bluuebunny/crossref_metadata_2025 huggingface dataset:
Health care practitioner prescribing patterns and perspectives on oral chemotherapy management: A survey of cancer centers in Toronto, Canada.
Authors: Pasetka Mark , Day Larissa , Ford Maggie , Boudreau Angela , Giotis Angie , Ko Yoo-Joung , Gandhi Sonal
Published: February 2017

48

Background: With an increasing number of patients receiving oral cancer therapies, evaluation of safe prescription practices, effective patient education, and toxicity monitoring of these agents is imperative. Methods: Multi-disciplinary oncology practitioners at several cancer centres in Toronto, Canada were surveyed using a web-based platform, to evaluate their prescription practices, use of patient education and symptom management tools, as well as their views on patient adherence and toxicity reporting. Results: Of 170 respondents, 43% were nurses, 34% were pharmacists, and 23% were physicians. Seventy nine percent considered patient education, medication adherence (76%), and toxicity management (78%) as “very important” components of oral chemotherapy management. Prescription methods varied: 59% of respondents used written prescriptions, 39% computerized physician order entry (CPOE), and 0% pre-printed orders, ≥50% of the time. Clinicians felt that patients report side effects from oral agents only “some of the time” (53%), and the most problematic toxicities were nausea (61%) and diarrhea (61%). Practitioners perceived the most common reasons for patient underreporting of side effects to be “fear of treatment interruption” (62%), and that “toxicities are part of the treatment” (66%). Seventy three percent of those surveyed felt individual counseling, follow-up calls (69%), and updated medication information (57%) would improve patient adherence and safety. Conclusions: A diverse group of surveyed oncology professionals expressed the importance of utilizing educational and toxicity monitoring tools for patients on oral cancer therapies, particularly as patients are thought to under-report symptoms. Prescription practices are variable, and CPOE use should be improved. The results of this survey will also be compared to a patient survey, to help develop better tools and policies to standardize practice, and improve patient adherence and toxicity management on oral cancer agents.
Implementing an innovation to improve coordination of care in breast cancer.
Authors: Bickell Nina A. , Franco Rebeca , Moss Alexandra , Lawrence Zoe , McAlearney Ann Scheck
Published: February 2017

52

Background: Underuse of adjuvant breast cancer treatments delivered by different specialists may be worsened by fragmented care and improved by effective coordination. To improve care coordination and adjuvant treatment delivery, we assessed the challenges to and feasibility of implementing a web-based Tracking and Feedback (T&F) innovation in hospitals serving predominantly minority breast cancer patients. Methods: We interviewed 67 key informants [Clinical (n = 39), Administrative (n = 14), Clerical (n = 11), Other (IT, Social Work) (n = 3)] from 8 inner-city hospitals to better understand how organizational characteristics might impact coordination of care and implementation of the T & F innovation. We used the constant comparative method of qualitative data analysis and standard techniques to code the data. Results: We found considerable variability across hospitals’ abilities to coordinate and track care. All sites have multi-disciplinary Tumor Board meetings and active Quality Improvement departments. Yet, in several sites, specialty care remains siloed, quality improvement efforts focus on inpatient care and communications systems across outpatient specialties are poor. All hospitals have electronic medical records but they are not integrated and are unable to track requested referrals. Many physicians rely on follow-up appointments to ascertain treatment receipt but sites vary in their ability to address “no-shows.” Several rely on staff to manually identify and follow up “no-shows,” but many of these staff are overwhelmed with ever increasing tasks and responsibilities. While quality was important, several interviewees felt they were bucking an inflexible system and devised ways to work around the obstacles. Perceived successful coordination factors included strong clinical leadership, designated accountabilities, and flexibility of staff. Conclusions: As care integration is encouraged by federal law, specialty care silos and rigid communication systems still pose barriers to change. Our results suggest that a web-based T&F innovation must be tailored to individual hospital characteristics, and flexible to permit modification of care processes at the organization level. Clinical trial information: NCT01544374.
How is KRAS testing associated with treatment and supportive care for patients with metastatic colorectal cancer? VA national assist project.
Authors: Parikh Aparna Raj , Kim Benjamin , Pantoja Philip , Tisnado Diana M. , Ahluwalia Sangeeta C , Walling Anne M. , Asch Steven M , Lorenz Karl
Published: February 2017

64

Background: EGFR monoclonal antibody (mAb) therapies improve quality of life and outcomes for metastatic colorectal cancer (mCRC), but only wild-type KRAS benefit from treatment. We evaluated KRAS testing and pharmacogenetic-guided treatment and supportive and end of life (EOL) care. Methods: Among a national random sample of 265 veterans diagnosed with mCRC in 2008 we evaluated KRAS testing, EGFR mAb therapy, supportive care using the Cancer Quality ASSIST indicators, and healthcare use. Three oncology nurses abstracted charts for care received 2008-2011. We linked chart to VA and Medicare administrative data and compared care received by KRAS testing and results. Results: 227/265 (85%) veterans died within 3 years and received an average of 48% of recommended supportive care processes. 96 / 265 (36%) underwent KRAS testing, of whom 41, 42, and 13 had wild-type, mutant, and indeterminant/unknown KRAS. 27/41 (66%) wild-type KRAS patients received an EGFR mAb; 18/45 (40%) patients receiving an EGFR mAb had mutant, indeterminant/unknown, or untested KRAS. KRAS testing was associated with increased systemic therapy but not differences in supportive care or intensity of care at the EOL. KRAS tested vs. not tested received hospice or palliative care (67 vs. 73%, p=0.55); any systemic therapy (96 vs. 40%, p<0.001) including new regimen in last month (0 vs. 6%); any chemotherapy in last 14 days of life (9 vs. 7%); and any acute care in last month of life (28 vs. 32%, p=0.78). Conclusions: KRAS testing was not performed for most veterans with mCRC in 2008, and EGFR mAb therapy was administered to many without wild-type KRAS. KRAS-tested patients were more likely to receive systemic treatments, and testing was not associated with greater intensity or inappropriate EOL care, and rates of such care were low among veterans.
The effect of guidelines, policy initiatives, and feedback tools on hospital adherence with the 12-node measure for colon cancer.
Authors: Paruch Jennifer L. , Merkow Ryan P. , Ju Mila H. , Winchester David Porter , Ko Clifford Y. , Bilimoria Karl Y.
Published: February 2017

65

Background: Examination of > = 12 lymph nodes after colectomy is one of few surgical process measures. Several initiatives have targeted this measure; one tool developed by the Commission on Cancer (CoC) provides benchmarked feedback on hospital performance (CP3R). Our objectives were to (1) examine changes in measure performance over time in response to guidelines, policy initiatives, and feedback, and (2) identify hospital characteristics associated with failure to improve adherence. Methods: Patients having surgery for Stage I-III colon cancer (1990-2010) were identified from the National Cancer Data Base (NCDB). For hospital-level analyses, NCDB and American Hospital Association (2010) data were merged. Hospital CP3R use was obtained from the user log system. Multivariable logistic regression adjusted for age and tumor factors was used to identify hospital characteristics associated with adherence in 2009-2010 (> = 12 nodes in > 80% of patients). Results: The percentage of patients with > = 12 nodes removed increased from 31.5% in 1990 to 84.1% in 2010 (p < 0.0001). The percentage of adherent hospitals increased from 2.2% in 1990 to 70% in 2010 (p < 0.0001). The steepest increase in adherence occurred with introduction of CP3R. Median CP3R use increased from 5 to 57 logins annually (2005-2010). Hospital predictors of poor adherence included low volume, community hospital type, private ownership, rural location, and lower number of specialists (Table). Conclusions: Guidelines, policy initiatives, and feedback tools have helped dramatically increase adherence with the 12-node measure, but small, non-academic hospitals have been slower to improve. Additional efforts are needed to understand barriers and improve adherence at these facilities. [Table: see text]
Breast cancer genetic risk evaluation and referral for assessment.
Authors: Fenton Mary Anne , Szyamnski Tara , Perez Kimberly , Benson Cindy , Phornphutkul Chanika
Published: February 2017

75

Background: ASCO Quality Oncology Practice Initiative (QOPI) provides tools for oncology practices to assess quality and adherence to clinical guidelines. Following each data submission a QOPI measures summary report is published providing practices the opportunity to compare themselves to QOPI Aggregates. In 2011, QOPI initiated a more stringent evaluation of family history documentation, which would improve rates of referral to genetic counseling for breast and colon cancer. Methods: A review of QOPI measure summary reports is performed by Rhode Island Hospital’s (RIH) Comprehensive Cancer Center Quality Improvement Team after each round of chart abstraction. Following review of QOPI practice results for genetic evaluation in 2011, our interventions included development and implementation of a 3 generation maternal and paternal family history intake form, genetics referral form with criteria to refer patients for genetic evaluation and initiation of a Genetics Clinic on site at the Cancer Center. Results: Presented is a summary of QOPI results for the Breast Cancer measures of complete family history documented and Genetic testing addressed appropriately. Conclusions: Our interventions included a patient intake form, genetics referral form with criteria to refer patients and a Genetics Clinic on site at the Cancer Center. The institution of a patient intake form resulted in a 19-fold improvement in complete family history documentation. The genetics referral form and establishment of an on-site Genetics clinic resulted in a 10% increase in referrals for genetic risk assessment. In spite of these interventions review of our Genetic Risk Evaluation data is notable for a 39% no show rate for the genetic risk assessment appointments. [Table: see text]
Hepatitis B surveillance in adult chemotherapy patients.
Authors: Gordon Sarah , Berenberg Jeffrey L. , Ferguson Tomas , Mitchell Jacqui D.
Published: February 2017

76

Background: The high prevalence of Hepatitis B virus (HBV) in the Hawaiian and Pacific Islander population and the death of two chemotherapy patients from reactivation led to a screening protocol to identify and treat chronic HBV. The goal of this quality improvement project was to assess the at risk population, compliance with screening between 2009 and 2011 and determine any necessary improvements. Methods: New intravenous chemotherapy patients are tested for Hepatitis B surface antigen (HBSAg), Hepatitis B core antibody (HBc), and Hepatitis B surface antibody (HBSAb) prior to initiation of chemotherapy. HBSAg positive patients receive Infectious Disease referral and treatment. HBc positive patients are monitored with serial hepatic function tests. We documented testing and if the patients were treated or followed with hepatic function tests. We reported all positive screening results (defined as HBsAg positive and HBc positive/HBsAb negative patients) and if the patients were treated or screened. We also characterized our patient population by race. Results: 329 patients received chemotherapy. HBsAg positive patients (5, 1.5%), were referred to Infectious Disease for treatment. The HBc positive patients (55) were followed with serial hepatic function tests for the duration of chemotherapy. 13 of these were HBsAb negative (4% of all patients). A total of 5.5% of all patients had a positive screening result as defined above. Overall compliance was 98%. 85% of individuals with a positive serology result self identified as either Asian or Pacific Islander. Conclusions: Reactivation of chronic HBV in individuals exposed to immunosuppressive treatments has a mortality rate of 4-41%. Expert societies do not agree regarding screening all patients. Hawaii has a higher prevalence of chronic hepatitis B (positive HBsAg) compared to the mainland US population (3.6% vs. 0.4% respectively). We screened 98% of intravenous chemotherapy patients. No patients developed evidence of reactivation. To improve upon our protocol we extended laboratory monitoring to three months following completion of chemotherapy and initiated vaccination for HBc positive HBsAb negative patients. We propose that screening at risk populations should be standard practice.
Structured approach to improving wait times and overall customer service in an oncology outpatient phlebotomy department.
Authors: Forde Patrick M. , Violette Kitty , Maylor Karen , Kasecamp Barbara , Rushworth Beth , Jefferson Cheryl , Wilmore Joan , Fetting John H. , Dean Richard , Cowperthwaite Suzanne , Krumm Sharon
Published: February 2017

77

Background: Demands on the Johns Hopkins phlebotomy service have increased exponentially over the past several years leading to increased patient (pt) waiting times and reduced patient and staff satisfaction. Methods: The goal of our project was to reduce waiting times for outpatient phlebotomy to <30 mins for 90% of pts by May 2013 using a multi-disciplinary lean sigma approach. The following interventions were implemented - Two weekly multidisciplinary lean sigma meetings; Move to set appointment times; Twice daily staff "huddles" to plan the work schedule; Ensure a minimum of 8 phlebotomists on duty daily; Expand training for clinical assistants (CAs) to access VADs; Introduce pager system for pts to reduce needless waiting; Introduce leadership positions among phlebotomy and CA staff to manage change. Results: Within 6 months of these concerted efforts wait times have reduced to <30 mins and patient satisfaction scores for >90% of pts are very good or excellent. Conclusions: Difficult problems such as increasing patient demand with constrained resources can be ameliorated with a multidisciplinary structured approach. The project as outlined may serve as a template for other oncology services dealing with the increasing demands of an aging population in a time of increasingly limited resources.
Oncology labels with clinical outcomes data since the final PRO guidance.
Authors: Foley Kathleen A. , Meyers Oren I
Published: February 2017

88

Background: FDA released draft Guidance on Patient-Reported Outcomes (PROs) in 2006 and finalized it in 2009. The Guidance applies equally to clinician and observer outcomes (ClinROs, ObsROs; collectively, clinical outcome assessments - COAs), and defines regulatory expectations for COA instruments in pivotal clinical trials and the inclusion of COA data in approved labeling. The purpose of this review was to survey labels for oncologic drugs approved in the three years since the “PRO Guidance” was finalized and to characterize any COAs in these labels. Methods: CenterWatch maintains a list of FDA approved drugs following definitions established by the Tufts Center for the Study of Drug Development, including only drugs or NMEs newly approved by the FDA Center for Drug Evaluation and Research. From 2010 through 2013, 45 oncologic drugs were approved by the FDA. The labels and other information from the Drugs@FDA website were reviewed. Results: Few of the approved labels included any reference to COAs or data collected using PROs, ClinROs, or ObsROs. Several (e.g., carfilzomib) had clear statements indicating approval for the product was based on a predefined response rate rather than “improvement in survival or symptoms.” The exceptions are fentanyl tablets and spray, and abiraterone, all with PRO data on pain. The number of PROs in the labels reviewed was low, but the trend suggests that products reviewed by Divisions outside the Office of Hematology and Oncology Products were more likely to have a PRO. Abiraterone was an exception as it was reviewed by Oncology Products I and included patient reported pain. Conclusions: There are several explanations for the low rate of COAs in oncology labels, e.g., oncology trials tend to be unblinded. The FDA has stated that open label designs cannot support PRO claims. Yet there is still a heavy reliance on outcomes such as progression free and overall survival. Three labels were identified with PRO data on pain, two of which were specifically indicated for pain rather than tumor control. This review suggests there are opportunities for sponsors and the FDA to increase the degree to which the patient’s voice is heard during the regulatory decision process, particularly, in programs reviewed by the oncology divisions.
Guideline adherence for diagnosis of liver cancer in veterans.
Authors: Sada Yvonne , David Eric , El-Serag Hashem , Singh Hardeep , Davila Jessica
Published: February 2017

89

Background: The incidence of hepatocellular cancer (HCC) is rising. Practice guidelines provide the recommended approach for HCC diagnosis, but adherence to diagnostic guidelines is unknown. Methods: In a national sample of veterans with confirmed HCC, we performed a retrospective chart review of patients with cirrhosis and a new liver mass on imaging between 2005 and 2011. Clinical data was used to assess adherence to American Association for the Study of Liver Diseases guidelines. Patients with inadequate data to assess guideline adherence (missing liver mass size, imaging technique, or diagnostic report) were excluded. We identified factors that contributed to guideline non-adherence. Initial liver mass date was the first date a liver mass was reported on imaging (CT, MRI, or ultrasound). Gold standard test date was the date a diagnosis of HCC could have been made by guideline recommended testing and criteria. Diagnosis date was the date a provider documented the diagnosis. Results: We reviewed charts for 380 patients. Overutilization of diagnostic tests after a gold standard test occurred in 112 patients (31%), and 17 (4%) had insufficient tests. Guidelines were not followed in 124 (33%). Of these 124, 68 (55%) had liver masses that increased in size during diagnostic work-up. The most common factors associated with guideline non-adherence were unnecessary testing such as biopsy after a gold standard image (43%) and the presence of a contraindication to a guideline recommended image or biopsy (12%). Patient factors (missed appointments, declining work-up) accounted for only 3% of cases. Median time between the initial liver mass and gold standard test was 15 days (IQR: 0-99). Median time between the initial liver mass and diagnosis was 50 days (IQR: 12-191). Most diagnoses were made by gastroenterology (51%), followed by primary care (19%), and oncology (10%). Conclusions: One-third of patients with HCC were not diagnosed based on guidelines. These concerns include confidence in diagnosis (lack of recognizing HCC diagnosis despite gold standard evidence) and over testing, which both lead to diagnostic delay. Our findings warrant further evaluation of contributory factors to develop interventions that improve the diagnostic process for HCC.
Measuring clinical pathway compliance using a simulated patient approach with clinical performance and value (CPV) vignettes.
Authors: Fields Karen K. , Soliman Hatem Hussein , Friedman Eliot Lawrence , Lee Rachel V. , Acelajado Maria Czarina , Tamondong-Lachica Diana , Peabody John W.
Published: February 2017

96

Background: Although clinical pathways have the promise to improve the quality of care, they have had limited success changing practice or standardizing care. Moffitt Cancer Center (MCC) has > 40 pathways incorporating interdisciplinary care strategies linked to evidence and decision support tools. Methods: To improve compliance with pathways we used an innovative measure to quantify quality of care, CPV vignettes. CPV vignettes are validated, simulated clinical scenarios constructed so that adherence to pathways is clear-cut. Providers care for identical cases so there is no need for case mix adjustment. After completing each case, providers are given personalized feedback. Twelve breast cancer (ca) vignettes were developed by MCC breast medical oncologists and surgeons and QURE, a healthcare measurement company. The cases were developed using MCC pathways, other evidence and core issues such as diagnostic work-up. The vignettes were randomized at the department level and given to all MCC providers who care for breast ca patients. A total of 18 providers took 34 CPVs: 7 medical oncologists, 6 advanced practitioners and 5 surgeons. QURE-trained physician abstractors blinded to the CPV-taker’s identity scored each vignette and provided confidential feedback. Results: Total scores for providers averaged 55.4%, s.d. 12.5%, a typical score for a CPV baseline study. Adherence to pathways varied by area with the highest concordance for radiation and hormonal therapy and the lowest for management of axillary lymph nodes (see Table). Conclusions: Adherence to pathways varied among providers and by clinical domain. Ongoing efforts will evaluate the impact of serial CPV measurement on pathway adherence. Simulations simplified the task of determining pathway adherence making pathway compliance at the physician level a reasonable expectation and standardization at the group level scientifically rigorous and feasible. [Table: see text]
Fast track multidisciplinary approach for gastrointestinal tumours.
Authors: Tytgat Kristien M. A. J. , Greuter H. H. , Molenaar J. , Heukels S. , Fockens Paul , Gouma Dirk J. , Klinkenbijl Jean H.G.
Published: February 2017

102

Background: The incidence of gastrointestinal (GI) tract tumours in the Netherlands is rising. However, GI oncological medical care is still delayed and fragmented. There is a need for better and faster diagnostic work-up, faster start of treatment, but also for expert multidisciplinary deliberation. Therefore, the GIOCA, Gastro Intestinal Oncological Centre Amsterdam, started in 2009 as a one day fast track multidisciplinary outpatient clinic for patients with GI malignancies. The goal was an admission time (AT, time from referral to consultation) of < 1 week and a run through time (RTT, time from multidisciplinary meeting to start of treatment) of < 3 weeks. The aim of this study was first to evaluate the AT and RTT at GIOCA and secondly to evaluate the subjective impact of this novel strategy on patients burden and satisfaction. Methods: Patients were seen at GIOCA in the morning on a colorectal (CRC ), an oesophago/gastric (OES) or a hepatopancreaticobiliary (HPB) day. That same morning (additional) diagnostics were performed. At the multidisciplinary meeting afterwards, a final diagnosis and treatment plan was made, which was later communicated to the patient. The patient then met all involved specialists. AT and RTT were prospectively recorded for all GIOCA patients. For HPB malignancies, AT and RTT could be compared to historical controls from the preceding year. Patient impact and satisfaction was evaluated using a before/after cohort study design, with a written questionnaire prospectively administered to all GIOCA patients and compared to data obtained 3 months prior to GIOCA start. Results: Analyses of 2009 and 2010 showed the following results: The average AT for CRC, OES and HPB was 7.6, 9.5 and 9 days respectively. The average RTT for CRC, OES and HPB was 20.8, 24 and 25 days respectively. For HPB malignancies, this was 10.4 days (AT) and 59.8 days (RTT) in the year preceding GIOCA. Higher levels of patient satisfaction were obtained in GIOCA patients compared to controls. More than 90% of the patients interviewed would advice the GIOCA outpatient approach to other patients. Conclusions: Progress has been made in the AT and RTT in GI malignancies in GIOCA, but the goals were still not all reached. Patients were very satisfied with this novel approach.
Single-center experience with paclitaxel (T), carboplatin (C), and capecitabine (X) in the treatment of advanced esophagogastric cancer.
Authors: Ruoff Carl Alex , Hong Bennett , Kaplan Barry H. , Pollack Simcha
Published: February 2017

116

Background: Epirubicin, cisplatin, and 5-FU (ECF) improves overall survival for advanced esopgagogastric adenocarcinoma compared with other protocols but is associated with considerable toxicity. A triple chemotherapy with TCX has shown improved survival with less toxicity at our institution. The aims of this study were to retrospectively analyze overall survival and toxicity of TCX in our patient population and to compare them with published results from ECF and paclitaxel, cisplatin, and 5-FU (TCF), a similar regimen to ours. Methods: We analyzed pts with locally advanced and/or metastatic esophagogastric adenocarcinoma treated in our institution from 2005 to 2012 with TCX (paclitaxel 80mg/m^2 day 1 & 8, carboplatin 5 AUC day 1, capecitabine 750mg/m^2 BID for 14 days). Pts had received no prior chemotherapy. Primary endpoint was overall survival and secondary endpoint was toxicity. We compared our data to historical results from trials of ECF and TCF. Results: 35 pts who received TCX were identified. The median age was 64 years (range 37-91). 20 pts had metastatic disease and 15 had locally advanced disease. Median survival was 21 months (95% CI: 13, 25 months). 1 year survival was 72% (95% CI: 54%, 90%). These data compare favorably to published ECF data (table) with a significant survival benefit of TCX over ECF (p<0.05%). When compared to TCF in pts with metastatic disease 2 year survival was 18%, compared to 32% (95% CI: 10%, 54%) with TCX. Though there is a survival benefit, it was not statistically significant. Grade 3-4 toxicity with ECF has been documented in several studies as above 40%. In our patients treated with TCX, only 4 pts (11%) suffered grade 3-4 toxicity (nausea, vomiting, hearing loss, and neutropenia). Conclusions: In our patient population, triple therapy of paclitaxel, carboplatin, and capecitabine (TCX) is associated with significant improvement in overall survival in advanced esophagogastric cancer with a low rate of toxicity compared to published ECF results. [Table: see text]
A prospective comparison of the FACT-e and EORTC-QLQC30 and OG25 questionnaires for evaluating changes in health-related quality of life in patients with esophageal cancer.
Authors: Darling Gail
Published: February 2017

130

Background: The FACT-E (Functional Assessment of Cancer Therapy– Esophageal) and the EORTC QLQ-C30 (European Organization for Research on Treatment of Cancer Quality of Life Questionnaire) and its cancer-specific module (OG25) are two validated instruments used to assess quality-of-life (QOL) in patients with esophageal cancer. This study investigates the differences between these two instruments. Methods: This is a prospective study of 22 consecutive patients treated with chemoradiation followed by surgery. Questionnaires were self-administered at each of the following: baseline (prior to treatment), 6-8 weeks and 12-14 weeks following start of chemoradiation, and 1, 3, 6, 9, 12, and 18 months following esophagectomy. Mixed model regression was applied to model the repeated measures of the two questionnaires to compare slopes. Results: Of the 22 patients, 20 proceeded to surgery. Overall survival and disease-free survival at 18 months were 59% and 55% respectively. Comparison of the QOL domains over time showed good correlation for physical and functional well-being, with an apparent variation in the magnitude of the changes over time for the latter. The questionnaires were discordant with respect to social and total well-being. Social well-being showed a return to baseline by 1 month post-op using the FACT, but never recovered to baseline for the EORTC. FACT Total well-being recovered to baseline by 9 months, while the EORTC only approached baseline values by 18 months. The disease-specific modules showed post-operative symptom improvement with the FACT and a deterioration with the EORTC. There was also discordance in emotional well being. Conclusions: Domain comparisons of the EORTC and FACT questionnaires showed differing results. Discordance was seen for emotional, social and overall QOL, as well as symptomatology. The EORTC total and physical well-being domains showed a similar pattern of change over time. These findings might result from the overall tendency of the EORTC to emphasize physical aspects of QOL. Thus these two instruments appear to measure different aspects of QOL, which may affect their clinical utility.
A comparison of outcomes for 3D conformal versus intensity modulated radiation therapy in postoperative gastric cancer.
Authors: McTyre Emory , Freilich Jessica , Chuong Michael , Fulp William J. , Almhanna Khaldoun , Meredith Kenneth , Hoffe Sarah , Shridhar Ravi
Published: February 2017

139

Background: Postoperative radiation therapy (RT) for gastric cancer results in increased survival. Treatment planning studies have demonstrated improved target coverage and normal tissue sparing with intensity modulated RT (IMRT) versus 3D conformal radiotherapy (3DCRT). The purpose of this study was to compare outcomes of gastric cancer patients treated with IMRT vs 3DCRT. Methods: An IRB approved database was queried for all postoperative gastric cancer patients who received adjuvant chemoradiation with either 3DCRT or IMRT between 2000 and 2012. The primary endpoints were survival and toxicity. Overall (OS) and disease-free survival (DFS) were calculated with Kaplan-Meier analysis and multivariate analysis (MVA) was performed using a Cox proportional hazard ratio model. Results: We identified 39 patients (23 3DCRT, 16 IMRT). Median followup for all patients, 3DCRT patients, and IMRT patients was 16.2, 24.6, and 14.4 months, respectively. The only difference between groups noted was the presence of more positive lymph nodes (p=0.015) and higher N stage (0.012) in the 3DCRT group. There was no difference in OS or DFS on univariate or MVA. The median OS was 27.6 for the IMRT patients versus 27.4 months in the 3DCRT patients (p=0.63). In patients treated with IMRT we observed a nonsignificant decrease in grade ≥3 toxicity (25% vs. 39%; p = 0.50), any hospitalization (25% vs. 30%; p = 0.74), and median weight change (7% vs. 9%; p=0.62). On MVA for grade >3 toxicity age, gender, stage, type of surgery, pre-operative chemotherapy, number of lymph nodes removed and radiation technique were all nonsignificant. The hazard ratio for radiation technique was 0.600 (95% CI 0.118-3.042; p value=0.537). Conclusions: Our data did not demonstrate differences in OS or DFS but did show a decrease in toxicity. Caution should be taken given small sample size and short follow up in IMRT patients. Comparative outcomes for these two techniques therefore warrant continued exploration.
Pancreatic injury, genetic variation of PNPLA3, and risk of pancreatic cancer.
Authors: Aly Mohammed , Sahin Ibrahim Halil , Li Donghui , Khalil Mohamed Fahd , Chang Ping , Fogelman David R. , Javle Milind M. , Abbruzzese James L. , Hassan Manal
Published: February 2017

141

Background: Similar to primary liver cancer, obesity, diabetes mellitus and hepatitis B virus infection have been associated with increased risk of pancreatic cancer (PC) development. A genome-wide association study has reported that a polymorphic variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene was associated with a higher susceptibility to fatty liver and liver cancer. The relationship between this variation and PC has not been previously examined. We investigated the correlation in the degree of organ damage between the liver and the pancreas in patients with PC. In addition, we examined the effect of PNPLA3genetic variation (rs738409: C>G) on PC development. Methods: Using resources of our case-control study in MD Anderson Cancer Center, we analyzed 544 pathologically confirmed PC patients and 498 healthy controls. Cases and controls were frequency matched by age, gender, and race. Multivariate logistic regression analysis was performed to adjust for the confounding factors. Medical records of PC patients were reviewed for pancreatic and liver fatty changes. Results: We found that 18.8% of PC patients had evidence of pancreatic steatosis, fibrosis, or pancreatitis. Fatty liver was observed in 14.5% of PC patients which was frequently detected in patients with pancreatitis (p=0.002). A significant correlation between pancreatitis and cirrhosis was observed in PC patients with a prior history of obesity but not in patients without a history of obesity (p=0.001). On the other hand, we observed no significant association between PNPLA3 genotype and risk of PC. The adjusted odds ratio (OR) was 1.4 (95% confidence interval [CI], 0.7-2.7) for the homozygous variant GG genotype compared with the CC/CG genotypes. Conclusions: We concluded that despite the similarities between the liver and the pancreas, genetic susceptibility to fatty infiltration and its effect on cancer development may differ between the two organs. Evaluation and assessment of nonalcoholic fatty pancreatic disease (NAFPD) in PC patients and genetic susceptibility of NAFPD may be warranted in future research.
Effect of the revised AJCC staging (7th edition) on prognostic stratification in patients with surgically resected esophageal squamous cell carcinoma.
Authors: Minella Gloria Terase , Luketich James D. , Davison Jon M. , Winger Dan , Levy Ryan M. , Gibson Michael K. , Pennathur Arjun , Nason Katie Sue
Published: February 2017

15

Background: Historically, the AJCC esophageal staging system separated patients into prognostic groups based on tumor, node, and metastasis (TNM) classifications. In 2010, the 7th edition (AJCC 7) significantly modified esophageal squamous cell cancer (ESCC) staging by separating ESCC from adenocarcinoma, incorporating tumor grade and location for node negative cancers, and stratifying by the number of involved regional nodes for node positive cancers. Our study aim was to determine whether AJCC 7 stage groupings provide improved survival prognostication compared to 6th edition (AJCC 6). Methods: We abstracted pathology and survival for 150 consecutive ESCC patients who underwent esophagectomy (1994-2012); 44 patients received induction therapy. AJCC 6 and AJCC 7 stages were assigned and overall survival analyzed from esophagectomy to death or most recent alive contact and censored at 60 months. Discriminatory ability and homogeneity within subgroups was assessed with Kaplan-Meier curves and monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) used to assess model fit. Results: Compared to AJCC 6, AJCC 7 upstaged 32 patients from IIa to IIb and 1 patient from IIb to IIIa and downstaged 3 patients from stage IIa to Ib. AJCC 7 subclassified 42 AJCC 6 stage III patients (17 IIIa, 10 IIIb and 15 IIIC). Median overall survival was 19 months. Kaplan-Meier log-rank statistic indicated stronger differentiation in AJCC 7 (19.8 vs 29.7). Cox regression likelihood (19.5 vs 26.1), AIC (618.1 vs 611.6), and linear trend chi-squared at 24- (17.5 vs 24.3) and 60-months (13.3 vs 17.3), were all superior for AJCC 7 stage groupings (AJCC 6 vs AJCC 7, respectively). Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, tumor location and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected ESCC patients, including patients who received induction therapy.
Effect of venous involvement on survival in locally advanced pancreatic cancer.
Authors: Hewitt Kelly C. , Madden Jesse L , Christensen Joslin C , Mulvihill Sean J. , Scaife Courtney L.
Published: February 2017

153

Background: Locally advanced pancreatic cancer is defined as tumor that extends beyond the pancreas into surrounding structures. Borderline resectable disease usually includes a description of superior mesenteric vein (SMV) or portal vein (PV) involvement, while the AJCC staging no longer includes venous involvement in the staging system. We reviewed our institutional cancer database to determine if venous involvement affects overall survival and should be included in pancreatic ductal adenocarcinoma (PDA) staging. Methods: A retrospective review was performed of all patients with stage II or III PDA identified through our institutional prospective Clinical Cancer Research Database, between 2007-2012. Patients with superior mesenteric artery (SMA) or celiac artery and/or venous (SMV or PV) involvement were compared to those without. Vascular involvement was defined as either vessel encasement or abutment on endoscopic ultrasound or CT imaging. Survival analysis was performed using the Kaplan-Meier method with log-rank test for comparison of survival curves. Results: A total of 194 patients were identified as having stage II or stage III pancreatic adenocarcinoma, with 85 having evidence of vascular involvement. In our patient population we found that in patients with stage IIA and IIB disease PV or SMV involvement did not portend statistically worse survival (median survival 14 months v 15 months p=0.63). In stage III patients survival was actually longer in patients with PV or SMV involvement, but this was not statistically significant (median survival 13 months v 7.9 months p=.066). When comparing those with PV or SMV involvement versus those with celiac axis or superior mesenteric artery (SMA) involvement in all patients with locally advanced pancreatic cancer (stage II or III), those with celiac or SMA involvement did significantly worse (mean survival 14 months v. 7.9 months p<0.001). Conclusions: Venous involvement does not portend a worse survival in patients with stage II and III pancreatic cancer. The addition of venous involvement to the current AJCC staging scheme would not provide additional survival information.
Diagnostic discrepancies between second-opinion and referring pathology reports of neuroendocrine tumors.
Authors: Lin Hillary , Longacre Teri A. , Khandelwal Vilay H. , Balise Raymond R. , Kunz Pamela L.
Published: February 2017

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Background: Neuroendocrine tumors (NETs) are rare malignancies that can arise from neuroendocrine cells throughout the body, most commonly in the lungs, gastrointestinal tract, and pancreas. The nomenclature and histologic classification schemes for NETs have historically been heterogeneous and inconsistent. Klimstra, et al published a set of NET pathology guidelines in 2010. We undertook a systematic evaluation of discrepancies between referring versus second-opinion NET pathology reports using these guidelines as our reference. Methods: We developed a cohort ofall NET cases seen at Stanford University Hospital between April 1998 and February 2012 with available Stanford and referring pathology reports for the same specimen to identify the discrepancies between their clinical diagnoses. Results: Of 141 cases, primary sites were identified as 39 (28%) pancreas, 21 (15%) small intestine, 49 (35%) other NET sites, and 32 (22%) unknown or missing. Most reports agreed on a diagnosis of NET, although twelve different terms were used to describe the NET diagnosis. There were 24 cases (17%) with major discrepancies by histologic description (NET vs. not NET). Grade, mitotic index (MI), and Ki67 were among the variables examined; they were missing from the majority of cases in one or both reports, yet more likely to be included in the Stanford report. Grade was not reported (NR) in one or both reports in 124 cases (88%); of the 17 cases reporting grade in both reports, 3 had major discrepancies. MI was NR in one or both reports in 105 cases (74%); of the 36 cases reporting MI in both reports, 5 had major discrepancies. Ki67 was NR in one or both reports in 127 cases (90%); of the 14 cases reporting Ki67 in both reports, 3 had major discrepancies. Conclusions: Clinically relevant differences were frequently found between Stanford and referring pathology reports for NETs. Our results suggest that it is beneficial for NET cases to be reviewed by NET pathology experts given the potential to impact treatment. Future studies of NET pathology discrepancies are warranted to allow additional time for adoption of the 2010 guidelines.
Performance of a novel TNM staging system for pancreatic neuroendocrine tumors versus the current AJCC staging system.
Authors: Qadan Motaz , Ma Yifei , Visser Brendan C. , Norton Jeffrey A. , Poultsides George A.
Published: February 2017

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Background: Adopting a unified staging system for pancreatic neuroendocrine tumors (PNET) has been challenging. Currently, the American Joint Committee on Cancer (AJCC) recommends the use of the pancreatic adenocarcinoma staging system for PNET. We sought to validate this recommendation on a large administrative population database. Methods: Surveillance, Epidemiology, and End Results (SEER) data were used to identify patients with PNET (excluding patients with large cell, small cell, or mixed endocrine-exocrine carcinoma) who underwent curative-intent surgical resection from 1983 to 2008. The discriminatory ability of the AJCC system (recorded by SEER since 2004) was examined and a new TNM system was devised utilizing extent of disease variables. Results: Of 1,202 patients identified, 51% were female. Median age was 55 years (range, 9-93). Lymph node metastasis (present in 43% of patients) was associated with worse overall survival (OS) after resection (10-year OS, 50% vs 63%, p<.0001), as was the presence of distant metastasis (present in 24% of patients, 10-year OS, 35% vs 63%, p<.0001).The current AJCC system (available in 412 patients) distinguished overall survival adequately only between stages I and II, but not between II and III, or III and IV (Table). By modifying the T stage to be based only on size (0-1 cm, 1-2 cm, 2-4 cm, and > 4 cm) and by revising the grouping allocation, we propose a novel TNM system with improved discriminatory ability (Table). Conclusions: In this study validating the current AJCC staging system for PNET, we found stages II, III, and IV to perform similarly. We propose a simplified TNM system that better discriminates between outcomes. [Table: see text]
The natural history of preoperative indeterminate pulmonary nodules in patients with resectable pancreatic adenocarcinoma.
Authors: Nguyen Dennis C. , Chang Stephanie , Gongfu Zhou , Wang-Gillam Andrea , Linehan David , Hawkins William G , Strasberg Steven M , Menias Christine , Raptis Constantine , Fields Ryan C.
Published: February 2017

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Background: Preoperative abdominal imaging often detects indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma. The natural history of IPN in this setting is not well characterized. Methods: Patients with adenocarcinoma of the head of the pancreas who underwent pancreaticoduodenectomy (PD) were queried from a prospectively maintained database. Pre- and postoperative imaging was reviewed and IPN characterized and analyzed for associations with nodule progression and overall survival (OS). Results: 463 patients underwent PD for adenocarcinoma of the head of the pancreas from 2000-2010. Of these, 329 (71%) had reviewable pre-operative imaging. 48 patients (15%) had pre-operative IPN (non-calcified) identified with follow-up imaging available for review. The only pre-operative factor associated with the presence of IPN was increasing age (68 v. 64 years; p=0.003). 8 patients (12%) had new or enlarging nodules, of whom 5 (7%) had confirmed pulmonary metastatic adenocarcinoma. There was no difference in OS between patients with or without pre-operative IPN (2-year OS 41% v. 38%, respectively; p=0.37). Further, no radiographic criteria of IPN (including # of, size of, bilateral, calcified, solid, spiculated, smooth, lobular, or ground-glass nodules) was associated with OS. On follow-up, new or enlarging nodules were not associated with OS. Conclusions: IPN are often found in patients undergoing PD for pancreatic adenocarcinoma. The majority of IPN remain stable on post-operative imaging. Neither the presence of IPN nor nodule characteristics was associated with OS. These data do not support the routine additional workup of pre-operative IPN in patients with resectable adenocarcinoma of the head of the pancreas; however, larger studies are needed to further characterize the significance of IPN in the preoperative evaluation of patients with pancreatic adenocarcinoma.
Usefulness of peripheral regulatory T-cells induced by Notch signaling pathway-driven indoleamine 2, 3-dioxygenase positive dendritic cell as a biomarker for the decision for IPMN surgical indications.
Authors: Ikemoto Tetsuya , Shimada Mitsuo , Utsunomiya Toru , Morine Yuji , Imura Satoru , Mori Hiroki , Arakawa Yusuke , Kanamoto Mami , Iwahashi Shu-ichi , Yamada Shinichiro , Asanoma Michihito
Published: February 2017

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Background: This study was performed to elucidate the expression of the Notch signaling pathway regulated by dendetric cell (DC) and their correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs) as a new biomarker for surgical indications. We already reported that regulatory T cells (Tregs) play an important role in tumor immunity (Pancreas 2006, ASCO-GI 2009), however, the whole mechanism of control of peripheral Tregs remains unclear. It is reported that Indoleamine 2, 3-dioxygenase (IDO) induces active Treg from naïve CD4+Tcells through dendritic cells. Otherwise, we also reported that the Notch signaling pathway is involved in tumor growth and DC function (JI 2010). Thus we focused that Indoleamine 2,3-deoxygenase(IDO)-Treg axis driven by Notch signaling in IPMNs. Methods: Peripheral blood samples and resected specimens from 20 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, anti-Notch2-intracellular domain and anti-IDO antibody staining) and compared to clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer. Results: Disease-free survival was significantly worse in the Notch1 high-expression group (P<0.05). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P< 0.05; Notch2-intracellular domain, P < 0.05). Jagged1 and IDO expressions were significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01). Conclusions: Notch signaling, especially Jagged1 expression, regulated by IDO+DC reflects IPMN aggressiveness. Our data strongly suggest that peripheral Treg induced by Notch signaling pathway driven IDO+DC may be a nobel biomarker for the decision for IPMN surgical indications.