bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized controlled phase II study of alternate-day S-1 as adjuvant chemotherapy for gastric cancer.
Authors: Nakamura Seiichi , Tatebe Shigeru , Shimizu Tetsu , Yamane Nariyuki , Nishidoi Hideaki , Kurisu Yasuro , Kanayama Hirotomo , Ogawa Haruaki , Tsujitani Shunichi , Ikeguchi Masahide ,   San-in Clinical Oncology Group
Published: February 2017

114 Background: Based on the results of ACTS-GC, oral administration of S-1 for 1 year is considered standard postoperative adjuvant chemotherapy for gastric cancer in Japan. However, the 1-year treatment completion rate was only 65.8%, and completion of the treatment is a problem to be solved. On the other hand, we experienced in clinical practice that the alternate-day administration of S-1 reduced adverse effects and was tolerable for advanced gastric cancer patients unwilling to continue the standard daily administration. We therefore conducted a multi-center cooperative prospective study to compare daily with alternate-day administration of S-1 as postoperative adjuvant therapy for gastric cancer. Methods: Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily administration (group A: S-1 80-120 mg/day according to BSA, days 1 to 28, every 6weeks, for 1 year) or alternate-day administration of S-1 (group B: S-1 80-120 mg/day according to BSA, every other day, for 15 months). The primary endpoints were treatment completion rate and relative dose intensity. Secondary endpoints were safety, overall survival, and relapse-free survival. Results: A total of 73 patients were enrolled. As of August 30, 2011 analysis of the compliance data of 62 cases had been completed. The results showed a treatment completion rate of 74.2% in group A and 93.5% in group B and relative dose intensity of 72.1% in group A and 85.6% in group B, and compliance tended to be better in group B. Assessment of survival time showed a median follow-up time of 545 days, a 1-year survival rate of 93.8% in group A and 96.9% in group B and 1-year relapse-free survival rate of 79.5% in group A and 90.7% in group B. Digestive system adverse events were less frequent in group B than in group A. Conclusions: We will report the data from the final analysis at this meeting. The current data show improved compliance and mitigation of adverse effects with alternate-day administration of S-1, and it appears to be a more sustainable option for adjuvant chemotherapy for Stage II and III gastric cancer.
Downstaging capacity of neoadjuvant chemotherapy in distal versus proximal gastric carcinoma: Preliminary data from a regional tumor registry.
Authors: Garlipp Benjamin , Meyer Frank , Burger Elke , Adolf Daniela , Stuebs Patrick , Bernarding Johannes , Gademann Guenther F.E. , Lippert Hans 
Published: February 2017

120 Background: Following the results of 3 randomized controlled trials, neoadjuvant chemotherapy has become standard of care for locally advanced gastric cancer in Europe. All of these trials included patients with cancers located in the gastric corpus, antrum, and pylorus (distal gastric cancers, DGC) as well as cancers of the esophagogastric junction and fundus (proximal gastric cancers, PGC). However, data suggest that DGC and PGC may be two distinct tumor entities. The aim of our study was to investigate if the capacity of neoadjuvant chemotherapy to downstage gastric cancers is different for DGC and PGC. Methods: We used data from the clinical regional tumor registry of Magdeburg which covers the northern section of the federal district of Saxony-Anhalt, Germany, to compare pretherapeutic (clinical) and postoperative (histopathological) UICC tumor stages in patients with DGC and PGC treated with neoadjuvant chemotherapy followed by surgery. Results: Of 2,460 gastric cancer patients entered into the registry between January 1993 and September 2010, 189 (7.7%) received neoadjuvant chemotherapy. Of these, 149 underwent surgery with curative intent. Pretherapeutic and postoperative UICC stages were not available for 34 of these patients. A further 42 patients had UICC stage IV documented at laparotomy; since this was likely due to peritoneal carcinomatosis which may have gone unnoticed at the start of neoadjuvant chemotherapy and thus does not reliably indicate upstaging, these patients were excluded from analysis. Of the 73 evaluable patients, 33 (45.2%) had DGC and 40 (54.8%) had PGC. UICC tumor stage decreased during therapy in 55.1% and 75.0%, remained unchanged in 16.3% and 20.8%, and increased in 28.6% and 4.2% of DGC and PGC patients, respectively (p=0.039, Fisher’s exact test). Conclusions: Despite the limited statistical power, these preliminary data suggest that DGC and PGC may differ in their response to neoadjuvant chemotherapy. With more widespread use of neoadjuvant chemotherapy in gastric cancer in recent years, we expect a steep increase in evaluable patients in the tumor registry which will allow for future multivariate analyses regarding this issue.
Feasibility study of neoadjuvant chemoradiotherapy with cisplatin plus 5-fluorouracil and elective nodal irradiation for stage II/III esophageal squamous cell carcinoma.
Authors: Kojima Takashi , Hashimoto Jun , Kato Ken , Ito Yoshinori , Igaki Hiroyasu , Daiko Hiroyuki , Onozawa Masakatsu , Hamamoto Yasuo , Shimizu Hideaki , Katano Susumu , Hara Hiroki , Tanaka Yoichi , Saito Yoshihiro 
Published: February 2017

130 Background: Based on the JCOG 9907 trial results, neoadjuvant chemotherapy with cisplatin (CDDP) plus 5-fluorouracil (5-FU) is considered a standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in Japan. However, patient survival remains unsatisfactory. We conducted a feasibility study of neoadjuvant chemoradiotherapy (NeoCRT) with CDDP plus 5-FU and elective nodal irradiation for stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (UICC 6th, non-T4) ESCC, PS 0-1, and age 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 a total 41.4 Gy in 23 fractions for primary tumor, metastatic lymph nodes and regional lymph nodes. After completion of CRT, transthoracic esophagectomy with extensive lymphadenectomy (>D2) was performed. The primary endpoint was the completion rate of NeoCRT and R0 resection. Results: From July 2010 to June 2011, 33 patients were enrolled, including 2 ineligibles. In 31 eligible patients, the median age was 63 years (range, 40–73); male/female: 28/3; PS0/1: 19/12; cStage IIA/IIB/III: 2/10/19. During CRT, the most common grade 3 or 4 toxicities were leukopenia (65%), neutropenia (65%), anemia (13%), thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis (16%), and hyponatremia (16%). In total, 31 patients (100%) underwent CRT and 25 (81%) underwent surgery; 1 patient (3%) did not undergo surgery due to disease progression, and the other 5 patients (16%) are scheduled for surgery. Among 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 63% after CRT completion. Pathological complete response was achieved in 11 patients (44%) who underwent esophagectomy. Conclusions: NeoCRT was well tolerated and appears to be highly promising. The randomized controlled trial compared with neoadjuvant chemotherapy is needed and will be started.
Use of optical biomarkers from nondysplastic metaplastic cells on the detection of high-grade dysplasia and adenocarcinoma from Barrett’s esophagus.
Authors: Brand Randall , Rizvi Sumera , Davison Jon M. , Bista Rajan , Staton Kevin , Hartman Douglas , Fasanella Kenneth , McGrath Kevin , Liu Yang 
Published: February 2017

14 Background: Patients with Barrett’s esophagus (BE), defined as presence of intestinal metaplasia (IM) in the esophagus, require surveillance due to an increased risk of developing esophageal adenocarcinoma (EAC). The biggest challenge in the current surveillance methodology (i.e., Seattle protocol) is random sampling with the inability to identify those patients with non-dysplastic BE on surveillance who have occult high grade dysplasia (HGD) or will eventually progress to HGD or EAC. We propose a novel approach based on the concept of field effect to detect HGD or EAC through the analysis of non-dysplastic IM, thus identifying a high risk BE population. Our group uses a unique microscope – spatial-domain low-coherence quantitative phase microscopy (SL-QPM) to detect changes in nuclear structure as small as 0.9 nm, a scale 1000 times smaller than what conventional microscopy detects. We hypothesize that the SL-QPM-derived optical biomarkers of non-dysplastic IM would distinguish BE patients with EAC/HGD from those without neoplasia. Methods: We performed a retrospective study of 60 BE patients who underwent Seattle protocol biopsies: 33 BE patients with IM only and 27 BE patients with HGD or EAC (21 HGD, 6 EAC). H&E stained slides with non-dysplastic IM on review by an expert pathologist were used. The distance between the selected IM biopsy and HGD/EAC was 1 to 4 cm. Forty to 60 columnar cells from each case were analyzed. Results: We identified three optical biomarkers (nuclear optical path length, intra-nuclear uniformity, entropy) that can distinguish non-dysplastic BE from patients with HGD and EAC with statistical significance (P < 0.01). A prediction model combining all three optical biomarkers can distinguish BE patients with HGD/EAC from those with IM only at 89% sensitivity and 76% specificity (accuracy = 0.87). Conclusions: The accurate assessment of nanoscale optical biomarkers by SL-QPM is a promising approach for detecting dysplastic/neoplastic Barrett’s epithelium from non-dysplastic IM. This approach could potentially simplify BE surveillance by identifying a subset of high-risk BE patients that warrant intensive surveillance.
Phase II feasibility study of adjuvant S-1 plus CPT-11 for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0801).
Authors: Kimura Yutaka , Fujitani Kazumasa , Ueda Shugo , Taniguchi Hirokazu , Imamura Hiroshi , Gofuku Junji , Tamura Shigeyuki , Kurokawa Yukinori , Takiuchi Hiroya , Furukawa Hiroshi ,   Osaka Clinical Study Supporting Organization (OGSG)
Published: February 2017

142 Background: An adjuvant chemotherapy with S-1 has become the standard treatment for patients (pts) with stage II/III gastric cancer (GC) in Japan. But, it is assumed that the survival benefit for stage III pts who received S-1 is modest. S-1 plus CPT-11 has not shown the superiority in median overall survival (OS), but shown the well response rate (56%) and tolerability in Phase III trial (TOP-002 study). The aims of this phase II study were to evaluate the feasibility and safety of adjuvant S-1 plus CPT-11 in pts with stage III GC who underwent D2 surgery. Methods: Pts with pathological stage IIIA and IIIB GC who underwent gastrectomy D2 dissection, age 20-75 years, performance status < 1, and informed consent received oral S-1 (80 mg/m2/day) administration for consecutive 3 weeks and intravenous CPT-11 (80 mg/m2) on day 1, 15, repeated every 5 weeks (1 cycle). The treatment was repeated for 4 cycles, followed by S-1 administration until 1 year after surgery. The primary endpoint was feasibility of the 4 cycles administration of S-1 plus CPT-11. Results: We enrolled forty-five pts, 22 males and 23 females with a median age of 61 years, between December 2008 and April 2010. Pathological stages included IIIA in 25 pts and IIIB in 20 pts. The feasibility of planned 4 cycles of treatment was 62.2% (95% CI 46.5-76.2%, p=0.068) with 28 pts out of 45 pts. Non-hematological toxicities of grade 3 or more involved diarrhea in 13%, anorexia in 16%, nausea in 7% and vomiting in 4%. No Grade 4 toxicities were observed. Conclusions: Adjuvant S-1 plus CPT-11 therapy had moderate hematological toxicities, but observed several severe non-hematological toxicities. Therefore, predicted feasibility was not achieved. Although the follow-up period is too short to evaluate OS and feasibility of S-1 administration, it is hoped that this regimen will be a candidate for future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after D2 dissection if OS will be improved.
Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E+O) or placebo (P+O) among patients with advanced neuroendocrine tumors (NET).
Authors: Yao James C. , Hainsworth John D. , Wolin Edward M. , Pavel Marianne E. , Baudin Eric , Gross David , Ruszniewski Philippe , Tomassetti Paola , Panneerselvam Ashok , Saletan Stephen , Klimovsky Judith 
Published: February 2017

157 Background: In this large phase III trial, median progression-free survival (PFS) improved by 5.1 mo with E+O compared to P+O in patients (pts) with NET associated with carcinoid syndrome. Randomization imbalances including WHO performance status (PS), and primary site favoring P+O confounded primary analysis. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers in NET. Analyses were performed to identify prognostic factors and adjust for randomization imbalances. Methods: Pts were randomized to E+O (n=216) or P+O (n=213). Potential prognostic factors including baseline CgA (≤2×ULN vs >2×ULN), baseline 5-HIAA (≤median vs >median), age (<65 vs ≥65), gender, race, WHO PS (0 vs 1, 2), primary site (lung vs other), prior somatostatin analog use (yes vs no), duration from diagnosis (<6 mo, 6-24 mo, 2-5 yr, >5 yr), and organs involved (liver, bone) were assessed in univariate analysis using the log rank test and a stepwise regression using Cox proportional hazards model. Results: Randomization resulted in significant imbalance in baseline CgA (median [ng/mL], 251 E+O vs 137 P+O). Median PFS (mo) was significantly longer for pts with nonelevated CgA (27 vs 11; P<.001) and nonelevated 5-HIAA (17 vs 11; P<.001). Analyses also indicated age (14 vs 12; P=.01), WHO PS (17 vs 11; P=.004), liver involvement (14 vs not reached; P=.02), bone metastases (8 vs 15; P<.001), and lung as primary site (11 vs 14; P=.06) as potentially prognostic. Multivariate analysis indicated that significant prognostic factors for PFS included baseline CgA (HR, 0.47; CI, 0.34-0.65; P<.001), WHO PS (HR, 0.69; CI, 0.52-0.90; P=.006), bone involvement (HR, 1.52; CI, 1.06-2.18; P=.02), and lung as primary site (HR, 1.55; CI, 1.01-2.36; P=.04). Adjusted for covariates, a 38% reduction in risk of progression was observed for E+O (HR, 0.62; 95% CI, 0.51-0.87; P=.003). Conclusions: In the phase III RADIANT-2 trial, baseline CgA levels, WHO PS, lung as primary site, and bone involvement were important prognostic factors. Exploratory analysis adjusted for these prognostic factors indicated significant benefit for everolimus therapy.
Evaluation of combination treatment benefits of nab-paclitaxel in experimental pancreatic cancer.
Authors: Awasthi Niranjan , Ostapoff Katherine , Zhang Changhua , Schwarz Margaret A. , Schwarz Roderich 
Published: February 2017

170 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human cancers and is characterized by early tissue invasion, metastasis and high resistance to systemic therapies. Gemcitabine, a standard cytotoxic therapy for pancreatic cancer, has shown limited clinical benefits. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel), an approved treatment for breast cancer, has shown efficacy as mono- and combination therapy in multiple tumor types including pancreatic, lung and ovarian cancer. We evaluated combination treatment benefits of nab-paclitaxel with gemcitabine in experimental pancreatic cancer. Methods: In vitro cell proliferation was evaluated by WST-1 assay in human PDAC cells. Animal survival studies were performed in murine xenografts. Results: Nab-paclitaxel inhibited in vitro proliferation of PDAC cell lines with IC50 levels of 7.6 mM, 208 nM, 519 nM and 526 nM for AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells. Nab-paclitaxel combination with gemcitabine had significant additive effect on inhibition of PDAC cell proliferation; 72-hour incubation demonstrated that nab-paclitaxel addition caused a 2.5, 2.5, 8.9 and 2.2-fold decrease in IC50 of gemcitabine in AsPC-1, BxPC-3, MIA PaCa-2 and Panc-1 cells, respectively. In an intraperitoneal murine xenograft model, 2-week therapy demonstrated that compared to controls (median survival: 23 days), animal survival increased after gemcitabine (27 days, p=0.05) and nab-paclitaxel monotherapy (35 days, p=0.0005). In a separate 3-week therapy experiment, animal survival was significantly longer in the nab-paclitaxel treated group (41 days, p<0.002 versus control and Gem) compared with gemcitabine (32 days, p=0.005 versus control), docetaxel (32 days, p=0.005) and controls (20 days). Animal survival in nab-paclitaxel / gemcitabine and docetaxel / gemcitabine sequential treatment group was 43 and 40 days, respectively. Conclusions: Nab-paclitaxel has significant antitumor activity as a single agent in experimental pancreatic cancer and can also enhance gemcitabine effects in combination. These findings provide a strong rationale for testing nab-paclitaxel in patients with pancreatic cancer.
Epidemiology and survival of neuroendocrine tumors in Ontario: A 15-year population-based study.
Authors: Cukier Moises , Law Calvin , Liu Ning , Saskin Refik , Singh Simron 
Published: February 2017

184 Background: A recent study of the SEER database in the United States showed a 5-fold increase in neuroendocrine tumours (NETs) over the last 30 years. An increasing incidence has also been reported in Norway, Sweden, England, Holland, Italy and Japan, but interestingly not in Denmark and Switzerland. The objective of our study is to describe the incidence, anatomical distribution and survival of NETs in Ontario. Methods: A population based study was initiated using the Ontario Cancer Registry, cross-linked with the Registered Persons Database and the Canadian Institute of Health Information Discharge Abstract Database. All cases of NETs were identified in Ontario (> 13 million persons) from 1994 to 2009. Baseline demographic, clinical and outcomes data were abstracted to allow for an analysis of annual incidence rates, and overall survival. Results: A total of N = 5619 cases were identified. The incidence rate increased from 2.46/ 100,000 (95% CI, 2.13-2.83) in 1994 to 5.86/ 100,000 (95% CI, 5.40 – 6.35) in 2009. The median age was 62 with 50.5% female cases. When divided by site, bronchopulmonary NETs where the most common (22%), then jejunum/ileum (17%) and rectal (16%) NETs, while pancreatic NETs (pNETs) and gastric NETs were 10% and 5% respectively. The absolute increase in the study period was most pronounced for pNETs (6-fold), rectal (5-fold) and gastric (5-fold) NETs. Metastatic disease was documented in 45% of the cases; 20% at diagnosis and 25% during follow-up. The 5-and 10-year overall survival (OS) was 61% and 46% respectively, for the entire population. Site specific 5-year OS were: rectal (87.0%), small bowel (73.4%), gastric (67.4%), colon (64.3%) and pancreas (48.8%). 5-year OS was compared for patients with and without metastatic disease after diagnosis (69.0% vs 40.1%, p<0.0001). Conclusions: There appears to be a significant increase of reported cases of NETs in Ontario, Canada, particularly pNETs, rectum NETs and gastric NETs. This supports much of the population-based reports worldwide. Survival appears to vary significantly according to anatomical site and extent of disease. Further research is required to understand the impact of this cancer previously perceived to be rare but clearly increasing.
Detection of biomarkers for esophageal cancer pathologic complete response (pathCR) in OE33 and NCI-H460 control cell lines using a clinical standard operating procedure (SOP) protocol.
Authors: Cook Robert W. , Ajani Jaffer A. , Inge Landon 
Published: February 2017

20 Background: The standard of care for esophageal cancer (EC) patients is a trimodality approach that includes chemo− and radiotherapy followed by surgery. Approximately 25% of EC patients exhibit pathCR to chemoradiotherapy, but undergo unnecessary surgical resection procedures. A set of three protein biomarkers (NF−kB, SHH, and Gli−1) able to effectively identify pathCR status from diagnostic patient biopsies was discovered at M. D. Anderson Cancer Center (uncorrected ROC=0.97; corrected ROC=0.96). To translate that discovery to the clinical laboratory, a standardized protocol utilizing clinical grade reagents and instrumentation for biomarker detection has been developed. PathCR determination with this clinical procedure would be a significant step toward individualized therapeutic options for EC patients. Methods: OE33 and NCI−H460 cells were grown to confluence, collected, and fixed with PFA as a cell pellet. Fixed cell pellets were paraffin embedded, sectioned, and adhered to microscope slides. IHC detection of NF−kB, SHH, and Gli-1 proteins was performed in each cell line using clinical grade reagents and instrumentation, and protein localization was determined by microscopy to verify concordance with research laboratory techniques and results. Results: The clinical SOP allowed for efficient staining of each pathCR biomarker. Nuclear localization of activated NF-kB and Gli-1 was observed in OE33 and NCI-H460 cells, respectively, and SHH localization to the cytoplasm of NCI-H460 cells was also confirmed. The results correlate well with staining protocols utilized during research laboratory procedures. Conclusions: The clinical SOP for IHC detection of EC pathCR biomarkers can efficiently detect NF-kB, SHH, and Gli−1 in the control cell lines OE33 and NCI-H460. The protocols presented should be adaptable to EC patient tumor biopsies, providing an effective method for determining pathCR that will facilitate an individualized approach to treatment methods for people suffering from EC.