bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of neoadjuvant chemoradiotherapy with cisplatin plus 5-fluorouracil and elective nodal irradiation for stage II/III esophageal squamous cell carcinoma: A 2-year follow up.
Authors: Kato Ken , Hashimoto Jun , Ito Yoshinori , Nagashina Kengo , Kojima Takashi , Daiko Hiroyuki , Akimoto Tetsuo , Hamamoto Yasuo , Matsushita Hisayuki , Katano Susumu , Hara Hiroki , Tanaka Yoichi , Saito Yoshihiro , Igaki Hiroyasu 
Published: February 2017

129 Background: Neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered the standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory and neoadjuvant chemoradiotherapy (NeoCRT) may improve the outcome of stage II/III ESCC patients. We conducted a feasibility study of NeoCRT with CDDP plus 5-FU and elective nodal irradiation in patients with stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, a Performance status (PS) of 0-1, and age of 20–75 years. Chemotherapy consisted of 2 courses of 5-FU infusion (1000 mg/m2, days 1–4) and a 2-h CDDP infusion (75 mg/m2, day 1), with a 4-week interval. Radiotherapy was concurrently administered to the primary tumor, metastatic lymph nodes, and regional lymph nodes (total dose of 41.4 Gy in 23 fractions. After completion of NeoCRT, transthoracic esophagectomy with extensive lymphadenectomy (>D2) was performed. The primary endpoint was the completion rate of NeoCRT with R0 resection. Results: Thirty-three patients were enrolled in this study between July 2010 and June 2011 and 2 were determined to be ineligible. Characteristics of the 31 eligible patients included, a median age of 63 years (range, 40–73 years), male/female: 28/3, PS 0/1: 19/12, and cStage IIA/IIB/III: 2/10/19. Median observation time was 30.0month. In total, 29 patients (93.5%) underwent NeoCRT with R0 resection. Among the patients who underwent surgery, there was 1 treatment-related death, and the incidence of operative morbidity was similar to that in previous studies. According to RECIST, the overall response rate was 78% (14/18) after CRT. Pathological complete response was achieved in 13 patients (42%) who underwent esophagectomy. The 2 years recurrence free survival rate 69.8%, and 2 years survival rate was77.4%, respectively. Conclusions: NeoCRT was well tolerated and found to be highly promising. A randomized controlled trial (JCOG1109) comparing with neoadjuvant chemotherapy was started. Clinical trial information: UMIN000004223.
Phase I/II trial of chemoradiotherapy concurrent with S-1 and cisplatin in patients with clinical stage II/III esophageal carcinoma: Results of the Japan Clinical Oncology Group study JCOG 0604.
Authors: Tahara Makoto , Fuse Nozomu , Mizusawa Junki , Sato Akihiro , Nihei Keiji , Kanato Keisuke , Kato Ken , Yamazaki Kentaro , Muro Kei , Takaishi Hiromasa , Boku Narikazu , Ohtsu Atsushi 
Published: February 2017

134 Background: We conducted a phase I/II trial of chemoradiotherapy (CRT) concurrent with S-1 and cisplatin to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and safety in patients with esophageal carcinoma. Methods: Eligibility criteria included histologically proven squamous cell or adeno carcinoma of the thoracic esophagus, clinical stage II/III excluded T4, PS 0-1, age 20 to 75, and no prior treatment. Chemotherapy consisted of administration of S-1 60-80 mg/m2/day on days 1-14, and cisplatin at 75 mg/m2on day 1, repeated twice every 4 weeks. Single daily radiation of 1.8 Gy in 28 fractions (total 50.4Gy) was given concurrently starting on day 1. For patients achieving an objective response after CRT, two additional cycles of chemotherapy were administered. The phase I part adopted the 3+3 cohort design. Planned sample size of 75 patients was calculated based on the weighting of threshold values of CR rate according to the registered proportion of T1-2 and T3. Results: Patient accrual was terminated early due to slow enrollment after 44 eligible patients were accrued from May 2007 to Sep 2011. Patient backgrounds were: 40 males, with median age 62 years, PS 0/1 (39/5), squamous cell carcinoma / adenocarcinoma (43/1), T1/T2/T3 (14/8/22) and N0/N1 (7/36). In the phase I part, two of six patients experienced DLTs at each level of S-1 (S-1 60 or 80 mg/m2/day). Considering treatment compliance, RD was determined as S-1 60 mg/m2/day. The CR rate, primary endpoint of phase II, was 59.5% (22/37; 90%CI, 44.6-73.1%; the weighted threshold, 57.2%; p=0.46) on central review. In the phase II part, 3-year progression-free survival was 47.3% and 3-year overall survival was 61.9%. Grade 3 or 4 toxicity in phase II part included leukopenia (57.9%) neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Conclusions: Although CRT with S-1 plus cisplatin showed acceptable toxicity and favorable 3-year survival, this study did not meet its primary endpoint. Clinical trial information: 000000710.
Thromboembolic events associated with cisplatin chemotherapy in patients with gastric and esophageal cancer: A single-institution experience.
Authors: O'Reilly Aine , Doherty Mark , Grogan William , Breathnach Oscar S. 
Published: February 2017

146 Background: Upper gastrointestinal tract malignancy, specifically gastric cancer (GC) , is associated with an increased risk of thromboembolic events (TEs). Cisplatin is important in the treatment of GC and oesophageal cancer (OC) but is associated with an increased risk of TEs. We aimed to characterise our experience of thromboembolism in patients (pts) with GC and OC receiving cisplatin. Methods: Patients with GC or OC who received cisplatin based chemotherapy from January 2011 to August 2013 were included in analysis. Retrospective review of patient’s clinical, laboratory and radiological data was pursued. Results: Seventy-four pts, 27 patients with GC and 47 pts with OC, received cisplatin based chemotherapy between January 2011 and August 2013. The median age at the start of chemotherapy was 67 (range 43-86), 48 patients (66%) were male. Nine pts experienced a TE. Seven pts experienced a venous TE (5 deep vein thrombosis (DVT), 1 pulmonary embolism (PE)), 1 pt experienced a middle cerebral artery occlusion and subsequently developed a PE while on therapeutic anticoagulation and 1 pt experienced 2 DVTs, the second occurred while therapeutically anticoagulated. Six pts received cisplatin in the context of metastatic GC, 3 (50%) pts experienced at least one TE. Haemoglobin level, leukocyte count, platelet count and body mass index (BMI) were not associated with TE risk. Twenty-one pts received cisplatin neoadjuvantly for locally advanced GC. Four pts (19%) in this subgroup experienced a least one TE. Haemoglobin level, leukocyte count and BMI were not associated with an increased risk of TE. Patients with a platelet count > 350,000/mm3 experienced more TEs (p<0.05). Forty seven pts were treated for OC, 7 pts with metastatic disease and 40 pts with locally advanced disease. Two pts experienced a single VTE (DVTs), both had locally advanced disease. Conclusions: Thromboembolic events are common in pts with metastatic and locally advanced GC, receiving cisplatin based chemotherapy. Future studies should focus on characterising the role of prophylactic anticoagulation in this subgroup and identifying biomarkers associated with increased risk of TE.
A mechanistic radiographic and biologic phase 2 study of sunitinib in relapsed/refractory esophageal (E) and gastroesophageal (GE) cancers.
Authors: Wu Christina Sing-Ying , Mikhail Sameh , Wei Lai , Martin Ludmila Katherine , Li Xiaobai , Timmers Cynthia Dawn , Chen James Lin , Tahiri Sanaa , Neal Alison , Walker Jon P , El-Dika Samer S , Rock Jonathan B , Clark Daniel , Yang Xiangyu , Foy Kevin , Liu James Jingyao , Knopp Michael V. , Kaumaya Pravin , Bekaii-Saab Tanios B. 
Published: February 2017

149 Background: Patients (pts) with relapsed or treatment-refractory E and GE cancers carry a poor prognosis. Inhibition of the vascular endothelial growth factor (VEGF) pathway may be a potential treatment approach. We conducted a phase II trial to assess the efficacy of sunitinib, a tyrosine kinase inhibitor that inhibits VEGFR 1 and 2. Methods: Pts received sunitinib 37.5 mg orally, daily. Primary endpoint was progression free survival (PFS) at 24 weeks. Secondary endpoints included overall response rate (ORR), overall survival (OS), PFS, and toxicity. Pts underwent serial functional imaging with DCE-MRI and measurements of serum VEGF, PIGF, VEGFR 2 and 3. Gene expression profiling and somatic mutational analysis using next-generation sequencing were also performed on tumor specimens (results to be presented at the symposium). Results: Clinical results are in the table. The PFS in the group that had clinical benefit [partial response (PR) + stable disease (SD)] with sunitinib was 99 days (95% CI: 74-161) vs. 39 days (95% CI: 26-42; Log-rank test p-value is <0.0001) in pts who had progressive disease (PD). By RECIST criteria, sunitinib non-responders demonstrated an initial reduction in tumor size but then subsequent rapid tumor size increase by week 6 as compared to baseline values. In contrast, sunitinib responders demonstrated at least stable disease through weeks 2-6. Changes in serum VEGF-A and VEGF-C levels from baseline to 2 weeks were associated with PFS (p=0.04 and p=0.03, respectively). Furthermore, baseline VEGF-C was also associated with PFS (p=0.03) and RECIST response (p=0.04). Conclusions: Although the primary endpoint was not met, these results suggest that there is a subgroup of patients with clinical response to sunitinib. Our correlative analysis indicated that circulating biomarkers, such as VEGF-C, are worthy of further research to help us identify this subgroup. Clinical trial information: NCT00702884. [Table: see text]
Association between polymorphisms of the FOXF1 and MHC locus genes and gastroesophageal reflux disease (GERD).
Authors: Liu Wei Fan , Lam Christine , Del Bel Ryan , Chan Kevin , Miller Linda , Brown M Catherine , Chen Zhuo , Cheng Dangxiao , Patel Devalben , Xu Wei , Darling Gail Elizabeth , Liu Geoffrey 
Published: February 2017

15 Background: GERD predisposes to Barrett’s Esophagus (BE), a precursor lesion to esophageal adenocarcinoma (EA). Recently a large genome-wide association study found two germline markers to be associated with BE, FOXF1 rs9936833 (C Allele) and MHC rs9257809 (A allele). An additional study linked FOXF1 rs9936833 to EA. We assessed whether these same polymorphisms are associated with GERD. Methods: Patients with reflux symptoms referred for esophageal manometry/24-hr pH monitoring at University Health Network (Toronto) were enrolled. DNA extracted from blood was genotyped using a Taqman PCR assay. GERD cases were defined as having DeMeester scores of ≥14.7 or prior evidence of reflux esophagitis on endoscopy. DeMeester < 14.7 defined controls. Logistic regression analysis, adjusted for clinical risk factors, was used to calculate odds ratios (95% confidence intervals) for each polymorphism relative to GERD. Results: Of 182 patients, the median age was 50 years, 62% were female and, 52% met the definition for GERD. Males, higher BMI, alcohol consumption, FOXF1, and MHC polymorphisms were each individually associated with GERD. In the multivariate analysis, after adjusting for gender and BMI, FOXF1 rs9936833 remained significant, with an aOR of 1.82 (95%CI: 1.1-3.0; p=0.02) for an increase in each C allele. MHC rs9257809 also remained significant, with an aOR of 9.36 (2.9-30; p<0.001) comparing AA to AG (there were no patients with GG). When both polymorphisms were placed in the same model, the aORs were 2.10 (1.2-3.5; p=0.006) and 11.0 (3.3-36; p<0.001), per increase in each risk allele, respectively. Conclusions: There are strong, significant associations for increased GERD risk by the C allele in FOXF1 rs9936833 and the A allele in MHC rs9257809 among patients complaining of reflux symptoms. FOXF1 is associated with development of gastrointestinal smooth muscle, possibly contributing to the contractibility of the gastroesophageal junction. The MHC polymorphism is in linkage disequilibrium with HLA alleles involved in T-cell regulation, suggesting the possibility of T-cell involvement in reflux esophagitis. WFL and CL are co-first authors. GL and GED are co-senior authors.
Real-world treatment patterns among patients with advanced gastric cancer in South Korea.
Authors: Cuyun Carter Gebra , Kaltenboeck Anna , Ivanova Jasmina , Liepa Astra M. , San Roman Alexandra , Koh Maria , Lee Hyun Jung , Rajan Narayan , Ballal Shaila , Birnbaum Howard , Bang Yung-Jue 
Published: February 2017

152 Background: This study explored treatment patterns, and cancer-related resource use of patients with metastatic and unresectable gastric cancer (MGC) in South Korea. Methods: Charts of patients ≥ 18 years old were reviewed by 30 physicians to collect de-identified data on MGC or gastroesophageal junction adenocarcinoma [diagnosis on or after January 1, 2009]. Patients received platinum/fluoropyrimidine first-line therapy followed by second-line therapy or best supportive care, had no other primary cancer, and did not participate in a clinical trial following MGC diagnosis. Patient characteristics and treatment patterns were summarized using descriptive statistics. Results: Of 198 patients, 74% were male; 78% were diagnosed with MGC after age 55 (mean=61 yrs); 47% were current or former smokers and 48% reported light to moderate alcohol consumption. The majority of tumors were located in the antrum/pyloris (52%); metastatic sites most often occurred in the peritoneum (54%), lymph nodes (48%), and liver (39%). At diagnosis, the mean Charlson comorbidity index was 0.4 (std dev=0.6). The most common comorbidities were chronic gastritis (23%) and cardiovascular disease (19%). Most patients (80%) received second-line treatment (ECOG scores: 0 -10%, 1 -66%, 2 -22%); 20% received best supportive care only. Single-agent fluoropyrimidine was reported for 22% of patients receiving second-line treatment; 20% were treated with irinotecan with a fluoropyrimidine or platinum agent. Second-line treatment was chosen mainly according to national guidelines (81%) and physician experience (35%). The most common symptoms during second-line treatment were nausea/vomiting (45%) and pain (11%), with antiemetics (45%), analgesics (37%) and nutritional support (11%) most often used as supportive care. Two-thirds of inpatient hospitalizations (30% of second-line patients had ≥ one) were for chemotherapy infusion. Outpatient hospitalization (16%) and visits to the oncologist (38%) were common among second-line patients. Conclusions: Most patients received second-line treatment, though regimens varied. Understanding MGC patient characteristics and treatment patterns in Korea will help address unmet needs.
Evaluation of usefulness of Royal Marsden Hospital prognostic index in second-line chemotherapy of advanced gastric cancer.
Authors: Sasaki Takahide , Komatsu Yoshito , Yuki Satoshi , Harada Kazuaki , Kobayashi Yoshimitsu , Fukushima Hiraku , Sakamoto Naoya 
Published: February 2017

163 Background: Royal Marsden Hospital prognostic Index (RMH-I), which was based on performance status, ALP, liver metastasis and peritoneal metastasis, was reported as prognostic factor of advanced esophago-gastric cancer before first line chemotherapy (Chau I, et al. J Clin Oncol 22:2395-2403, 2004). Usefulness of RMH-I in second line chemotherapy is not elucidated. Methods: Advanced gastric cancer patients who started second line chemotherapy in Hokkaido University Hospital from July 2001 to May 2013 with prior fluoropyrimidine plus platinum administration were retrospectively analyzed. Univariate and multivariate analysis for overall survival were performed using patient characteristics (RMH-I, hemoglobin, CRP, CEA, Alb, TTP in first line, primary lesion resection, and bone metastasis). Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 77 eligible patients. Male/Female were 52/25, median age was 60 years (range 31-80) and unresectable/recurrent were 70/7. Median survival was 7.1 months. The distribution and median survival for RMH-I groups were as follows: good risk (n = 8), 8.2 months; moderate risk (n = 57), 9.6 months; and poor risk (n = 12), 4.4 months. Although poor risk group showed shorter survival time, there were not significant difference regardless of RMH-I in Cox multivariate analysis (HR 1.12, 95%CI 0.61-2.09, P=0.72). Conclusions: In this retrospective analysis, RMH-I was not independent prognostic factor in second line chemotherapy of advanced gastric cancer. Prognostic factors in this population need to be investigated further.
Prospective phase II study of capecitabine and temozolomide (CAPTEM) for progressive, moderately, and well-differentiated metastatic neuroendocrine tumors.
Authors: Fine Robert Lance , Gulati Anthony Paul , Tsushima Dawn , Mowatt Kelley B. , Oprescu Anna , Bruce Jeffrey N. , Chabot John A. 
Published: February 2017

179 Background: We found in our lab that capecitabine (CAP), the prodrug of 5-FU, and temozolomide (TEM) were synergistic in inducing apoptosis in BON neuroendocrine tumor (NET) cell lines. We were the first to report in 2004 the use and mechanism of action of CAP and TEM (CAPTEM) in well differentiated NETs with promising results. Here we describe the interim analysis of an ongoing Phase II trial. Methods: 28 patients with metastatic well-moderately differentiated NET (ki-67 ≤20%) who had shown progression only on 60mg Sandostatin LAR (if octreotide scan positive) were treated with the following regimen: CAP 1,500mg/m2/day (PO divided BID, maximum 2,500 mg/day) on d1-14, and TEM 150-200mg/m2/day (PO divided BID, lower dose for patients who had prior chemotherapy or extensive radiation) on d10-14, with the next two weeks off, in a 28 day cycle. Primary objective was RR based upon RECIST, and secondary objectives included PFS, OS (from time of initiation of therapy), and toxicity evaluation. Other inclusion criteria were: age <80, ECOG PS 0-2, and adequate hematologic, renal, and liver function, and failure on high dose Sandostatin LAR. Results: 28 of 38 planned patients were enrolled with various NET subtypes (table). Overall RR was 43% (11% CR) and SD rate was 54%, with clinical benefit in 97%. ORR was 41% in carcinoid tumors. Ongoing mPFS is >20mo for all subtypes with 18/28 (64%) having progressed at this time. Twelve of 28 had died at this analysis with ongoing mOS of >25.3mo. The most common G3/4 toxicities were lymphopenia (32%), hyperglycemia (15%, unlikely related), thrombocytopenia (3%), and diarrhea (3%). No hospitalizations, opportunistic infections, or deaths occurred from CAPTEM. Conclusions: CAPTEM is an effective treatment for patients with progressive NET who failed high dose octreotide, with high PR and SD rates in carcinoids and insulinomas. The ongoing PFS in pancreatic NETs (>18.2 mo) is 150% greater than reported with everolimus and sutent. Clinical trial information: NCT00869050. [Table: see text]
TRC105 for the treatment of hepatocellular carcinoma: Preclinical data and preliminary results from two clinical trials evaluating monotherapy and combination with sorafenib.
Authors: Duffy Austin G. , Ma Chi , Ulahannan Susanna Varkey , Fioravanti Suzanne , Venkatesan Aradhana , Turkbey Ismail B. , Choyke Peter L. , Trepel Jane B. , Cao Liang , Compton Kathryn , Figg William Douglas , Greten Tim F. 
Published: February 2017

211 Background: Endoglin (CD105), is an endothelial cell membrane receptor highly expressed on proliferating tumor vasculature, including in 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 acts by endothelial cell growth inhibition, ADCC and apoptosis. Methods: Preclinical: Murine BNL HCC cells were grown subcutaneously in wildtype Balb/c mice and treated with antibody to murine CD105, (clone MJ7/18; 10-200ug) ± sorafenib (10 mg/kg daily p.o.) or sorafenib alone. Clinical: Patients with HCC (Childs Pugh A/B7), ECOG 0/1, were enrolled in a phase I study of TRC105 at 3, 6, 10, 15mg/kg q 2wks plus sorafenib 400mg bid; or (if sorafenib-refractory) a phase II study of TRC105 at 10 or 15mg/kg q 2wks. Correlative biomarkers: DCE-MRI; FDG-PET; color Doppler ultrasonography; circulating endothelial and endothelial progenitor cells, plasma levels of angiogenic factors; soluble CD105 and tumor IHC for CD105. Results: Preclinical studies: CD105 expression was increased in BNL HCC tumors of mice treated with sorafenib. Anti-CD105 + sorafenib was more effective than sorafenib alone. Clinical trials (N=16): M:F 13:3; Median age = 55 (range 24-67); Phase I with sorafenib (N=8): 1 DLT (increased AST) occurred at 10mg/kg. The most frequent toxicity has been epistaxis. One patient with coronary stenosis developed a fatal MI and one patient with thrombocytopenia developed G3 cerebral tumor hemorrhage. Phase II (N=8): No grade 3/4 treatment-related toxicities . Most frequent toxicities headache (G2; N=3) and epistaxis (G1; N=4). No patient was progression free at 4 months. Median time on study: Phase I- 4 months; Phase II - 2 months. Preliminary evidence of biologic response seen on DCE-MRI in 1pt (of 3 evaluable) with a reduction in Ktrans and kep and 3pts (of 3 evaluable) with reduction in intra-tumoral color flow on Doppler. Conclusions: TRC105 is well tolerated both as single agent and combined with sorafenib. Evidence of biological activity was observed. Full preclinical, clinical and correlative data will be presented. Clinical trial information: NCT01306058, NCT01375569.