bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-institutional predicting nomogram for BCLC stage C hepatocellular carcinoma after stereotactic body radiotherapy.
Authors: Huang Wen-Yen , Lin Yu-Ju , Cheng Jason C. , Que Jenny , Lee Mei-Hsuan , Tsai Chiao-Ling , Lo Cheng-Hsiang 
Published: January 2019

353 Background: The study aimed to develop a nomogram to predict overall survival (OS) among hepatocellular carcinoma (HCC) patients with BCLC stage C after stereotactic body radiotherapy (SBRT). Methods: Clinical data from the multicenter study consisted of 270 HCC patients with BCLC stage C. The patients underwent SBRT with a median dose of 40 Gy (range: 25-60 Gy) in 2-6 fractions. The model included age, gender, ECOG performance status, etiology (HBV, HCV, and non-B, non-C), number of tumor, tumor size, AFP level, presence of macrovascular invasion, Child-Pugh class, N stage, M stage, sorafinib use, and biologically effective dose. Cox’s proportional hazards models were utilized to estimate regression coefficients of death risk predictors and derive risk scores. The area under receiver operating curve (AUROC) was used to evaluate the performance of the risk models. Results: The median survival was 12.6 months, with 1-year and 2-year OS rates of 51.6% and 30.8%, respectively. Multiple regression showed age (with 5-year increase, HR = 0.89, p = 0.002), ECOG (1 vs. 0, HR = 1.72, p = 0.016; 2 vs. 0, HR = 2.64, p = 0.002), number and size of tumors ( > 5 tumors or > 8 cm vs. ≤5 tumors and ≤ 8 cm, HR = 1.83, p = 0.003; > 5 tumors and > 8cm vs. ≤5 tumors and ≤ 8 cm, HR = 2.04, p = 0.013), macrovascular invasion (yes vs. no, HR = 2.22, p < 0.001), Child-Pugh class (B vs. A, HR = 2.83, p < 0.001), and M stage (1 vs. 0, HR = 2.30, p = 0.001) are statistically significant predictors for OS. All of these significant predictors were included in the risk prediction model. The total risk score of the prediction model ranged from 0 to 48. Each score had its corresponding risk of OS. The AUROC for predicting 1-year OS was 0.820. Conclusions: The nomogram we generated among HCC patients undergoing SBRT had discrimination satisfactory predictability for OS. It can be used to stratify high-risk patients and select appropriate patients for future clinical trials.
Comparisons between intestinal and diffuse gastric cancer in response to apatinib: Data from post-marketing phase IV study.
Authors: Zhang Guifang , Qin Shukui , Li Jin , Deng Wenying , Wen Lu , Wang Junsheng , Zhong Haijun , Jia Tongfu , Yang Jianwei , Ba Yi , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Bai Yuxian 
Published: January 2019

36 Background: Intestinal and diffuse gastric cancer are main histological types of gastric cancer, based on Lauren’s classification, which account for 34–47% and 46–57%, respectively. Patients (pts) with intestinal gastric cancer have better prognosis. The present study aimed to compare the safety and efficacy of apatinib between the two intestinal gastric cancer, based on data from post-marketing Phase IV study (Ahead-G201). Methods: The single-arm, open-label, multi-center, Phase IV trial enrolled advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction after failure of ≥2 lines of chemotherapy. Data of pts with intestinal and diffuse gastric cancer were collected and compared. Results: As of 2017/7/10, 96 intestinal and 104 diffuse pts were recruited. Differences in age (64 vs. 55 yrs), gender (male: 77.1% vs. 57.7%) and disease duration ( > 12 months: 71.3% vs. 56.7%) were detected. Between intestinal and diffuse gastric cancer, there was no discrepancy in incidences of adverse events (AEs) (78.1% vs. 73.1%) and Grade ≥3 AEs (41.7% vs. 38.5%). The incidences of typical AEs associated anti-angiogenesis drugs were also comparable (hypertension 26.0% vs. 16.4%; proteinuria 14.6% vs. 20.2%; hand-foot-skin reaction 16.7% vs. 9.6%). No statistical difference was observed in best overall response rate (12.8% vs. 14.3%) and disease control rate (76.0% vs. 64.3%). Survival benefit in pts with intestinal gastric cancer was detected (progression free survival: 5.52 vs. 2.76 months, p = 0.036; overall survival: 8.11 vs. 4.70 months, p = 0.047). However, the multivariable Cox regression model analysis showed that histological type was not independently prognostic factors for survival, indicating that clinical benefit of pts with intestinal gastric cancer was influenced by other factors. Conclusions: Compared with diffuse gastric cancer, pts intestinal gastric cancer have more clinical benefit after treated by apatinib. However, histological type based on the Lauren’s classification was not independently prognostic factors for survival, which needs to be further analyzed, considering the small sample size. Clinical trial information: NCT02426034.
Impact of adjuvant hepatic arterial infusion chemotherapy using high-dose 5-fluorouracil with systemic gemcitabine for resectable pancreatic cancer.
Authors: Nakamura Kota , Akahori Takahiro , Nagai Minako , Nishiwada Satoshi , Nakagawa Kenji , Tanaka Toshihiro , Nishiofuku Hideyuki , Kichikawa Kimihiko , Tamamoto Tetsuro , Hasegawa Masatoshi , Ikeda Naoya , Sho Masayuki 
Published: January 2019

360 Background: Despite recent advances in cancer treatment, postoperative recurrence remains an unsolved issue for resectable pancreatic cancer. To prevent hepatic recurrence and prolong postoperative survival, we introduced postoperative adjuvant chemotherapy of high-dose 5-fluorouracil (5-FU) hepatic arterial infusion (HAI) with systemic chemotherapy using gemcitabine in 2006. We retrospectively evaluated the clinical impact of HAI. Methods: A total of 251 patients who underwent pancreatic resection for PC were analyzed. Patients received weekly high-dose 5-FU through the hepatic artery using a port-catheter system (1000 mg/m2 for 5 h) plus concurrent systemic gemcitabine (1000 mg/m2) followed by systemic 3 cycles of gemcitabine or 4 cycles of S-1. Patients were divided into two groups. The patients who completed planned adjuvant chemotherapy of HAI were classified as the completion group (HAI), and the patients who failed to complete HAI or received systemic adjuvant chemotherapy other than HAI were classified as the control group. Results: One hundred thirty-eight patients (55%) completed planned adjuvant chemotherapy of HAI. On the other hand, 28 patients (11%) failed to complete HAI and 85 patients (34%) received systemic adjuvant chemotherapy alone. The reasons for incompletion of HAI were as follows: any recurrence during HAI treatment in 8, poor general condition of patients in 4, hepatic arterial stenosis in 4 and catheter trouble in 3. Initial hepatic metastasis rate was significantly lower in the HAI group than the control group (15.2 vs. 26.3%, p=0.029), and liver metastasis free survival was significantly better in the HAI group than the control group (p=0.001). The HAI group had a better prognosis than the control group (58.1 vs. 26.9M, p < 0.001). Prognostic factor analysis indicated that failure to complete HAI (p < 0.001, HR 1.95), borderline resectable tumor (p = 0.028, HR 1.63), and lymph node metastasis (p = 0.018, HR 1.59) were the independent adverse prognostic factors. Conclusions: Our data demonstrate that HAI can significantly prevent hepatic recurrence and also improve the postoperative prognosis in pancreatic cancer.
Phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma.
Authors: Lee Sunyoung S. , Miller Austin , Krishnamurthi Smitha S. , Estfan Bassam N. , Frazer Andrea , Wang Chong , Iyer Renuka V. 
Published: January 2019

364 Background: Sorafenib has been the only FDA-approved medication for inoperable HCC (iHCC) as first line. Agents with better tolerability and potential to improve progression-free-survival (PFS) are needed. Tivozanib (TIVO) is an inhibitor of vascular endothelial growth factor (VEGF) tyrosine kinase, inhibiting angiogenesis critical in HCC. Methods: This is a phase 1b/2 study with HCC patients (pts) having a measurable disease, Child-Pugh class A, and no prior systemic therapy. Phase 1b portion followed a modified 3 + 3 design; phase 2 portion was a two-stage, single arm, un-blinded study. Adverse events were categorized based on CTCAE, and tumor imaging was assessed per RECIST. Results: At 3 centers with IRB approval, 21 eligible pts were enrolled. In phase 1b, 8 pts were enrolled at a starting dose of 1mg once daily q21days with one week off. Upon escalation to 1.5mg, two pts had dose limiting toxicities (DLTs, grade 3 mucositis and hypertension) and came off study without completing the DLT period. The dose of TIVO was de-escalated to 1 mg, and the accrual of remaining patients to phase 2 portion occurred at 1 mg. In a total of 19 pts, median follow up was 16.9 months (mo). The primary endpoint of median PFS was 5.5 mo. Partial response (PR) was seen in 4/19 (21%) and stable disease (SD) in 8/19 (42%): disease control rate was 63%. Overall survival (OS) at 6 and 12 mo was 58% and 25%. Median OS was 7.5 mo. Three pts have remained on TIVO for > 2 years. Viral loads of hepatitis B and C remained stable during the study. Adverse events (AEs) related to TIVO included grade 3 fatigue (15.7%), decreased appetite (5.3%), pulmonary embolism (5.3%), hand-foot syndrome (5.3%), elevated LFT (10.5%), and grade 4 hypertension (5.3%). Conclusions: TIVO is tolerable at 1 mg in iHCC. In few pts, TIVO had deep and durable responses. Biomarker driven studies of TIVO in the context of immunotherapy are warranted. Acknowledgment: We appreciate support from NCCN. Clinical trial information: NCT01835223.
Perioperative and long-term impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer.
Authors: Nagai Minako , Akahori Takahiro , Nishiwada Satoshi , Nakagawa Kenji , Nakamura Kota , Tanaka Toshihiro , Nishiofuku Hideyuki , Kichikawa Kimihiko , Tamamoto Tetsuro , Hasegawa Masatoshi , Ikeda Naoya , Sho Masayuki 
Published: January 2019

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m2) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P < 0.0001, P = 0.006, P < 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.
Correlation of tissue plasminogen regulators expressed by esophageal adenocarcinoma with VEGF family members.
Authors: Kolesnikov Evgeniy N. , Kit Oleg Ivanovich , Frantsiyants Elena , Bandovkina Valeria A. , Kozlova Larisa S. , Kozhushko Mikhail Anatolievich , Kazieva Tanzila Beksultanovna , Sanamyants Sergey V. , Trifanov Vladimir 
Published: January 2019

37 Background: Esophageal cancer is known for its high potential of early lymphogenous metastases. The biological activity of plasminogen (PG) regulators, VEGFs and their receptors controls the growth and differentiation of cells, including malignant ones, the stability of the extracellular matrix, as well as processes of destruction of membranes and extracellular matrix, invasion of malignant cells, angio- and lymphangiogenesis. Our purpose was to study the role of PG regulators in the activation of VEGFs and their receptors in esophageal adenocarcinoma (EA) and its perifocal zone (PZ). Methods: Levels of uPA-Ag, uPA-act; tPA-Ag, tPA-act; PAI-1-Ag and PAI-1-act, VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were determined by ELISA in surgical specimens of EA (n = 28, st II, G2, T2-3N0-1M0). Statistical analysis was performed using Microsoft Office Excel 2010. Results: Levels of all proteins, except tPA, were higher in tumor (T) tissues than in the resection line (RL, p < 0.01). Protein levels, except uPA-Ag and tPA, in PZ were between levels in T and RL (p < 0.01); uPA-Ag, tPA-Ag and tPA-act were decreased in T and PZ compared with RL (p < 0.01); PAI-1-Ag in T and PZ was higher than in RL by 9.4 and 6.3 times, and PAI-1-act – by 10.7 and 1.9 times. Levels of VEGF-А, VEGF-R1, VEGF-С and VEGF-R3 were increased in T (p < 0.001), and in PZ they were between levels in T and RL (p < 0.001). Strong correlations were registered in EA T between uPA and VEGF-А (r = 86), uPA and VEGF-R1 (r = 81), uPA and VEGF-С (r = 79), uPA and VEGF-R3 (r = 76). A strong correlation between uPA and PAI-1 in T (r = 88) did not exclude PAI-1 biological effects in EA T and its PZ. PZ showed strong correlations between uPA and PAI-1 (r = 87), uPA and VEGF-А (r = 84), uPA and VEGF-С (r = 78). Conclusions: The strong correlations between the activation of uPA, PAI-1, VEGF-А, VEGF-С and their receptors in EA indicate interactions between them, realized both directly and through plasmin. The expression of the studied proteins in T and its PZ, compared to RL, demonstrates the effect of T on the content and activity of uPA, PAI-1, VEGF-A, VEGF-C and their receptors, with the following realization of biological properties that promote the progression of EA.
Three fluoropyrimidine-based regimens in second-line therapy following nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer: Efficacy and tolerance in clinical practice.
Authors: Pointet Anne Laure , Tougeron David , Pernot Simon , Pozet Astrid , Bechade Dominique , Trouilloud Isabelle , Lourenco Nelson , Hautefeuille Vincent , Locher Christophe , Williet Nicolas , Desrame Jérôme , Thirot Bidault Anne , Pezet Denis , Taieb Julien 
Published: January 2019

370 Background: Combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a valid first-line treatment (1L) in metastatic pancreatic adenocarcinoma (MPA) in patients (pts) with performance status (PS) of 0,1 or 2, but there is currently no standard second-line treatment (2L) after this new 1L option. We evaluated survival outcomes and tolerability of three usual fluoropyrimidine-based regimens: FOLFOX, FOLFIRI or FOLFIRI.3 (FOLFIRI1/3), and FOLFIRINOX after N+G failure in MPA pts. Methods: We prospectively identified 138 pts from 11 French centers who received 1L N+G for unresectable pancreatic adenocarcinoma. After disease progression or unacceptable toxicity, we excluded pts with locally advanced cancer, or who underwent secondary resection/chemoradiotherapy. Three subgroups of 2L chemotherapy were identified: FOLFOX, FOLFIRI1/3 and FOLFIRINOX regimens. Response was evaluated by RECIST criteria, progression-free survivals (PFS1, PFS2), and overall survival (OS1, OS2) were calculated using Kaplan-Meier method and compared with the Log-rank test. Results: 61 pts with MPA received a 2L. Persistent neuropathy was present in 27% of pts. Median age was 71.7 years [41-83]. PS was 0, 1 or 2. Median 1L duration, number of metastatic sites, PS, CA19.9, albumin, and bilirubin levels, and persistent neuropathy grade were statistically comparable between the 3 subgroups. Median OS for all 2L pts was 6.0 months [4-8]. Third line regimen was used in 32.8% of 2L pts without statistical significance between the subgroups. Main grade 3/4 adverse events reported were thrombocytopenia (18%), anemia (7.7%), neutropenia (21.4%) and nausea (5.4%). No toxic deaths occurred. Conclusions: This study suggests a clinical benefit and a manageable toxicity profile of 2L fluoropyrimidine-based regimens after N+G failure in patients with MPA, in particularly combined with irinotecan.[Table: see text]
Impact of insurance status on survival in neuroendocrine tumors: A multi-institutional Study from the U.S. Neuroendocrine Study Group.
Authors: Marincola Smith Paula , Lopez-Aguiar Alexandra G , Dillhoff Mary , Beal Eliza W , Poultsides George A. , Makris Eleftherios , Rocha Flavio G. , Crown Angelena , Cho Clifford , Beems Megan , Winslow Emily , Rendell Victoria , Krasnick Bradley A. , Fields Ryan , Maithel Shishir , Idrees Kamran 
Published: January 2019

371 Background: Insurance status predicts access to medical care in the United States. Previous studies show uninsured and government insured patients have worse outcomes than those with private insurance. However, the impact of insurance status on survival in patients with Gastrointestinal Neuroendocrine Tumors (GI-NETs) is unclear. We evaluate the association between insurance status and survival in patients with GI-NETs. Methods: Our analysis includes 2022 patients who had surgical resection of GI-NETs at 8 institutions in the U.S. Neuroendocrine Study Group. Patients were categorized based on insurance as private (PI), government (GovI) or uninsured (UI). Factors associated with insurance status were assessed by uni- and multi-variate analysis. Primary endpoint was overall survival. Results: Patient demographics between the insurance categories were similar in ECOG performance status and tumor size at presentation. GovI patients had a higher median age than PI or UI (66 vs. 54 vs. 56 years respectively; p<0.01). Uninsured patients were more likely African American (21.5%) or Latino (5%) compared to PI (11.5%, 2%) or GovI (15%, 2%) (p<0.01). The UI group had a higher proportion of patients who underwent no surveillance imaging post-operatively (39%) compared to PI (26%) and GovI patients (26%) but this was not statistically significant (p=0.15). There was no difference in operative intent (curative vs. palliative) between groups (p=0.2). Five-year overall survival was 86% for PI, 82% for GovI, and 73% for UI patients (p<0.01). On multivariate regression analysis, being uninsured was independently associated with reduced survival when controlling for ASA Class, ECOG, race, tumor location, neoadjuvant and adjuvant chemotherapy, Somatostatin analog, or radiation therapy (HR 1.39, p = 0.012). Conclusions: This is the first systematic analysis of insurance status’s association with overall survival in GI-NET patients. Our analysis shows uninsured or government insured patients have shortened survival compared to the privately insured. The disparity is likely underrepresented in this study, as we examined only patients who underwent surgical resection.
Curative intent surgery and associated overall survival variation between elderly and younger patients in the National Cancer Database.
Authors: Anderson Eric , David John , Lo Simon , Nissen Nicholas N. , Hendifar Andrew Eugene , Tuli Richard 
Published: January 2019

373 Background: Margin negative oncologic resection drastically improves survival in pancreatic cancer (PC) with low morbidity and mortality rates. Increasing age at the time of surgery may have an impact on overall survival (OS) in PC. We aimed to describe the likelihood of receiving surgery in elderly patients (EP) compared to younger patients and whether this predicted OS. Methods: Non-metastatic PC patients were identified in the National Cancer Database (NCDB). Baseline demographics, clinical, and pathologic factors were compared between patients older (EP) and younger (YP) than age 75. Kaplan-Meier survival methods were used to describe differences in OS. Cox regression methods were performed to describe the impact of multiple variables on OS. Results: From 2004-2014, there were 39,804 PC patients with median age 69 years (range 19-90) and median follow up 47.2 months. Of 12,337 (31.0%) EPs, 2598 (21.1%) underwent surgery, while 9809 of 27467 YPs (35.7%) underwent surgery (p < 0.001). EP were less likely to receive surgery across clinical stages (CS, p < 0.001): CS 1 - 29.5% EP vs. 55.6% YP, CS 2 - 23.4% EP vs. 40.3% YP, CS 3 - 3.1% EP vs. 7.5% YP. EP receiving surgery were more likely to have baseline medical comorbidities (38.8% vs. 35.9%, (p = 0.065) and less likely to receive chemotherapy (47.4% vs. 73.6%, (p < 0.001). Improvement of median OS was seen in EPs undergoing resection (16.9 months vs. 6.4 months, p < 0.001), as well as YP undergoing resection (22.8 vs. 11.2 months, p < 0.001). Multivariate Cox regression revealed that surgical intervention (HR 0.47, 95% CI 0.45-0.48, p < 0.001) and younger age (0.62, 0.60-0.63, p < 0.001) were highly protective. Patient medical comorbidities (1.15, 1.12-1.18, p < 0.001) and T stage (1.38, 1.31-1.44, p < 0.001) predicted poor OS. Conclusions: EPs with PC are less likely to receive definitive surgical resection in the setting of higher or similar medical comorbidities. EPs are also less likely to receive chemotherapy for their non-metastatic disease. In spite of this, surgery portends a significant increase in median OS for these EPs. Given adequate risk stratification and functional assessment, EPs should be strongly considered for surgical resection.