bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weekly docetaxel and cisplatin with capecitabine and bevacizumab (AVDCX) in patients with advanced esophagogastric cancer: Results of a phase Ib/II study.
Authors: Purim Ofer , Kundel Yulia , Sadeh Gonik Udi , Idelevich Efraim , Medalia Gal , Gordon Noa , Sulkes Aaron , Brenner Baruch 
Published: March 2020

e15078 Background: Many efforts are being made to improve treatment options for advanced esophagogastric cancer (AEGC). The aim of this phase Ib/II study was to evaluate the safety and efficacy of a novel regimen, AVDCX, consisting of weekly docetaxel and cisplatin together with capecitabine and bevacizumab, in AEGC. Methods: Patients with AEGC received treatment with different dose levels of AVDCX (cisplatin and docetaxel 25-35 mg/m2, days 1,8, capecitabine 1,600 mg/m2days 1-14, bevacizumab 7.5 mg/kg, day 1, Q:21 days). To assure regimen's safety a short phase Ib part, with three dose levels, was planned. The study's primary objectives were to establish the recommended phase II doses of docetaxel and cisplatin in AVDCX and to determine the tumor response rate. Results: The study was closed early, after the accrual of 22 patients, due to accumulating toxicity-related deaths. The median age was 59 years and 77% of patients had gastric or gastroesophageal adenocarcinomas. Grade ≥3 adverse events were documented in 18 patients (82%) and these were usually neutropenia (36%), fatigue (54%) or diarrhea (23%). There were three fatal toxicities (14%): mesenteric thromboembolism, gastric perforation and pancytopenic sepsis. Eventually, the recommended phase II doses of cisplatin and docetaxel were determined to be 25 mg/m2 and 30 mg/m2, respectively. Twenty-one patients were evaluable for response: 12 (54%) had partial response (PR), 4 (18%) had stable disease (SD) and none had complete response (CR). The objective response rate (CR+PR) was 54% and the disease control rate (CR+PR+SD) was 72%. Eighteen patients (82%) derived a clinical benefit: improvement of pain, weight or performance status without a deterioration of any of these factors, from treatment. The median overall survival was 11.3 months (range, 1.5-39.2+ months) and median progression-free survival was 8.7 months (range, 1.3–26.6 months). The 2-year OS rate reached 22.7%. Conclusions: AVDCX was associated with bevacizumab-related fatal toxicities. It seems to reproduce the efficacy of bevacizumab regimen AVAGAST trial, without a clue for significant improvement over common docetaxel regimens in AEGC.
Assessment of prognosis in hepatocellular carcinoma (HCC) using biomarkers and serum measurements.
Authors: Teng Mabel Joey , Nathavitharana Ravindhi Lakmalee , Fox Richard , Berhane Sarah , Skowronska Anna , Johnson Philip James 
Published: March 2020

e15093 Background: Factors that influence prognosis in HCC are well-recognised. They include tumour size and number, the severity of liver dysfunction and the symptomology. Several staging systems combining a number of these factors offer an estimate of prognosis. Some concerned that these staging systems encompass factors that are inherently subjective, e.g. the extent of HCC in CLIP or the use of performance status in BCLC. This have led to the development BALAD score by Toyoda et al, using serum Bilirubin and Albumin and three biomarkers: alpha-fetoprotein-L3 (L3), Alpha-fetoprotein (AFP) and Des-gamma-carboxy prothrombin (DCP). This system was developed in a Japanese population which has mainly HCV-related HCC. Our aim was to develop an objective staging system using the three biomarkers for a western population and compared it to BALAD to assess its performance. Methods: 317 subjects with HCC were recruited from Birmingham, UK between 2007 and 2011. Blood samples were collected at the time of diagnosis. Liver, renal functions plus AFP, L3 and DCP were measured. L3 and DCP were measured by microchip capillary electrophoresis and liquid-phase binding assay on a uTASWako i30 auto analyzer (Wako Pure Chemical Industries Ltd, Japan). Results: Univariable and multivariable regression analyses were performed. Our scoring system (CRCTU score) was developed based on a flexible baseline hazard functions fitted using restricted cubic splines. Suitable fractional polynomials (FP) were used to explain relationship between the outcome and covariates. The level of discrimination achieved using the risk groups was assess by Harrell’s–C statistic. The CRCTU score permitted identification of 4 clearly distinct subgroups as indicated both graphically and by Harrell’s-C values. Both the CRCTU and BALAD scores return Harrell’s-C values of 0.7. Conclusions: We have shown that it is possible to use entirely objective markers to predict prognosis of HCC in a western population. Our model is comparable to the BALAD with the same variables included. However, our treatment of variables with FP is much more robust statistical technique for continuous variable as compared to having artificial categories that were seen in the BALAD system.
A phase II study of cabazitaxel in patients with previously treated metastatic gastroesophageal adenocarcinoma.
Authors: Austin Trevor Clark , Perez Kimberly , Fontes-Borts Lucia , Luppe Denise , Jean Maureen , Olszewski Adam J. , Rosati Kayla , Rathore Bharti , Safran Howard 
Published: March 2020

e15095 Background: Cabazitaxel is a semi-synthetic novel taxane with activity in docetaxel refractory prostate cancer. We sought to determine the response rate of cabazitaxel in patients with advanced gastroesophageal adenocarcinoma that had progressed after at least 1 prior therapy for metastatic disease. Methods: This open label single arm phase II study followed a Simon two-stage design. The study was designed to differentiate between a 10% level of activity and a 30% level of activity and was to be terminated if the response rate was unlikely to be > 10%. Eligibility criteria included patients with gastroesophageal cancer with measurable disease after at least 1 prior regimen for metastatic disease. ECOG PS 0-2; ANC > 1,500/µL, AST/ALT ≤ 3x ULN, total bili ≤ ULN. Pts initially received cabazitaxel 25 mg/m2 IV every 21 days but after 9 patients were entered, the dose was reduced to 20 mg/m2due to toxicity. Results: The data safety monitoring board (DSMB) reviewed data after 13 pts were entered. Pt characteristics included 11 men, 2 women; median age, 70 yrs [range, 55-80]. Nine pts had ≥ 2 prior regimens. Ten pts had previous treatment with a taxane. Of 13 pts, no objective antitumor responses were observed and all 13 developed evidence of disease progression. A median of 2 cycles were given, up to a maximum of 6 cycles in 2 pts. The PFS rate at 3 months was 15%. The DSMB considered cabazitaxel ineffective and terminated the study. The probability of erroneously concluding the treatment was active (p ≥ 0.3) was < 0.0419. Grade 3 or 4 adverse events occurred in 6 pts (46.1%), in which neutropenia (n=4) and pneumonia (n=1) were grade 4. Grade 3 toxicities included ANC (n=1), anemia (n=2), nausea (n=2), weakness (n=2), diarrhea (n=1), pleural effusion (n=1), typhilitis (n=1), vomiting (n=1). Conclusions: Cabazitaxel monotherapy demonstrated no antitumor efficacy in previously treated gastroesophageal cancer. Clinical trial information: NCT01365130.
Treatment of right-sided hepatocellular carcinoma with uni-lobar y-90 radioembolisation and induction of hypertrophy in the the contralateral left lobe.
Authors: Chow Pierce K. H. , Teo Jin Yao , Allen John Carson , Ng David Chee Eng , Lo Richard H. G. , Tay Kiang Hiong , Goh Anthony , Khor Andrew Yu Keat , Goh Brian , Cheah Foong Koon 
Published: March 2020

e15102 Background: Yttrium-90 microsphere (Y90) is currently used to treat locally advanced hepatocellular carcinoma (HCC) including those where resection is precluded because of inadequate future remnant liver. Hypertrophy of the contralateral lobe after Y90 treatment has been reported. This study aims to quantify this hypertrophy and identify factors predictive of this response. Methods: Radiological review of patients undergoing Y-90 with treatment delivered via right hepatic artery for advanced HCC between January 2008 – January 2012 was performed. Diagnosis of HCC was by AASLD criteria and patients must have at least one follow-up scan in our institution. Excluded were: tumour in the contralateral lobe, concomitant other treatment for HCC, patients enrolled in clinical trials. Pre- and post-treatment images were reviewed and volumes were measured using 3D software. Statistical analysis was conducted using SPSS version 16.0. Results: During this period 50 patients treated with Y90 for HCC had follow-up imaging at our institution. Of 37 patients with right-sided Y90 treatment, 11 had concomitant left-sided disease treated with TACE and RFA, 7 had follow-up scans of inadequate quality to perform accurate volumetric assessment, 2 had pre-treatment scans performed at another institution which were not accessible for study purposes. Seventeen (17) patients thus fulfilled criteria. Mean and median left-lobe hypertrophy were 34.2% (SD±35.9%) and 31.7% (range -19.0 – 106.5%) respectively at a median of 5 months post-treatment. Univariate analysis identified no specific pre-treatment factor predictive of the degree of left lobe hypertrophy. There were no cases of acute liver failure after administration of SIRT in this study and none of the patients developed disease in the contralateral lobe over the study period. Conclusions: In patients with HCC receiving SIRT to the right lobe via the right hepatic artery, a significant degree of left lobe hypertrophy results. This opens the possibility of the utilisation of SIRT as neoadjuvant therapy for borderline resectable HCC, thus increasing the pool of potentially operable and curable patients.
A prospective cohort study to reduce operative risk in stage I gastric cancer patients with metabolic syndrome: Preoperative exercise versus surgery alone.
Authors: Cho Haruhiko , Tsuburaya Akira , Hirabayashi Naoki , Shirai Junya , Aoyama Toru , Hayashi Tsutomu , Yamada Takanobu , Yoshikawa Takaki , Morita Satoshi , Sakamoto Junichi 
Published: March 2020

e15112 Background: Although obesity influences the technical difficulty of surgery, a reasonable marker of abdominal obesity is not confirmed and effective intervention has never been applied to reduce the operative risk in patients with abdominal obesity. Methods: To reduce the surgical difficulty and risk in gastric cancer patients with abdominal obesity, a preoperative exercise protocol was designed for stage I gastric cancer patients who were diagnosed to have metabolic syndrome (MetS). Results: In total, 51 patients (33 who underwent surgery alone, 18 who were treated with preoperative exercise) were registered in this study. Visceral fat areas (VFA) were estimated by CT scan, and they were associated most strongly with waist, followed by HDL cholesterol, and BMI. In the exercise group, all patients completed protocol treatment, without disease progression and > grade2 exercise-associated adverse events. VFA of the exercise group were larger than that of the surgery alone group at registration (221cm2 /180cm2, p=0.028), then reduced after exercise to non-significant level with surgery alone group (201cm2 /180cm2, p=0.264). There were no significant differences of intraoperative blood loss (262mL/201mL: p=0.465) and incidence of perioperative morbidity (27.7%/29%, p=1.000) between exercise and non-exercise groups. Multivariate logistic regression analysis detected intraoperative blood loss (> 380mL) as significant risk factor (p=0.023) for perioperative morbidity. Conclusions: Waist was surrogate marker for VFA in this study, thus can be a candidate of simple indicator of abdominal obesity. Preoperative interventional exercise did not directly reduce operative risk of gastric cancer with MetS; however, it was associated indirectly with risk reduction by improving surgical difficulty.
Benefits of percutaneous ethanol injection in the treatment of advanced hepatocellular carcinoma.
Authors: Misauno Micheal Ayedima , Isichei Mercy Wakili 
Published: March 2020

e15119 Background: Hepatocellular carcinoma (HCC) is a devastating disease in which survival measured in months from time of diagnosis. Incidence is highest in Asia and Africa with high prevalences of hepatitis B and hepatitis C being strong predisposing factors. HCC is screened and diagnosed early in developed countries but this is not obtainable in our practice where patients present late, with severe abdominal pain and mass and therapeutic options are limited. Percutaneous ethanol injection (PEI) introduced twenty years ago for palliation of inoperable hepatocellular carcinoma is an option we are just exploring. This study was aimed at evaluating the benefits of percutaneous ethanol injection in the management of advanced hepatocellular carcinoma. Methods: With IRB clearance, informed consent was obtained from consecutive patients diagnosed with HCC. Patients with jaundice, signs of liver failure and coma were excluded from this study. They were randomized to Ethanol treatment in form of absolute alcohol manufactured by Riedel-de Haen, Germany “Group one” or routine pain control management (DF118) “Group two”. Baseline investigations and pain score using Visual Analogue Scale (VAS) was obtained for both groups. PEI was administered via ultrasound guided intra-tumour injection of 10- 50mls of ethanol at each sitting. Investigation and pain score were obtained weekly for four weeks then monthly at follow up. Data obtained from August 2010 to July 2012 was analyzed using Epi Info. Results: “Group one” 32 patients had (PEI), “Group two” 32 (DF118) out of an initial 82; 18 patients were excluded. Mean age was 40.4+/- 14.2 yrs, range of 18 to 60 yrs. Group one had 28 (87.5%) males and 4 (12.5%) females; Group two 29 (90.6%) males and 3 (9.4%) female. All patients had Right hypochondrial pain and mass. Pre intervention pain score ranged from 6-9 for both groups while post intervention pain score a week after was 1 -2 for group 1, and group 2 required regular analgesics to control their pain. Mean survival durations were 8 months and 2.5 months for groups 1 and 2, respectively. Conclusions: We conclude that percutaneous ethanol injection significantly reduces the pain of advanced hepatocellular carcinoma.
Clinicopathologic characterization and prognostic factor in extraintestinal neuroendocrine tumors.
Authors: Leon Rodriguez Eucario , Perez Alvarez Sandra Ileana , Macedo Omar , Escobar Elizabeth 
Published: March 2020

e15131 Background: The frequency, prognostic factors and long-term survival of E-NET are poorly known. Methods: A retrospective analysis of clinical, histological characteristics and survival of patients with E-NET were done. Survival analyses were assessed by the Kaplan-Meier method and prognostic factors of overall survival were tested by uni/multivariate analysis. Results: Between 1997-2010, 241 patients were identified with NET. 31 Patients were E-NET (12.8%): median age was 55 years (16-79) and 55% were females. Primary location was lung, 58%, prostate 13%, breast 10%, urinary bladder 7%, and others 12%. At diagnosis 87% patients had symptoms and 52% were localized. A functioning tumor was in 7 patients (6 ACTH). Initial treatment was surgery 61%, chemotherapy 26% (23% had objective response) and palliative care 13%. After complete resection 4/14 patients recurred. With follow-up of 15months, the cancer-specific mortality was 55%. Overall 1- and 5-year survival were 72% and 35% respectively, which were lower than survival for GEP-NET (p=0.001, Figure 1). 5 year survival differed significantly according to age at diagnosis (47% ≤50 vs 27% >50 years); location (60% lung vs 10% non-lung); extension (58% localized vs 15% metastatic/locally advanced); stage at diagnosis (59% stage I-II vs 13% III-IV); histology (52% NET/carcinoid vs 14% NEC); degree of differentiation (44% well/moderately vs 0% poorly differentiated); initial treatment (55% surgery, 25% palliative care and 0% chemotherapy); and recurrence (100% absent vs 25% present). In univariate analysis, the negative prognostic factors were age >50 years, no lung site, symptomatic, metastatic/locally advanced disease, extrahepatic metastases, NEC, poor differentiation and recurrence. In multivariate analysis, only age >50 years was an independent predictor of survival (p=0.027). Conclusions: In our experience, E-NET represent 13% of all the NET. Present symptoms with a fewer frequency, are less functional, have more frequently metastases, and a worst prognosis (5-year survival 34 vs 72%). The most important prognostic factor for overall survival was age >50 years.
Gemcitabine combined with capecitabine compared to gemcitabine with or without erlotinib as first-line chemotherapy in patients with advanced pancreatic cancer: Comparative effectiveness study.
Authors: Cho Jangho , Lim Jae Yun , Cho Jae Yong 
Published: March 2020

e15132 Background: Gemcitabine is the standard treatment for advanced pancreatic cancer. Though capecitabine and erlotinib are accepted as combination agent with gemcitabine, those two combination regimens have not been compared directly in clinical trial. This study compared the efficacy and tolerability between gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM) as first-line chemotherapy in patients with advanced pancreatic cancer. Methods: We collected data ofpatients if they met the following criteria: histologically or cytologically confirmed ductal adenocarcinoma of the pancreas; unresectable/metastatic disease; treated with one of GEM, GEM-X, and GEM-T as first-line treatment; measurable or evaluable lesion; age more than 18 years; Eastern Cooperative Oncology Group performance status 0, 1, or 2; and adequate hematologic, hepatic, and renal function before first-line chemotherapy. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Results: Between January 2007 and November 2011, a total of 127 patients received one of GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved the objective response rate (21.2% vs. 12.7% and 15.9%), progression-free survival (8.9 vs. 5.2 and 3.9 months; p < 0.001) and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. The incidence of adverse events was not significantly different among groups. Conclusions: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in locally advanced and metastatic pancreatic cancers. It is worthy to further investigate which agent has clinical advantage as combination drug with gemcitabine in pancreatic cancer and to explore predictive markers for each regimen leading to personalize anti-cancer treatment.
Locally advanced or metastatic pancreatic adenocarcinoma (PA): Prognostic factors for prolonged survival.
Authors: Ploquin Anne , Cozzolino Camille , Truant Stephanie , Piessen Guillaume , Desauw Christophe , Cattan Stéphane , Hebbar Mohamed 
Published: March 2020

e15134 Background: Prognosis of pts with locally advanced or metastatic PA is poor, with median survival of 6-9 months. Yet, since the use of gemcitabine, some patients survive more than one year. Recently, FOLFIRINOX regimen yielded better results in selected patients, but with more toxicity. We assessed the value of baseline predictive factors of prolonged survival in non-selected pts treated with gemcitabine. Methods: We conducted a monocentric, retrospective study (1999 to 2010) on all pts treated for locally advanced or metastatic PA. Demographical, clinical, tumoral and biological variables were included into the analysis. The primary end-point was the 12 months survival. All parameters were assessed in univariate and multivariated analyses. We then built a prognostic scoring system integrating the independent prognostic factors. Results: The study was performed on 160 pts: median age 61.1 years, sex ratio (M/F) 93/67, ECOG 0-1/2-3: 60/98, jaundice 62 (38.8%), initially resectable : 36 (22.5%), intra-pancreatic primary location: head: 110 (68.8%), body: 19 (11.9%), tail: 27 (16.9%). The adenocarcinoma was histologically document in 124 cases (77.5%). The median number of metastasis sites was 1 (71.3% liver). The median Ca 19-9 concentration was 925 IU/ml. 155 pts (96.9%) received chemotherapy, of which 124 (80.0%) with gemcitabine in first line. Fifty-two patients (32.5%) were alive 12 months after diagnosis. In univariate analysis, male gender, PS, initial stage, differentiation, primary tumor location, Ca 19-9 were prognostic factors. In multivariate analysis, male gender, head or body locations and low Ca 19-9 concentration (< 111 IU/ml) were associated with a better prognosis. The score with a cut-off between 2 and 3 points was discriminant, with positive and negative predictive values of 64.7% IC-95% [59.2-70.2] and 75.3% IC-95% [74.4-76.2], respectively. The rate of correctly classified pts was 73.6% IC-95% [72.8-74.4]. Conclusions: Male gender, pancreatic head or body location, and Ca 19-9 < 111 are independent prognostic factors for prolonged survival. Further analyses are needed to determine more accurately pts suitable for gemcitabine or the more recently validated regimen FOLFIRINOX.
A three-gene expression signature model to predict neo-chemoradiotherapy response of esophageal squamous cell carcinomas.
Authors: Wen Jing , Yang Hong , Luo Kongjia , Hu Yi , Zhang Xu , Wang Geng , Chen Yuping , Chen Zhijian , Lin Ting , Wang Huiyun , Liu Mengzhong , Fu Jianhua 
Published: March 2020

e15135 Background: Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could prediction CRT response. In this study, we aim to identify mRNA markers for ESCC CRT-response prediction. Methods: Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery. Surgical specimens were assessed for the pathological response to CRT. The identified differentially expressed genes were validated by real-time quantitative polymerase chain reaction (qPCR), based on which a classifying model was built up by Fisher’s linear discriminant analysis. The predictive power of this model was further assessed in another set of 32 ESCCs. Results: The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than 2-fold changes between pathological complete responsers (pCRs) and less than pCRs (<pCRs), among which 6 genes (LIMCH1, SDPR, Clorf226, SLC9A9, GSTM3, and IGSF10) were down-regulated and 4 genes (MMP9, MMP1, MMP12 and OASL) up-regulated in pCRs versus <pCRs. A prediction model based on qPCR values of 3 genes was built up, Y=-10.388 - 0.343 × MMP1 + 0.642 × LIMCH1 + 0.921 × Clorf226 with a cut-off value of 0.607. It provided a predictive accuracy of 85.7% with leave-one-out cross-validation. Further, the predictive power of this model was validated in another set of 32 ESCCs, among which a predictive accuracy of 81.3% was achieved. Conclusions: The combination of three genes by qPCR identified by microarrays in our study provides possibility for ESCC CRT prediction, which will facilitate individualization of ESCC treatment. Further perspective validation in larger independent cohorts is warranted to fully assess the predictive power of this prediction model.