bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcome of a randomized phase III trial exploring the significance of extensive intraoperative peritoneal lavage in addition to standard treatment for ≥ T3 resectable gastric cancer: CCOG 1102.
Authors: Morimoto Daishi , Misawa Kazunari , Mochizuki Yoshinari , Sakai Mitsuru , Teramoto Jin , Takase Tsunenobu , Nakayama Hiroshi , Ishigure Kiyoshi , Matsui Takanori , Kobayashi Daisuke , Ito Seiji , Morita Satoshi , Kodera Yasuhiro 
Published: January 2019

1 Background: Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer reportedly improved survival by physically removing and reducing intraperitoneal-free cancer cells in a small-scale randomized trial (Ann Surg 2009). To confirm this, we conducted a multicenter randomized Phase III trial. Methods: Eligibility criteria: (i) histologically confirmed primary gastric adenocarcinoma, (ii) clinically T3(SS), T4a(SE) or T4b(SI), (iii) clinically M0, and (iv) scheduled for total or distal gastrectomy. Patients were intraoperatively randomized to either the EIPL group or the non-EIPL group after confirming the ≥T3 status and resectability. In the EIPL group, peritoneal lavage was conducted at least 10 times using 1L of saline before the closure of the abdomen. In the non-EIPL group, the lavage was conducted with ≤3L of saline. The primary end-point was disease-free survival (DFS). To detect the difference of 15% in 3-year DFS with a both-sided alpha of 5% and 80% power, the planned sample size was 300 cases. This study was registered as UMIN000005907. Results: Between July 2011 and January 2014, 314 patients were registered from 15 institutions. After excluding the R1/R2 resection cases, 295 patients (145 in the EIPL group and 150 in the non-EIPL group) were analyzed. There were no significant differences between the groups in clinicopathologic characteristics. The median volume of saline for the peritoneal lavage was 10.0 L (10 - 12) for the EIPL group and 3.0 L (1 - 4) for the non-EIPL group. No difference was observed in the incidence of postoperative complications. The 3-year DFS was 63.9% in the EIPL group and 59.7% in the non-EIPL group (p = 0.25, Hazard ratio 0.81 [95% CI 0.57-1.16]). The overall survival rate of the EIPL group and non-EIPL group were 75.0%, 73.7% (3 years), and 62.5%, 57.1% (5 years), respectively (p = 0.65). In the subset analysis, no subgroup with significant difference in survival was identified. Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.
Changes in bone metabolism after gastric cancer surgery in men: A prospective observational study.
Authors: Atsumi Yosuke , Rino Yasushi , Wada Hiroo , Kitani Yuichi , Ozawa Yukihiro , Sato Tsutomu , Oshima Takashi , Yukawa Norio , Yoshikawa Takaki , Masuda Munetaka 
Published: January 2019

10 Background: Several reports have showed that bone disorders occur after gastric cancer surgery, however there are few studies that compared pre- and postoperative bone mineral density of the same patient. The purpose of this study was to assess changes in bone metabolism after gastric cancer surgery prospectively. Methods: We prospectively enrolled 39 men undergoing gastrectomy for early gastric cancer. We excluded women to avoid the effect of menopause. Patients with severe kidney disease requiring dialysis treatment, patients with severe liver disease and patients with treatment with bisphosphonates or any other bone-active drugs were also excluded. Dual energy X-ray absorptiometry (DEXA) was performed before and 1 and 2 years after surgery to evaluate bone mineral density (BMD). The serum levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), estradiol, and alkaline phosphatase (ALP) were measured before surgery and every three months until two years after surgery. Results: DEXA revealed that BMD was significantly decreased by 0.036±0.033 g/cm2 at 12 months after gastrectomy (P < 0.001). The serum ALP was significantly increased by 38.88±6.42 IU/l at 24 months after surgery (P = 0.013), and there was a marginally significant correlation between the changes in BMD and the changes in the serum ALP at 24 months after surgery; the correlation coefficient was -0.30 (P = 0.090). The serum 25(OH)VD was significantly decreased by 4.88±6.42 ng/ml at 24 months after surgery (P < 0.001), however there was no significant correlation between the changes in BMD and the changes in the serum 25(OH)VD. The serum 1,25(OH)2VD and estradiol were not significantly changed before and after surgery. The factor significantly correlated to the reductions of BMD at 12 months after surgery included preoperative lower body mass index (BMI); the correlation coefficients was 0.37 (P = 0.025). Conclusions: This study showed a significant reduction in the BMD of gastric cancer patients at 12 months after gastrectomy and suggested that low preoperative BMI could be a high risk factor for the bone disorder after gastric cancer surgery.
Apatinib as third-line or beyond therapy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction: An open-label, multicenter, post-marketing phase IV study (Ahead-G201).
Authors: Qin Shukui , Deng Wenying , Wen Lu , Wang Junsheng , Zhang Guifang , Zhong Haijun , Jia Tongfu , Yang Jianwei , Ba Yi , Bai Yuxian , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Li Jin 
Published: January 2019

103 Background: The clinical benefit and safety profile of apatinib in advanced gastric cancer have been established in the randomised controlled phase III clinical trial (J Clin Oncol. 34(13):1448-54). A post-marketing study to confirm the safety and efficacy of apatinib is ongoing in a broad range of patients (pts). Methods: This is a single-arm, open-label, multi-center, Phase IV trial with the target sample size of 2000+ (ClinicalTrials.gov Identifier: NCT02426034). Pts were recruited to receive oral apatinib until disease progression, death or unacceptable toxicity. The primary objective was safety, and the secondary objectives included overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results: Herein, we report the preliminary data as documented in the EDC System. As of Jul 10, 2017, 1037 pts were enrolled from 138 hospitals across China. Pts characteristics were: median age 59 yrs, male/female 72.0/28.0%, ECOG PS 0/1/≥2 16.6/66.2/17.2%, stage IV 91.0%. 336 (32.4%) pts interrupted treatment and dose modification occurred in 172 (16.6%) pts (reduction 132/12.7%; rise 87/8.4%). Eventually, the mean dosage was 526.2 mg/d. 652 (62.9%) pts had 4407 drug-related adverse events (DRAEs). Grade ≥3 DRAEs occurred in 300 (28.9%) pts. Severe AEs were reported by 221 (21.3%) pts. The most common DRAEs were proteinuria (19.3%), hypertension (18.8%), leukocyte decrease (16.4%), fatigue (14.2%), platelet decrease (13.6%), hand-foot-skin reaction (11.1%) and neutrophil decrease (10.1%). 820 pts were evaluable for efficacy analysis. The best ORR and DCR were 10.7% and 70.0%, respectively. The median PFS and OS were 4.60 (95%CI, 3.25–4.73) and 6.57 (95%CI, 5.78–7.59) months, respectively. Conclusions: Apatinib monotherapy is effective and has a favorable toxicity profile in real-world clinical setting. The preliminary results of this Phase IV study confirmed the safety and efficacy of apatinib demonstrated in the Phase II and III trials. Updated results will be discussed. Clinical trial information: NCT02426034.
Development of a radiomic signature for prediction of pathological complete response following neoadjuvant chemoradiotherapy in esophageal cancer.
Authors: Rishi Anupam , Eaford India , Zhang Geoffrey , Viera Alexander , Latifi Kujtim , Frakes Jessica M. , Pimiento Jose Mario , Fontaine Jacques-Pierre , Hoffe Sarah E. 
Published: January 2019

106 Background: Pivotal to personalized therapy is accurate pre-treatment patient selection based on predictive biomarkers. We developed a radiomic signature model to predict pathological complete response (pCR) following neoadjuvant chemo-radiotherapy (NACRT) in esophageal cancers. Methods: We retrospectively identified 68 patients with esophageal cancer, treated with NACRT followed by esophagectomy, with baseline 18F-fluorodeoxyglucose Positron Emission Tomography (PET) and computed tomography (CT) scans performed at our institution. In-house data-characterization algorithm was used to extract 3D radiomics features from the segmented primary disease. Prediction models were constructed and internally validated (2/3rd training, 1/3rd validation) using machine learning software. Cox regression hazard used to assess association with relapse free survival (RFS). Results: pCR was observed in 34 (50%) patients. A total of 126 features were extracted individually from PET and CT scans. On univariate analysis, 16 PET and 14 CT features were found to independently predict pCR. Three separate predictive models were built for CT, PET and combined CT+PET. Individually, both CT and PET had a good predictive power with AUC 0.74 and 0.730, respectively. Combined CT+PET radiomic features resulted in a significant improvement of predicting power, with AUC 0.856. Good discrimination (82.6%) was observed in validation dataset. Final model was: 13.439-34.632(CT-eccentricity)-2.469(CT-LRLGE)+10.626(CT-Gnorm_HIE)-2.094(CT-SD_Lac2)-19.337(CT-FD_SD)-0.344(PET-Contrast), where eccentricity is shape feature, LRLGE a gray level run length feature, Gnorm_HIE gray-level size zone feature, SD_Lac2 a fractal dimension feature. Stratifying patients with low vs. high radiomic signature score predicted RFS: median RFS 80.1 vs. 40.1 months; and 2-year RFS 77.4% vs. 52.6% [Hazard Ratio: 2.24, 95% CI 1.01-5.58], respectively. Conclusions: The developed radiomics signature models were highly predictive of pCR following NACRT. Further validation in larger data sets is needed to determine whether the model can predict clinical outcomes.
Comparison of S-1 and S-1 plus cisplatin as post-operative chemotherapy for gastric carcinoma with peritoneal lavage cytology positive or localized peritoneum metastasis: A multicenter retrospective study.
Authors: Aizawa Masaki , Yamaguchi Toshifumi , Takashima Atsuo , Nagashima Kengo , Ema Akira , Yuasa Yasuhiro , Haruta Shusuke , Taniguchi Hiroki , Kobayashi Daisuke , Nishikawa Kazuhiro , Yunome Gen , Takagi Masakazu , Niwa Hirotaka , Yamada Takanobu , Hato Shinji , Fukagawa Takeo , Boku Narikazu , Katai Hitoshi 
Published: January 2019

109 Background: Peritoneal lavage cytology of class V and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Because patients (pts) with CY1 and/or P1 have poor prognosis after resecting all macroscopically visible disease by standard surgical resection, post-operative chemotherapy (post-Cx) is commonly performed in the clinical practice in Japan. However, no standard chemotherapy has not been established. The aim of this study was to investigate the efficacy of post-Cx in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: PS 0-2, histology of adenocarcinoma, no distant metastasis other than CY1 or P1, no prior treatment for GC. The subject of this study was the patients who received surgery followed by post-Cx. Results: A total of 824 pts were collected from 34 institutions. Of the 506 eligible pts, 444 pts underwent standard gastrectomy followed by post-Cx: S-1 (n=267), S1 plus cisplatin (SP) (n=114) or others (n=63). 62 pts did not receive post-Cx (non-Cx). Median age for the S1/SP/Others/non-Cx group were 69/63/66/75. In the S-1 group, pts with P0CY1/P1CY0/P1CY1 were 197/44/26, and those were 81/21/12 in SP, 45/9/9 in Others, and 44/7/11 in non-Cx. Conclusions: Post-Cx may have survival benefit after surgery for GC with CY1 or P1, while there seems no additional benefit over S-1. [Table: see text]
The effect of adjuvant chemotherapy in patients without local nodal metastases following neoadjuvant chemoradiotherapy and esophagectomy for locally advanced esophageal cancer.
Authors: Nevala-Plagemann Christopher Duane , Francis Samual , Cavalieri Courtney Christine , Lloyd Shane , Garrido-Laguna Ignacio 
Published: January 2019

111 Background: Neoadjuvant chemoradiation therapy (CRT) followed by esophagectomy is the current standard of care for patients with locally advanced esophageal cancer. The potential benefit of additional postoperative chemotherapy is still under investigation. In this study, we utilized the National Cancer Database to assess the effect of adjuvant chemotherapy in patients who were found to have node negative disease (pN0) following surgery. Methods: Patients with locally advanced esophageal cancer who received neoadjuvant CRT followed by esophagectomy from 2004 to 2014 were retrospectively identified using the National Cancer Database. Patients who were postoperatively staged as pN0 were then separated based on whether or not they received adjuvant chemotherapy. Using Kaplan-Meier estimation and a multivariate cox regression analysis, the overall survival of those who received adjuvant therapy was then compared to those who received neoadjuvant CRT alone. Results: 3,159 patients with locally advanced esophageal cancer underwent neoadjuvant CRT and were found to be pN0 following surgery. 119 of these patients received postoperative chemotherapy. The 1, 5, and 8-year overall survival in those receiving adjuvant therapy was 95.9%, 49.9%, and 47.7% compared to 85.8%, 44.6%, and 33.0% in those receiving neoadjuvant CRT alone, respectively (p = 0.019). Based on multivariate analysis, receiving adjuvant chemotherapy was independently associated with increased overall survival (p = 0.011; HR 0.658; 95% CI, 0.476 to 0.908). Conclusions: Adjuvant chemotherapy may improve survival in patients with locally advance esophageal cancer who have no evidence of local nodal metastases following surgery. Additional clinical trials are needed to further confirm which patients may benefit from adjuvant therapy and to determine the optimal postoperative therapeutic regimen.
The impact of American Indian and Alaska Native ethnicity on the presentation and surgical treatment of gastric cancer: An NCDB analysis from 2004-2014.
Authors: Vuong Brooke , Klempner Samuel Jacob , Nguyen Trang , Young Stephanie , Dehal Ahmed , Graff-Baker Amanda , Chang Shu-Ching , Bilchik Anton J. , Goldfarb Melanie , Fischer Trevan D 
Published: January 2019

13 Background: American Indian/Alaska Natives (AI/ANs) with gastric adenocarcinoma (GC) have an incidence and mortality nearly double that of matched Non-Hispanic Whites (NHW) in historical data sets. However, the impact of AI/AN ethnicity on disease presentation and treatment is underrepresented in gastric cancer epidemiologic studies and has not been evaluated in a contemporary population. Methods: The National Cancer Data Base (NCDB) was queried from 2004-2014 to identify patients with gastric cancer who identify as AI/AN or NHW. Patient demographics, tumor characteristics, and treatment details, including surgical quality metrics, were compared using Chi-square and Student's t-tests. Results: There were 22,286 NHW and 115 AI/AN GC patients with complete staging information. Compared to NHW, AI/ANs were younger (age ≤65) at diagnosis (p < 0.001), which translated to a younger median age at death (NHW:70 years, AI/ANs:60 years, p < 0.001). AI/ANs more often lived over 100 miles from their treatment facility (p < 0.001) in non-metropolitan cities (p < 0.001). Stage distribution was not different for the AI/AN population when compared to the NHW population: 37% vs. 35% Stage I; 33% vs. 37% Stage II; 10% vs. 11% Stage III; and 19% vs. 16% Stage IV (p = NS). However, AI/ANs had a higher rate of signet ring cell histology and linitis plastica (26% vs. 15%, p = 0.002) compared to NHWs. More AI/AN patients compared to NHW patients had delays over eight weeks to initiation of treatment, 19% vs. 11% (p = 0.008). There were no statistically significant differences for surgical quality metrics, including type of surgery, rate of ≥15 lymph nodes retrieved, margin positivity, or 30-day mortality (p = NS). Conclusions: Both biological and social disparities are evident for AI/ANs with gastric cancer. AI/ANs develop and die from gastric cancer at younger ages compared to NHWs and present with higher rates of aggressive histology. They also travel longer distances for treatment and experience greater treatment delays. These features may partly underlie the higher mortality rates previously described.
Prospective, multicenter, noninterventional and registry clinical study of apatinib in patients with advanced gastric cancer.
Authors: Bai Chunmei , Zhong Diansheng , Zhang Ruixing , Ren Xiubao , Liu Likun , Du Nan , Yu Junyan , Yang Mudan , Zang Aimin , Diao Jianfeng , Ren Yuchuan , Fu Zhanzhao , MA Liwen , Zhang Lei , Gao Jinghua , Li Guozhong , Guo Jun , Zhang Junping , Jia Junmei , Zhang Wenzheng 
Published: January 2019

137 Background: The aim of this study was to observe the safety of apatinib in the real world with wider inclusion criteria. The efficacy of apatinib was evaluated including overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Methods: This trial enrolled patients from 32 centers in china with advanced gastric adenocarcinoma who had progressed after undergoing at least two lines of systemic chemotherapy, or patients who were considered to benefit from the treatment. We recommended starting from oral administration of 500mg qd, 28 days for a cycle. Dose could be appropriately adjusted according to the patients’ physical condition. Results: Between March 2015 and September 2017, 326 patients were enrolled. The average age was 62 years old, and the ratio of male to female was about 2:1. Patients received perioperative, first-line, second-line, and third-line or more treatment were 1,39,69 and 217 people respectively. There were 192 patients received efficacy evaluation, 9 patients achieved partial response(PR), 125 had disease stability(SD). The ORR and DCR were 4.6% and 69.8% respectively. The median PFS and median OS were 3.7 months and 7.3 months respectively. In the 326 patients, there were 153 patients with initial dose of 500 mg, 3 and 55 patients achieved PR and SD, respectively. The ORR and DCR were 3.3% and 63.7%, respectively. The median PFS and median OS were 3.5 months and 8.4 months, respectively. There were 237 patients in all 326 patients received safety analysis. Common adverse events were hypertension (57%), hand-foot skin reactions (26.6%), fatigue (29.5%), proteinuria (19.0%), bleeding (10.1%) and diarrhea (8.0%). The grade 3 to 4 adverse events were hypertension (6.3%), hand-foot skin reactions (3.8%), proteinuria(3.0%) and bleeding (2.1%). Conclusions: This real-world data in which more patients were given apatinib 500mg or less qd showed similar efficacy to Phase III clinical trial (850mg qd).The incidence of adverse events was consistent with that of Phase III clinical data,there was no new adverse events had been seen. Clinical trial information: NCT02668380.
Nonoperative management of locally advanced esophageal and junctional (GEJ) cancers: The University of Rochester experience.
Authors: David Rachel Julie , Baran Andrea , Katz Alan W. , Dunne Richard Francis , Noel Marcus Smith , Hezel Aram F. , Tejani Mohamedtaki Abdulaziz 
Published: January 2019

144 Background: Neoadjuvant (NA) chemoradiation (CRT) followed by surgery is a standard treatment for locally advanced esophageal/GEJ tumors. The optimal management strategy is less clear for unresectable tumors or in patients (pts) who are medically inoperable. Methods: We retrospectively identified all pts with stage II/III esophageal/GEJ cancers treated without surgery at our institution from 2011-2015. Objectives were to describe treatment regimens used and assess outcomes based on clinicopathologic features. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Results: 38 pts were identified. 66% were male; median age was 69 years (range 43-91). 19 pts had adenocarcinoma, 18 had squamous cell, and 1 had small cell. Primary sites were distal (n = 22), mid (n = 13), and cervical esophagus (n = 3). 31 pts were treated with curative intent, 7 with best supportive care. 30 pts underwent CRT: 16 in a NA setting, 14 in a definitive setting. Chemotherapy regimens used were Carboplatin/Paclitaxel (19 pts) and Cisplatin/5-FU (10 pts). Median NA radiation (RT) dose was 45 Gy vs 50.4 Gy in the definitive setting (p = 0.008). Best response included 6 pts with complete responses (CR), 12 with partial responses, and 12 with progressive disease/death (PD). In the NA group, resection was avoided due to PD (n = 10), comorbidities (n = 4), unresectability (n = 1), and CR (n = 1). Median PFS and OS for all 38 patients were 6.5 and 11.1 months (mos). Median PFS and OS for adenocarcinoma pts were 4.6 and 7.2 mos, compared to 9.1 and 12.5 mos for pts with squamous. Compared to NA CRT, pts treated with definitive CRT had significantly prolonged PFS (18.5 vs 2.5 mos, p = 0.001) and OS (27.1 vs 5.3 mos, p = 0.03). Conclusions: In the absence of resection, outcomes for locally advanced esophageal/GEJ tumors remain poor, especially for adenocarcinoma pts who progress during NA CRT. A PET-directed approach as suggested by CALGB 80803 may help to identify these pts earlier in their course, allowing for treatment change. Multidisciplinary assessment to identify non-surgical candidates at diagnosis is critical since RT doses used in the definitive setting are generally higher.
Potential of SUSD2 as a predictor of recurrences after curative resection of gastric cancer.
Authors: Umeda Shinichi 
Published: January 2019

15 Background: Gastric cancer (GC) is the third common leading cause of cancer-related death worldwide with a high recurrence rate. Development of sensitive biomarkers to predict recurrences is needed to improve patient management. Methods: We conducted a recurrence pattern-specific transcriptome analysis of 57751 molecules for screening of candidate molecules specific for hematogenous metastasis with stageⅢ GC patients who underwent curative resection followed by S-1 adjuvant. Subsequently, mRNA expression analysis, PCR array analysis and siRNA-mediated knockdown experiments were performed using GG cell lines. Expression levels in primary GC tissues from 154 patients with resectable GC were determined and correlated to clinicopathological factors. Results: We identified 21 candidate molecules overexpressed significantly specifically in the hepatic recurrence group and decided to focus on Sushi domain containing 2 (SUSD2). PCR array analysis revealed that SUSD2 expression levels are positively correlated with Frizzled-7 , Cadherin 2 and ZEB1. Functional analysis revealed that knockdown of SUSD2 significantly reduced the proliferation, migration and invasion abilities of GC cells. Patients with high SUSD2 expression had a significantly higher prevalence of hematogenous recurrences and were more likely to experience shorter disease-free and overall survival, particularly in stage III patients. Conclusions: SUSD2 may serve as predictor of recurrences after curative resection of GC.