bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-field versus two-field lymphadenectomy for carcinoma of the middle and lower esophagus: Short-term results of a randomized controlled trial.
Authors: Li Bin , Chen Haiquan 
Published: September 2018

4036 Background: The safety and efficacy of esophagectomy with 3-field lymphadenectomy remain controversial. Methods: We did this randomized trial in Fudan University Shanghai Cancer Center in China. Between March 2013 and November 2016, 400 patients with cancer located in the middle and lower esophagus were recruited and randomly assigned to receive 3-field or 2-field lymphadenectomy at a 1:1 ratio. Postoperative complications between the 3-field group (n = 200) and 2-field group (n = 200) were compared on the basis of the intention-to-treatment principle. Results: There was no significant difference between the two arms in terms of gender, age, BMI, FEV1, and tumor location. Median operative time was 183 minutes (range 125 to 331) in 3-field group versus 168 minutes (range 116 to 375) in 2-field group, P< 0.001. Overall morbidity was 28% (56/200) in the 3-field group and 30.5% (61/200) in the 2-field group, P= 0.583. The mortality rate was 0% (0/200) for the 3-field group and 0.5% (1/200) for the 2-field group, P= 1.000. Although more reintubation occurred in the 3-field group than in the 2-field group (3% [6/200] vs. 0% [0/200], P= 0.030), the distribution of severity (stratified according to the Clavien-Dindo classification) and hospital stay were similar between the two groups. A significantly higher number of lymph nodes were retrieved in the 3-field group (median 37, range 3 to 85) compared to those in the 2-field group (median 24, range 7 to 61) ( P< 0.001). 44 patients (22%) had positive cervical nodes in the 3-field group. Conclusions: Morbidity after esophagectomy with 3-field lymphadenectomy is comparable with that after 2-field lymphadenectomy. Cervical lymphatic involvement is common in patients with middle and lower esophageal cancer. 3-field lymphadenectomy may offer more accurate tumor staging related to cervical lymphatic metastasis. TABLE. Regions of lymph nodes metastases Clinical trial information: NCT01807936. [Table: see text]
Early presence of antiangiogenesis-related adverse events as a potential biomarker of antitumor efficacy in patients with metastatic gastric cancer treated with apatinib.
Authors: Liu Xinyang , Qin Shukui , Wang Zhichao , Xu Jianming , Xiong Jianping , Bai Yuxian , Zhe-Hai Wang , Yang Yan , Sun Guo-ping , Wang Liwei , Zheng Leizhen , Xu Nong , Cheng Ying , Guo Weijian , Yu Hao , Liu Tian Shu , Lagiou Pagona , Li Jin 
Published: September 2018

4052 Background: Reliable biomarkers of apatinib response in gastric cancer (GC) are lacking. We investigated the association between early presence of common adverse events (AEs) and clinical outcomes in metastatic GC patients. Methods: We conducted a retrospective cohort study using data on 269 apatinib-treated GC patients in two clinical trials. AEs were assessed at baseline until 28 days after the last dose of apatinib. Clinical outcomes were compared between patients with and without hypertension (HTN), proteinuria or hand and foot syndrome (HFS) in the first 4 weeks using Kaplan–Meier methods, Cox proportional hazard regression and logistic regression models. Landmark analyses were performed as sensitivity analyses. Predictive model and risk scores were analyzed to predict overall survival (OS). Results: Presence of AEs in the first 4 weeks was associated with prolonged median OS (169 vs. 103 days, log-rank p=0.0039; adjusted hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.64-0.84, p=0.001), prolonged median progression-free survival (PFS, 87 vs. 62 days, log-rank p=0.0309; adjusted HR 0.69, 95%CI 0.53-0.91, p=0.007), and increased disease control rate (54.67% vs. 32.77%; adjusted odds ratio 2.67, p<0.001). Results remained significant in landmark analyses. An AE-based prediction model and subsequently derived scoring system showed high calibration and discrimination in predicting OS. Conclusions: Presence of HTN, proteinuria or HFS during the first cycle of apatinib treatment was a viable biomarker of antitumor efficacy in metastatic GC patients. [Table: see text]
Safety in numbers? Gastric cancer survival varies with total retrieved lymph nodes.
Authors: Tabatabaie Omidreza , Kasumova Gyulnara G. , van Roessel Stijn , Ukandu Promise , Ng Sing Chau , Schlechter Benjamin L. , Savarese Diane M. F. , Tseng Jennifer F. 
Published: September 2018

4058 Background: Recently published AJCC 8thTNM-staging guidelines recommend a minimum of 16 lymph nodes be assessed in gastric cancer surgery with more lymph nodes ( 30) being desirable. However, the independent effects of greater numbers of lymph nodes excised on the overall survival of patients with gastric adenocarcinoma are understudied. Methods: National Cancer Database (NCDB) was reviewed from 2010 to 2014 for patients who underwent potentially curative surgery for gastric adenocarcinoma. Patients with zero or unknown number of harvested lymph nodes were excluded, as were those with metastatic or in-situ disease, or who received neoadjuvant chemo- or radiotherapy. Cox proportional hazards modeling was used for multivariate survival analysis. Results: Of the 12,507 patients who met selection criteria, 4,880 (39.0%) were female. The median age was 69 years [IQR: 59-77]. Median number of lymph nodes examined for each clinical T and N-stage is provided in the table. Overall, 51.0% of patients had < 16 lymph nodes examined. After adjusting for clinical T and N-stages, sex, age, tumor size, grade, facility type, receipt of adjuvant chemotherapy, resection type and race, and compared to patients with < 16 nodes examined, the hazard ratios for death in patients with 16-29, 30-44 and ≥45 examined lymph nodes were 0.87 (95% CI = 0.82-0.93), 0.79 (95% CI = 0.71-0.88) and 0.68 (95% CI = 0.56-0.83), respectively. Conclusions: Total lymph node count is an important independent predictor of overall survival in resectable gastric cancer, with an increased number of excised lymph nodes being associated with progressively decreased risk of death. These findings support the latest AJCC guidelines that higher number of lymph node retrieval is desirable. The recommended oncologic standard for at least 16 nodes to be assessed pathologically is not attained in more than half of upfront gastric resections performed for cancer. [Table: see text]
Treatment patterns for resected gastric cancer using the National Cancer Database.
Authors: Ogunleye Foluso Nelson , Sura Karna Tushar , Blankenship Leann , Ezekwudo Daniel , Gbadamosi Bolanle , Jaiyesimi Ishmael A. , Kabolizadeh Peyman 
Published: September 2018

4061 Background: The optimal management of patients with resected gastric cancer remains a therapeutic challenge. Although the benefit of peri-operative chemotherapy or adjuvant concurrent chemoradiotherapy for these patients is clearly established, recurrence and mortality rates remain high despite aggressive treatment. The goal of this study was to characterize the treatment patterns employed for patients with resected gastric cancer using the National Cancer Database (NCDB). Methods: The NCDB was queried between 2004-2013 for patients with invasive resected gastric cancer and negative margins, excluding those with metastatic disease. Results: We identified a total of 21,156 cases. The median age was 67 (range 55-79). A majority of patients were white (74%) followed by black (14%) and other (12%). Most patients had either insurance through the government (58%) or private insurance (37%). 47% of patients had surgery alone with approximately 53% of these patients diagnosed with stage I gastric cancer. The remainder of the patients had radiation alone (1.4%), chemotherapy alone (15.2%), or combined chemotherapy and radiation (36.7%). Table 1 includes the further breakdown of treatment. Conclusions: A majority of patients with resected gastric cancer had treatment with either radiation, chemotherapy, or a combination of both. However, it is interesting to note that in patients receiving adjuvant or neoadjuvant treatment, only a portion of the patients received treatment options with level 1 evidence such as the MAGIC or McDonald regimens. [Table: see text]
A randomized, open-label, multicenter trial of the concurrent chemoradiotherapy of capecitabine with or without oxaliplatin versus cisplatin with 5-FU for Chinese squamous esophageal cancer: An interim report from CRTCOESC.
Authors: Jia Ruinuo , Shan Tanyou , Zhou Fuyou , Zheng Anping , Wan Lixin , Xu Zhiqiao , Zheng Guobao , Luo Xiaoyong , Zheng Yingjuan , Cui Yanhui , Zhang Guifang , Zhou Dan , Sun Jiachun , Kong Guoqiang , Yuan Xiaozhi , Yang Ruina , Ren Jing , Wang Wei , Wang Xinshuai , Gao Shegan 
Published: September 2018

4063 Background: CRT with 5- FU and cisplatin (PF) has shown greater clinical efficacy for local advanced esophageal cancer (EC) but with high rate of acute toxicities (ATs). CRTCOESC is a randomized, open-label, multicenter trial designed to evaluate the effect and safety of capecitabine with or without oxaliplatin versus PF with CRT in Chinese EC. Methods: Pts with biopsy-proven squamous EC (T2-4N0-2M0) were randomized to single capecitabine (Arm1), capecitabine plus oxaliplatin (Arm2), or PF (Arm3), while daily radiation 50Gy/2Gy for all. Pts were stratified by different regimens cycles. Both grade3-5 ATs and 2-year OS were the primary endpoint, with a planned accrual of 249 pts to detect a decrease in Grade3-5 ATs from 40% to 20%. The secondary endpoint included objective response rate (ORR) and 2-year progression free survival (PFS). Interim analysis of ATs and ORR was planned for the first 120 pts. Results: The study accrued 128 pts from 2014.10-2016.12, 118 were eligible. 86 patients were finished 16-weeks follow-up at least and analyzed in the interim report (Arm1: Arm2: Arm3 = 24: 37: 25). There was no difference between three arms on pts pretreatment characters (age, gender, weight, performance status, clinical stage, lymphonodus status, and pathology grade). Incidence of grade3-5 ATs in Arm1/2/3 were 25%: 32.4%: 64% ( p = 0.03); it was significantly lower in Arm1/2 than Arm3 (Arm1 vs Arm3, p = 0.041; Arm2 vs Arm3, p = 0.022); and there no meaningful different between Arm1 and Arm2 ( p = 0.738). The pCR rate and ORR were 50%: 48.6%: 48% and 87.5%: 83.8%: 100% in Arm1/2/3 ( p = 0.99; p = 0.133). 56 patients had been finished 1 year follow-up (Arm1: Arm2: Arm3 = 12: 26: 18). The 1-year OS and PFS were 75%: 91.9%: 76% and 66.7%: 62.2%: 60% in Arm1/2/3 ( p = 0.166; p= 0.926). Conclusions: Compared with PF, CRT with single capecitabine with or without oxaliplatin shown lower incidence of ATs and similar ORR and 1-year OS. The single capecitabine seemly carried out a benefit of lower ATs than it plus oxaliplatin; there was no meaningful difference for them on ORR and 1-year OS. Ruinuo Jia and Tanyou Shan did equal work. Clinical trial information: NCT02025036.
Results of a phase II randomized study evaluating the potential benefit of a postoperative intraperitoneal immunotherapy after resection of peritoneal metastases from gastric carcinoma metastases (IIPOP- NCT01784900).
Authors: Goere Diane , Glehen Olivier , Mariette Christophe , Auperin Anne , Elias Dominique 
Published: September 2018

4064 Background: Prognosis of patients with peritoneal extension from gastric carcinoma remains poor. The aim of this multicentre, open-label, phase 2 randomized study was to analyze the potential survival benefit of an immediate postoperative intraperitoneal immunotherapy using a bi-specific (anti-EpCAM, anti-CD3), trifonctional agent named catumaxomab. Methods: Patients with limited synchronous carcinomatosis from gastric carcinoma (Peritoneal cancer index (PCI) ≤ 12), were treated after complete resection (gastrectomy plus all peritoneal deposits), by an intraperitoneal infusion of catumaxomab during 5 days. Patients were randomized between 2 arms according to the total doses administered of catumaxomab (100µg vs 140µg). The first end-point was the 2-year overall survival (OS). Forty randomized patients were required (20 in each arm), considering that a 2-year OS rate ≤ 30% would be considered as unacceptable, and ≥ 55%, a promising survival rate. The study was stopped prematurely due to the manufacturing stop of the catumaxomab. Results: Between March 2013 and September 2014, 26 patients were included in the study; among them, 11 were randomized, with a median PCI of 9 [1-12]. Seven patients received the whole planned treatment of catumaxomab; in the remaining 4 patients, interruptions were related to postoperative complications. One patient died postoperatively of multiorgan failure and grade 3-5 complications occurred in all the patients, without difference between the 2 groups. At the end of the follow-up, 3 were alive (25, 30, 36 months). The median OS was 19 months, and the 1 and 2- year OS rates were 63.6% and 36.4% respectively. Conclusions: This study has to be stopped prematurely; however, encouraging results regarding overall survival were observed. Intraperitoneal immunotherapy represents an innovative and promising treatment in patients with peritoneal metastases, considering the poor response to systemic chemotherapy and the “immunocompetence” of the peritoneum. The evaluation of a potential benefit of a local immunotherapy has to be pursued. Clinical trial information: NCT01784900.
Updated antitumor activity and safety of FPA144, an ADCC-enhanced, FGFR2b isoform-specific monoclonal antibody, in patients with FGFR2b+ gastric cancer.
Authors: Catenacci Daniel V.T. , Rha Sun Young , Bang Yung-Jue , Wainberg Zev A. , Chao Joseph , Lee Keun Wook , Korn Wolfgang Michael , Kim Yeul Hong , Song Eun-Kee , Chiu Chang-Fang , Yen Chia-Jui , Berlin Jordan , Kim Jin-Soo , Sikorski Robert S. , Collins Helen , Clark Lee , Inamdar Sandeep P. , Zhang Charlie , Lee Jeeyun 
Published: September 2018

4067 Background: FGFR2b-overexpressing gastric cancer is characterized by poor prognosis. FPA144, a humanized monoclonal IgG1 antibody that specifically binds to and blocks FGFR2b, has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC). FPA144-001 is a two-part Phase 1 study of FPA144 monotherapy in patients with advanced solid tumors, including gastric and gastroesophageal cancers (GEJ cancers). Methods: Part 1A was a 3+3 design to assess safety and PK and to establish a recommended dose (RD) of FPA144. Patients with gastric cancer were enrolled in Part 1B to assess PK in gastric cancer. Part 2 includes 4 cohorts of gastric cancer patients with either high, moderate, low or no FGFR2b overexpression based on a centralized immunohistochemistry (IHC) assay. Here, we describe results of gastric cancer patients that highly overexpress FGFR2b (FGFR2b+ High) enrolled in Parts 1 and 2 of the study. Results: As of October 28, 2016, 18 FGFR2b+ High (IHC 3+ ≥10% tumor membrane staining) patients were enrolled in the study. 12 of these patients received the RD of 15 mg/kg every 2 weeks. Enrolled patients received a median of 3 prior treatment regimens. Fatigue (22.2%, none ≥ gr 3) and infusion reaction (16.7%, 5.6% gr 3) were the most common treatment-related AEs. Treatment-related SAEs were reported in 2 patients: Grade 2 ulcerative keratitis and Grade 3 infusion reaction. There were 5 PRs, 4 confirmed and 1 unconfirmed. Disease control (PR+SD) was 55.6%, including a confirmed ORR of 22% with median DOR of 15.4 weeks. ctDNA analysis of a responding patient revealed baseline elevated FGFR2 gene copy (165 copies in the blood, mutation allele burden 66%) that decreased after monotherapy (nadir 75 copies, mutation allele burden 38.5%) corresponding with clinical response, serum tumor markers and near complete response on PET imaging. Conclusions: The demonstration of activity and an acceptable safety profile supports further development of FPA144 in patients with FGFR2b+ tumors. FGFR2 gene amplification detected in ctDNA may provide a non-invasive diagnostic test for patient selection. Updated data will be presented. Clinical trial information: NCT02318329.
Safety and clinical activity of durvalumab monotherapy in patients with hepatocellular carcinoma (HCC).
Authors: Wainberg Zev A. , Segal Neil Howard , Jaeger Dirk , Lee Kyung-Hun , Marshall John , Antonia Scott Joseph , Butler Marcus , Sanborn Rachel E. , Nemunaitis John J. , Carlson Cheryl Ann , Finn Richard S. , Jin Xiaoping , Antal Joyce , Gupta Ashok Kumar , Massard Christophe 
Published: September 2018

4071 Background: Durvalumab, an anti-PD-L1 mAb, has shown early and durable clinical activity with manageable safety in an ongoing Phase 1/2, multicenter, open-label study in pts with advanced solid tumors. Interim analyses from the HCC cohort in the dose-expansion part of this study are reported here. Methods: Patients with HCC (Child-Pugh class A) received durvalumab 10 mg/kg i.v. q2w for 12 months or until confirmed progressive disease, whichever occurred first. The primary objective was to evaluate the safety profile; secondary objective was to assess the antitumor activity (investigator-assessed RECIST v1.1). Clinical activity was evaluated for the total HCC population and by viral status. Results: As of Oct 24 2016, 40 HCC pts with median 23.9 (range 2.4–34.7) weeks follow-up received durvalumab. 93% had prior sorafenib. Treatment-related AEs occurred in 80.0% of pts, most commonly fatigue (27.5%), pruritus (25.0%) and elevated aspartate aminotransferase (AST) (22.5%). Grade 3–4 treatment-related AEs were reported in 20.0% of pts, most commonly elevated AST (7.5%) and elevated alanine aminotransferase (5.0%). 7 (17.5%) pts completed the initial 12-month treatment and 7 (17.5%) pts discontinued treatment because of an AE (none related to treatment). There were no deaths due to treatment-related AEs. Clinical activity is presented in the table. 4 pts achieved a PR; 2 were ongoing at data cut-off. Conclusions: Durvalumab had an acceptable safety profile and showed promising antitumor activity and OS in pts with HCC, particularly HCV+ pts. Clinical trial information: NCT01693562. [Table: see text]
Theranostic trial of well differentiated neuroendocrine tumors (NETs) with somatostatin antagonists 68Ga-OPS202 and 177Lu-OPS201.
Authors: Reidy Diane Lauren , Pandit-Taskar Neeta , Krebs Simone , O' Donoghue Joseph A. , Raj Nitya Prabhakar , Cruz Elizabeth , Pham Hanh , Lashley Alicia , Bodei Lisa , Weber Wolfgang 
Published: September 2018

4094 Background: Radiolabeled somatostatin receptor 2 (sstr2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than agonists in preclinical models. We performed a phase I study to evaluate the safety and radiation dosimetry of the sstr2 antagonists 68Ga-OPS202 and 177Lu-OPS201 (68Ga/177Lu-DOTA-JR11) in patients (pts) with metastatic well differentiated NETs (NCT02609737). Efficacy data after 177Lu-OPS201were recorded. Methods: Pts with RECIST disease progression underwent a 68Ga-OPS202 PET/CT to confirm in-vivo binding of the sstr2 antagonists and if positive, underwent treatment with 3 doses of 177Lu-OPS201. The first dose of 50 mCi 177Lu-OPS201was used to calculate tumor and normal organ radiation doses. Dosimetry was then calculated to administer 177Lu-OPS201in divided doses for the 2nd and 3rdfractions, 8-10 weeks apart. Results: 19 pts enrolled (primary tumors: 1 lung, 7 small bowel, 8 pancreatic NETs, 1 gastric NET, 1 rectal NET, 1 kidney). Average age was 55 y (22-73 y), 52% female; mean number of prior treatments was 3. All pts received 1 therapeutic dose of 177Lu-OPS201, 7 pts received 2 doses. All tumors were visualized by 68Ga-OPS202 PET/CT. With the exception of the kidneys and bladder, no organ demonstrated uptake of 68Ga-OPS202 above background. Tumor radiation doses ranged from 0.15 Gy/mCi to 0.48 Gy/mCi. Subacute hematologic toxicity after cycle 1 was mild-moderate (G3 2/19 leukopenia that reversed before cycle 2). 4/7 (57%) pts that received the second dose of 177Lu-OPS201had G4 hematological toxicities, which occurred 4-6 weeks after administration. G 3/4 toxicities in the four pts have resolved to G2 or lower; none of these pts demonstrated fever, infection, bleeding, or renal toxicity. Substantial efficacy was observed: 1 patient achieved a CR (1/19, 5%), 32% PR (6/19), 47% SD (9/19) and 16% POD (3/19). Median PFS has not yet been reached. Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of 68Ga-OPS202/177Lu-OPS201 as a theranostic combination for imaging and therapy. Additional studies are planned to determine an optimal therapeutic dose and schedule. Clinical trial information: NCT02609737.
Use of antiresorptive therapy (ART) and skeletal-related events (SREs) in patients with bone metastases of neuroendocrine neoplasms (NEN).
Authors: Apostolidis Leonidas , Jaeger Dirk , Winkler Eva Caroline 
Published: September 2018

4096 Background: Antiresorptive therapy (ART) with bisphosphonates or denosumab is effective in preventing skeletal-related events (SREs) in patients with bone metastases (BM). In neuroendocrine neoplasms (NEN), BM are a negative prognostic factor, however tend to be asymptomatic and SREs are considered a rare event. The role of ART in preventing SREs in NEN has not been investigated so far. Methods: Retrospective analysis of all patients with bone metastases in the NEN database of the National Center for Tumor Diseases who presented at our center between 12/2012 and 01/2017. Overall survival (OS) from diagnosis of BM as well as time to SRE (TTSRE) were calculated. In patients experiencing an SRE within 1 month after diagnosis (i.e. before efficacy of ART could be assessed), TTSRE was defined as the time to a subsequent SRE. Results: In a total of 513 patients in the database, 108 patients with BM could be identified. Median OS was not reached in a median follow-up of 15.2 months. ART was applied to 42.6 % of patients. OS with or without ART did not differ significantly (p = 0.2538). 28.7 % of patients experienced at least 1 SRE, 20.4 % after more than 1 month. Median TTSRE was 63.8 months with ART and 127.0 months without ART (p = 0.1751). TTSRE was shortened in grade 3 vs. grade 1+2 NEN (172 months vs. not reached, HR 4.058, p = 0.0032), as well as in lytic vs. non-lytic metastases (24.5 vs. not reached, HR 7.319, p < 0.0001), however not significantly different in oligometastatic vs. disseminated bone disease (not reached vs. 63,8 months, HR 1.415, p = 0.4287). Application of ART did not significantly change TTSRE in either of these subgroups. Significant toxicity attributable to ART was observed in 15.2 % of ART patients. Conclusions: SREs in NEN patients with BM were not uncommon, especially in patients with grade 3 NEN and osteolytic metastases. Application of ART did not significantly alter median OS or TTSRE, no subgroup with a benefit of ART could be identified. The use of ART in NEN should be questioned and evaluated prospectively.