bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cost-effectiveness of transarterial chemoembolization treatments.
Authors: Shaya Fadia T. , Breunig Ian Michael , Hanna Nader , Chirikov Viktor , Seal Brian S. , Mullins C. Daniel 
Published: March 2020

e14626 Background: Transarterial chemoembolization (TACE) is often a treatment for patients precluded from surgery. TACE recipients may get ≥1 TACE treatment, yet little is known about the cost-effectiveness of such additional TACEs. Methods: The study population includes 1,095 Medicare patients with a 1st diagnosis of 1ry HCC in 2000-07 who got TACE, or both TACE+ablation (LD) where one occurred prior to any other treatments. Patients were studied through end of 2009, in SEER-Medicare A-B. Stratifying by ablation, Cox proportional hazards models were built to assess the impacts of successive TACEs on all-cause/HCC-mortality, adjusting for clinical (cancer stage, underlying health status, liver conditions) and demographics. Average HCC-related Medicare costs (US$2,011) attributed to additional TACEs was estimated with generalized least squares, obtaining incremental cost effectiveness ratios (ICERs) and 95% confidence intervals, controlling for systemic chemotherapy and radiation therapy in the follow-up period. Results: Cancer stages 1, 2, 3, and 4 represented 34%, 16%, 19%, and 5% of the 1095 patients, respectively: 26% unstaged, 68% male, 71% Caucasian, 6% African American, and 17% Hispanic. 474 non-LD TACE patients had one TACE, 218 two, 93 three, 70 ≥four. Among LD patients, 121 got 1 TACE, 58 two, 34 three, 27 ≥four. In non-LD patients, further reductions in all-cause/HCC mortality were associated with the 2nd (HR .76, p<.01; HR .78, p=.045) and 3rd (HR .68, p<.01; HR .61, p<.01) TACE, but not the 4th; only the 3rd TACE further reduced mortality risk in LD patients (HR .48, p=.01; HR .34, p .01). For non-LD patients, using HCC mortality, the 2nd TACE was attributed to $19,969 per life year (LY) added, 95%CI $8,634, $31,303, the 3rd $10,290/LY ($2,815, $17,764); using all-cause mortality, the 2nd $27,813/LY ($15,943, $39,684), the 3rd ICER was statistically N.S. All ICERs were N.S. for LD patients. Conclusions: Additional TACEs provide survival benefit for HCC Medicare patients in clinical practice. However, that benefit may decrease after the 3rd exposure, which is more cost effective than a 2nd one. Additional TACEs may be confounded if ≥4 TACEs are intended to treat biologically aggressive disease.
Prognostic significance of autophagy-related proteins expression in resected pancreatic cancer.
Authors: Won Hye Sung , Ko Yoon-Ho , Cho Young-Seok , Jeon Eun Kyoung , Lee Myung Ah 
Published: March 2020

e14634 Background: Autophagy is a critical intracellular pathway for removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins on clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods: The expression of five autophagy-related proteins in the PDCA tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. Results: Of the 73 patients, autophagy-related proteins expression frequencies were 49.3% (36/73) for ATG5, 63.9% (46/72) for Ambra 1, 47.9% (35/73) for Beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was statistically significant in all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (p = 0.059). Multivariate analysis revealed that Beclin 1 overexpression or increases in alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio 5.365, p=0.001 and hazard ratio 5.270, p=0.022, respectively). Conclusions: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDCA. The awareness and inhibition of autophagy offer a potential therapeutic target for PDCA.
Demographic and prognostic factors in ampullary adenocarcinoma: A retrospective review of 74 sequential cases undergoing multidisciplinary management between 1997 and 2009.
Authors: Marsh Robert de Wilton , Pandey Romy , Bentrem David J. , Baker Marshall , Ding Xian , Stocker Susan , Brown Eric , Talamonti Mark 
Published: March 2020

e14642 Background: Ampullary adenocarcinoma represents 1% of GI cancers but accounts for almost 30% of Whipple operations at major centers. Prognosis falls between that of pancreatic and duodenal cancer, but demographic and prognostic factors are not well delineated. Methods: Retrospective review, with patient consent, of an IRB approved common surgical database at two academic institutions. This includes all cases operated on for ampullary adenocarcinoma between 1997 and 2009. Demographics and factors with potential relevance for prognosis by literature review were examined via Kaplan Meier and/or Cox models. Results: 74 cases were identified: 50 had conventional and 22 pylorus preserving Whipple procedures with 2 unresectable cases. Demographics: 38 males, 36 females; 64 Caucasian, 6 African American and 4 others; age 23-83, median 63.08 years. Tumor characteristics: Tis -1, T1-10, T2-22, T3-27, T4-12, Unknown-2; N0-35, N1-38, Unknown-1; pre-existing adenomas in 37 (50%). Tumor markers: CEA 2/34 and CA 19-9 16/37 tested were abnormal. Adjuvant therapy given (chemo and/or chemoRT): 33/74. Status: 34 patients alive and 41 deceased with a median follow-up of 22 months. Factors associated with poor outcome: Perineural invasion (PNI) p = 0.02; Pre-existing adenoma p = 0.001; Weight loss of 10 lbs or more p = 0.01; RBC transfusion in the OR p = 0.001. Factors not statistically prognostic: T stage, lymph nodal status, lymphovascular invasion, jaundice, CEA or CA 19-9 values and absence of adjuvant therapy. Pancreaticobiliary versus intestinal subtype was assessed by H and E staining but one third of cases were indeterminate, and while these appeared to have a worse prognosis, IHC will be performed for accurate classification and determination of significance. Conclusions: This dataset describes the demographics of patients treated for ampullary adenocarcinoma over 12 years and identifies PNI, weight loss, pre-existing adenoma and transfusion in the OR as adverse factors. These prognostic factors (and potentially histologic subtype) should be considered in patient care and future study design.
Definitive chemoradiotherapy with capecitabine and cisplatin in elder patients with squamous cell esophageal carcinoma.
Authors: Xing Ligang , Zhang Jiandong , Wang Fuli , Liu Fengjun , Yu Xinshuang , Song Meijuan 
Published: March 2020

e14643 Background: The purpose of this study is to investigate the feasibility and efficacy of concurrent or sequential chemoradiotherapy (CRT) with capecitabine and cisplatin in elderly patients with squamous cell esophageal carcinoma. Methods: 75 patients elder than 70 years with histologically proven squamous cell esophageal carcinoma were retrospectively reviewed. 40 patients were treated with concurrent CRT (CCRT) consisted of two cycles of intravenous cisplatin and oral capecitabine during and after radiotherapy. 35 patients were treated with sequential chemoradiotherapy (SCRT) as two cycles of capecitabine plus cisplatin before and after radiotherapy. The response rate, overall survival (OS), progression free survival (PFS) and toxicity were compared between two groups. Results: The response rate in the CCRT group was significantly higher than those in the SCRT group (82.5% vs 60.0%, p=0.023). The median OS time and PFS time of the CCRT group were significantly longer than those of the SCRT group (OS: 30.5 vs. 15.7 months, p=0.01; PFS: 25.4 vs. 11.6 months, p=0.014). The acute toxicities was more frequent in the CCRT group than SCRT group, but the grades 3 and 4 acute and late toxicities were similar in the two groups. Conclusions: It suggested that both CCRT and SCRT with capecitabine and cisplatin are tolerable and effective in elderly patients with esophageal squamous cell carcinoma. Concurrent CRT might be superior to sequential chemoradiotherapy.
A prospective, nonrandomized phase II/III trial of definitive chemoradiation, with or without cetuximab, in advanced esophageal squamous cell carcinoma.
Authors: Chen Yongshun , Wang Jianhua , Wu Xiaoyuan , He Chunyu , Wang Wen , Liu Jinsong , Guo Wei , Tan Bo , Wang Yanxia 
Published: March 2020

e14645 Background: Chemoradiotherapy is the standard treatment option for patients with esophageal cancer unsuitable for surgery, but the majority of patients will die of their disease, most commonly with local tumor progression/recurrence. We initiated this study to determine the efficacy and safety of the addition of cetuximab with paclitaxel, cisplatin, and radiation for patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 127 patients with clinical stage II–IVa disease were selected to receive combined-modality therapy consisting of cetuximab (400 mg/m2/wk week 1, then 250 mg/m2/wk week 2-8), paclitaxel (45 mg/m2/wk) and cisplatin (20 mg/m2/wk) in weeks 2-8 with 59.4 Gy of radiation (Group A, n = 29) versus the same chemoradiotherapy schedule but without cetuximab (Group B, n = 98). Results: At the time of this analysis, 27 and 88 patients were available for evaluation of response and survival in Group A and B respectively. In Group A, 20 patients (74.1%) achieved complete response (CR) and 7 (25.9%) achieved partial response (PR), resulting in an objective response rate (ORR) of 100%. The 1- and 2-year progression-free survival (PFS) was 91.2% and 85.1%, the median PFS was not reached. No association between tumor EGFR expression and response or survival was found. In Group B, 33 patients (37.5%) achieved CR, 51 (58.0%) achieved PR and 4 (4.5%) had stable disease, thus the ORR was 95.5%. The 1- and 2-year PFS was 89.0% and 50.5%, with the median PFS of 24.3 months. The difference in PFS between the two groups was statistically significant (p = 0.011). Treatment-related toxicities were generally grade 1 or 2. The most common toxicities were rash (89.3%), followed by neutropenia (71.4%) and esophagitis (60.7%) in chemoradiation-plus-cetuximab group. Adverse events were most often neutropenia (81.8%) and esophagitis (76.1%) in chemoradiation group. Locoregional failure rate was 3.7% and 15.9% in Group A and B, respectively. Conclusions: Cetuximab can be safely administered with chemoradiation and may prolong progression-free survival for Chinese patients with ESCC.
L-asparaginase loaded red blood cells (RBC) in pancreatic cancer: A phase I clinical study.
Authors: Godfrin Yann , Liens David , Andre Thierry , Adenis Antoine , Joly Florence 
Published: March 2020

e14650 Background: L-asparaginase (L-asp) efficacy is based on sensitivity of tumoral cells to asparagine deprivation due to a lack of asparagine synthethase (ASNS). However its use is hampered by significant toxicities of which allergic reaction, coagulation disorders and pancreatic impairment take a prominent place. Deficiency in ASNS and therefore potential sensitivity to L-asp treatment has been reported in multiple tumor cell lines including pancreatic cancer, however tentative to use L-asp in solid tumor, and especially in pancreatic cancer is reported in the literature but all attempts so far have failed due to toxicity. Recently, a new formulation of L-asp loaded inside RBC (GRASPA) has shown a very promising safety profile in leukemic patients. Methods: GRASPANC is the first phase I clinical study with GRASPA in patients with pancreatic carcinoma. Primary objective was to find the Dose Limiting Toxicity (DLT) of this cell-based formulation in this setting. Secondary objectives were to assess overall safety profile and activity (defined as serum asparagine depletion) of GRASPA. Patients with non resectable, relapsed pancreatic cancer were included by cohort of 3 and treated with one injection of increasing dose (25, 50, 100 or 150 IU/kg) of GRASPA. An independent Safety Monitoring Board assessed toxicities at the end of follow-up of each cohort to decide for next dose. Results: Twelve patients were included between Dec 2009 and Feb 2011 by 3 centres in France. Mean age was 60.4 years (min: 42.6; max: 71.9) with 9 Male and 3 female. No limiting toxicity has been found up to the GRASPA highest dose (150 IU/kg) planned in the study and the DLT was not reached. No specific other unexpected non limiting toxicity was evidenced. In addition, at all doses GRASPA was shown to be effective at depleting serum asparagine with a trend toward longer activity with increasing dose. Conclusions: Preliminary conclusion is that the dose of 150 IU/kg of GRASPA is safe and appears suitable for further clinical development in patients with pancreatic carcinoma. In order to maximise potential efficacy of this new therapy, selection of patients should be made according to their screening for a none or low expression of ASNS in their tumour cells.
Intensive up-front treatment versus a sequential approach in advanced gastric cancer patients: Does first-line matter?
Authors: Bittoni Alessandro , Scartozzi Mario , Pistelli Mirco , Galizia Eva , Del Prete Michela , Giampieri Riccardo , Faloppi Luca , Bianconi Maristella , Maccaroni Elena , Cascinu Stefano 
Published: March 2020

e14663 Background: The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. A recent meta-analysis suggested that the addition of a third drug to a doublet regimen should be considered the state-of-the-art strategy to improve overall survival. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients. Methods: Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A=three drugs; group B= two drugs). Results: A total of 390 patients were eligible for our analysis. 211 patients (54%) received three chemotherapeutic agents (group A) and 179 patients (46%) received a two drugs regimen as first-line combination chemotherapy (group B). The 2 groups of patients resulted comparable for all known prognostic factors of clinical relevance. RR for group A and B was 46.5% and 28%, respectively (p=0,0007), median PFS was 7.12 months in group A and 3.96 months in group B (p<0,0001). No significantly difference resulted for the median OS of patients in the two groups (13 months for group A and 11.8 months for group B; p= 0.962). Conclusions: The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, a triplet regimen may represent an optimal choice, particularly when response and PFS are relevant treatment endpoints. Nevertheless the use of a sequential approach may also represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS.
Analysis of new N descriptors on prognosis of esophageal cancer with positive lymph nodes in a Chinese population.
Authors: Xu Yaping 
Published: March 2020

e14678 Background: The 7th edition of the American Joint Committee on Cancer / Union International Against Cancer (AJCC/UICC) TNM staining system for esophageal cancer (EC) has been published. N descriptors are now divided into N0, N1, N2 and N3. In this study, we aimed to validate the prognostic ability of the new N staging system in patients with resectable EC and positive lymph nodes, and evaluate whether the new N staging system can help the decision-making for postoperative adjuvant therapy in this population. Methods: From 2002 to 2008, patients with stage T1-4N1-3M0 EC who underwent esophagectomy were retrospectively analyzed. EC was classified according to the new N staging system. Kaplan-Meier method and Cox regression analysis were employed to compare overall survival (OS). Results: A total of545 patients met the inclusion criteria: 346 (63.5%) received esophagectomy alone, 199 (36.5%) received esophagectomy and adjuvant radiotherapy, and 36.1% (197/545) received esophagectomy and adjuvant chemotherapy. Univariate analysis and multivariate analysis revealed significant difference in OS among patients with EC at different N stages (p<0.001). Significant difference in OS was also present among patients receiving radiotherapy (p<0.001) and those undergoing chemotherapy (p<0.001). Subgroup analysis indicated that postoperative adjuvant therapy did not significantly affect the OS among patients with EC at different N stages. Conclusions: Our results validated the prognostic ability of new N staging system. N descriptor is an independent prognostic factor in patients with resectable EC who were positive for lymph nodes. Further studies are required to clarify the role of new N staging system in the decision-making for postoperative adjuvant therapy in this population.
R0 resection of locally advanced pancreatic cancer encasing major visceral arteries using arterial reconstruction: Short- and long-term results.
Authors: Genyk Yuri , Matsuoka Lea , El-Khoueiry Anthony B. , Iqbal Syma , Buxbaum James , Selby Rick , Vandam Jacquez , Lenz Heinz-Josef 
Published: March 2020

e14679 Background: Locally advanced disease is found in about 40% of patients with pancreatic cancer at initial presentation. Tumors involving major visceral arteries are commonly deemed unresectable. In this study we analyzed the feasibility of R0 resection of locally advanced pancreatic cancer encasing major visceral arteries using arterial reconstruction. Methods: The following data were collected: age, gender, operative details, post-operative complications, chemotherapy and/or radiation therapy and overall and disease free survival. Patient survival was calculated utilizing Kaplan-Meier survival probability estimates. Results: From Dec., 2002 to Jan., 2012, 13 patients underwent pancreatic resection with concomitant resection and reconstruction of major visceral arteries for pancreatic cancer (9 males and 4 females, median age 63 yrs (range: 50–82 yrs)). The arterial involvement included celiac artery (n=6), superior mesenteric artery (n=4) and hepatic artery (n=3). Resections included pancreatico-duodenectomy (n=9), distal pancreatectomy (n=3), and total pancreatectomy (n=1). Management of the arterial involvement included: resection of celiac axis without reconstruction (n=2), reconstruction of one artery (n=6), two arteries (n=4) and three arteries (n=1). Nine of the 13 patients underwent simultaneous venous reconstruction. R0 resection was accomplished in 11, R1 in 1, and R2 in 1 patient. Ten of the 13 patients received neoadjuvant and/or adjuvant chemo- or chemo-radiation therapy outside protocols. To date, 4 patients are alive and disease free at 1, 4, 15 and 111 months, and 1 patient is alive with recurrence at 100 months. Six-month patient survival was 65% and median overall survival was 17 months. The probability of 5-year survival was 22%. Conclusions: Our study indicates that in select patients with locally advanced pancreatic cancer with involvement of major visceral arteries R0 resection is feasible by performing pancreatic resection with arterial reconstruction. The survival data in this group of patients are encouraging and provide the opportunity to reconsider the contraindications to surgical management of such patients.
HER2 positive gastroesophageal cancer in an Irish population.
Authors: Jayaram Anuradha , Battley Jodie E , O'Connor Kate , Bennett Michael WIlliam , Jamaluddin Muhammad Faisal , Boychak Oleksandr Volodymyrovych , Sheehan Margaret , Power Derek Gerard , Leonard Gregory 
Published: March 2020

e14687 Background: Gastroesophageal cancer is a major cause of cancer-related mortality. HER2 is overexpressed in ~ 7-34% of gastroesophageal (GE) adenocarcinomas. The ToGA study, established the benefit of trastuzumab in combination with chemotherapy in HER2 positive metastatic GE tumours. In this study, 22% of patients were HER2 positive {immunohistochemistry (IHC)3+ or fluorescence insitu hybridization (FISH)(+)}. Potential heterogeneity of HER2 amplification, overexpression, and incomplete membrane staining of HER2 by IHC leaves some ambiguity in HER2 testing and definition of HER2 positive GE tumours. We report a multi-center Irish experience by examining HER2 status by IHC and FISH in GE tumours. Methods: HER2 testing was performed on adenocarcinoma biopsy or resection specimens of patients with early stage and metastatic GE tumors between 2008 - 2011. We defined HER2 positive as IHC3+ or FISH(+) {HER2:17ch ≥ 2}. In addition, age, gender, smoking history, histology, stage of disease, treatment, and survival data were recorded. Results: A total of136 Caucasian patients with early stage and metastatic GE cancers were identified. Median age was 69 yrs (ranging from 25 – 96). Data available for analysis was conducted from 111 patients with 10% FISH(+). There are 73 patients with early stage and 38 with metastatic disease. Five metastatic cases (13%) were FISH(+) (of whom 3 IHC3+, 1 IHC2+, 1 IHC1+), 33 cases were FISH(-). Sites of metastatic disease in the FISH(+) cohort were liver, peritoneal, and bone metastasis. In the FISH(-) group, sites of metastatic disease were predominantly liver. Interestingly CNS disease is seen exclusively in the FISH(-) cohort. Of the early stage patients, only 6 patients (8.2%) were FISH(+) (of whom 3 IHC3+, 2 IHC2+, 1 IHC1+). With respect to tumour heterogeneity of HER2 amplification, in IHC3+, 82% were FISH(+), IHC2+, 17% were FISH(+) and IHC1+, 6% were FISH(+). There was 100% concordance between IHC0 and FISH(-). Conclusions: HER2 positive GE adenocarcinomas in the analyzed cohort displays similar pattern of heterogeneity in IHC staining and FISH positivity but with lower incidence (10%) of HER2 amplification than was reported in the ToGA study. Further data on location, histological pattern and survival will be reported.