bluuebunny/crossref_metadata_2025_split huggingface dataset:
Best supportive care (BSC) with or without low-dose chemotherapy (chemo) in frail elderly patients with advanced gastroesophageal cancer (aGOAC): The uncertain randomization of the GO2 phase III trial.
Authors: Swinson Daniel , Hingorani Mohan , Stokes Zuzana , Dent Jo , Guptal Kamalnayan , Chatterjee Anirban , Kamposioras Konstantinos , Grumett Simon Aird , Khan Mohammad , Marshall Helen , Ruddock Sharon , Allmark Christine , Katona Eszter , Howard Helen C , Velikova Galina , Lord Simon , Hall Peter S , Seymour Matthew T. 
Published: May 2019

4051 Background: Before 2000, trials comparing BSC +/- chemo for aGOAC showed overall survival (OS) benefit, but in predominantly fit patients (pts). We have revisited this question in a modern context, using low-dose chemo in a frail population, with comprehensive baseline health and frailty assessment. Methods: In the GO2 trial, elderly and/or frail aGOAC pts with a “certain” indication for chemo were randomised between 3 chemo doses. In this GO2 substudy, pts with an “uncertain” indication for chemo were instead randomised to BSC ± the lowest dose chemo. Pts were eligible if clinician and pt agreed the indication for chemo was uncertain. There was no PS threshold, but eGFR ≥30 and bili < 2xULN were required. Baseline assessment included global QL, symptom & functional scales, frailty and comorbidity. Randomisation was 1:1 to BSC alone, or with oxaliplatin 78 mg/m2 d1, capecitabine 375 mg/m2 bd d1-21 (modified if eGFR 30-50 ml/min or bili 1.5-2.0 xULN), q21d. QL was reassessed after 9 and 18 wks. The primary endpoint analysis was OS, adjusted for baseline factors. The sample size for this exploratory sub-study was not pre-set, but around 60 pts were anticipated. Results: 558 pts entered GO2 at 61 centres 2014-17, of whom only 45 pts (8%) at 21 centres entered this uncertain randomisation. This would provide 80% power at p = 0.05 (2-tailed) to detect an OS HR of 0.3. OS was shorter in pts with worse baseline PS (p<0.01) or distant mets (p<0.05). OS was not significantly improved with chemo; however we cannot exclude HR >0.32. QL deteriorated less with BSC+chemo than with BSC alone. Conclusions: In this frail, poor PS population, we observed a small survival benefit with chemo but this did not reach statistical significance. Clinicians should carefully consider BSC alone as a valid treatment option for aGOAC pts with poor PS and/or frailty. Clinical trial information: 44687907. [Table: see text]
Phase 1 open label trial of intraperitoneal paclitaxel (IPP) in combination with intravenous cisplatin (C) and oral capecitabine (X) in patients with advanced gastric cancer and peritoneal metastases.
Authors: Vatandoust Sina , Bright Tim F , Abbas M Nazim , Roy Amitesh Chandra , Watson David I. , Gan Susan S H , Scott-Hoy Alex , Bull Jeff A , Karapetis Christos Stelios 
Published: May 2019

4061 Background: IPP is a potential treatment option in patients with gastric cancer with peritoneal metastasis. IPP with a dose of 20 mg/m2 is well tolerated in combination with S1; however, this has been achieved in a specific genetic pool (Japanese population), and S1 is not available in some countries. We investigated the Maximum Tolerated Dose (MTD) of IPP in addition to a standard chemotherapy combination in an Australian population. Methods: Study population included synchronous or metachronous metastatic HER-2 non-amplified gastric adenocarcinoma with histologically/cytologically proven peritoneal involvement and adequate organ function. Intra-peritoneal catheter was placed surgically. 3 + 3 standard dose-escalation design was used. MTD was defined as the highest dose level at which ≤ 33% of patients had Dose Limiting Toxicity (DLT). DLT was defined within the first 3 cycles. Recommended Phase-2 Dose was defined as equal to the MTD, or cohort-3 dose if MTD was not reached. Treatment: maximum of six 21-day cycles of C (80mg/m2 IV day 1) + X (1000mg/m2 PO BD days 1-14) + IPP (days 1 and 8). IPP doses for Cohort-1, 2 and 3 were 10, 20 and 30mg/m2 respectively. Primary endpoint was the MTD of IPP. Secondary endpoints included safety, tolerability, overall response rate, ascites response rate, progression free survival and overall survival. Results: 15 patients were recruited in 3 cohorts: 9 males (60%), median age at study entry: 61y (range 32-82). All had synchronous metastatic disease and were chemo-naïve. Cohort-1 expanded to 6 patients due to 1 DLT (grade 3 diarrhea), cohort-2 included 3 patients (no DLT) and cohort-3 was expanded to 6 patients as planned and 1 DLT occurred (febrile neutropenia). MTD was not reached and Recommended Phase 2 Dose was determined as 30mg/m2. 8 patients (53%) completed all 6 cycles of treatment. The last patient on the study has completed 3 cycles and is expected to complete 6 cycles by April 2019. No grade 4 or 5 toxicity was recorded. Conclusions: MTD of IPP was not reached. IPP is safe in combination with C + X and the Recommended Phase 2 Dose is 30 mg/m2. Survival data will be presented when available. Clinical trial information: ACTRN12614001063606.
Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastroesophageal cancer.
Authors: Ma Lucy Xiaolu , Espin-Garcia Osvaldo , Lim Charles Henry , Sun Peiran , Jiang Di Maria , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Suzuki Chihiro , Chen Eric Xueyu , Liu Geoffrey , Swallow Carol Jane , Darling Gail Elizabeth , Wong Rebecca , Hafezi-Bakhtiari Sara , Conner James , Elimova Elena , Jang Raymond Woo-Jun 
Published: May 2019

4069 Background: A microscopically positive (R1) resection margin following resection for gastroesophageal (GE) cancer has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. Methods: A retrospective analysis was performed for patients (pts) with GE cancer treated at the Princess Margaret Cancer Centre from 2006-2016. Electronic medical records of all pts with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. Results: We identified 78 GE cancer pts with an R1 resection. 11% had neoadjuvant chemotherapy, 14% chemoradiation (CRT), 75% surgery alone. 28% had involvement of the proximal margin, 13% distal, 56% radial, 3% had multiple positive margins. By the American Joint Committee on Cancer 7th edition classification, 88% had a pT3-4 tumour, 66% pN2-3 nodal involvement, 64% grade 3, 68% with lymphovascular invasion. 3% were pathological stage I, 21% stage II and 74% stage III. Adjuvant therapy was given in 46% of R1 pts (24% CRT, 18% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS for all pts was 12.6 months (95% CI 10.3-17.2). Site of first recurrence was 71% distant, 16% locoregional, 13% mixed. Median OS was 29.3 months (95% CI 22.9-50) for all pts. The 5 year survival rate was 23% (95% CI 12%-43%). There was no significant difference in RFS (log-rank test p = 0.63, adjusted p = 0.14) or OS (log-rank test p = 0.68, adjusted p = 0.65) regardless of adjuvant therapy. Conclusions: Most pts with positive margins after resection for GE cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one pt had reresection. The main failure pattern was distant recurrence, suggesting that pts being considered for adjuvant RT should be carefully selected. Further studies are required to determine factors to select pts with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.
Ramucirumab (RAM) for sorafenib intolerant patients with hepatocellular carcinoma (HCC) and elevated baseline alpha fetoprotein (AFP): Outcomes from two randomized phase 3 studies (REACH, REACH2).
Authors: Llovet Josep M , Yen Chia-Jui , Finn Richard S. , Kang Yoon-Koo , Kudo Masatoshi , Galle Peter R. , Assenat Eric , Pracht Marc , Lim Ho Yeong , Rau Kun-Ming , Borg Christophe , Hiriart Jean-Baptiste , Daniele Bruno , Berg Thomas , Chung Hyun Cheol , Godinot Nathalie , Wang Chunxiao , Hsu Yanzhi , Schelman William R. , Zhu Andrew X. 
Published: May 2019

4073 Background: Oral multikinase inhibitors that have shown improvements in overall survival (OS) in HCC are associated with clinically important toxicities that commonly require dose adjustment or discontinuation (D/C) due to intolerance. REACH and REACH-2 studied RAM in patients (pts) with HCC who progressed on or were intolerant to sorafenib (SOR), and REACH-2 only enrolled pts with baseline AFP ≥400 ng/mL. In REACH-2 RAM treatment (trt) improved OS compared to placebo (P), supporting findings in REACH pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by reason for D/C of SOR was performed. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or P Q2W. A pooled independent pt data analysis (stratified by study) of REACH-2 and REACH pts (AFP ≥400 mg/mL) was performed. Results are reported by reason for SOR D/C (intolerance or disease progression). OS and PFS were evaluated using Kaplan-Meier method and Cox proportional hazard model. Objective response rate (ORR), disease control rate (DCR) and safety are reported. Results: Baseline characteristics in the pooled population were generally balanced between trt arms in each subgroup. Median durations of prior SOR were 2.5 mo for SOR intolerant (n = 70) and 4.0 mo for SOR progressors (n = 472). Median OS (RAM v P) was 10.2 v 6.7 mo for SOR intolerant and 8.0 v 4.7 mo for SOR progressors (Table). Rates of D/C due to trt-related adverse events (AEs) (Table) (7% in each subgroup), and Grade ≥3 AEs (most frequently hypertension) were consistent with those observed in each study. Conclusions: Acknowledging limitations of sample size, the RAM trt benefit in SOR intolerant pts was consistent with that in the ITT population. RAM was well tolerated in SOR intolerant pts with low rates of D/C due to related-AEs. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]
Multicentric prospettive study of validation of angiogenesis-related gene polymorphisms in hepatocellular carcinoma patients treated with sorafenib: Interim analysis of INNOVATE study.
Authors: Casadei Gardini Andrea , Marisi Giorgia , Dadduzio Vincenzo , Faloppi Luca , Ielasi Luca , Vivaldi Caterina , Rizzato Mario Domenico , Fornaro Lorenzo , Lonardi Sara , Gramantieri Laura , Pecora Irene , Foschi Giuseppe Francesco , Silvestris Nicola , Fornari Francesca , Orsi Giulia , Rovesti Giulia , Santini Daniele , Zagonel Vittorina , Cascinu Stefano , Scartozzi Mario 
Published: May 2019

4075 Background: In the ePHAS study we analyzed three eNOSpolymorphisms and at univariate analysis, patients with eNOS-786 -TTgenotype had significantly shorter median Progression Free Survival (PFS) and Overall Survival (OS) compared to those with other genotypes. On the basis of these preliminary results, our aim is to validate in a prospective study this data in patients with HCC treated with sorafenib. Methods: This is a prospective Italian multicenter study, that includes 141 HCC patients receiving sorafenib. We analyzed eNOS-786and itwas analyzed by Real Time PCR in relation to the primary end point (OS). Event-time distributions were estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Results: 141 HCC patients (122 males and 19 females), prospectively treated with sorafenib from May 2015 to September 2018 were included. Median age was 69 years (range 28-88 years). 120 patients had Child-Pugh A and 21 had Child-Pugh B7. 43 had BCLC-B and 98 patients had BCLC-C. Atunivariate analysis, we confirmed that eNOS-786 TT genotype were significantly associated with a lower median OS than the other genotypes (8.8 vs 15.7 months, HR 1.69, 95% CI 1.02-2.83 p=0.0424). Following adjustment for clinical covariates (age, gender, etiology, BCLC stage, serum α-FP level, MELD score), multivariate analysis confirmed eNOS- 786 and BCLC stage as the independentsprognostic factors predicting OS (TTvsTC+CC; HR: 2.39, 95% CI 1.14-5.03 p=0.0211; C vs B;2.23, 95% CI 1.44-4.77 p=0.039). Conclusions: Our prospective study confirms the prognostic role of eNOS-786 in advanced HCC patients treated with sorafenib. Clinical trial information: NCT02786342.
IGF-Child-Pugh score as a predictor of treatment outcome in advanced hepatocellular carcinoma patients treated with sorafenib.
Authors: Abugabal Yehia I. , Hassan Manal , Pestana Roberto , Xiao Lianchun , Girard Lauren , Raghav Kanwal Pratap Singh , Morris Jeffrey , Abdel-Wahab Reham , Wolff Robert A. , Yao James C. , Amin Hesham M. , Kaseb Ahmed Omar 
Published: May 2019

4076 Background: Our recent published studies concluded that Lower levels of Insulin like growth factors-I (IGF-I) is correlated with shorter overall survival (OS) in HCC, and IGF-CP scores assigned based on serum bilirubin, serum albumin level, prothrombin time, and plasma IGF-1 provides better prognostic stratification. Sorafenib is the first frontline drug approved for the treatment of CP class A patients with advanced HCC. CP class A is the standard criterion for active therapy and trials entry in HCC. In this study we aimed at evaluating the predictive ability of IGF-CP to sub-stratify old CP classes and better predict sorafenib outcomes. Methods: Total of101 patients were prospectively enrolled from MD Anderson Cancer Center (MDACC). Blood sample were collected and tested for IGF-I and IGF-CP was calculated into class A, B and C. Median OS and progression free survival (PFS) were analyzed, and log rank test was used to compare PFS and OS between subgroups of IGF-CTP score of patients. Results: Among CP class, patients who were reclassified as IGF-CP (B) (Old A/new B) had significantly shorter OS in months (m) was 7.6m (95% CI= 5.23-26.51m ) and PFS of 2.99m (95% CI=2.53-5.26m) with (P<0.001) in both, as compared to patients’ who classified as class A by both scoring systems (AA), who had OS of 15.43m (95% CI=12.3-31.18m) and PFS of 4.97m (95% CI=3.26-7.2m), (P<0.001) in both. Conclusions: IGF-CTP score sub-stratified CP A class, and provided better prognostic stratification and accuracy than CP score in predicting sorafenib survival outcomes in HCC. This approach may lead to a paradigm shift in predicting efficacy and toxicity of systemic HCC therapies and in stratifying patients for active therapy and selection in HCC clinical trials.
Randomized clinical trial of transcatheter arterial chemoembolization plus radiofrequency ablation versus transcatheter arterial chemoembolization for hepatocellular carcinoma with intermediate stage (BCLC stage B) hepatocellular carcinoma beyond Milan criteria.
Authors: Yin Xin , Tang Bei , Gan Yu-Hong , Wang Yan-hong , Chen Yi , Ge Ning-lin , Chen Rongxin , Zhang Lan , Zhang Boheng , Ren Zhenggang 
Published: May 2019

4077 Background: To determine treatment efficacy and safety of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) (hereafter, TACE+RFA) in patients with intermediate stage (BCLC stage B) hepatocellular carcinoma (HCC) beyond Milan criteria. Methods: In this randomized clinical trial, 110 patients with intermediate stage HCC beyond Milan criteria (single tumor with diameter 5-7cm, median; 3-5 multiple nodules with diameter less than 5cm) were included and randomly assigned to TACE+RFA group (n=55) and TACE group (n=55) at liver cancer institute, Zhongshan hospital. The primary endpoint was overall survival (OS). The secondary end point was progression-free survival (PFS) , time to progress (TTP) and best objective response (BOR). Results: The median OS in TACE+RFA and TACE group were 29 and 18 months, respectively. The median TTP and BOR were 15.7 months and 69.1 % in TACE+RFA group and 12.4 months and 40.0 % in TACE group (P=0.004). The 1-, 3-, and 4-year overall survivals for TACE+RFA group and TACE group were 97.2%, 67.9% and 59.4% versus 84.0%, 46.7% and 37.3% , respectively (P = 0.008). The corresponding PFS were 47.3%, 27.2% and 21.7% versus 35.6%,15.3% and 11.4% , respectively (P = 0.04).The incidences of major complications in TACE+RFA group were comparable to those in TACE group (P=0.14). Conclusions: TACE+RFA was superior to TACE in improving tumor response and overall survival for patients with intermediate stage (BCLC stage B) hepatocellular carcinoma beyond Milan criteria. Clinical trial information: NCT03636620.
Final analysis of phase II trial of regorafenib (REG) in refractory advanced biliary cancers (BC).
Authors: Kim Dae Won , Sanoff Hanna Kelly , Poklepovic Andrew Stewart , Tariq Fatima , Nixon Andrew B. , Liu Yingmiao , Kim Richard D. 
Published: May 2019

4083 Background: While gemcitabine plus cisplatin has demonstrated significant antitumor activity as 1st line therapy of BC, there is no effective treatment after failure of gemcitabine-based therapy. REG is an oral multi-kinase inhibitor that targets angiogenesis, oncogenesis and cancer proliferation/metastasis. We evaluated the efficacy of REG in BC. Methods: Patients (pts) with histologically proven BC who progressed on at least one line of systemic therapy received REG 160 mg daily 21 days on 7 days off, in 28 day cycles. The primary endpoint was 6-month (mo) overall survival (OS) and the secondary endpoints were median OS, progression free survival (PFS) and response rates (RR). Pre and post-treatment plasma were collected for cytokine evaluation. Results: A total of 39 pts received at least 1 dose of REG; 32 pts were evaluable for efficacy. Median age was 62 (range: 27-88) years and the primary sites of tumor were intrahepatic cholangiocarcinoma (68.8%), extrahepatic (18.8%), and gallbladder (12.5%). Pts were considered evaluable for efficacy if patients received more than 1 cycle of REG. For 32 evaluable pts, 6 mo OS was 52% with median PFS of 2.8 mo (95% CI: 1.1-4.5) and median OS of 7.9 mo (95% CI: 0-18.7). Median PFS and OS of the pts (n=20) failed 1 line of therapy were 3.7 mo (95% CI: 3.2-4.1) and 13.8 mo (95% CI: 1.8-25.8), respectively. Median PFS and OS of the pts (n=12) failed 2 lines were 1.8 mo (95% CI: 1.63-1.97) and 4.5 mo (95% CI: 2.6-6.3), respectively. RR was 9.4% (2 PR and 1 unconfirmed PR) and DCR was 62.5%. Total 71.8% of grade 3/4 adverse events (AE) were observed, and the most common AE were fatigue (56.4%) and hypertension (53.8%). Dose modification was required in 49% of the pts. Among the 23 cytokines analyzed, elevated baseline VEGF-A was associated with good prognosis (HR 0.62, p=0.01). Elevated baseline TIMP-1 (HR 1.79, p=0.04) and IL-6 (HR 1.33, p=0.05) were associated with poor prognosis. REG treatment decreased BMP-9, GP130, VEGF-R2 and VEGF-R3 and increased IL-6, PIGF, TIMP-1, VCAM-1 and VEGF-A significantly. Conclusions: The primary endpoint was met in this study. VEGF-A may be further evaluated as a predictive biomarker for REG in BC. Further randomized trials are warranted to confirm the efficacy and the correlative data. Clinical trial information: NCT02115542.
Clinical and molecular features of patients with cholangiocarcinoma harboring FGFR genetic alterations.
Authors: Boileve Alice , Baiev Islam , Dinicola Caroline , Horick Nora K , Tazdait Melodie , Zhu Andrew X. , Hollebecque Antoine , Goyal Lipika 
Published: May 2019

4084 Background: Genetic alterations (GAs) in the fibroblast growth factor receptor (FGFR) pathway are emerging as promising therapeutic targets in CCA. The clinical and molecular features of patients (pts) with CCA harboring FGFR GAs are reported here. Methods: A retrospective chart review was performed in pts with CCA who were found to have an FGFR GA on tumor molecular profiling as part of routine care. Data on demographics, risk factors, pathology, systemic therapy, radiographical response, progression free survival (PFS), and overall survival (OS) were collected. Results: Among 65 pts, the median age at diagnosis was 55 years old (range = 27-92), and 38 (58%) pts were female, 63 (97%) had intrahepatic CCA, and 5 (11%) had chronic HBV. At presentation, 37% of pts had resectable disease. Of 47 pts with a known CA 19-9 at the time of initial diagnosis, 21 (45%) had a value < 35U/mL. FGFR2 fusions were the most common FGFR GA (78%), followed by FGFR2 mutations (14%), FGFR3 mutations (4%), FGFR3 fusion (2%) and FGFR1 amplification (2%). The most common fusion partners were BICC1 (20%), POC1B (6%), SORBS1 (6%), DBP (4%), and TACC2 (4%). The most common co-alterations were in ARID1A, CDKN2A/B, TP53, BAP1, IDH1, HER2, BRCA2, and PTEN. The median lines of palliative systemic therapies received was 3 (range = 0-8), and 9/65 (14%) pts had > 1 FGFR inhibitor (FGFRi). For the 30 (46%) pts with FGFR2 fusions who received gemcitabine/platinum as first line palliative systemic therapy, the median PFS was 4.7 months (95% CI: 2.1-6.0). In the overall population, the median OS from time of initial diagnosis was 35.8 months (95% CI:29.7-52.7). Among 46 pts who received an FGFRi on a clinical trial and had ≥ 1 follow-up scan, the overall response rate (ORR) by RECIST v1.1 in pts with FGFR2 fusions, was 35.8% (14/39) on their first FGFRi; ORR was 16.7% (1/6) for pts with FGFR2 mutations. Conclusions: Pts with CCA harboring FGFR GAs were found to have a high rate of normal CA 19-9 and short median PFS on first line gemcitabine/platinum compared to historical controls but additional comparative studies are necessary to evaluate these findings.
Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma: A phase 2 study.
Authors: Sun Yongkun , Zhou Ai-Ping , Zhang Wen , Yang Lin , Cui Chengxu , Jiang Zhichao 
Published: May 2019

4089 Background: Gemcitabine plus cisplatin or S-1 can be used as first-line treatment for advanced or metastatic biliary tract adenocarcinoma. Multiple phase 2 studies found that gemcitabine, oxaliplatin, capecitabine, S-1 were not superior to gemcitabine plus cisplatin. Nab-paclitaxel plus S-1 was effective and well-tolerated in pancreatic cancer. Methods: Patients with pathological confirmed advanced or metastatic biliary tract adenocarcinoma (gallbladder carcinoma, intrahepatic cholangiocarcinoma ICC, extrahepatic cholangiocarcinoma ECC) were treated with Nab-paclitaxel plus S-1(Nab-paclitaxel 120mg/m2, d1 and d8; S-1 80-120mg/d, d1-14; q21d). Patients that received PR or SD (RECIST1.1)after 6 cycles were given S-1 maintenance treatment. The primary endpoint was ORR. The study used Simon’s Two Stage design. Results: From March 2016 to September 2018, we recruited 54 patients, with 27 males (50%). The median age was 58(34-73yrs). As of Dec 31 2018, the median treatment cycle was 4(1-6 cycles). 51 patients were evaluable for efficacy: PR 14(27.5%), SD 22 (DCR=PR+SD: 70.6%), PD 15 (29.4%). The median PFS was 6 months, and the median OS was 13.2 months. The response rate varied in different tumor location: gallbladder carcinoma 53.8% (7/13), ICC 18.2% (6/33), ECC 20% (1/5).Common grade 3/4 AEs were: leucopenia 17 (31.5%), hyperbilirubinemia 5(9.3%), Mucositis 4 (7.4%), neurotoxicity 2 (3.7%), diarrhea 2 (3.7%), omit 1(1.9%), fatigue 1 (1.9%), thrombocytopenia 1 (1.9%), ALT increase 1 (1.9%). Conclusions: Nab-paclitaxel plus S-1 as first line treatment for advanced or metastatic biliary tract adenocarcinoma was effective and well-tolerated, especially for gallbladder carcinoma (ORR 53.8%). This regimen need further exploration. Clinical trial information: NCT03830606.