bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of radioembolization among patients who met the inclusion criteria for Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP).
Authors: Sangro Bruno , Carpanese Livio , Cianni Roberto , Gasparini Daniele , Golfieri Rita , Ezziddin Samer , Kolligs Frank T , Izzo Francesco 
Published: March 2020

e14654 Background: SHARP was pivotal in determining the safety and efficacy of sorafenib in advanced hepatocellular carcinoma (HCC) in patients with predominately good liver function. In practice, many patients with advanced HCC receive radioembolization (RE). Investigators from the European Network on RE with yttrium-90 resin microspheres (ENRY) group conducted an analysis of safety and survival among consecutive patients who met the SHARP inclusion criteria. Methods: 58% of patients (189 of 325) who had received RE between 09/2003 and 12/2009 were considered SHARP-equivalents. Of these, 11.6% received sorafenib 4.7 months (median) after RE for a median duration of 2.8 months. Safety and tolerability analyses were conducted up to day 90 post RE; changes from baseline were recorded and transitions in CTCAE grades >3 tested. Statistical analyses used SAS (SAS, Cary NC) version 9.2 XP Pro. Results: Like the SHARP sorafenib cohort, most patients had advanced HCC (BCLC stage C: 72.5%), good liver function (Child–Pugh class A: 100%) and ECOG performance status (0–1: 90.5%). Macroscopic vascular invasion (MVI), extrahepatic spread (EHD) or both was present in 33.9%. 20.1% had received prior surgical procedures, 8.5% prior ablative procedures and 33.3% prior vascular [chemo]embolization. RE was predominantly a single whole-liver procedure (median activity 1.7 GBq). Median overall survival was 10.8 months (95% CI: 8.8–12.8) in the SHARP-equivalent cohort, 10.2 months (8.3–11.8) in patients with MVI/EHD, 9.7 months (7.6–10.9) in advanced HCC (BCLC stage C) and 16.6 months (11.2–22.8) in intermediate HCC (BCLC stage B). Treatment-related adverse events (all grades; grade >3) were: fatigue (50.3%; 2.1%), abdominal pain (25.9%; 2.1%), nausea/vomiting (31.2%; 0.5%) and GI ulcer (3.2%; 1.0%). At baseline, raised bilirubin (all grades) was present in 20.3%, increasing to 49.4% of patients evaluated up to day 90. Bilirubin grade was unchanged in 58.1% and increased in 37.8%; 4.0% had ≥grade 3 events. Conclusions: In patients matching the inclusion criteria for SHARP, RE was well tolerated with a median overall survival which compares favorably with sorafenib.
Activation of hedgehog pathway in neuroendocrine tumors.
Authors: Dong Mei , Sangai Takafumi , Zhao Qiang , Rashid Asif , Meric-Bernstam Funda , Yao James C. 
Published: March 2020

e14662 Background: Neuroendocrine tumors (NETs) are rare tumors and often follow an indolent course, especially the tumors of low-to-intermediate grade. Nonetheless, they are incurable and lethal when advanced. The genetic etiology of sporadic NET is largely unknown. Numerous established oncogenes and tumor suppressor genes have been studied, but no mutations have been consistently identified, indicating tumorigenesis of NET may follow distinct mechanisms. It is well known that significant amount of patients with NETs may have harbored the slow-growing lesions since very young age, suggesting it could result from alterations of pathways involved in development. Hedgehog (Hh) signaling has been found to be important in embryonic patterning, stem cell maintenance and tissue repair; and is normally silenced in most mature adult tissue. However, it frequently undergoes gain-of-function mutations or reactivation due to ligand overproduction and has been linked to the etiology of a variety of tumors. Specific inhibitors of Hh pathway have been developed and tested in clinical trials with very promising results. Methods: In this study, the functional status of Hh pathway was examined in archival tissue specimmen using immunohistochemistry and its role in tumorigenesis was tested using an xenograft mouse model. Results: we have found that Hh ligand is overproduced in 48% (27/52) of small bowel NETs, 28% (9/32) of pancreatic NETs, and 28.6% of lung carcinoids. Hh signaling blockade led to decreased survival of NET cells in vitro, and tumor shrinkage in vivo using a xenograft mouse model. Conclusions: we conclude that Hh pathway is involved in the tumorigenesis of NETs, and can be used as a potential therapeutic target for NETs.
Relationship between treatment duration and outcomes in patients receiving concurrent chemoradiotherapy (CCRT) and surgery for locoregionally advanced (LRA) esophageal and gastroesophageal junction (E/GEJ) adenocarcinoma (ACA).
Authors: McNamara Michael J. , Rybicki Lisa A. , Rice Thomas W. , Rodriguez Cristina P. , Videtic Gregory M.M. , Saxton Jerrold P. , Bodmann Joanna , Ives Denise I. , Adelstein David J. 
Published: March 2020

e14665 Background: Retrospective studies in breast, colon, and head and neck cancer have suggested that delays in administration of adjuvant chemotherapy result in inferior outcomes. We explore this question in patients with LRA E/GEJ ACA. Methods: From 11/99 to 7/06, 152 patients with cT3, N1, or M1a disease were enrolled on one of two clinical trials at the Cleveland Clinic. Two courses of CCRT consisting of 30Gy radiation (@1.5Gy BID) with continuous infusion cisplatin (20mg/m2/day x 4 days) and 5Fu (1000mg/m2/d x 4 days) were given both before and after surgical resection. In the second trial, 75 patients also received gefitinib during the 4 week induction and for a total of two years postoperatively. Using recursive partitioning analysis (RPA), we retrospectively explored the relationship between treatment duration and loco-regional control (LRC), distant metastatic control (DMC), freedom from recurrence (FFR), and overall survival (OS) in the 115 patients (76%) who completed all treatment. Outcomes were estimated using the Kaplan-Meier method and compared among groups using the log-rank test. Results: RPA analysis identified three groups of patients: 19 patients in whom resection occurred ≤45 days from the start of CCRT to resection (short treatment), 63 patients who underwent resection >45 days from the start of CCRT and required <50 days to complete treatment after surgery (intermediate treatment), and 33 patients who underwent resection >45 days from the start of CCRT but required ≥50 days to complete treatment after surgery (prolonged treatment). With a median follow-up of 90 (range 57-126) months, we found that patients with shorter treatment times had better 5 year DMC [64% (short) v 26% (intermediate) v 16% (prolonged); p=0.004], FFR [57% (short) v 23% (intermediate) v 16% (prolonged); p=0.015)], and OS [42% (short) v 30% (intermediate) v 12% (prolonged); p=0.08]. LRC was not different between the groups. Conclusions: Treatment delays in patients receiving multimodality therapy for LRA E/GEJ ACA may result in a greater risk of recurrence and decreased survival.
Randomized, single-centered, phase II clinical trial of nimotuzumab plus cisplatin and S-1 as first-line therapy in patients with advanced gastric cancer.
Authors: Wang Jin-Wan , Chi Yihebali , Zheng Zhao-xu , Qu Tao , Zhou Ai-Ping , Yang Lin , Jiang Wen-chang , Shi Shu-zhen , Sun Yong-kun , Song Yan , Kang Su-yi 
Published: March 2020

e14668 Background: Nimotuzumab, a humanized IgG1 anti-EGFR monoclonal antibody, has demonstrated efficacy associated with an absence of severe skin toxicity in many phase I/II cancer trials. Methods: This is a single-center, parallel assignment and open-label study randomized to receive a infusion Cisplatin (30mg/m2/d, on day 1 and 2) and oral S-1 (80mg/m2/d, twice daily on day 1-14) every 3 weeks, either alone or together with Nimotuzumab (200 mg as a infusion on day 1, 8 and 15) (CS or NCS) as 1st line in patients with advanced or metastatic gastric cancer. The observation points were ORR, TTP, PFS, 1-year survival rates and safety. Results: 62 patients, 43 men and 19 women, median age 57 years (22-76 years), on good performance status (ECOG PS 0-2, one prior regimen) were treated with NCS (n = 31) or CS (n = 31). Up to 2012-01-16, 57 patients (NCS 30 cases compared with CS 27 cases) have undergone efficacy assessment. The objective response rate (ORR: PR 15) was 50% (15/30) in NCS group compared with (ORR: pCR 2+ PR 15) 63.0% (17/27) in CS group. Disease control rate was 96.7% and 96.3%, respectively. Until the same day, 36 patients have achieved progression in both groups (NCS 15: CS 11), median TTP was 5 months in NCS group compared with 3 months in CS group, and average TTP was 4.9 months and 4 months, respectively. The incidence of adverse events was similar between both groups. Adverse events included grade 3/4 hypo-hemoglobin 13.33%/7.41%, grade 3/4 thrombocytopenia 3.33%/0 and grade 3/4 neutropenia 3.33%/0. One patient experienced grade 3/4 digestive side effects 3.33%/0. Conclusions: The results have demonstrated benefit in TTP improvement. Further investigation is ongoing.
A study of activated carbon nanoparticles guided dissection of lymph nodes in radical gastric cancer surgery.
Authors: Keshari Rajiv Prasad , Zhou Zhiwei , Chen Gong , Yuan Shuqiang 
Published: March 2020

e14674 Background: Gastric cancer is common and a leading cause of cancer deaths in the world. Lymph node(LN) status is important prognostic factor. As per AJCC, atleast 15 LNs to be dissected for accurate nodal staging and prognosis. More LNs dissections may reduce the possibility of skip metastases, thus, less recurrence and proper staging of the disease. Activated Carbon Nano-particle(AcCNP) can map a large number and even smallest lymph nodes. The objective of this study is to detect and dissect maximum number of LNs during radical gastrectomy by using AcCNP lymphatic mapping. Methods: 40 patients, Gr. A (22) experimental and B (18)control group, pathological diagnosis- Adenocarcinoma of stomach, AJCC staging I-IIIB. Time duration- 2008 to 2009, Institution- SYSUCC, Guangzhou,China, Plan- Radical Gastrectomy with extended lymphadenectomy. Neo-adjuvant given patients were excluded. A 1 ml of AcCNP was injected in the subserosa of the stomach at four different sites of the tumor border. All visible stained/nonstained LNs were dissected. The LN's size and the number were recorded. After pathological reports, descriptive analysis and t-test were performed to calculate the mean, median, ratio, range, frequency and predictive value for the accuracy and viability of the study. Results: Total LNs dissected-1254, Gr.A-772 (mean-35.41) and Gr.B- 482 (26.78). There was difference between total LNs dissected (p-value- 0.046). In Gr. A, 590 blackened and 182 non-blackened LNs resected. The ratio to the total number of LNs was ≥70%. LNs size in Gr. A was 0.03 to 0.5 cm and 0.80 to 1.5 cm in Gr. B, p-value: 0.000. No statistical differences between the two groups in age, sex, pTNM staging and histo-pathological type with p-value - 0.305, 0.369, 0.828 and 0.425 respectively, and in tumor size, Gr. A (5.59 cm) and Gr. B (3.72), p-value of 0.78. Conclusions: Lymph node detection procedure by intra-operative injection of Ac. carbon nanoparticle during radical gastrectomy is feasible in all stages of gastric cancer, with high detection rate and almost nil morbidity or mortality. It is safe, cost-effective and an effective tracer for lymphatic mapping procedure. It can be an appropriate tool for more accurate staging of gastric cancer.
Comparative outcome of sorafenib treatment in central Europe and Russia.
Authors: Bisovskaya Yulia , Pinter Matthias , Scheithauer Werner , Peck-Radosavljevic Markus 
Published: March 2020

e14681 Background: Sorafenib is the standard treatment for advanced stage HCC. Here we compare outcomes in 2 cohorts of HCC patients from two large oncologic referral centers in Russia (R) and Austria (A). Methods: 69 pts (19 f/50 m) with HCC (BCLC A/B/C/D 1/30/38/0) in R and 148 pts (27 f/121 m; n. s. between cohorts) with HCC (BCLC A/B/C/D 0/26/104/18) in A were treated with standard dose of sorafenib 400 mg bid until progression or death between 2006 and 01/2012. Dose reductions were due to side effects. Survival was evaluated using Kaplan-Meier analysis and compared by log-rank test. Prognostic factors evaluated were pretreatment BCLC stage, Child-Pugh stage, and etiology of liver disease (viral/non-viral). Results: BCLC-staging distribution was significantly different between R and A centers with more patients in advanced st BCLC-C in A (A 70% vs. R 55%, p<0.0001). Patients also had more advanced stage liver disease in A (Child-Pugh stage A/B/C = 52/37/11%) compared to R (A/B/C = 85/15/0%; p<0.0001). Overall survival in A (median 7.4 mo; 95% CI 5.5 – 9.3) compared to R (median 9 mo; 95% CI 7.6 – 10.4) was not significantly different between the two cohorts (p=0.144). When analyzed according to BCLC-stage (B and C), survival in st B pts (A 11.2 vs. R 11.0; p=0.286) as well as st C pts (A 8.9 vs. R 6.4; p=0.62) was not different between the two cohorts. When evaluated according to severity of liver disease (non-cirrhotics/Child-Pugh A and Child-Pugh B), survival in non-cirrhotics/Child-Pugh A patients (A 11.3 mo vs. R 9.0 mo; p=0.746) and Child-Pugh B patients (A 5.5 mo vs. R 3.3 mo; p=0.481) was again not different between these two cohorts. Patients with viral etiology were more common in R (48%) than in A (34%) but not significantly so (p=0.06). Survival in patients with viral (A 10.2 mo vs. R 8.7 mo; p=0.644 ) or non-viral etiology of chronic liver disease (A 6.7 mo vs. R 9.7 mo; p=0.089) was also not significantly different. Conclusions: Overall survival and survival in various subgroups analyzed was not significantly different between the two cohorts. Sorafenib treatment in Russia compared to European Institutions seems to offer a comparable benefit for patients with intermediate/advanced stage HCC, independent of severity or etiology of the underlying liver disease.
An educational tool as an aid for making decisions about the initial treatment of gastric cancer.
Authors: Ravdin Peter , Peterson Lindsay , Rowe Julie 
Published: March 2020

e14684 Background: Tools for making individualized numerical estimates of outcomes and to provide useful information are revolutionizing medicine. We have produced such a tool for decision making for patients with gastric cancer [GC] for whom neo/adjuvant therapy might be an option to be considered. Methods: We widely reviewed the medical literature and meta-analyses about adjuvant and neoadjuvant treatment for potentially resectable [GC]. We also reviewed the guidelines' statements about what is considered appropriate treatment for patients. In addition we used information about individual prognosis based on information from the SEER registry, the AJCC, and also as supplemented from the medical literature. Results: Examination of the medical literature shows the value of adjuvant chemotherapy and radiation for [GC]. For example, and recent GASTRIC meta-analysis of 31 trials found that a benefit for overall survival (hazard ratio [HR], 0.82; 95% CI, 0.76-0.90) and for disease-free survival (HR, 0.82; 95% CI, 0.75-0.90). There is also a substantial literature supporting the use of these regimens in the neoadjuvant setting (such as the MAGIC study with benefit in overall survival (HR for death, 0.75; 95% CI, 0.60 to 0.93). We found however that these HRs were rarely accompanied with estimates of absolute benefit. A typical quote from the GASTIC analysis is "Five-year overall survival increased from 49.6% to 55.3% with chemotherapy," which reflects the outcomes for an average patient. This information is implied as the basis for treatment recommendations for treatment, but numerical estimates of what is gained are not given in such texts as the NCCN guidelines. Our analysis of the SEER data showed disease specific [GC] mortality at 3 years to range from 4% for patients with low grade stage 1a disease to 49 % for patients with high grade stage IIIa disease. Conclusions: Integrating the information about the base line risks for negative outcome with hazard ratio estimates of the effective therapy we can make individualized estimates of outcome. We have also included in the tool substantial additional information about the nature of the disease, past and ongoing trials, and the safety and efficacy of the treatment opinions.
The clinical significance of neutrophil-lymphocyte ratio versus platelet-lymphocyte ratio in patients with metastatic gastric cancer.
Authors: Lee Suee , Oh Sung Yong , Kwon Hyuk-Chan , Kim Sung-Hyun , Lee Ji Hyun , Kim Min Chan , Kim Ki-Han , Kim Hyo-Jin 
Published: March 2020

e14686 Background: Several inflammatory response materials could be biomarkers for prediction of prognosis of cancer patients. The neutrophil/lymphocyte ratio (NLR), and the platelet/lymphocyte ratio (PLR) has been introduced for prognostic scoring system in several cancer. The objective of this study was to determine whether the neutrophil-lymphocyte ratio (NLR), or the platelet-lymphocyte ratio (PLR) are significant prognostic marker in metastatic gastric cancer. Methods: We analyzed 150 patients with metastatic gastric cancer who received mFOLFOX regimen as the first-line chemotherapy. The NLR and PLR were calculated from complete blood counts in baseline laboratory test before the first cycle chemotherapy. Results: The overall response rate was 34.7% and stable disease was 38.7%. The median progression-free survival (PFS) was 4.2 months (95% CI, 3.5-4.8 months) and the median overall survival (OS) was 13.1 months (95% CI, 10.6-15.5 months). Kaplan-Meier analysis and log-rank test revealed that higher NLR (≥3) was a good prognostic biomarker of OS (p=0.024), but not associated with PFS (p=0.838). The PLR was not associated with PFS and OS (p=0.373 and p=0.304, respectively). In Cox regression analysis for predicting OS, younger age, good performance status, response of chemotherapy, and lower NLR (<3) were independent prognostic markers (Hazard ratio 2.052, 95% CI 1.370-3.075, p<0.001, hazard ratio 8.467, 95% CI 1.937-37.017, p=0.005, hazard ratio 1.889, 95% CI 1.222-2.921, p=0.004, and hazard ratio 1.616, 95% CI 1.080-2.416, p=0.019, respectively). Conclusions: Although prognosis in metastatic gastric cancer was associated with age and performance status, the NLR might be simple and prognostic index for metastatic gastric cancer.
Prognostic factor analysis of second-line chemotherapy in advanced biliary tract cancer.
Authors: Lee Sang-Cheol , Kim Kyoungha , Kim Hanjo , Kim Hyun Jung , Kim Se Hyung , Bae Sang-Byung , Kim Chan Kyu , Lee Namsu , Lee Kyu Taek , Park Sung Kyu , Won Jong-Ho , Yun Jina , Hong Dae Sik , Park Hee Sook 
Published: March 2020

e14688 Background: There is no evidence that second-line chemotherapy in advanced biliary tract cancer (BTC) will result in substantial prolongation of survival. The purpose of this study was to evaluate prognostic factors for the survival of patients with advanced biliary tract cancer who was refractory BTC for first-line chemotherapy. Methods: We reviewed 89 patients retrospecitively with advanced biliary tract cancer who had enrolled in two clinical trials at three branches of Soonchunhyang university hospital. They received palliative chemotherapy with 2 regimens (biweekly GEMOX and modified FOLFOX-6). GEMOX is consist of gemcitabine 1,000 mg/m2 intravenously on day 1 and oxaliplatin 85 mg/m2 intravenously on day 2 every 2 weeks and mFOLFOX-6 is that oxaliplatin 85mg/m2 and folinic acid 400 mg/m2 on day 1 follwed by a 5-FU bolus 400 mg/m2 and 46-h infusion 2400 mg/m2 every 2 weeks. To evaluate the clinicopathologic factors that affected overall survival, univariate and multivariate analyses were performed on the baseline factors. Results: 89 patients were enrolled from Sep 2006 to Aug 2010. Medain age was 62.14 years (range 35-81). Univariate analysis revealed 4 prognostic factors affecting overall survival after first-line chemotherapy. Performance status of 0-1 vs >2 (p=0.014), salvage chemotherapy (p=0.021), locoregional disease vs disseminated disease (p=0.046) and responder of first-line chemotherapy (p=0.025) was revealed. Multivariate analysis found 2 prognostic factors affecting overall survival. They were salvage chemotherapy and initial responder. Conclusions: This results suggest that 2nd-line chemotherapy is needed for patients with good performance and responder of initial chemotherapy.
Imageable orthothopic metastatic mouse models for the identification of the antitumor and antimetastatic efficacy of traditional Chinese medicine (TCM).
Authors: Zhang Lei , Wu Chengyu , Zhang Yong , Wang Xiaoen , Reynoso Jose , Hoffman Robert M. , Zhao Ming 
Published: March 2020

e14700 Background: Traditional Chinese Medicine (TCM) is still poorly understood with regard to the types of cancer it is effective against, as well as its mechanism of action. Modernization of TCM evaluation is necessary in order for TCM to be effectively developed. We report here on the use of patient-like orthotopic nude-mouse models of metastatic cancer to obtain proof-of-concept that TCM combinations can have anti-tumor and anti-metastatic activity. Methods: In the present study, human and mouse lung cancer and pancreatic cancer cell lines (H460, Lewis lung carcinoma [LLC] and MIA-PaCa-2, respectively), labeled with red fluorescent protein (RFP) or green fluorescent protein (GFP) were used. The cells were initially implanted subcutaneously or injected in the tail vein in nude mice. Subcutaneous tumors were harvested to obtain tissue fragments which were implanted orthotopically in nude mice. These models were used to evaluate the anti-tumor and anti-metastatic efficacy of the TCM termed Fufang LQ (LQ), which contains a mixture of Chinese herbs. Results: LQ (gavage, 600 mg/kg/day) significantly inhibited pancreatic and lung cancer tumor growth as measured by imaging, tumor and weight in both subcutaneous and orthotopic models. LQ was significantly efficacious against primary and metastatic cancer in the above models without weight loss in contrast to drugs such as doxorubicin and cisplatin, which caused significant weight loss. Survival of tumor-bearing mice was also prolonged by LQ treatment. Conclusions: The results of the present study indicate that TCM can have non-toxic efficacy, in contrast to standard chemotherapy drugys, against metastatic pancreatic and lung cancer in clinically-relevant orthotopic mouse models of cancer, an important step toward the clinical development of TCM.