bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil (5 FU) and cisplatin for locally advanced resectable esophageal cancer: A retrospective study.
Authors: Almhanna Khaldoun , Hoffe Sarah , Shridhar Ravi , Strosberg Jonathan R. , Dinwoodie William R. , Meredith Kenneth 
Published: February 2017

119 Background: Neoadjuvant CCRT has become the standard treatment for esophageal cancer. Most clinicians use a conventional cisplatin/5 FU combination which is associated with moderate to severe toxicity. For the last 15 years we have used contiuous low-dose 5-FU combined with two doses of cisplatin. Methods: Between July 1997 and June 2012, 155 patients with locally advanced esophageal cancer (T3 or N1 and higher), received CCRT consistent of cisplatin 75 mg/m2 on day 1 and day 29 and continuous infusion of 5-FU (225 mg/m2/day) on the days of radiation. Results: Median age of patients was 63 year (30-76).Seventeen percent of pts were female and 85% had adenocarcinoma. (3, 34, 86 and 31 pts had stage I, II, III and IVa disease respectively. One hundred and twenty seven pts had N1 disease. Radiation dose (RT) ranged from 45-60 Gy (median 56Gy). Median weight loss was 6.5%. All patients completed treatment. 20% of patients had >=grade 3 toxicity, with 29 patients requiring hospital admission. 53% of patients had surgical resection between 37-149 days following CCRT (median 62 days). R0 resection was achieved in 96% of patients. A pathological complete response was achieved in 38 of 83 pts (45%) who underwent surgical resection. With a median follow up of 26 months (1.2 -144 months), 36% of pts recurred and total of 50% died. Conclusions: Compared to conventional chemotherapy regimen, our CCRT regimen for locally advanced esophageal cancer is well tolerated and associated with a high pathological response rate.
Comparison of lymph node staging system in gastric cancer using time-dependent ROC analysis with Harrell’s concordance index.
Authors: Bando Etsuro , Sugisawa Norihiko , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Kinugasa Yusuke , Kanemoto Hideyuki , Uesaka Katsuhiko , Terashima Masanori 
Published: February 2017

12 Background: The aim this study was to clarify what the most informative pathologic lymph node staging system in gastric cancer is, by using time-dependent receiver operating characteristic (ROC) analysis with Harrell’s concordance (c) index. Methods: This study enrolled 2747 primary gastric cancer patients, without prior chemotherapy, who underwent R0 or R1 macroscopically curative resection. We calculated concordance indices of different 3 nodal staging systems (anatomical level based on JPN 13th edition vs. numbers of metastatic nodes based upon TNM 7th edition vs. ratio of metastatic nodes; derived from Yu’s definition {Yu et al. Br J Surg;1997,N0:0, N1;0-0.1, N2;0.1-0.25, N3;0.25-}) for survival. Results: (Anatomical level) Harrell’s c-index was 0.754 with 5-year survival rate of N0; 93%, N1; 73%, N2; 51%, N3; 19%. C-index without node-negative patients was 0.628. (Numbers of positive nodes) C-index was 0.767 with 5-year survival rate of N0; 93%, N1; 81%, N2; 68%, N3; 37%. C-index without node-negative patients was 0.669. (Ratio of nodal involvement) C-index was 0.770 with 5-year survival rate of N0; 93%, N1; 80%, N2; 63%, N3; 29%. C-index without node-negative patients was 0.691, which is significantly larger than those in anatomical level or numbers of positive nodes (p<0.001, p=0.014, respectively). (Comparison of Staging System) If combined pT category with ratio grading system without pStage IA, new staging system is the significantly most informative (c-index; 0.760) than JPN 13th (c-index; 0.735) or TNM 7th (c-index; 0.742) (p=0.009, p=0.023, respectively). Conclusions: Lymph node staging system based on the conception of ratio of metastatic nodes is the most informative staging system than those with anatomical location or numbers of metastatic nodes. These results suggested that in gastric cancer pathologic staging system in next TNM classification should include the ratio of metastatic nodes.
Various clinical outcomes in patients with esophageal or gastroesophageal junction (E-GEJ) adenocarcinoma undergoing trimodality therapy: Prognostic implications.
Authors: Suzuki Akihiro , Xiao Lianchun , Taketa Takashi , Sudo Kazuki , Blum Mariela A. , Komaki Ritsuko , Liao Zhongxing X. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Hofstetter Wayne Lewis , Swisher Stephen , Ajani Jaffer A. 
Published: February 2017

120 Background: Preoperative chemoradiation (trimodality therapy) has the strongest evidence in trimodality-eligible patients with E-GEJ adenocarcinoma. Pathological complete response (pathCR) and clinical complete response (clinCR) are favorable prognostic factors. We hypothesized that pathCR is associated with best prognosis. Methods: Patients with E-GEJ adenocarcinoma undergoing trimodality therapy were identified from the prospectively maintained databases at our institution. Multiple statistical methods were used. Results: For 314 esophageal cancer patients, the median follow-up time was 44.0 months (95% CI; 34.2-50.9). 107 of 314 patients died at this analysis. 80 patients (25.5%) had a pathCR. 160 patients (51.0%) had a clinCR prior to surgery but did not have pathCR. The remaining 74 (23.6%) had <pathCR and <clinCR. Median OS were: not achieved in pathCR patients, 82.8 months (95% CI; 63.9, NA) in clinCR patients and 27. 6 months (95% CI; 19.4, NA) <pathCR/<clinCR (p<0.001). The median recurrence-free survival (RFS) were: 79.6 months (95% CI; 37.4, NA) in pathCR patients, 67.4 months (95% CI; 31.8, NA) in clinCR patients and 13.5 months (95% CI; 10.4, 21.4) in <pathCR/<clinCR (p<0.001). In multivariate analysis, no lymph node metastasis (p<0.001), not poorly differentiated adenocarcinoma (p=0.002) and pathCR (p=0.02), and cCR (p<0.001) were independent prognosticators of OS and RFS. Conclusions: pathCR and clinCR are independent prognosticators (pathCR producing the best results) and may be helpful in devising new therapeutic and surveillance strategies.
An open, multicenter, phase II clinical trial to evaluate efficacy and safety of S-1 split cisplatin in patients with advanced gastric cancer (AGC): HGCSG0702—Safety analysis.
Authors: Iwanaga Ichiro , Yuki Satoshi , Fukushima Hiraku , Ishiguro Atsushi , Takahata Takenori , Miyagishima Takuto , Kudo Mineo , Uehata Yasuko , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

121 Background: From the results of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with AGC in Japan. However, many facilities are forced hospitalization of hydration upon administration of high dose Cisplatin (60mg/m2). Therefore, in Hokkaido Gastrointestinal Cancer Study Group (HGCSG), to investigate the safety and efficacy, we conducted a multicenter phase II clinical trials of S-1 plus split cisplatin as a therapeutic strategy that can be administered in the outpatient. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40-60 mg depending on patients body surface area) was given orally, twice daily for 3 consecutive weeks, and 30 mg/m2 cisplatin was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and duration of hospitalization. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7. Median no. of cycles was 3. The most common non-hematological adverse events (AE) were anorexia (70%), nausea (60%), fatigue (60%) and diarrhea (48%) and hematological AE were anemia (88%), neutropenia (83%), leukocytopenia (68%) and thrombocytopenia (60%). The main grade 3-4 AE were neutropenia (40%), anemia (30%), anorexia (30%) and fatigue (15%). These AE were as expected. The median dose intensity of S-1 was 270mg/m2/week (relative dose intensity (RDI) 80%), and cisplatin was 10.1mg/m2/week (RDI 84%). These toxicities were tolerable and manageable. No treatment-related death was observed. Conclusions: We conclude that this S-1 plus split cisplatin regimen was well tolerated in the treatment of AGC, and most patients could be administered in the outpatient. We are planning the final efficacy analysis for February 2013.
Resting palliative chemotherapy in patients with gastric cancer.
Authors: Lee Hee Yeon , Hong Young Seon , Jeon Hae Myung , Park Cho Hyun , Song Kyo Young , Roh Sang Young 
Published: February 2017

122 Background: In gastric cancer, platinum and fluorouracil combination chemotherapy (CTx) is commonly used. But the optimal duration of CTx in palliative setting is not known. Thus, we reviewed the pts who rested CTx despite of persistent disease control. Methods: From Mar 2007 to Feb 2012 at Seoul St. Mary’s hospital, we retrospectively reviewed pts as follows; (1) had metastatic or recurrent gastric cancer, (2) received 9 cycles of FOLFOX as 1st-line, (3) had no progressive disease (PD) and rested after completion of 9th cycle. Results: Total 25 pts were reviewed. Median age was 54 (36~77) and 15 pts (60%) were male. 13 pts (52%) had recurrent disease and 12 metastatic initially. All pts were treated with oxaliplatin 100 mg/m2, leucovorin 400 mg/m2 on day 1 and 5-FU 1200 mg/m2 on day 1-2 every 2 weeks. All pts had metastasis; carcinomatosis peritonei (CP, 56%), lymph node (36%), liver (20%) and bone (8%). Nine pts (48%) had non-measurable lesions and 3 no evidence of disease (NED) on CT after palliative surgery. Response evaluation was done every 3 cycles. Among 22 pts with evaluable disease, 5 (20%) showed complete response (CR), 8 (32%) partial response (PR), 2 (8%) stable disease (SD) and 7 (28%) non-CR/non-PD as best response. Median progression free survival (PFS) was 14.2 m (95% CI, 6.6-21.9). The PFS in CP vs. non-CP was 9.9 vs. 21.5 m (log rank P = .037). And PFS according to best response were as follows; 25.5 m in CR + NED group, 15.7 PR, 13.4 non-CR/non-PD and 4.3 SD (log rank P = .014). Other factors did not seem to affect PFS. Conclusions: This study suggested that resting CTx in selected pts would be reasonable in gastric cancer. Especially the presence of CP and the grade of response seemed to be important in patient selection.
Significance of multimodality therapy for esophageal cancer synchronously or metachronously associated with head and neck cancer.
Authors: Kimura Yasue , Morita Masaru , Kawano Hiroyuki , Ohtsu Hajime , Ando Koji , Ida Satoshi , Saeki Hiroshi , Oki Eiji , Kusumoto Tetsuya , Maehara Yoshihiko 
Published: February 2017

132 Background: Esophageal cancer is highly aggressive and until recently is associated with a poor prognosis. Another clinical problem of esophageal cancer is the frequent association of head and neck cancer. The therapy for esophageal cancer and head and neck cancer is difficult. Definitive chemoradiotherapy is frequently indicated, while invasive surgical resections have been aggressively performed for patients with esophageal cancer associated with head and neck cancer. Methods: The Japanese 202 patients underwent esophagectomy were divided into two groups according to the association of head and neck cancer. The clinicopathological factors and the method of operations were evaluated and statistically analyzed. Results: The double cancer group included 26 (12.9%) patients that had the cancer of esophagus and the head and neck either synchronously or metachronously, while the control group included 176 (87.1%) patients with esophageal cancer. Seventeen patients were operated synchronously in double cancer group. No statistically significant differences were recognized in other clinical backgrounds such as the gender, location of the tumor, etc. Several types of operations were performed for two groups, such as subtotal esophagectomy, total laryngo-pharyngo-esophagectomy, cervical esophagectomy and laryngo-pharyngectomy and free jejunal transfer.salvage esophagectomy, and two-staged operation after definitive chemoradiotherapy. Salvage esophagectomy was performed in five patients with either remnant or recurrent esophageal cancer after definitive chemoradiotherapy. The mortality as well as morbidity rate of the double cancer group was not significantly different from the control group. Furthermore, patients’ prognosis was similar in the two groups. Conclusions: Esophagectomy can be an effective treatment option by adopting techniques that appropriate for each cases, such as staged operations after definitive chemoradiotherapy, muscular flaps and microvascular anastomosis, even in patients with double cancers of the esophagus and the head and neck cancer.
Prognostic factors after R2 surgery in patients with advanced gastric cancer.
Authors: Tokunaga Masanori , Goto Hironobu , Makuuchi Rie , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: February 2017

140 Background: In patients with advanced gastric cancer, chemotherapy is a standard treatment if they have non-curable factors. However, gastrectomy is sometimes performed even in patients having non-curable factors, particularly when they have tumor associated symptoms. The aim of this study is to investigate clinicopathological characteristics of patients who underwent R2 surgery, and to identify prognostic factors. Methods: This study included 157 patients who underwent gastrectomy with macroscopic residual disease (R2 surgery) between September 2002 and June 2011 at the Shizuoka Cancer Center. Clinicopathological characteristics and surgical outcomes were investigated. In addition, we conducted Cox-proportional Hazards model which included age, sex, number of non-curable factors, chemotherapy, macroscopic type, histology, and postoperative intraabdominal infectious complications as covariates, to identify independent prognostic factors after R2 surgery. Results: There were 103 male and 54 female patients with median age of 69 years. The reasons why R2 surgery was performed were low oral intake due to stenosis in 120 patients and bleeding in 54 patients. Total gastrectmy was the most frequently performed procedure (93 patients) followed by distal gastrectomy (61 patients) Median operation time and intraoperative blood loss were 193 minutes and 337 mg, respectively, and intraabdominal infectious complications (Clavien-Dindo classification grade II or more severe) were observed in 24 patients (15.3%). Chemotherapy was given after surgery in 112 patients (71.3%) with median survival time of all patients being 8.7 months. Multivariate analysis identified postoperative chemotherapy (Hazard ratio, 0.34; 95% confidential interval, 0.24 – 0.65) and postoperative intraabdominal infectious complications (Hazard ratio, 1.74; 95% confidential interval, 1.06 – 2.88) as independent prognostic factors. Conclusions: The incidence of postoperative infectious complications after R2 surgery was thought to be higher than that after curative gastrectomy reported before. Safe procedure and administration of postoperative chemotherapy would be necessary to offer improved overall survival after R2 surgery.
Identification of germline genetic mutations in patients with pancreatic adenocarcinoma.
Authors: Salo-Mullen Erin E , O'Reilly Eileen Mary , Kelsen David Paul , Lowery Maeve Aine , Yu Kenneth H. , Rau-Murthy Rohini , Siegel Beth , Saltz Leonard , Kurtz Robert C , Offit Kenneth , Robson Mark E. , Stadler Zsofia Kinga 
Published: February 2017

159 Background: The emergence of PARP-inhibitors for potential treatment of BRCA-associated cancers highlights the importance of identifying germline mutations in individuals with pancreatic adenocarcinoma (PAC) (NCT 01585805 for PARP-i in PAC). Optimal selection of PAC patients for genetic testing remains to be determined. Our objective was to investigate prevalence of germline mutations in our PAC patients. Methods: MSKCC Clinical Genetics database was reviewed for PAC patients offered germline testing from 1/1/2011 to present. Clinical data was extracted from records. Pedigrees were reviewed to verify NCCN (PAC at any age with ≥2 close relatives with breast/ovarian/PAC at any age) and/or other testing criteria. Results: 70 PAC patients (33 males, 40 Ashkenazi Jewish (AJ)) were seen; 36 met NCCN criteria and 16 were AJ with 1 close relative with breast/ovarian/PAC. Of 18 not meeting these criteria, 7 were AJ, 3 were early-onset, and 7 were non-AJ with at least 1 additional BRCA-associated cancer in either themselves or a close relative. 63 patients accepted BRCA testing: 6 (9.5%) had a BRCA1 (n=2) or BRCA2 (n=4) mutation. Only 2 of these met NCCN criteria; 3 were AJ with 1 close relative with a BRCA-associated cancer; and 1 was non-AJ descent with 1 close relative with early-onset breast cancer. 36 AJ patients pursued BRCA testing: 4 (11.1%) had a BRCA1 (n=1) or BRCA2 (n=3) mutation; all were founder mutations. Additional genetic testing, based on family history, identified 1 MSH2 mutation, 1 MSH6 mutation, and 1 p16 mutation. Overall mutation detection rates were 13.6% (9/66) in total cohort who pursued any genetic testing and 15.8% (6/38) in tested AJ group. 6 patients with PAC before age 50 were tested: 1 non-AJ patient had a BRCA1 mutation and 1 (with history of melanoma) had a p16 mutation. Conclusions: With mutation detection rates of nearly 14% in total tested population & 16% in AJ cohort, germline genetic testing is important for PAC patients with potential implications for treatment and for relatives. By limiting BRCA testing to patients who meet current NCCN testing criteria, 66.7% (4/6) of our patients with BRCA mutations would not have been identified. Reassessment of testing criteria is needed for optimal care of PAC patients.
Clinicopathologic correlations of gallbladder cancer by ethnicity in New Mexico, 1980-2009.
Authors: Madden Kathleen , Wiggins Charles , Nir Itzhak , Rajput Ashwani , Morris Katherine T. 
Published: February 2017

160 Background: Gallbladder cancer (GBCA) is a rare malignancy; however, within the U.S. incidence varies geographically. GBCA has a higher occurrence in the American Indian (AI) population versus non-Hispanic whites (NHW) and Hispanics (H). The goal of the study is to determine if clinicopathologic features correlate with ethnicity. Methods: Incident GBCA diagnosed in New Mexico from 1980-2009 were identified from the population-based New Mexico Tumor Registry. Average age-adjusted incidence rates were calculated by direct method using the United States 2000 standard population. Chi-squared statistic was used to assess ethnicity differences in case distribution at diagnosis by sex, age, stage and grade. Cause-specific survival was calculated by the Kaplan-Meier method and assessed with log-rank statistic. Results: GBCA incidence rates in New Mexico are highest for AI (7.6 per 100,000–95% confidence interval (CI)=6.5-8.9), followed by H (2.8 per 100,000 – 95% CI=2.5-3.2) and NHW (1.0 per 100,000 – 95% CI=0.9-1.1). Females are predominantly affected (Table). Median ages varied among NHW (74 years), H (71 years) and AI (69 years). There are no appreciable differences with respect to stage and tumor grade. Cause-specific survival at 60 months is also similar among NHW (20.25%), H (17.94%), and AI (22.43%) (log-rank p-value=0.7388). Conclusions: GBCA has a higher prevalence in AI. Regardless it shares similar characteristics in all evaluated ethnicities as it is predominantly a disease of older females, with similar tumor grade and stage and with equally poor survival. [Table: see text]
The role of microRNA-9 in hepatocellular oncogenesis.
Authors: Drakaki Alexandra , Hatziapostolou Maria , Polytarchou Christos , Iliopoulos Dimitrios 
Published: February 2017

168 Background: Hepatocellular carcinoma (HCC) is the main type of liver cancer. MicroRNAs are non-coding RNAs that have been involved in the pathogenesis of different cancer types. Our aim was to identify microRNAs that have functional and clinical significance in liver oncogenesis and understand how manipulation of their levels could have a therapeutic potential. Methods: MicroRNA expression analysis was performed in 38 HCC tissues and 25 normal liver tissues. A microRNA library (318 microRNAs) was transfected in SNU-449 liver cancer cells and invasiveness was measured 24 h later by a matrigel invasion assay. Cell growth and matrigel invasion assays were performed in SNU-449 cells that were transfected with miR-9 or antisense-miR-9 (20nM). TargetScan algorithm was used to identify miR-9 direct downstream target genes. The mRNA levels of PPARalpha, and E-cadherin were assessed by real-time PCR 48h after miR-9 overexpression and down-regulation in SNU-449 cells. Results: MicroRNA expression analysis in 38 HCCs and 25 normal liver tissues identified a 25-microRNA signature of HCC. Integration of the library screen and patient data revealed that miR-9 has clinical and functional relevance for liver cancer. Specifically, we found that miR-9 increases 2.7-fold the invasiveness and the growth of SNU-449 cells, 48h post transfection. Bioinformatic analysis revealed that miR-9 has a binding site in the 3’UTR of PPARalpha gene. MiR-9 overexpression inhibited 35% PPARalpha 3’UTR luciferase activity and 60% mRNA levels, while miR-9 down-regulation led to 75% increased PPARalpha mRNA levels. These data suggest that miR-9 targets directly the 3'UTR of PPARalpha and regulates its expression levels in liver cancer cells. In addition, miR-9 overexpression led to 95% suppression of E-cadherin mRNA levels in SNU-449 cells, thus increasing their metastatic potential. Conclusions: We found that miR-9 is highly overexpressed in liver cancer patients and its up-regulation increases the growth and metastatic potential of liver cancer cells. Overall these data suggest that miR-9 is a novel oncogene involved in liver oncogenesis and its suppression could have therapeutic potential in liver cancer patients.