bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between dose to skeletal muscle area ratio and gemcitabine nab-paclitaxel toxicity in pancreatic ductal adenocarcinoma.
Authors: Wong Rachel , Freckelton Julia , Croagh Daniel , Holt Darcy Quinn , Fox Adrian , Lee Margaret , Moore Gregory Thomas 
Published: January 2019

492 Background: Combination gemcitabine and nab-paclitaxel (Gem-Nab-P) is a common regimen used to treat metastatic pancreatic ductal adenocarcinoma (PDAC). Toxicity is less than that associated with other combination metastatic regimens (FOLFIRINOX), but it is still associated with significant morbidity. Currently, Gem-Nab-P is dosed using estimated body surface area. This study investigates whether skeletal muscle assessment could be a useful tool in the dosing of Gem-Nab-P in metastatic PDAC. Methods: This study involved two sites and included patients who had received Gem-Nab-P between January 2013 and March 2017. A review of medical records was used to identify demographic, disease and first-cycle treatment information. Chemotherapy toxicity was defined as grade 3 or 4 adverse events using the National Cancer Institute Common Toxicity Criteria Adverse Events manual v4.0. Body composition analysis was performed on computed tomography scans at spinal level L3, using SliceOmatic software. SPSS software was used to for all statistical analysis, with a p value of < 0.05 considered significant. Results: We identified 52 patients treated with first-line Gem-Nab-P for PDAC. Median age was 65 years (57-73) and 24 (47%) were male. Median BMI at commencement of Gem-Nab-P was 24.7 kg/m2 (21.3-27.4) and 38 (58%) of the patients were myopenic before starting chemotherapy. Fourteen (27%) patients experienced toxicity during the first cycle of chemotherapy. Patients who experienced first-cycle chemotherapy-associated toxicity did not have a different median SkMA to those who did not (128.6 cm2 vs. 111.4 cm2, p= 0.2). There was also no difference in the gemcitabine dose to SkMA ratio (14.1 mg/cm2 vs. 14.4 mg/cm2, p=0.8), nab-paclitaxel to SkMA ratio (1.8 mg/cm2 vs. 1.8 mg/cm2, p=0.6) or combined dose equivalent to SkMA ratio (2.8 mg/cm2 vs. 2.9 mg/cm2, p=0.9) between the patients that experienced first cycle toxicity versus those that did not. Conclusions: This study suggests that a pancreatic cancer patient’s skeletal muscle area is unlikely to be a useful addition to conventional body surface area in the dosing of first line Gem-Nab-P, to reduce first-cycle toxicity.
Indoleamine 2,3-dioxygenase (IDO1), PD-L1, and overall survival (OS) of patients diagnosed with esophageal cancer.
Authors: Rosenberg Ari , Wainwright Derek , Rademaker Alfred , Galvez Carlos , Genet Matthew , Zhai Lijie , Lauing Kristen , Villaflor Victoria Meucci 
Published: January 2019

50 Background: Immune checkpoint inhibition of PD-L1 is emerging as an important therapeutic target for patients with advanced esophageal cancer. However, response rates to therapy remain low. IDO1 is a rate-limiting immunosuppressive enzyme that has emerged as an important immunotherapeutic target in human cancer. The role, expression pattern, and relevance of IDO1 in esophageal cancer are currently unknown. Here, we utilize gene expression analysis of the cancer genome atlas and quantitative immunohistochemistry (IHC) to understand whether IDO1 contributes to a poor esophageal cancer patient prognosis. Methods: mRNA expression was assessed using Hi-RNA sequencing in an esophageal squamous cell carcinoma (SCC) cohort of 87 patients and an adenocarcinoma (AC) cohort of 97 patients. Survival data was obtained from the Cancer Genome Atlas. Patient survival was analyzed by the Kaplan-Meier Method. IHC for a second cohort of 93 cases of esophageal SCC were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic immunoscoring analysis. Correlation between markers was analyzed using Fisher’s exact test. Results: The median OS for high versus low IDO1 mRNA levels was 15.9 months vs 41.5 months, respectively (p =0.02) in the SCC cohort. The median OS was 20.1 months and 58.6 months in the high vs low IDO1 mRNA levels, respectively (p = 0.036) in the esophageal AC cohort. High co-expression for IDO1 and PD-L1 vs low co-expression of these markers, demonstrated a median OS of 15.1 months and 41.5 months, respectively, in the SCC cohort, and 13.7 months and 41.5 months, respectively, in the AC cohort. IHC for IDO1 SCC showed a significant correlation with PD-L1 (p = < 0.0001) and CD3ε (p = < 0.0001). PD-L1 expression also significantly correlated with CD3ε expression (p = < 0.0001). Conclusions: Esophageal cancer with high IDO1 and PD-L1 levels is associated with significantly decreased survival. The expression of IDO1 and PD-L1 is significantly enhanced by the coincident intratumoral increase of T cells. These data suggest that combinatorial approaches for combination therapies that simultaneously inhibit IDO1 and PD-(L)1 may enhance T-cell mediated control of esophageal cancer in patients.
Neoadjuvant therapy outcomes in nonmetastatic pancreatic cancer.
Authors: Muniz Kovtun Jeanette , Kovtun Konstantin , Mortele Koenraad , Moser James , Bullock Andrea J. 
Published: January 2019

501 Background: The optimal multidisciplinary treatment algorithm for pancreatic ductal adenocarcinoma (PDAC) is not well established. We studied outcomes in non-metastatic PDAC treated with chemotherapy and stereotactic body radiation therapy (SBRT) with or without pancreatic resection. Methods: Between August 2011 and July 2015, 73 patients with non-metastatic PDAC were treated with chemotherapy and SBRT with or without resection. Variables considered included: ECOG, CA 19-9, clinical stage, vascular involvement, pathologic stage and margin status. Resectability status was determined by an expert abdominal radiologist on initial staging imaging. Chemotherapy included FOLFIRINOX, FOLFOX, gemcitabine monotherapy (gem) or with nab-paclitaxel (gem/nab). SBRT was delivered as 30 Gy in 3 fractions over 5 days via CyberKnife. The Kaplan-Meier method and log-rank test were used to compare median overall survival (mOS), local progression free survival (LPFS) and metastasis free survival (MFS). Results: After a median follow-up of 19.3 months (mo) the mOS was 30.0 mo (95% CI, 19.4 to 36.5). The surgical group had longer mOS (36.5 vs 19.4 mo; P < 0.001), LPFS (29.0 vs 16.3 mo; P = 0.03) and MFS (29.0 vs 15.1 mo; P < 0.001) as compared to the nonsurgical group. FOLFIRINOX or gem/nab was associated with better mOS as compared to other chemotherapy (33.2 vs 12.8 mo; P < 0.001). There was a trend towards longer mOS in pts with initial imaging deemed less resectable (36.5 vs 30.1 vs 13.0 mo in unresectable vs borderline vs resectable; P = 0.19). In a multivariate analysis significant predictors of OS were resection, ECOG and FOLFIRINOX or gem/nab chemotherapy. Conclusions: Patients who had surgery after neoadjuvant chemotherapy and SBRT had significantly longer mOS, LPFS and MFS than those without surgery. FOLFIRINOX or gem/nab and better ECOG were also associated with improved outcomes. Worse resectablity status per imaging was associated with longer OS despite less likelihood of surgery; This may reflect more intensive neoadjuvant therapy or suggest that radiologic resectability status is a poor predictor of OS. Further investigation of factors underlying this discrepancy may have implications on neoadjuvant strategy and resectability determination.
Survival outcomes among patients with advanced hepatocellular carcinoma (aHCC) treated with systemic therapies.
Authors: Bonafede Machaon , Cai Qian , Singh Prianka , Jariwala-Parikh Krutika , Cappell Katherine , Parikh Neehar D. , Sill Bruce , Korytowsky Beata 
Published: January 2019

503 Background: HCC is the most common primary liver cancer. Despite the wide use of screening among high-risk individuals, about 45% of cases are diagnosed at the advanced stage. Sorafenib is the only FDA-approved first-line (1L) treatment for aHCC. This study aims to characterize survival by lines of therapy among commercially insured patients with aHCC treated with systemic therapy in the United States. Methods: Adults with ≥ 2 medical claims (30–180 days apart) for primary HCC ( ICD-9 155.0x) from 1/1/2008 to 9/30/2015 were identified in the MarketScan Research Databases. Continuous enrollment was required 6 months before and 1 month after diagnosis. Patients were further categorized into 1L and 2L cohorts if they initiated a targeted therapy, immunotherapy, or chemotherapy. Index date of 1L was the date of the first claim for a systemic agent after diagnosis; index date of 2L was the date of the first claim for a different agent after the end of 1L therapy. Date of death was determined based on records from the linked Social Security Administration Master Death File or on inpatient discharge status. Survival time was measured from the 1L/2L index date to the death date; patients without a death date were censored at end of continuous enrollment or study period, whichever occurred first. Results: 758 patients met the selection criteria for the 1L cohort (mean age, 62.5 ± 10.3 y; 21.9% female); 87 patients (11.5%) went on to receive 2L therapy (mean age, 61.8 ± 9.8 y; 20.7% female). Over half the patients (1L, 54.0%; 2L, 52.9%) died during the follow-up period; median survival time was 205 days (interquartile range [IQR], 290 days) in 1L patients and 280 days (IQR, 232 days) in 2L patients. 32.6% of 1L patients and 34.5% of 2L patients survived ≥ 1 year, and 12.4% of 1L patients and 16.1% of 2L patients survived ≥ 2 years after treatment initiation. Conclusions: Findings suggest that the vast majority of patients with aHCC do not receive 2L therapy. A high 1-year mortality rate represents the lack of effective treatment options in aHCC. Improved therapies are urgently needed for this highly morbid malignancy.
Role of FDG PET/CT scan in preoperative pancreatic cancer staging.
Authors: Ghanta Bhargavi , Thambi-Pillai Thavam C. , Timmerman Gary , Fischer Christopher , Nelson Annie , Bleeker Jonathan Scott 
Published: January 2019

511 Background: Guidelines do not recommend routine FDG PET/CT (PET) as preoperative staging for pancreatic cancer, although many single center series have demonstrated that PET can lead to changes in management in a sizable minority of patients. We performed a retrospective analysis of patients undergoing PET for potentially resectable pancreatic adenocarcinoma at our institution to help define the utility of PET in this setting. Methods: We reviewed patients with pancreatic adenocarcinoma diagnosed at our center from June 2010 to May 2017 and included patients with pancreatic adenocarcinoma felt to be potentially resectable following standard staging studies [computed tomography (CT), magnetic resonance imaging (MRI) and endoscopic ultrasound (EUS)] who also underwent preoperative PET. Data collected and analyzed included: demographics, pre-PET staging, CA19-9 levels, PET results and surgical outcomes. Results: Forty eight patients with pancreatic adenocarcinoma felt to be surgically resectable underwent PET. PET changed management in 4/48 (8.3%) of these patients. In all 4 of these patients, hepatic metastatic disease was detected on PET and planned surgery was canceled; metastatic disease was confirmed by biopsy in 1 of these patients. 1/48 (2.1%) of patients had a false positive PET scan, where a focus of suspected metastatic disease on PET was biopsied and found to be benign, allowing the patient to proceed to surgery. 3/48 (6.3%) of patients had a false negative PET; 2 patients had hepatic metastatic disease and one had peritoneal disease discovered during surgery. Mean time from negative PET to surgery in these 3 patients was 31 days (range 21-45). Degree of CA19-9 elevation and primary tumor FDG avidity did not correlate with detection of metastatic disease on PET. Conclusions: PET changed management in a smaller number of patients in this cohort than in many previously reported series with a nearly equal number of patients with false negative PET results proceeding to unnecessary surgery. These results are consistent with the currently uncertain role of PET in preoperative staging for pancreatic cancer and further work must be undertaken to optimize presurgical staging in this population.
Clinical benefit of entrectinib for patients with metastatic pancreatic cancer who harbor NTRK and ROS1 fusions.
Authors: Pishvaian Michael J. , Rolfo Christian Diego , Liu Stephen V. , Multani Pratik S. , Chow Maneval Edna , Garrido-Laguna Ignacio 
Published: January 2019

521 Background: Despite recent improvements in chemotherapy for pancreatic cancer that have demonstrated improvements in survival, response rates remain at less than 50%. Distinct molecular subgroups of pancreatic cancer that harbor specific actionable molecular alterations have recently been identified. These include gene fusions of the receptor tyrosine kinases NTRK and ROS1. Entrectinib is a CNS-active, potent, and selective TRK and ROS1 inhibitor that has shown substantial clinical activity in patients with locally advanced or metastatic solid tumors that have NTRK or ROS1 fusions (Drilon A, et al. Cancer Discov. 2017;7[4]:400-409). Methods: We examined 3 cases of pancreatic cancer where an actionable gene rearrangement was identified: 2 with a TPR-NTRK gene fusion, and 1 with an SCL4-ROS1 gene fusion. All 3 patients were treated with entrectinib 600 mg daily in a phase 2 trial (NCT02568267). Results: Entrectinib was well tolerated with mostly grade 1-2 adverse events consisting primarily of arthralgias, myalgias, and fatigue. All 3 patients showed evidence of clinical improvement, with normalization of the tumor biomarker CA19-9 and confirmed partial responses as per RECIST v1.1 in the 2 patients with a TPR-NTRK fusion, 1 of which was associated with a significant decrease in metabolic activity as assessed by PET/CT scan. The patient with the SCL4-ROS1 fusion had stable disease for at least 6 months. All 3 patients had an improvement to, or maintenance of, a high quality of life while on study. At the time of data cutoff, 1 of the patients with a TPR-NTRK fusion remained on treatment > 1 year. Conclusions: Entrectinib treatment was associated with response and prolonged disease control in these 3 patients with NTRK or ROS1 fusion-positive pancreatic cancer. NTRK and ROS1 gene fusions are rare in pancreatic cancer. The true incidence is unknown, as routine testing for gene fusions in pancreatic cancer is not yet standard practice. Given the benefit seen here with entrectinib and the clinical need for improved therapeutics, there may be value in broader and earlier molecular testing of patients with pancreatic cancer for these actionable fusions. Clinical trial information: NCT02568267.
Effect of epigallocatechin-3-gallate from green tea on 5-flurouracil-induced intestinal mucositis.
Authors: Lee Jung Min , Yoon Kichul , Min Geeho , Kim Woojung , Choi Seong ji , Kim Seung Han , Lee Jae Min , Choi Hyuk Soon , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Chun Hoon Jai , Lee Hong Sik , Kim Chang Duck 
Published: January 2019

522 Background: Chemotherapy-induced mucositis is a common complication during anticancer treatment. Epigallocatechin-3-gallate (EGCG), derived from green tea, has been shown to have antioxidant effects and immunomodulatory activities. However, studies on EGCG for chemotherapy-induced mucositis have been scarce. In this study, we aimed to prove the protective effect of EGCG in murine chemotherapy-induced mucositis model Methods: Twenty-four 8-wk-old male C57BL/6 mice were randomized to 4 groups : control, EGCG, 5-Flurouracil (5-FU), EGCG plus 5-FU. Mucositis was induced by intraperitoneal injection of 5-FU (400mg/kg). EGCG (50mg/kg) was administered orally for 5 days from the day before administration of 5-FU. After 6 days of 5-FU injection, the mice were sacrificed and intestinal tissue was obtained. WBC count was performed with whole blood from Inferior vena cava of mice. The end points were villus height, villus/crypt ratio, histologic characteristics, and mRNA expression of tumor necrosis factor ( TNF)-α, and interleukin ( IL)-6. Results: In 5-FU group, neutropenia was confirmed by laboratory test (5-FU, 0.650 K/μL; Control, 5.317 K/μL), indicating sufficient 5-FU effect. Histologic findings showed that crypt dilatation, villus stunting, and villus atrophy were reduced in EGCG plus 5-FU group than in 5-FU group. Quantitatively, mean villus height (EGCG plus 5-FU, 352 μm; 5-FU, 319 μm) and villus/crypt ratio (EGCG plus 5-FU, 3.28; 5-FU, 2.31) in EGCG plus 5-FU group, compared with 5-FU treated group, were significantly higher. mRNA expression of TNF-α was significantly lower in EGCG plus 5-FU group compared with 5-FU group (P < 0.05) (Figure 2). Conclusions: EGCG derived from green tea reduced 5-FU induced intestinal mucositis, suggesting a possibility for novel treatment of chemotherapy-induced mucositis.
Age distribution of tumor gene expression in patients with stage II/III colon cancer.
Authors: Hochster Howard S. , Lau Anna , Turner Michelle , Russell Christy Ann 
Published: January 2019

552 Background: Colorectal cancer (CRC) incidence and mortality have been rising in the US among adults <55 y. Younger patients with CRC are more likely than older patients to receive postoperative systemic chemotherapy, despite lack of consensus on the prognostic value of age in this disease. CRC diagnosed in younger patients may be biologically different from that in older patients, but characteristics are unknown. Thus, we examined whether age-specific differences were measurable by tumor gene expression using the 12-gene Oncotype DX Colon Recurrence Score (RS) test (Genomic Health, Inc. [GHI]; Redwood City, CA). The Colon RS test is validated to predict risk of recurrence in patients with stage II/III colon cancer. Methods: We analyzed Colon RS test results and single-gene results for the 12 genes by age group (age <40, 40-54, 55-64, and ≥65) using data from the GHI clinical laboratory dated 1/2010 to 7/2017. Results: As of 7/2017, 21,925 Colon RS reports have been delivered. Median age was 63 y; 50% were male. About 23% of patients were <55 y (Table). Mean (SD) RS result was 25 (11). Colon RS result distributions were similar by age group (Table). Expression of individual tumor genes measured in the Colon RS test were also similar by age group (data to be presented). Conclusions: The etiology of the increase in both incidence and mortality from CRC in adults <55 y is poorly understood. Our findings suggest that colon cancer in younger patients is not biologically different from that in older patients, as measured by the Colon RS test in a large cohort referred for testing. As shown by this test in the GHI clinical laboratory experience, most patients with stage II/III colon cancer have low-risk disease, including patients <55 years. Our findings support a biology-driven approach to disease management of patients with stage II/III colon cancer regardless of age. This well-validated genomic assay may identify a group of younger patients for whom adjuvant chemotherapy might represent overtreatment. [Table: see text]
Nivolumab in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): Long-term survival according to prior line of treatment from CheckMate-142.
Authors: Overman Michael J. , Bergamo Francesca , McDermott Raymond S. , Aglietta Massimo , Chen Franklin , Gelsomino Fabio , Wong Mark , Morse Michael , Van Cutsem Eric , Hendlisz Alain , Neyns Bart , Moss Rebecca Anne , Zhao Huanyu , Cao Z. Alexander , Kamble Shital , Kopetz Scott , Andre Thierry 
Published: January 2019

554 Background: Nivolumab (NIVO) provided durable responses (ORR, 32% per central assessment) and disease control (DCR, 64%) in pre-treated pts with dMMR/MSI-H mCRC (NCT02060188; Overman MJ et al Lancet Oncol 2017). NIVO was approved in the US for pts with dMMR/MSI-H mCRC who progress after standard chemotherapy (SC) with a fluoropyrimidine (F), oxaliplatin (Ox), and irinotecan (Iri). Here we present long-term survival and outcomes by prior chemotherapy with NIVO in CheckMate-142. Methods: Pts with dMMR/MSI-H mCRC received NIVO 3 mg/kg Q2W. The primary endpoint was ORR per RECIST 1.1. Other endpoints were DCR, DOR, PFS, OS, and safety/tolerability. Results: Of 74 pts evaluated, 53 had received F, Ox and Iri (group A); 21 pts had ≤ 2 SC regimens (group B). Median follow-up was 21 mo. Efficacy by central assessment is shown in the Table. In the 74 pts, ORR was 34%; CRs increased from 3% in prior database lock (DBL) to 9%. Numerically higher responses were noted in group B vs group A (Table). Grade 3–4 TRAEs were reported in 20% (all pts), 25% (group A), and 10% (group B) of pts. No treatment-related deaths were reported. Conclusions: NIVO continued to provide clinically meaningful durable responses and long-term overall survival in pts with dMMR/MSI-H mCRC. Of note, CR rate increased with longer follow-up. No new safety signals were reported with long-term follow-up. Enhanced responses in pts with ≤ 2 SC regimens support ongoing evaluation of NIVO combinations in first-line setting. Clinical trial information: NCT02060188. [Table: see text]
Genetic profile of polyps and risk of advanced metachronous lesions.
Authors: Murcia Oscar , Juárez Miriam , Rodriguez-Soler Maria , Hernández-Illán Eva , Egoavil Cecilia , Giner-Calabuig Mar , Alustiza Miren , Alenda Cristina , Mangas Carolina , García Araceli , Aparicio José Ramón , Ruiz Francisco Antonio , Martínez Juan Francisco , Casellas Juan Antonio , Soto José Luís , Zapater Pedro , Jover Rodrigo 
Published: January 2019

555 Background: The role of genetic profile of polyps to predict advanced metachronous lesions (AML) remains unknown. The aim is to study the relation between genetic profile of polyps and both risk of AMLs and time to develop them in surveillance. Methods: 308 patients with colonic polyps were consecutively enrolled between 2007 and 2009 for this cohort study, and followed up to 2014 (median 26 months, range 63). Variables as age, sex, smoking, weight, number of colonoscopies and number and characteristics of polyps were collected. 995 polyps were analyzed for somatic mutations on BRAF and KRAS genes using allelic discrimination by real-time PCR and direct DNA sequenciation, respectively. High level of methylation on CpG islands (CIMP-H) was also tested using MS-MLPA. AML was defined by a size higher than 9mm, high grade dysplasia or villous component. Risk of developing AML for individual genetic markers was studied using Chi-square tests and logistic regression. Log-rank test with Kaplan Meier survival curves and Cox-regression model were also performed. Multivariate analysis were adjusted by sex, age, familial colorectal cancer, smoking and features of AML in first colonoscopy. Results: 21% of polyps in first colonoscopy were CIMP-H. KRAS and BRAF mutations accounted for 25% and 17% of polyps, respectively. In univariate analysis, KRAS-mutated polyps were related to higher risk of AML in surveillance (52% KRAS-mutated polyps vs 31% non-mutated; p = 0.01). Similar results were obtained regarding CIMP-H (77% CIMP-H polyps vs 38% non-CIMP; p = 0.005). Logistic regression showed CIMP-H as the unique genetic marker of risk for AML (OR 11.41, 95% CI 2.04-63.70; p = 0.006). Regarding time to develop AML, shorter intervals were found related to CIMP-H (median of 31 vs 48 months in non-CIMP-H; p = 0.002) and KRAS-mutations (median of 36 vs 49 months in non-mutated; p = 0.029) in univariate analysis. Multivariate analysis highlighted CIMP-H as the unique independent marker associated to shorter time to develop AML (HR 4.01, 95% CI 1.36-10.46; p = 0.01). Conclusions: Presence of CIMP-H in polyps associates higher risk of subsequent AML and shorter interval to their development. Genetic profile of polyps emerges as useful tool for colonoscopy surveillance.