bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors for survival in gastric cancer after radical resection: A retrospective study of 1,594 patients in Shanghai.
Authors: Sun Yihong , Wang Cong , Shen Zhenbin , Zhao Naiqing , Chen Weidong , Wang Xuefei , Wang Hongshan , Fang Yong , Liu Fenlin , Tang Zhaoqing , Li Haojie , Lv Chentao , Qin Jing , Wang Yanna , Piao Yongzhe , Wang Lisa , Chu Laura , Dong Wei , Qin Xinyu 
Published: March 2020

e14575 Background: Gastric Cancer (GC) is the second leading cause of cancer death in Shanghai,and the overall treatment response remains poor. This study aimed to describe overall survival and identify prognostic factors for survival among GC patients (pts) after radical resection. Methods: Clinical data of 1594 GC pts (Shanghai residents) who had undergone R0 or R1 resection in Zhongshan hospital, January 2003 to June 2010, were analyzed. Potential prognostic factors including demographic and tumor characteristics were collected. Survival was calculated by the Kaplan-Meier method and Log-rank test was used to determine statistical significance. Prognostic factors were analyzed using Cox regression multivariate analysis. Results: Overall 5-year cumulative survival for all pts was 55.8%. The 5-year cumulative survival by TNM stage I, II, III, and IV (classified using AJCC 7th edition staging system) were 93.8%, 72.7%, 33.3%, and 12.7%, respectively. The distribution of pts by AJCC stage I-IV was 22.5%, 23.1%, 51.7% and 2.8% respectively. In univariate analyses, gender and the number of lymph nodes removed was not associated with survival (p>0.05). However, age, tumor differentiation, tumor site, lympahtic/venous invasion, depth of infiltration, presence of lymph node metastasis, and presence of distant metastasis were related to survival (p<0.05). In multivariate Cox regression model analysis, age (p<0.001), tumor site (p=0.004), lymphatic/venous invasion (p<0.001), TNM stage(p<0.001) were independent prognosticators. Among pts with TNM stage III , number of lymph nodes removed was also an independent prognostic factor (p<0.001). Conclusions: Age, tumor site, lymphatic/venous invasion, TNM stage in all patients, and the number of lymph nodes removed in TNM stage III patients, were independent prognostic factors. GC remains a significant unmet medical need in China and effective therapies are urgently needed.
A pilot study of evaluation of a phosphorylation signature from pancreatic cancer tumors.
Authors: Wang-Gillam Andrea , Wani Sachin , Early Dayna S , Edmundowicz Steven Alphonse , Mullady Daniel , Murad Faris , Jonnalagadda Sreenivasa , Gao Feng , Hollander Thomas , Langley Emma J. , Meyer Gary , Singh Sharat , Kim Phillip Sangwook , Lim Kian-Huat , Linehan David , Azar Riad 
Published: March 2020

e14584 Background: The development of targeted therapy in pancreatic cancer has been hindered by minimal material available for molecular analysis from diagnostic endoscopic ultrasound-guided fine-needle aspirations (EUS/FNA). Revealing the phosphorylation status of key pathway mediators would allow optimal selection of patients for kinase inhibitor clinical trials. We launched a pilot study to evaluate the feasibility of detecting phosphorylation signatures from FNA samples using an ultrasensitive multiplexed protein microarray platform (CEER, Prometheus). Methods: Patients who underwent routine diagnostic EUS/FNA for a suspicious lesion in the pancreas underwent two additional EUS passes. Mediators of multiple signaling pathways including HER1/EGFR, HER2, HER3, IGF-IR, and their downstream mediators, AKT, MEK, ERK, et al were evaluated by CEER. Circulating tumor cells (CTCs) and resected tumor specimens were collected as available from patients for comparison. Results: From January-September, 2011, 57 patients were enrolled with a planned final enrollment of 100. This is an interim analysis. Thirty-nine (68.4%) had carcinoma cytology, 9 had atypical and 9 had negative cytology. HER2 (median value of 18 CU vs. 2 CU, p = 0.021) and HER3 (median value of 547 CU vs. 168 CU, p = 0.008) showed significantly higher levels of phosphorylation in malignant FNAs over their counterparts with negative cytology. Robust levels of CK expression were also observed in FNAs with carcinoma cytology (median CK level 1030 CU vs. 106 CU, p = 0.007). The wide range of phosphorylation signatures detected indicates this is a feasible clinical approach. For example, the expression levels of phosphorylated PI3K were 16 (22.5% - low), 28 (39.4% - medium low), 23 (32.4% - medium high), and 2 (2.8% - high). The correlation of p PI3K between 2 passes was 0.59 (p = 0.018) based on the Spearman Correlation. A CEER comparison of FNA vs. surgical specimens and FNA vs. CTCs is forthcoming. Conclusions: Profiling the phosphorylation status of pancreatic cancer pathways from FNA samples is feasible. If further validated, patients with pancreatic cancer can be screened for targeted therapy by their phosphorylation signature.
Correlation between classical prognostic factors and overexpression of HER2 and HER3 in localized gastric cancer.
Authors: Perez-Fidalgo Jose Alejandro , Tarazona Noelia , Navarro Samuel , Lopez-Mozos Fernando , Marti Roberto , Rosello Keranen Susana , Roda Perez Desamparados , Mongort Cristina , Cervantes-Ruiperez Andres 
Published: March 2020

e14589 Background: Although HER2 overexpression has been identified as a predictive factor for targeted therapy in advanced gastric cancer (GC), little is known about its role in localized GC. Recent studies suggest that not only HER2 but also HER3 might have a role in prognosis in GC. Our study aimed to identify the prevalence of HER2 and HER3 overexpression in a series of localized GC and to describe correlations of these with traditional prognostic factors Methods: We performed a retrospective analysis of HER2 and HER3 overexpression in archived tumour samples in pts diagnosed with GC at stage I-III. HER2 was assessed with herceptest, (negative if 0 or 1+, or positive with 2+ or 3+). Staining of HER3 was determined with the Rajkumar score (HER3+ when score > or = 8). Correlation between the HER receptors expression and the clinicopathologic parameters was statistically analyzed. Statistical analysis of the correlation of HER2 and HER3 with other variables was performed with chi-square test or with the Mann Witney U for continuous variables. Impact on survival was analysed with Kaplan-Meier and log-rank tests. Results: From Jan 2003 to Sep 2011, 125 patients with clinical stage I-III GC were included. Median age was 73 years (35-91) and most frequent location was antrum (47.2%). Up to 43.2% of the patients were treated with preoperative chemotherapy. HER2 was + in 18 patients (14.4%) and HER3 in 38 (30.4%). HER2 was more likely to be overexpressed in older patients (median age: 78.4 vs 68.4; p<0.0001) and in low grade adenocarcinomas (grade 1-2: 13.8% vs grade 3: 1.1%; p=0.006). HER3 was more frequently overexpressed at advanced stages (I and IIA: 10.3% vs IIB and III: 20.3%; p=0.004) and in adenocarcinoma with intestinal subtype (intestinal: 21.4% vs difuse/mixed: 8.5%; p=0.03) or without evidence of signet ring cells (absent: 26.8% vs present: 4.1%; p=0.03) . HER2 and HER3 were significantly related (p=0.0012) with an OR of 3,52 times more frequently HER3+, if HER2 was +. No significant impact was shown in survival for either HER2 or HER3. Conclusions: HER2 and HER3 overexpression seems to identify a particular subgroup of patients with favourable classical prognostic factors.
Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin-C for invasive anal carcinoma in HIV-positive patients receiving highly active anti-retroviral therapy versus non-HIV patients.
Authors: Rubinstein Paul G. , Sreenivasappa Shylandra B. , Gupta Shweta , Jain Shivi , Pattali Shinoj , Blumetti Jennifer , Mullane Michael Russell 
Published: March 2020

e14590 Background: In the non-HIV population, radiotherapy (RT), fluorouracil (5FU) with mitomycin (MMC) has become the standard in the non-metastatic setting for anal carcinomas (AC). To date, most studies with AC in HIV patients (pts) are small case series where multiple chemoradiation (CRT) regimens were used and analyzed as one cohort. In addition, little data exists on the inner city HIV population. Cook County Hospital (CCH) is the largest health provider for HIV pts in Chicago and together with its outpatient clinic, the Ruth M. Rothstein CORE Center (CC) 5,500 HIV+ pts are treated per year. The County Hospital (CCH) AIDS Malignancy Project (CHAMP Study) is a retrospective study of all HIV cancer pts treated for the past 14 years. Methods: We identified all HIV+ pts with invasive AC in CHAMP cohort. We analyzed HIV characteristics, overall survival (OS), PFS and pt demographics and compared it to a HIV- cohort from the same institution. All AC treated without MMC/5FU/RT were excluded. Statistics: Time to local recurrence (TLR), time to distant metastasis (TDM), and OS data was analyzed using Kaplan-Meier analysis and a Cox Proportional Hazards model. Results: 35 HIV + and 52 HIV - pts were included. Of the HIV+ vs. HIV- pts, 89 vs. 52% were male, 82 vs. 48% were AA and the average age in HIV+ vs. HIV- was 44 vs. 52 yrs. 45 % of the HIV pts presented with stage IIIA or IIIB disease vs. 46% in HIV- pts. 15 % HIV- pts had stage IV vs. 0% HIV +. The median survival in the HIV+ vs. HIV- was 34 vs. 39 mo (p>0.5). In the HIV- population, 22% survived 120 months, while no HIV pt survived over 90 months. TLR was 20 months shorter in the HIV+ arm (p<0.5). OS based on CD4 count did not differ. Conclusions: HIV associated AC is an AA male disease compared to HIV- pts in the inner city. More stage IV disease was reported in the HIV- cohort, but the median survival was equal with no long-term survivors in the HIV+ arm, possibly due to TLR, which was 20 months shorter, implying more aggressive disease. Both inner city groups present late but tolerate chemotherapy equally well. Education is needed in both HIV+ and HIV- pts to diagnose the cancers early so the OS can match the national average.
Effect of BPM 31510 on survival outcomes when used in combination with gemcitabine in a preclinical model of pancreatic cancer.
Authors: Jimenez Joaquin J. , Mauro Lucia M , Akmaev Viacheslav R , McCook John , Du Min , Luan Shen , Song Paul Y. , Sarangarajan Rangaprasad , Narain Niven R 
Published: March 2020

e14593 Background: BPM 31510 is a novel small molecule that targets the metabolic machinery of the cancer microenvironment to create a hallmark shift from lactate dependency towards mitochondrial oxidative phosphorylation, reversing the Warburg effect. Effector downstream signaling results in re-capitulation of BCL-2 mediated apoptosis and disruption in tumor vasculature by modulation of VEGF. This study reports on the therapeutic benefit associated with BPM 31510 used in combination with gemcitabine in animal model of pancreatic cancer. Methods: The NGS mouse devoid of innate and adaptive immune system were implanted with human pancreatic cancer cells, Mia PaCa-2. The animals were randomized (n=30/group) to the following dose regiment cohorts: 50 mg/kg body weight (BW) once or twice daily ± gemcitabine (150 mg/kg BW once/week) for 3 weeks followed by one week rest. A group of animals received 75 mg/kg BW thrice daily ± gemcitabine (150 mg/kg BW once/week) for 3 weeks followed by one week rest. Untreated or group treated with gemcitabine alone with corresponding treatment regimen served as controls. The primary objective was to evaluate the difference in overall survival of the animals when treated with gemcitabine alone compared to combination regimens with BPM 31510. Results: All tumor bearing untreated animals (control arm) expired by Day 21 of the study. In contrast, the once daily BPM 31510 dose regimen was associated with significant increase in duration of overall survival (p<0.009) with all animals expiring by Day 142 compared to gemcitabine alone. The combination of BPM 31510 with gemcitabine was associated with significantly increase in overall survival compared to BPM 31510 (p=0.002) or gemcitabine (p = 7.3E-8) alone. This was associated with significant reduction in tumor size and weight (p<0.001). Increased frequency of BPM 31510 dosing alone or in combination with gemcitabine was associated with significant increases in survival rates. Conclusions: The data herein suggest that BPM 31510 may be a viable agent for combination therapy in pancreatic cancer via employment of a novel metabolic pathways.
Phase I trial of dose escalated whole liver irradiation (WLRT) with hepatic arterial (HA) fluorodeoxyuridine (FUDR)/leucovorin (LV)/streptozotocin (STZ) chemotherapy followed by chemoembolization with mitomycin C (MMC) for patients with neuroendocrine hepatic metastases.
Authors: Shilkrut Mark , Schipper Matthew J , Ensminger William D. , Ben-Josef Edgar , Lawrence Theodore Steven , Feng Mary Uan-Sian 
Published: March 2020

e14603 Background: Phase I trial combining HA chemotherapy, chemoembolization and dose-escalated WLRT was conducted to determine if the maximum safe dose of 32 Gy in 2 Gy fractions could be delivered to patients (pts) with neuroendocrine (NE) hepatic metastases. Methods: Pts with symptomatic liver metastases from NE tumors who failed somatostatin analog therapy were eligible. HA FUDR (3 mg/m2/d) and LV (300 mg/m2/d) were given for 12 days; STZ (500 mg/m2/d) was given on days 5,8,10. Concurrent WLRT was prescribed in 2 Gy/day with doses escalated from 24 Gy to 32 Gy using the time-to-event continual reassessment method for dose allocation with a target rate of dose-limiting grade ≥3 radiation-induced liver disease (RILD) of 10%. 8 weeks later, for patients without RILD and other grade ≥4 toxicities, 72-h infusion with HA FUDR (3 mg/m2/d) and LV (300 mg/m2/d) was given, followed by chemoembolization with mitomycin C (20 mg) and polyvinyl alcohol. Results: 19 pts were enrolled in the trial, 11 pts completed the entire protocol. 7 pts received 24 Gy, 2 - 26 Gy, 1 - 28 Gy, 2 - 30 Gy and 6 - 32 Gy. One pt stopped at 14 Gy because of STZ-induced grade 4 renal failure. No pts developed RILD at any dose level; 4 - had grade 3-4 increased liver function tests, 4 - had other grade 4 toxicities during or after the first part of the treatment; 1 - had other grade 4 toxicity during the second part. Posterior estimates of probabilities of RILD were all <10% (table). Three pts (14%) had partial response, 16 (84%) - stable disease. Median freedom from local progression for all pts was 35.3 (9.3-58.9) months. Conclusions: The study showed that chemotherapy can be safely combined with a full dose of WLRT and subsequent chemoembolization without producing RILD. [Table: see text]
Survival outcomes in patients with early-stage, resectable pancreatic cancer: A comparison of gemcitabine and 5-fluorouracil based chemotherapy and chemoradiation regimens.
Authors: Kizilbash Sani Haider , Ward Kevin , Jaiyesimi Ishmael A. , Lipscomb Joseph 
Published: March 2020

e14608 Background: Beyond curative surgery, the optimal treatment for early stage pancreatic cancer is still a matter of debate. We conducted a comparative survival analysis between patients with resectable pancreatic cancer who received adjuvant treatment with either gemcitabine or 5-fluorouracil based chemotherapy and chemoradiation regimens. Methods: The Surveillance, Epidemiology and End Results (SEER)-Medicare database was used to identify patients with pancreatic cancer diagnosed from 1998 to 2005 who received curative surgery and adjuvant chemotherapy with either 5-fluorouracil or gemcitabine. These groups were subdivided by treatment with radiotherapy. Patients were followed until death, study endpoint or a maximum of five years after diagnosis. Results: 359 patients received 5-fluorouracil and 346 received gemcitabine. Compared to chemoradiation with 5-fluorouracil, outcomes for patients who received chemoradiation with gemcitabine did not differ. Patients who received gemcitabine without radiation had increased hazards (hazard ratio (HR) = 1.50 for high grade tumors (HGT), HR = 1.32 for low grade tumors (LGT)). However, outcomes of patients who received 5-fluorouracil without radiation varied with tumor grade. In LGT, patients had better outcomes with 5-fluorouracil when compared with chemoradiation with 5-fluorouracil (HR = 0.43). In HGT, the opposite was true (HR 2.10). Conclusions: Patients with low grade resectable pancreatic cancer may have better outcomes with 5-fluorouracil based chemotherapy without radiation when compared to 5-fluorouracil with radiation.
Safety and efficacy of modified FOLFIRINOX in pancreatic cancer: A retrospective experience.
Authors: Mahaseth Hemchandra , Kauh John S. , Brutcher Edith , Hawk Natalyn Nicole , Kim Sungjin , Chen Zhengjia , El-Rayes Bassel F 
Published: March 2020

e14614 Background: Conroy et al reported a significant improvement in overall survival of patients with metastatic pancreatic cancer treated with FOLFIRINOX compared to single agent gemcitabine. The regimen was associated with significant grade 3/ 4 toxicities, such as myelosuppression(46%), fatigue(24%), vomiting(15%) and diarrhea (13%). In order to improve the toxicity profile, we have modified FOLFIRINOX (mFOLFIRINOX) regimen by removing the bolus 5-FU and adding the routine use of growth factor prophylaxis. We present our experience with mFOLFIRINOX in patients with locally advanced or metastatic pancreatic cancer. Methods: After obtaining IRB approval, patients with a diagnosis of pancreatic cancer were identified from the Emory University tumor registry. Twenty eight patients who received at least one dose of mFOLFIRINOX (5-FU 2400 mg/m2 CIVI over 46 hours, leucovorin 400 mg/m2, oxaliplatin 85 mg/m2, irinotecan 180 mg/m2 and pegfilgrastim 6 mg every two weeks ) were selected and their charts were retrospectively reviewed for safety, response, and survival. Results: Of 28 patients, 14 (50%) were male, 18 (64%) white, 8 (29%) black and other 2(7%). Median age was 63 (50-75) and ECOG performance status 0-1. Nineteen (68%) patients had primary tumor located in head of pancreas. Eight patients (29%) experienced grade 3/4 toxicities, i.e., nausea/vomiting (11%), diarrhea (11%), fatigue (11%), neuropathy (4%), neutropenia (4%), thrombocytopenia(4%), and sepsis not-related to neutropenia (4%). No grade 3/4 anemia or febrile neutropenia was noted. mFOLFIRINOX controlled the disease in 20 patients (71%) with 2 CR, 4 PR and 14 SD. With a median follow up of 5.5 months, median overall or progression free survival is not reached. Two patients have died and six patients have progressed. Conclusions: Modified FOLFIRINOX is well tolerated in this US population. The clinical activity appears very promising with majority of patients being free of progression.
FOLFIRINOX in locally advanced and metastatic pancreatic cancer.
Authors: Faris Jason Edward , Hong Theodore S. , McDermott Shaunagh , Borger Darrell R. , Guimaraes Alexander R , Wo Jennifer Yon-Li , Sahani Dushyant , Dias Lauren Elizabeth , Allen Jill N. , Zhu Andrew X. , Murphy Janet E. , Kwak Eunice Lee , Ryan David P. , Clark Jeffrey W. , Blaszkowsky Lawrence Scott 
Published: March 2020

e14615 Background: The phase III trial of 5-FU, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) demonstrated improved survival compared to gemcitabine in good performance status (PS) patients (pts) with metastatic pancreatic cancer (Conroy et al, NEJM 2011). Less is known about the efficacy and tolerability of FOLFIRINOX in the non-clinical trial setting. In this retrospective analysis, we report our institutional experience with FOLFIRINOX. Methods: 38 pts with locally advanced (LAPC) or metastatic pancreatic cancer (MPC) who began treatment with FOLFIRINOX between 7/2010 and 6/2011 were identified. Clinical characteristics, gradable toxicities, and molecular genotyping results were tabulated. Formal radiographic review was performed to determine best overall response rates (ORR). All pts receiving FOLFIRINOX were assessed for toxicities, while pts receiving ≥2 cycles were assessed for response. Results: 26 pts received FOLFIRINOX for MPC and 12 pts for LAPC. The median age was 60 (range 39-76). 29/38 pts were men, 26/38 had received no prior chemotherapy, and 11/38 had biliary stents. Overall, 12 partial responses (PR) were observed in 33 evaluable pts (ORR 36%); 11/12 partial responses were in chemo-naïve pts. In evaluable pts with MPC, there were 7 PR (ORR 33%), and 11 pts with stable disease (SD). In LAPC, there were 5 PR (ORR 42%), and 7 pts with SD. Following FOLFIRINOX, two pts with LAPC have subsequently undergone R0 resection. 18/38 pts required an ED visit or hospitalization during treatment. Grade 3/4 neutropenia was observed in 12 pts; 8/12 had not received prophylactic growth factor from the start of FOLFIRINOX. There were 6 pts with febrile neutropenia, 6 pts with grade 3/4 thrombocytopenia, and 5 pts with grade 3/4 anemia. 1 pt died with bacteremia in the setting of febrile neutropenia. 22 pts had molecular genotyping at multiple loci performed: 17/22 were KRAS mutation positive, and 3 pts with KRAS mutations also had TP53 mutations. 4 pts were wild-type at all loci tested, and 3 of these pts had a PR on FOLFIRINOX. Conclusions: In a non-clinical trial setting, FOLFIRINOX demonstrated activity in both LAPC and MPC, but is associated with significant toxicities, with nearly half of pts requiring an ED visit or hospitalization.
Combination of docetaxel, cisplatin, and capecitabine (DCX) as a first-line chemotherapy in patients with metastatic gastric carcinoma: A phase II study.
Authors: Narimanov Mekhty , Tryakin Alexey , Bazin Igor , Kanagavel Dheepak , Tjulandin Sergei 
Published: March 2020

e14623 Background: Docetaxel is an active agent for treatment of metastatic gastric carcinoma. We launched this phase II trial to evaluate the efficacy and safety of docetaxel, cisplatin and capecitabine (DCX) combination in patients (pts) with metastatic gastric carcinoma. Methods: Pts with metastatic gastric carcinoma received docetaxel 75 mg/m2 i.v. day 1, cisplatin 75 mg/m2 i.v. day 1, capecitabine 1650 mg/m2 per os days 1-14 every 3 weeks. Up to 6 cycles were provided. G-CSF was not routinely used for primary prophylaxis. Results: From 2007 to 2011, 37 pts were included in the study, all pts were available for response. Pts characteristics and results are shown in the table. Median number of cycles delivered was 5 (range, 1-5). Grade 3-4 toxicity (per cycle) included: neutropenia – 24,9%, deep venous thrombosis – 2%, diarrhea – 6.2%, stomatitis – 3.8%, infection – 11%; anemia 14% pts. Six pts had dose reductions, 2 pts stopped chemotherapy due to toxicity. No toxic deaths were observed. Median progression-free survival (PFS) and median overall survival (OS) were 7,5 months (95% CI 6,076-8,857) and 14,5 months (95% CI 10,054-18,880), respectively. Conclusions: Compare with combination of docetaxel, cisplatin and 5-FU, evaluated in V325 study, our regimen had more favorable toxic profile with similar efficacy. Further investigation of this regimen in randomized controlled trials is warranted. [Table: see text]