of heart exposed to 5 Gy, 10 Gy and 15 Gy were: mV5 ≤ 4% (range 1 to 42%), mV10 ≤ 3% (0 to 30%), mV15 ≤ 2% (0 to 24%). Conclusions: The average doses we registered are lower than those (4.9 Gy, range 0.03 to 27.72) reported in the large investigation by Darby et al.*. Although related to a small case series, our data confirm that contemporary 3D conformal techniques allow reduced median doses to the whole heart with potential favorable impact on the risk of radiation-induced cardiac disease in the coming decades. Estimate of cardiac involvement in breast cancer radiotherapy based on older case series and outdated treatment techniques may be misleading. *Darby SC et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. NEJM 368, 11, 2013.
Breast cancer disparities in Duval County, Florida.
Authors: Samiian Laila , Kraemer Dale F. , Butterfield Ryan , Osian Sarah Rausch 
Published: February 2017

117 Background: The age-adjusted death rate from breast cancer in Duval County is higher than the national average, with 26 deaths per 100,000 for all women. Breast cancer mortality is 38% higher for black women (37 per 100,000) in Duval County, than for white women (24 per 100,000). We sought to evaluate county specific breast cancer disparity data, in an effort to begin designing effective targeted interventions to reduce the disparities. Methods: Data on female breast cancer cases from 2004-2010 was extracted using the Florida Cancer Data System (FCDS). This data was analyzed using traditional descriptive statistics. Additional classification included health zones within Duval County, race, insurance, and age. Government (Tricare) and private or commercial insurance were combined in one group. The primary outcome was Stage at diagnosis, and time from diagnosis to treatment. Results: Using the FCDS, 6,502 new breast cancers were identified in Duval County from 2004–2010. Of these women, 73% were white, 24% black, 5% Hispanic, 2% Asian, and 2% unknown/other. Health Zone 1 which represents the urban core, has the largest population of Black women with breast cancer (76%), followed by health zone 5 and 4 (35% and 19%). Health Zone 1 has the highest volume of uninsured (10% vs 4% average for zones 2-6), and Medicaid breast cancer patients (8% vs 4% average for zones 2-6), and the lowest number of breast cancer patients with Government/Private insurance (33% vs 56%). Black women had higher percentage of advanced stage IV disease than any other race (8 % vs 4 %, p< .001). Women in Health Zone 1 are more likely to present with stage IV breast cancer than any other health zone in Duval County (10% vs 5%, p<0.01). Medicaid patients followed by the uninsured had the highest rate of stage IV at diagnosis (20% and 12% vs 4%, p<.001). Time from diagnosis to treatment was found to be longest in Black women (29 days vs 26 days, p< .001), Health Zone 1 (30 days vs county average 27 days, p<. 001), and those who were uninsured or had Medicaid (34 days vs 25 days for private insurance, p<0.001). Conclusions: Living in the urban core, black race, lack of insurance, and Medicaid funding was significantly associated with advanced stage at diagnosis and longer time from diagnosis to treatment in Duval County, Florida.