bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II trial of sorafenib (S) and capecitabine (C) for hepatocellular carcinoma (HCC) in cirrhotic patients (pts).
Authors: Rojas-Hernandez Cristhiam Mauricio , Patt Yehuda Z. , Fekrazad M. Houman , Steinberg Kim A. , Roach Mary , Lee Fa-Chyi 
Published: March 2020

e15136 Background: S is the currently approved treatment for HCC. C has antitumor activity in HCC and biliary tree cancers. The combination of the two, if tolerated, could possibly improve antitumor response, and patient-overall survival (OS). Methods: This phase II trial of S and C accrued unresectable HCC pts. with histologically confirmed disease or radiological characteristics of HCC in cirrhotics with an elevated AFP of > 400 ng/mL. Eligibility criteria were: ECOG Performance status of ≤ 2, Child-Pugh (CP) class A or B-7 cirrhosis, hemoglobin ≥ 8.5 g/dL, platelets ≥ 50,000/µL, ANC ≥ 1500 cells/µL, and a serum creatinine of ≤ 2.0 mg/dL (creatinine clearance > 30 mL/minute). HIV+ patients were excluded. All subjects received a combination of S and C, on a 14-day treatment schedule. S dose was started at 400 mg BID daily with dose adjustments for hand foot syndrome. Starting C dose was 850 mg/m2BID for 7 days and a 7-day break; doses were adjusted as tolerated. The primary end point was assessment of safety and tolerability. OS and disease control rate (DCR) were also estimated. Results: 15/47 assessed pts. met inclusion criteria. One patient was never treated and excluded from analysis. Response data were available on 13 and safety data on all 14. Median pts.’ age was 64 years (56-79), and 75 % were male. Etiologies included viral hepatitis (64%), or viral hepatitis and alcohol in another 29%; 50% of pts. had CP class A (5-6) and 50% B-7 cirrhosis. With a median follow up of 12 months (M), median OS (mOS) was 11.3 (95% CI, 2.7-21.3) M. DCR was 54% (CR 8%, PR 15% and SD 31%). Grade 3-4 adverse events included: thrombocytopenia 9(64%), neutropenia 1(7%), anemia 2(14%); electrolyte imbalance, hypophosphatemia 3(21%), hypomagnesemia 2(14%), hypocalcaemia 1 and hyponatremia 1 (7%) each. Liver abnormalities included; hyperbilirubinemia 3(21%), increased AST 2(14%). Skin and mucosal abnormalities included hand-foot syndrome 3(21%), mucositis 1, alopecia 1 and skin rash 1 each. DVT occurred in 3 (21%). Conclusions: At tolerable doses, S and C seem active and safe palliative treatment for HCC in CP A & B-7 cirrhotics. It was associated with a DCR of 54% and mOS of 11.3 M. The small sample size does not allow comparison with single agent S. Clinical trial information: NCT01032850.
Early therapy response assessment by apparent diffusion coefficient (ADC) quantification following glass-based yttrium-90 radioembolization for unresectable hepatocellular carcinoma (HCC).
Authors: Kokabi Nima , Camacho Juan C. , El-Rayes Bassel F. , Kauh John S. , Kim Hyun Sik 
Published: March 2020

e15140 Background: Early objective imaging biomarker assessment of infiltrative HCC following Y90 radioembolization is not well understood. Early diffusion weighted imaging (DWI) of treated lesions was evaluated and correlated with anatomical treatment response using modified response evaluation criteria in solid tumors (mRECIST). Methods: In an IRB approved prospective proof of concept study, 10 consecutive patients (89% men, median age 55) with unresectable infiltrative HCC and portal vein thrombosis underwent Y90. MR imaging was obtained pre-Y90, 1 and 3 months post-Y90. DWI fat-suppressed single-shot echo-planar sequence with tri-directional diffusion gradient was performed (b=50,400,800 s/mm2). Using pixel-based ADC maps, mean values of treated lesions and surrounding tumor-free liver were measured by manually drawing a noncircular region of interest around corresponding areas on the same image slice. Treatment response was evaluated using mRECIST with complete response as non-enhancement of treated lesion. T-test was performed using SPSS Statistics v20.0 (IBM, Armonk, NY) and significance set at < 0.05. Results: On 30 day post therapy MR and based on mRECIST, 70% of patients had objective response (CR=30%, PR=40%, SD=20%, PD=10%). Mean pre and post-Y90 ADC value of cancer-free liver was 1.10 × 10−3 and 1.08 × 10−3 mm2/sec (p=0.65). Mean ADC value of all treated tumors pre and post-Y90 was 0.82 × 10−3 and 1.19 × 10−3 mm2/sec respectively (p <0.001). Correlating with mRECIST treatment response, mean post-Y90 ADC of lesions with objective and those with no objective response were 1.03 × 10−3 mm2/sec and 1.26 × 10−3 mm2/sec respectively (p=0.003). While there was a significant difference between ADC values of lesion with objective response vs. others, no significant difference was observed at baseline ADC of tumors with eventual objective response vs. others. Corresponding ADC values on 30 and 90 day followup scans were unchanged. Conclusions: Mean ADC value measured 30-days post-therapy shows promises as an objective imaging biomarker to assess treatment response following Y90 therapy for infiltrative HCC.
PERCIST criteria to predict survival at 3 months following intra-arterial resin-based yttrium-90 (Y-90) radioembolization therapy of unresectable intrahepatic cholangiocarcinoma refractory to standard chemotherapy: A proof of concept study.
Authors: Camacho Juan C. , Kokabi Nima , Schuster David M. , Kim Hyun Sik 
Published: March 2020

e15141 Background: To investigate the prognostic value of PET Response Criteria in Solid Tumors (PERCIST) on predicting survival in patients with unresectable intrahepatic cholangiocarcinoma (ICC) after resin-basedYttrium-90 (Y-90) radioembolization. Methods: IRB approved prospective correlative study in ICC patients refractory to standard chemotherapy who had 18F-FDG PET-CT before and after Y-90 therapy. Measurable tumor was defined as a lesion ≥ 1 cm in diameter and maximum standardized uptake ((max) SUV) ≥ 2.5. (Max) SUV was measured in targeted and non-targeted lesions after local therapy (overall response). PERCIST criteria defined complete response (CR) as no FDG uptake within target lesion, and partial response (PR) as reduction of 30% in FDG (max) SUV peak in measurable lesions. Objective response included PR/CR. PET imaging was acquired pre-treatment, 1-3-and-6 months following Y90. Survival analyses were carried out with Kaplan–Meier and Log-Rank proportional models using SPSS software v20 (IBM, Armonk, NY) with significance set at <0.05. Results: 9 consecutive patients were enrolled (56% men, mean age 58). Median overall survival from Y90 was 21.7 months. Average max SUV pretreatment was 10.02 and after Y90, 6.03. At 1-month after Y90, target PERCIST criteria showed CR= 1 (11.1%), PR=1 (11.1%), SD=7 (33.3%) and PD=0 (0.0%). Following 3-month after Y90, target response was CR= 2 (22.2%), PR=3 (33.3%), SD=3 (33.3%) and PD=1 (11.1%). No correlation between survival and either target or overall PERCIST criteria response on 1-month follow-up scan was seen(p=0.260). Statistically significant prolonged overall survival was observed for patients with objective targeted response based on PERCIST criteria at 3-month scan (P=0.022). In addition, objective overall PERCIST response at 3-month showed significant correlation with overall survival (p= 0.011). Conclusions: In patients with unresectable ICC refractory to standard chemotherapy, PERCIST criteria at 3-months following Y-90 therapy predict overall survival.
A retrospective analysis of early CA19-9 progression in salvage-chemotherapy for refractory pancreatic cancer.
Authors: Nakai Yousuke , Isayama Hiroyuki , Sasaki Takashi , Takahara Naminatsu , Kogure Hirofumi , Yamamoto Natsuyo , Hirano Kenji , Ijichi Hideaki , Tateishi Keisuke , Tada Minoru , Koike Kazuhiko 
Published: March 2020

e15146 Background: Early response assessment is important to differentiate patients (pts) who will benefit from salvage chemotherapy (sCx) for refractory pancreatic cancer (PaC), given its palliative nature. CA19-9 has been reported as a prognostic factor in the first-line treatment, but little data is available in sCx. Methods: Pts receiving sCx for refractory PaC at the University of Tokyo Hospital were retrospectively studied. Serum CA19-9 was measured prior to the initiation of each course. Cumulative progression-free (PFS) and overall survival (OS) were calculated by Kaplan-Meier analysis and compared by log-rank test. Prognostic value of CA19-9 change prior to 2nd course was evaluated using a landmark method. Finally, multivariate analyses by the Cox proportional hazard model were performed for PFS and OS. Possible prognostic factors were age, gender, PS, disease status, metastatic site, pretreatment albumin, LDH, CRP, CA19-9, CA19-9 change prior to 2nd course, prior PFS, treatment line (2ndline or beyond) and sCx agents. Results: A total of 167 pts (a median age of 65, 95 males, 21 recurrent and a median previous PFS of 5.8 Mo) received 239 regimens as sCx including S-1(n=87), CPT-11 (n=53), GEM+oxaliplatin(Ox) (n=20), S-1+Ox(n=29), GEM (n=14) and S-1+paclitaxel iv+ip (n=12). Median PFS and OS were 2.7 (95%CI, 2.4-3.1) and 6.1 (95%CI, 5.3-7.2) Mo, respectively. Early CA19-9 progression was defined as CA19-9 increase >17.8%, a median value of CA19-9 change prior to 2nd course in this study population. Median PFS and OS were 2.6 vs. 1.0 Mo and 7.5 vs. 3.6 Mo (p<0.001) after landmark CA19-9 measurement in pts with and without CA19-9 response. Multivariate analyses demonstrated early CA19-9 progression was a negative prognostic factor of both PFS and OS (HR 1.75 and 2.04, p<0.001). Pretreatment serum markers (albumin, LDH, CRP and CA19-9) were prognostic of OS, but not PFS. Conclusions: Early CA19-9 progression was a negative prognostic factor of both PFS and OS in S-Cx for refractory PaC. Early termination should be considered in these patients who would less likely benefit from sCx.
The clinical effects of hepatic artery infusion of recombinant adenoviral human p53 gene combined with local chemo- and radiotherapy in treatment of advanced hematocarcinoma.
Authors: Xiao Shaowen , Geng Jianhao , Zhang Shanwen 
Published: March 2020

e15166 Background: Advanced are generally resistant to both chemo- and radio-therapy. P53 gene has multiple anti-cancer functions including sensitizing tumor cells to chemo- and radio-therapy. Methods: Twenty-two patients with an age of 51.5±19.0 years old, 15 males and 7 females, 21 in stage IV and 1 in stage III, were treated with combination of p53 gene, chemo- and radio-therapy. Recombinant adenoviral human p53 gene (rAd-p53) was given through hepatic artery pump at a dose of 2 x 1012 viral particles once per week for 4-9 times. The chemo-regimen consisting of doxorubicin 20mg/m2 and Oxaliplatin 40mg/m2were administered through the same pump once a week for 4-8 times. Intensity modulated radiation therapy were given at a total dose of 20 – 60 Gy in 4 weeks. Results: The overall response rate at 3 months after treatment was 31.7% (7/22, 1/22 in CR and 6/22 in PR). Thirteen patients (59.1%) were stable. Medium overall survival and progress free survival time were 11 and 5.5 months, respectively. The survival rates of one year, two years and three years were 31.8%, 13.6%, and 4.5%, respectively. No serious adverse events or complications observed. Conclusions: Combination of local p53 gene, chemo- and radio-therapy is effective and safe treatment regimen for advanced hepatocarcinoma.
Epidermal growth factor receptor as a prognostic predictor to chemoradiotherapy in the primary lesion of esophageal squamous cell carcinoma.
Authors: Gao Zhenhua , Meng Xue , Mu Dianbin , Sun Xindong , Yu Jinming 
Published: March 2020

e15167 Background: Concurrent chemoradiotherapy (CCRT) is standard performed for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Some reports have revealed that patients who responded well to CCRT had favorable outcomes, whereas poor responders conversely showed a worse prognosis. The aim of this study was to identify molecular markers predicting prognosis to CCRT. Methods: Forty-seven patients with locally advanced ESCC who were treated with CCRT were included in the present study.The regimen comprised 5-fluorouracil and cisplatinumcombined with radiation therapy (1.8-2Gy/day). The chemotherapy was repeated every 3 weeks and the total radical radiation dose was 60-64Gy.The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of epidermal growth factor receptor (EGFR), which were determined by immunohistochemistry in biopsy specimens obtained before treatment. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patients survival. Results: Overall the indices of the overexprssions of EGFR (the percentage of immunoreactivetumor cells≥50%) in all patients were 59.6%. EGFR expression was no significantly associated with gender,age,tumor differentiation grade,tumor location,depth of invasion, and metastasis status except for lymph node status (P=0.011). A significant difference was seen in the overall survival between patients with or without EGFR overexpression group(P=0.024). However, overexpression of EGFR was not associated with local recurrence or distant metastasis.In addition, a relationship between overall survival and sex (P=0.021),age (P=0.018),T stage(P=0.035), and tumor location (P=0.023) was detected.Local recurrence was found has a relationship with T stage(P=0.015) and metastasis status (P=0.026),and distant metastasis was found has a relationship with age (P=0.048). Conclusions: EGFR overexpression determined in pretreatment biopsy specimens maybe a clinically useful biomarker for predicting the overall survival of ESCC patients.
Comparative efficacy and safety analysis of sorafenib in patients with advanced hepatocellular cancer (HCC) with varying liver dysfunction: A south Texas institutional analysis.
Authors: Al-Rajabi Raed Moh'd Taiseer , Ketchum Norma , Dierschke Nicole A. , Lu Ting Wei , Pollock Brad H. , Mahalingam Devalingam 
Published: March 2020

e15171 Background: Sorafenib (SOR) is the first systemic therapy to improve survival in patients (pts) with advanced (HCC), mainly amongst pts with Child-Pugh (CP) A cirrhosis. In the US however, HCC pts often present with ECOG status ≥ 1 and CP B cirrhosis. The GIDEON study reported variation in disease characteristics and treatment patterns for US pts compared to rest of the world. Our aim was to further assess clinical efficacy and safety of SOR at our institution’s minority rich South Texas HCC population. Methods: We reviewed medical records of HCC pts who received SOR from 2008-2011. The association between demographic, clinical and laboratory variables with overall survival (OS) and progression free survival (PFS) were assessed by comparison of Kaplan-Meier curves. Groups were statistically compared by the log rank test and the magnitude of association with outcome was summarized as the hazards ratio with 95% confidence interval (CI). Results: A total of 67 pts were included. Median age 55 (range 41-93), males 83%, Hispanic 76%, CP A 59% vs B 39%. The median OS (mOS) was 10.0 months (mo) (95% CI: 7.2-18.3) and median PFS (mPFS) was 4.9 mo (95% CI: 3.1-7.1); both comparable to reported efficacy of the SHARP trial. In subgroup analysis, mOS was 12.8 (95% CI: 7.7–18.3) vs 7.2 mo (95% CI: 2.6–24.4) for CP A and B (HR 0.72, 95% CI: 0.37–1.38, p = 0.32), respectively. CP A pts had a mPFS of 5.9 (95% CI: 1.6–10.0) vs 3.6 mo (95% CI: 4.4–7.6) with CP B pts (HR 0.77, 95% CI: 0.45–1.34, p = 0.36). Pts on SOR daily dose of 800 mg had a better mOS at 12.8 (95% CI: 6.9–24.4) vs 8.7 mo (95% CI: 2.0–15.8) compared to those on 400 mg (HR 0.58, 95% CI: 0.29–1.15, p = 0.11). Although no significant difference in efficacy was noted between ethnicities, pts ≥ 60 years had an improved mOS at 15.9 (95% CI: 6.9–24.4) vs 7.9 mo (95% CI: 2.0–15.8) amongst pts < 60 (HR 0.56, 95% CI: 0.28-1.12, p = 0.10). There was no difference in toxicity observed. Conclusions: SOR was well tolerated in both CP A and B groups. Efficacy analysis showed a trend towards improved survival among pts with CP A treated with a daily dose of 800mg. The improved efficacy of SOR among pts ≥ 60 may be related to a more indolent HCC in this age group.
A phase II study of TR105 in patients with hepatocellular carcinoma (HCC) who have progressed on sorafenib.
Authors: Duffy Austin G. , Rahma Osama E. , Ulahannan Susanna Varkey , Fioravanti Suzanne , Venkatesan Aradhana , Turkbey Ismail B. , Choyke Peter L. , Trepel Jane B. , Figg William Douglas , Greten Tim F. 
Published: March 2020

e15177 Background: CD105, also known as endoglin, is an endothelial cell membrane receptor that is highly expressed on tumor vasculature, including HCC. CD105 is essential for angiogenesis and its expression is upregulated by hypoxia and VEGF inhibition. TRC105 is a chimeric IgG1 anti-CD105 monoclonal antibody that inhibits angiogenesis and tumor growth by endothelial cell growth inhibition, ADCC and apoptosis. Methods: Patients with HCC and compensated liver function (Childs Pugh A/B7), ECOG 0/1, were enrolled to a single arm phase II study of TRC105 15mg/kg IV every 2 weeks. Patients must have progressed on or been intolerant of prior sorafenib. A Simon optimal 2-stage design was employed with a 50% 4-month PFS target for progression to the second stage. Correlative biomarkers evaluated included: DCE-MRI; FDG-PET; color Doppler ultrasonography; circulating endothelial progenitor cells, plasma levels of angiogenic factors; soluble CD105 and tumor IHC for CD105. Immunogenicity studies were also performed. Results: 8 pts have been treated so far; M:F 6:2; Median age = 58 (range 24-67); 7 pts had progressed following sorafenib (N=1 intolerant). N=1 pt had fibrolammellar HCC. There were no grade 3/4 treatment-related toxicities. Most frequent toxicities were headache (G2; N=3) and epistaxis (G1; N=4). One patient with a history of ischemic heart disease developed acute cardiac syndrome during the first infusion and was replaced. No patient was progression free at 4 months by RECIST criteria. Median time on study was 8 weeks (range 4-16 weeks). Median no. of doses administered was 4 (range 2-7). Preliminary evidence of biologic response was seen on DCE-MRI in 1pt (of 3 evaluable) with a reduction in kTrans and kep and 3pts (of 3 evaluable) who demonstrated reduction in intra-tumoral color flow on color Doppler. Conclusions: TRC105 is well tolerated in this HCC population post-sorafenib. Although there was biological evidence of antiangiogenic activity it is unlikely that the study will proceed to the second stage. Full clinical and correlative data for the first stage of the study will be presented. Future role of TRC105 in HCC will most likely be as combination therapy with sorafenib or other anti-VEGF therapy. Clinical trial information: NCT01375569.
Laparoscopic transhiatal esophagectomy with neoadjuvant chemotherapy to treat carcinoma of the upper esophagus.
Authors: Wu Ji-xiang , Yu Lei , Li Jian-ye 
Published: March 2020

e15181 Background: Esophagectomy for Carcinoma of the upper esophagus has traditionally been performed by open methods. Results from most series include mortality rates in excess of 5% and hospital stays frequently greater than 14 days. Laparoscopic transhiatal esophagectomy (LTHE) with neoadjuvant chemotherapy has the potential to improve these results and may lead to a sound outcome, but only a few articles have reported it. The objective of this study is to investigate the method of LTHE with neoadjuvant chemotherapy treating cervical esophageal cancer. Methods: From 2011 to 2012, LTHE was performed in 15 patients with carcinoma of the upper esophagus. There were 11 men and 4 women. Median age was 64 years (range, 44–79). Indications for operation included high-grade dysplasia (n = 4) and cancer (n = 11). Neoadjuvant chemotherapy was used in 15 patients. Results: There was no conversion to open procedure. LTHE was successfully completed in 15 patients. The median intensive care unit stay was 1.5 days (range, 1–8); hospital stay was 10.5 days (range, 8–23). Anastomotic leak rate was 6.7% (n=1). At a mean follow-up of 13 months (range, 1–24), quality of life scores were similar to preoperative values and population norms. Conclusions: LTHE with neoadjuvant chemotherapy is a safe and relatively advanced, complex procedure with little blood loss and less-invasion. Its long-term outcome needs to be investigated with large-volume cases.
Clinical features of long-term survivors (LTS) of advanced hepatocellular carcinoma undergoing molecular targeted therapy (MTT).
Authors: Lu Li-Chun , Shao Yu Yun , Chan Soa-Yu , Hsu Chih-Hung , Cheng Ann-Lii 
Published: March 2020

e15182 Background: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is generally dismal. However, some patients enjoyed long survival under MTT. This study sought to clarify the clinical features of these patients. Methods: Patients with advanced HCC (Barcelona-Clinic Liver Cancer stage C) who were enrolled in six clinical trials of first-line MTT between May 2005 and December 2010 at National Taiwan University Hospital, Taipei, Taiwan were included. LTS (> 2 years) were identified, and their clinical variables were reviewed and analyzed. Results: Twenty-two LTS (11.6%), with a median age of 58.3 years, were identified from 189 patients. The median overall survival of LTS was 58.7 months. Among them, 17 (77.3%) patients were male, and 13 (59.1%) patients had chronic hepatitis B virus infection. Compared with patients who survived less than 2 years, LTS were less likely to have α-fetoprotein > 400 ng/mL, liver involvement, or macrovascular invasion. LTS were more likely to have Okuda stage I disease, and lower Cancer of the Liver Italian Program scores. Regarding response to the first-line therapy, LTS had significantly higher response rates (50.0%) and disease control rates (86.4%). The median progression free survival of LTS was 13.0 months. After first-line treatment failure, 13 (59.1%) LTS received 2nd-line or more systemic therapies, and 15 (68.2%) LTS underwent loco-regional therapy, such as surgery, radiofrequency ablation, or transarterial chemoembolization. Seven (31.8%) LTS who received salvage loco-regional treatments remained disease-free for a median time of 27.0 months. Conclusions: LTS of advanced HCC appear to be a group of patients who had less aggressive disease status and were able to receive further loco-regional therapy.