bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).
Authors: Masuishi Toshiki , Kawase Tomono , Nishikawa Kazuhiro , Kunisaki Chikara , Matsusaka Satoshi , Segawa Yoshihiko , Nakamura Masato , Sasaki Kinro , Nagao Narutoshi , Tsuji Akihito , Yuasa Yasuhiro , Asami Shinya , Takeuchi Masahiro , Furukawa Hiroshi , Fujii Masashi , Nakajima Toshifusa 
Published: February 2017

106 Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. In patients with HER2-positive AGC, ToGA trial showed survival benefit with the addition of trastuzumab to capecitabine plus cisplatin or fluorouracil plus cisplatin and HERBIS-1 trial demonstrated promising antitumor activity with the addition of trastuzumab to SP. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. And these disadvantages of cisplatin are noticeable in elderly patients. We evaluated the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. Methods: Patients, 65 years or older, with HER2-positive AGC received S-1 (80–120mg per day) orally on days 1–28 of a 42-day cycle and trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg /kg) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary endpoints were overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and adverse events. The sample size was 40 to 60 patients estimated on the basis of threshold RR=20%, expected RR=35%, alpha=0.1 (one-sided) and power=80 to 90%. Results: A total of 51 patients were enrolled. One patient was ineligible, therefore in the full analysis set of 50 patients (actual statistical power = 87.5%), the median age was 71 years (range=65-85), male: female was 37:13 and ECOG PS was 0/1/2= 33/14/3. The confirmed RR (CR/PR/SD/PD=3/17/23/7) was 40.0% (80% confidence interval (CI); 31.1-48.9%, 95% CI; 26.4-53.6%), and the null hypothesis was rejected. The disease control rate was 86.0% (95% CI; 76.4-95.6%). Median OS, PFS, and TTF were immature. Major grade 3 or 4 adverse events included neutropenia (10.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: The primary end point was met. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects in elderly patients with HER2-positive AGC. Clinical trial information: UMIN000007368.
The prognostic value of preoperative helicobacter pylori infection in resected gastric cancer.
Authors: Postlewait Lauren McLendon , Squires Malcolm Hart , Kooby David A. , Poultsides George A. , Weber Sharon M. , Bloomston Mark , Fields Ryan C. , Pawlik Timothy M. , Votanopoulos Konstantinos Ioannis , Schmidt Carl Richard , Ejaz Aslam , Acher Alexandra W. , Worhunsky David J. , Saunders Neil , Swords Doug S. , Jin Linda X. , Cho Clifford Suhyun , Cardona Kenneth , Staley Charles A. , Maithel Shishir Kumar 
Published: February 2017

137 Background: Limited data exist on the prognostic implication of pre-operative Helicobacter pylori (H. pylori) infection in gastric adenocarcinoma (GAC). Our aim was to assess the association of H. pyloriwith recurrence and survival in patients undergoing resection of GAC. Methods: All patients who underwent curative intent resection for GAC from 2000 to 2012 at seven academic institutions comprising the US Gastric Cancer Collaborative were included. 30-day mortalities were excluded. Survival analyses were conducted with Kaplan Meier log rank and multivariate Cox regression. Primary endpoints were recurrence-free survival (RFS) and overall survival (OS). Results: Of 965 patients, 559 met inclusion criteria and had documented pre-operative H. pylori testing. 18.6% (n=104) of patients tested positive for H. pylori pre-operatively. Data regarding treatment of H. pylori was not available. H. pylori infection was associated with younger age (62.1 vs 65.1 years; p=0.041), distal tumor location (82.7% vs 71.9%; p=0.033), and receipt of adjuvant radiation therapy (47.0% vs 34.9%; p=0.032). There were no significant differences in ASA class, margin status, Grade, PNI, LVI, or nodal metastases. The distribution of TNM stage I-III was similar between the two groups. H. pylori status was not associated with tumor recurrence. However, pre-operative H. pylori infection was associated with longer OS (84.3 mo vs 44.2 mo; p=0.008). When accounting for differences in age, tumor location, and delivery of radiation therapy, H. pylori infection persisted as a positive prognostic factor for OS (HR 0.60; CI 0.40-0.91; p = 0.016). Conclusions: Patients with and without preoperative H. pylori infection had no significant differences in adverse pathologic factors including positive margin, high grade, lymph node metastases, or advanced TNM stage. Despite similar disease presentation, pre-operative H. pylori infection was independently associated with improved overall survival. Further studies examining the interaction between H. pylori and tumor immunology and genetics are needed to better understand the relationship between H. pylori and survival in gastric cancer.
Intra-arterial, abdominal chemoperfusion with chemofiltration in the treatment of progressive stage IV gastric cancer.
Authors: Sendler Andreas , Aigner Karl R. 
Published: February 2017

141 Background: Treatment of patients (pts.) with progeressive stage IV gastric cancer remains a therapeutical problem. Survival of the pretreated pts. is low and the therapeutic options are sparse. In this situation, locoregional therapeutic strategies could be an option. Methods: 28 pretreated pts. (17 male, 11 female, mean age 59 y.) after resection and at least second line systemic chemotherapy were included in a phase II study of isolated abdominal perfusion and subsequent chemofiltration. All pts. had liver metastases (mets.), 50% (n = 14) had peritoneal carcinomatosis with malignant ascites. No pat. had cerebral, pulmonal or bone mets.. After insertion of a venous and arterial 21 ch. stop flow catheter via a femoral access, the v. cava was blocked beneath the right atrium, the arterial catheter was blocked above the celiac trunk. The thighs were blocked by pneumatic cuffs. Chemotherapy consisted of 35 mg/m2 cisplatinum, 20 mg/m2 adriamycin and 12 mg/m2 mitomycin q 3 weeks till progress or dead. The agents were administered via the arterial access, followed by 15 min of hypoxic abdominal perfusion via an external pump, followed by chemofiltration for 45 min. The procedure was done under general anaesthesia. Primary endpoint of the study were overall survival, secondary endpoint was control of the ascites. Results: A total of 92 cycles (mean 3.25) were administered. Toxicity was low with leucopenia CTC grad I in 9 pts., gastrointestinal disorders grad II in 8 pts. and surgical complications grad II in 40 % of the pat. (lymphatic fistula). In 9/14 (65%) of pts. with ascites, the ascites was at least controlled or vanished. One year survival was 28.6% (Kaplan-Meier), 2 year survival was 11.4%. Median survival was 6 months. Conclusions: Intra-arterial, isolated abdominal chemoperfusion with consecutive chemofiltration in heavily pretreated patients with gastric cancer metastasized to the abdominal cavity is a valuable option for palliative treatment with low side effects. In 65% of the affected pts., malignant ascites was controlled sufficiently, ameliorating the quality of life.
Comparison of long-term outcome between endoscopic submucosal dissection and surgical resection for early gastric cancer.
Authors: Kim Boo Gyeong , Kim Byung-Wook , Kim Joon Sung , Park Sung Min , Lim Keun Joon , Kim Jin Il , Park Jae Myung , Oh Jung-Hwan 
Published: February 2017

144 Background: The aim of this study is to evaluate the long-term clinical and oncologic outcome of ESD for differentiated EGC of an expanded indication compared to surgical resection. Methods: Retrospective analyses were performed in patients who underwent ESD or surgical resection for EGC of an expanded indication from 2006 and 2008 in Incheon St. Mary’s Hospital, Seoul St. Mary’s Hospital, Yeouido St. Mary’s Hospital, and St. Paul’s Hospital. First arm study was performed according to pre-ESD diagnosis including pathologic diagnosis and endoscopic findings. Second arm study was obtained from post-ESD final pathologic result. All the patients were checked with endoscopy and stomach CT regularly at least 5 years. Clinical outcomes, disease free survival and overall survival were compared between the ESD group and surgical resection group in each arm. Results: In first arm study, 41 patients who received ESD and 106 patients who received surgical resection were enrolled. Metachronous recur was found in 4 patients among ESD group and in 2 patients among surgical resection group during the follow up period. There was no local recurrence in both groups. The disease free survival was not different between the two groups (ESD vs surgical resection; 87.8 vs 95.3%, p=0.291). The 5-year overall survival rate was 100% in both groups. In second arm study, 74 patients who received ESD and 165 patients who received surgical resection were enrolled. Metachronous recur was found in 5 patients among ESD group and in 2 patients among surgical resection group during the follow up period. Local recurrence did not occur in both groups. Surgical resection group was superior to ESD group in disease free survival (97.6% vs 87.6%, p=0.002). The 5-year overall survival rate was 100% in both groups. Conclusions: ESD for EGC might be acceptable considering the overall survival rates. However, intensive surveillance should be performed to find the metachronous recur after ESD.
Comparison of transthoracic esophagectomy with definitive chemoradiotherapy as initial treatment for esophageal squamous cell carcinoma in patients who could tolerate transthoracic esophagectomy.
Authors: Matsuda Satoru , Tsubosa Yasuhiro , Niihara Masahiro , Takebayashi Katsushi , Kawamorita Keisuke , Mori Keita , Tsushima Takahiro , Yokota Tomoya , Ogawa Hirofumi , Onozawa Yusuke , Yasui Hirofumi 
Published: February 2017

145 Background: Transthoracic esophagectomy (TTE) and definitive chemoradiotherapy (dCRT) have been recognized as initial curative treatments for esophageal squamous cell carcinoma (ESCC). We aimed to compare TTE with dCRT as initial treatments in patients who had potentially curable ESCC and could tolerate TTE. Methods: Consecutive patients who were histologically diagnosed as ESCC with stage I/II/III (excluding cT4 or cN3) or stage IV due to supraclavicular lymph node metastasis and were planned to undergo surgery or chemoradiotherapy as an initial treatment were eligible for this retrospective study. In order to select patients who could tolerate TTE, respiratory function, ECOG PS and preoperative complications were additionally considered in patients’ selection. Patient characteristics, recurrence free survival (RFS), 3-year and 5-year overall survival (3yOS, 5yOS) and the treatments after failure of initial treatments were investigated. Results: 112 patients were included in TTE, 65 in dCRT. No significant differences were observed in age, sex and clinical stage between TTE and dCRT (stage I/II/III/IIV of 29/47/46/10 in TTE, 23/15/20/7 in dCRT). R0 resection rate was 87% in TTE and CR rate was 68% in dCRT. In intension to treat analysis, there was no significant difference in RFS of non-stage IA patients. In contrast, 3yOS was significantly longer in TTE than dCRT (TTE, 66.3%; dCRT, 51.0%; P=0.029).In non-stage IA patients, after initial treatment failure, significantly more patients could undergo local treatment (radiotherapy or surgery in TTE, surgery or endoscopic resection or photodynamic therapy in dCRT) in TTE than dCRT (TTE 74%, dCRT 40%, P=0.003). Conclusions: In patients with locally advanced ESCC who could tolerate TTE, TTE could extend short term survival, which might be encouraged by utilizing local treatment after initial treatment failure.
Phase I/II docetaxel, oxaliplatin, and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer.
Authors: Kim Sung Rok , Park Sung-En , Yuh Young Jin , Sohn Byeong Seok , Lee Hye Ran , Song Hong-Suk , Lee Kyung-Hee 
Published: February 2017

162 Background: The results of recent studies with duo- or triple regimen for the advanced gastric cancer are still not satisfactory and the optimal doses of combinations with taxanes, fluorouracil and platinum analogues were not determined yet. The aim of this study is to determine the optimal dose of docetaxel and oxaliplatin in combination with 5-fluorouracil(FU) [DOF], with the efficacy and toxicity in patients (pts) with advanced gastric cancer. Methods: The pts with unresectable, metastatic, or relapsed gastric cancer were enrolled for a phase I/II study. The dose of docetaxel and oxliplatin was escalated from 50 mg/m2 and 80 mg/m2 day 1, respectively by traditional 3+3 design, and 5-FU was fixed at 850 mg/m2/day 24 hour continuous infusion day 1-4, all every 3 weeks. All pts had measurable disease and were assessable for toxicity. Results: A total of 50 pts including 12 patients from phase I study were enrolled. The recommended phase II dose of docetaxel and oxaliplatin were 60mg/m2 and 100mg/m2 on day 1 (cohort 2), respectively. A total of 335 cycles of chemotherapy was administrated (median: 6, range 1–24) and the dose intensity of docetaxel, oxaliplatin, and 5-FU were 96.3%, 96.2% and 98.5%, respectively. Twenty two (44.0%) of 50 patients showed partial response, 22 (44.0%) stable disease, and 1 (2.0%) complete response. The overall response rate was 46.0% (95% confidence interval [CI]: 32.2–60.0%) and the disease control rate 90.0% (95% CI: 81.7–98.3%). The median progression free survival was 6.5 months (95% CI, 3.3–9.8) and the overall survival 10.7 month (95% CI, 7.0–14.3). Grade 3/4 neutropenia and thrombocytopenia occurred in 81 (24.1%) and 3 cycles (0.9%), respectively [27 (56%) and 3 (6%) in 50 pts, respectively]. Grade 3/4 stomatitis, diarrhea and neuropathy occurred in 2 (0.6%), 6 (1.8%) and 6 cycles (5.7%), respectively. Conclusions: The recommended phase II dose of docetaxel and oxaliplatin was 60mg/m2 and 100mg/m2, respectively. This DOF combination chemotherapy has no better efficacy than reference regimen. The toxicities were substantial in some pts, but generally manageable.
The relationship between pathologic nodal disease and residual tumor viability (RV) in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving induction chemotherapy, surgery, and postoperative chemoradiotherapy (CRT).
Authors: McNamara Michael J. , Rybicki Lisa A. , Rodriguez Cristina P. , Videtic Gregory M.M. , Stephans Kevin L. , Greskovich John , Sohal Davendra , Murthy Sudish C. , Raja Siva , Ives Denise I. , Bodmann Joanna , Adelstein David J. 
Published: February 2017

165 Background: A complete pathologic response to induction CRT has been identified as a favorable prognostic factor for patients with LRA ACA of the E/GEJ. Less is known, however, about the impact of pathologic regression after induction chemotherapy. Methods: Between 2/08 and 1/12, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. RV was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results: Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier (KM) projected 3 year OS for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (p<0.001). The KM projected 3 year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) RV was 67%, 42%, and 17% respectively (p=0.004). On multivariable analysis, both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3yr OS 85% (0-25% viable) v 51% (>25% viable), p=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3yr OS 20% (0-25% viable) v 21% (>25% viable), p=0.55]. Conclusions: RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of viability. Clinical trial information: NCT00601705.
Phase I study of combination chemotherapy consisting of capecitabine plus fractional cisplatin for unresectable gastric cancer in an outpatient setting.
Authors: Takahashi Tsunehiro , Saikawa Yoshiro , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Kawakubo Hirofumi , Takeuchi Hiroya , Takaishi Hiromasa , Kitagawa Yuko 
Published: February 2017

173 Background: The combination chemotherapy of capecitabine and cisplatin is one of the standard regimen for unresectable gastric cancer. However, the high dose of cisplatin could cause the nephrotoxicity and require the adequate hydration to avoid the damage of renal during the administration. For that reason, the hospitalization is recommended for the patients to receive the chemotherapy including high dose of cisplatin. The present study aimed to establish the proper dose of fractional cisplatin in the combination with capecitabine in an outpatient setting. Methods: Capecitabine was administered orally every day from the evening of day 1 to the morning of 15. Cisplatin were infused on days 1, 8 and 15 for 60 minutes without hydration. The starting dose of cisplatin was 15 mg/m2 as level 1. The following cisplatin dose could be given to subsequent cohorts of patients depending on safety findings observed in the previous cohort: level 2, 20 mg/m2 and level 3, 25 mg/m2, respectively. Serum concentration of total platinum was analyzed before the administration of cisplatin on days 1, 8 and 15. Results: A total of 9 patients were recruited. The median age was 64 years and there were 8 males and one female. Histological types included intestinal (n=5) and diffuse (n=4). Eight patients had multiple metastatic sites, including lymph nodes (n=8), peritoneum (n=5), liver (n=3), lung (n=2) and bone (n=1). The major toxicities were thrombocytopenia (67%), leukopenia (56%) and neutropenia (22%). However, no dose-limiting toxicity was observed in each level. Therefore, the recommended dose of cisplatin was 25 mg/m2. Of the 9 patients, 6 patients had measurable lesions and 5 patients had partial responses, resulting in an overall response rate of 83%. The median administered course was four. In patients at level 3, the mean concentration of total platinum on days 8 and 15 were 0.25μg/ml and 0.42μg/ml, respectively. Conclusions: The recommend dose of cisplatin was confirmed with 25 mg/m2 weekly. Although its safety and feasibility should be evaluated in further clinical trial, this regimen could be expected as an outpatient treatment for unresectable gastric cancer. Clinical trial information: 000005708.
Effect of sarcopenia on prognosis of patients with gastric cancer.
Authors: Iwagami Shiro , Baba Hideo 
Published: February 2017

192 Background: Recently, some studies reported the correlation between low skeletal muscle mass (sarcopenia) of patients with cancer and poor prognosis. There were no reports mentioned the relationship of sarcopenia to patients with gastric cancer. Objective: To evaluate the impact of sarcopenia on survival of patients with gastric cancer. Methods: From April 2005 to December 2010, 243 patients with gastric cancer underwent gasrectomy. Patients were divided in two groups, sarcopenia and nonsarcopenia group. Sarcopenia was defined as muscle mass below the median on preoperative CT scan. Muscle mass was assessed by psoas muscle density and total psoas area. The third lumbar vertebra (L3) was chosen as the standard landmark. We examined the relationship between sarcopenia and overall survival (OS), cancer specific survival (CSS), and disease free survival (DFS). Results: The mean age was 67.6 years old. 95 patients underwent total gastrectomy, 150 did distal gastrectomy, and 18 did proximal gastrectomy. The number of laparoscopic surgery was 62 cases. The CSS and DFS of patients in sarcopenia group were significantly shorter than nonsarcopenia group (p=0.012, p=0.023). The OS of sarcopenia tented to shorter (p=0.12). Conclusions: The presence of sarcopenia was found to significantly increase a patient’s risk of gastric cancer.
Long-term outcomes of preoperative chemotherapy with modified DCS therapy for highly advanced gastric cancer with distant metastasis.
Authors: Matsuki Atsushi , Nashimoto Atsushi , Yabusaki Hiroshi , Aizawa Masaki 
Published: February 2017

193 Background: Among patients (pts) with advanced gastric cancer (AGC), the poor prognosis was exhibited and many pts died even after R0 resection. The aim of this study is to evaluate the preoperative chemotherapy with docetaxel, cisplatin and S-1 (modified DCS therapy) for treatment in highly AGC with distant metastasis. Methods: A retrospective analysis was performed in 58 pts (man/woman; 49/9, median age; 64.5-years) treated with preoperative modified DCS therapy in our hospital between 2009 and 2012. Eligibility criteria included StageIV AGC with distant metastasis (H1;14, P1;18,CY1;31, LYM;25, PUL;2, OTH;2), a Performance status of 0-2 and no prior chemotherapy. The regimen consisted of docetaxel and cisplatin infusion (35mg/m2, days 1 and 15) and oral administration of S-1 (80mg/m2, days 1-14) every 4 weeks. Surgery was planned 3 to 4 weeks after the chemotherapy. Pathological response was graded according to the JGCA criteria. Almost all pts were treated with S-1 as postoperative adjuvant chemotherapy. Results: The median cycles was 2 (1-13). The incidence of grade 3/4 toxicity was neutropenia 53.4%, anemia 8.6%, anorexia 15.5%, nausea 5.2%, and diarrhea 3.4%. All of these toxicities were well tolerable and there was no TRD. According to RECIST, The overall response rate was 79.3%. Forty-tree pts underwent gastrectomy (R0/R1/R2; 27/8/8), respectively. Postoperative morbidity rate was 20.9% and there was no mortality. Over all 5 years survival rate (5YSR) was 21.4 % and that of R0 was 44.8%, on the other hand 5YSR and MST of chemotherapy alone was 0% and 14.5 month. Pathological response rate (>=1b) was 60.5% and complete response was achieved 1 pts. 5YSR of pathological responders who underwent R0 resection was 81.4% and that of non-responders who underwent even R0 resection was 22.5% (P<0.05). Conclusions: Preoperative modified DCS therapy for AGC was tolerable, and survival benefit of pathological responders with R0 surgery was promising and warrants further investigation.