bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer.
Authors: Kim Jae J. 
Published: February 2017

87 Background: To suggest an appropriate surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancers, based on incidence and patterns of local, metachronous, and extragastric recurrence. Methods: Between 2003 and 2011, 1497 consecutive patients with 1539 differentiated-type early gastric cancers meeting absolute or expanded indication criteria underwent curative ESD. They were followed up with esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) under a standardized surveillance protocol. Long-term outcomes were analyzed for 1306 patients with at least 1 year’s follow-up. Results: Incidences of residual and synchronous lesions detected within 1 year were 0.13 % and 0.87 %, respectively. During median 47 months of follow-up, there was 1 local recurrence (0.08 %; early gastric cancer) and 47 cases of metachronous recurrence (3.6 %; 44 early gastric cancers, 3 pT2 advanced gastric cancers); all were curatively treated. During a 5-year surveillance, the cumulative incidence curve of metachronous recurrence increased linearly. Median time from ESD to metachronous recurrence was 30 months. There were 2 extragastric recurrences (0.15 %) in lymph nodes, at 5 and 4 years, respectively, after curative ESD for absolute and expanded indications. The patient with the expanded indications underwent a palliative operation and died of gastric cancer progression. Conclusions: There was a constant incidence rate of metachronous recurrence during a 5-year surveillance period and there was extragastric recurrence at least 4 years after ESD of early gastric cancer even for absolute indications. Therefore, annual or biannual surveillance EGD and abdominal CT might be necessary for at least 5 years after curative ESD for early gastric cancers, with absolute as well as expanded indications.
The ratio of major and minor axis by EUS as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.
Authors: Hwang Jae Jin , Park Young Soo , Lee Dong Ho , Jung Hyun chae 
Published: February 2017

9 Background: The aim of this study was to evaluate the efficacy of the ratio of major and minor axis by endoscopic ultrasonography (EUS) as a possible predictive marker for the diagnosis of submucosal invasive gastric cancer. Methods: Between March 2014 and December 2014, the medical records of 51 patients with unclear distinction between mucosal and submucosal gastric cancer were retrospectively reviewed. Patient and tumor characteristics, accuracy rate and factors associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer were analyzed. Results: The mean age was 62.0 ± 12.6 (range, 35-79 years) and the male to female ratio was 1:0.45. The mean tumor size was 25.8 ± 14.7 mm. The overall accuracy was 60.7% (31/51) using the EUS and 82.3% (42/51) using the EUS ratio index (p = 0.045). The sensitivity, specificity, positive predictive value and negative predictive value to submucosal gastric cancer were 68.1, 55.1, 53.5, 65.9% using the EUS and 81.8,82.7,78.2,85.7% using the EUS ratio index, respectively. In the multivariate analysis, differentiated (Odds ratio [OR]: 1.42, 95% confidence interval [CI]: 0.95-1.89), no ulceration (OR: 1.96, 95% CI: 1.49-2.43), and deep submucosal invasion ( > 500 μm, OR: 2.77, 95% CI: 2.16-3.34) were independent factors, associated with correct diagnosis of submucosal invasive tumor in Ratio for gastric cancer (p < 0.05) Conclusions: The ratio of major and minor axis by endoscopic ultrasonography (EUS ratio index) might be a possible predictive marker for the diagnosis of submucosal invasive gastric cancer.
Neoadjuvant chemoradiotherapy versus chemotherapy and surgery for patients with locally advanced esophageal squamous cell carcinoma.
Authors: Hao Daxuan , Li Xue , Yang Yuanyuan , Zhang Yougai , Wu Xiaoyuan , Chen Yongshun , He Chunyu , Wang Wen , Liu Jinsong , Wang Jianhua 
Published: February 2017

91 Background: Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been recommended as the standard treatment for locally advanced esophageal cancer in western countries. However, in clinical practice, neoadjuvant chemotherapy (nCT), rather than nCRT, is preferred for a large cohort of patients with locally advanced esophageal squamous cell carcinoma (ESCC) for fear of increasing the odds of postoperative morbidity in China. The aim of this study is to compare the clinical efficacy of nCRT and nCT in terms of postoperative morbidity, tumor pathology and survival in patients with locally advanced ESCC. Methods: A total of 111 patients with locally advanced ESCC (T2-4N0-1M0) received neoadjuvant treatment at our institution from January 2009 through January 2014.Among these patients, 53 cases received one cycle of neoadjuvant chemotherapy with concurrent radiotherapy while the remaining 58 cases received two cycles of neoadjuvant chemotherapy only before surgery. Results: pCR was observed in 15 patients in nCRT group (28.3%) and 8 patients in nCT group (13.8%, P= 0.060). Postoperative morbidity was 32.1% in nCRT group and 37.9% in nCT group (P= 0.660). Disease-free survival rates at 1, 2, 3 years were 73.1%, 66.7%, 53.6% in nCRT group and 73.7%, 60.4%, 52.2% in nCT group (P= 0.848). Overall survival rates at 1, 2, 3 years were 88.5%, 78.0%, 59.5% in nCRT group and 89.5%,72.9% and 56.2% in nCT group(P= 0.749). No significant differences were found in recurrence rate between two groups (P= 0.836). Conclusions: Neoadjuvant CRT may achieve higher pCR rate than neoadjuvant CT without increasing the odds of postoperative morbidity. Both neoadjuvant CRT and CT can prolong survival in patients with locally advanced ESCC. Further study is needed to prove which one is better.
Multimodal analgesia combined with intravenous administration of acetaminophen in perioperative management of esophagectomy using modified ERAS protocol.
Authors: Ogata Takashi , Nakajima Tetsushi , Kano Kazuki , Segami Kenki , Maezawa Yukio , Sato Tsutomu , Cho Haruhiko , Yoshikawa Takaki 
Published: February 2017

94 Background: In perioperative management of esophagectomy, we have performed modified ERAS protocol including preoperative oral rehydration, early enteral nutrition, early mobilization, intestinal peristalsis promotion, pain control, and so on. We think these elements are related closely and useful in reducing complication and early recovery after surgery in case of high invasive surgery such as esophagectomy with 3 field lymph node dissection. And we think pain control is particularly close relationship with early mobilization, so multimodal analgesia is very important for postoperative pain control. Methods: We evaluated whether it is possible to reduce postoperative breakthrough pain by using postoperative pain control combined with acetaminophen IV. 124 patients were treated by esophagectomy with 3-field LN dissection from January 2013 to June 2015. Before May 2014, 49 patients were treated without acetaminophen IV protocol (Group A), and after May 2014, 75 patients were treated with acetaminophen IV protocol (Group B). We compared the number of analgesic drug until postoperative day 7, and compared the ratio of liver dysfunction in both groups. Both groups were used epidural anesthesia as postoperative pain management, and intravenous administration of acetaminophen 1000mg/day has been added between day3 to day 7 in Group B. Results: The number of analgesic drug use due to breakthrough pain(Group A / Group B) were day3:1.12/0.55, day4:1.58/0.83, day5:1.76/0.57, day6:1.24/0.49, and it was reduced significantly in Group B (p < 0.01). And liver damage as a side effect by acetaminophen IV, the rise of ALT(Group A / Group B) were seen 32.7%/66.7% in day6, and seen 20.4%/62.7% in day 8, and it was significantly higher in Group B at day6 and day8 (p < 0.01), but was no significant difference in day 30 between both groups. Conclusions: In perioperative management of esophagectomy, pain control combined with acetaminophen IV was useful as multimodal analgesia. Also was ALT rise is seen by liver damage, but it was the minor change in the acceptable range for natural healing.
Avelumab (MSB0010718C), an anti-PD-L1 antibody, as a third-line treatment in patients with advanced gastric or gastroesophageal junction cancer: A phase Ib JAVELIN Solid Tumor trial.
Authors: Oh Do-Youn , Lockhart Albert C. , Wong Deborah Jean Lee , Taylor Matthew Hiram , Bajars Marcis , von Heydebreck Anja , Moehler Markus H. , Safran Howard 
Published: February 2017

TPS188 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. The phase Ib study (NCT01772004) is an open-label, parallel-group expansion trial in patients (pts) with locally advanced or metastatic (LA/M) solid tumors that includes a heavily pretreated cohort of pts with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) to evaluate safety and efficacy of avelumab in the 3rd-line setting. Prior to adding this 3rd-line cohort, this trial had enrolled a separate cohort with advanced GC/GEJ who had received prior 1st-line chemotherapy (Chung et al, ECC 2015). Methods: This trial cohort is enrolling pts with histologically confirmed unresectable LA/M GC/GEJ who have been previously treated with 1st-line combination chemotherapy and 2nd-line ramucirumab, alone or in combination, and whose disease has progressed during or after ramucirumab treatment. Pts who have received prior treatment with trastuzumab and pts with HER2+ status are allowed. Eligible pts also must have tumor archival material or fresh biopsy, an ECOG performance status of 0 or 1 at the time of trial entry, and disease with ≥ 1 measurable lesion according to RECIST 1.1. Exclusions include prior therapy with immune checkpoint drugs or history of autoimmune disease. Up to 150 eligible pts will receive avelumab at 10 mg/kg as an IV infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or any criterion for withdrawal occurs. Primary endpoint is confirmed best overall response (RECIST 1.1) as adjudicated by an IERC. Secondary objectives include assessment of progression-free survival, overall survival, and immune-related efficacy assessments. Association between tumor PD-L1 expression and efficacy will be evaluated. Adverse events will be assessed and graded according to NCI-CTCAE v4.0. Tumor evaluation will be performed every 6 wks until progression. Enrollment in this cohort began in June 2015. *Proposed INN Clinical trial information: NCT01772004.
Cell-free DNA genotyping using digital PCR for early detection of pancreatic neoplasm.
Authors: Karasaki Hidenori , Ono Yusuke , Koizumi Kazuya , Andoh Kiyohiro , Asahara Shingo , Yokochi Tomoki , Takahashi Kuniyuki , Maguchi Hiroyuki , Yamada Masataka , Ogata Munehiko , Sugitani Ayumu , Kono Toru , Nagashima Kazuo , Mizukami Yusuke 
Published: February 2017

TPS464 Background: Pancreatic ductal adenocarcinoma (PDA) is still a dismal disease, and there is an urgent need to establish novel tool for early diagnosis of the tumor. There are two main types of pathologically and genetically distinct precursors for PDA — pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). Non-invasive markers for these precursor lesions have the potential to predict subsequent invasive tumor. Methods: Circulating cell-free DNA (cfDNA) released from tumor cells into the blood has been intensively studied as a novel way to monitor the genetic changes. To detect the cfDNA representing for the initiation and progression of PDA could be of the candidate for them. The role of cfDNA genotyping targeting the major driver mutations in these precursors, such as KRAS and GNAS, are currently under investigation in Japanese patients who have pancreatic tumors (UMIN000012810). The major technical challenge is to specifically detect the small fraction of tumor-derived DNA in patient plasma and urine. Since sequencing of target mutant alleles in cfDNA has a limitation to detect very low frequency variants, we sought to establish protocols for super-sensitive and absolute quantification of the “key drivers” for pancreatic tumor using a droplet digital PCR platform (Bio-Rad; QX200). The primary endpoint of this multi-center prospective analysis is to evaluate whether such an approach can appropriately monitor the risk of IPMN progression and detect localized early-stage PDA. Thirty cases of PDA and 90 cases of IPMN have been enrolled thus far. Detailed protocol for the study and improved technical points to quantify low-frequency variants will be discussed.
A phase I/II study combining tosedostat with capecitabine in patients with metastatic pancreatic adenocarcinoma.
Authors: Teague Andrea S. , Amin Manik A. , Lim Kian-Huat , Lockhart Albert C. , Masood Ashiq , Picus Joel , Singh Preet Paul , Suresh Rama , Tan Benjamin R. , Wang-Gillam Andrea 
Published: February 2017

TPS471 Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Recent advances with fluorouracil in combination with oxaliplatin and irinotecan (FOLFIRINOX) and nab-paclitaxel combined with gemcitabine (AG) have improved survival in patients with PDAC. A fluorouracil-based regimen is recommended for patients who progress after a gemcitabine-based regimen. Tosedostat is an oral aminopeptidase inhibitor shown to have anti-proliferative effects in malignancies. Aminopeptidase inhibitors disrupt the cleavage of amino acids from peptides downstream of proteasomal degradation, preventing the recycling of amino acids needed for new protein synthesis. This leads to intracellular depletion of amino acids, resulting in a cellular stress response known as the amino acid deprivation response, which leads to apoptosis. Because pancreatic cancer cells frequently upregulate expression of these aminopeptidases, aminopeptidases inhibitors hold therapeutic promise. Methods: This is a single institution phase I/II open-label trial to evaluate the safety and tolerability of tosedostat plus capecitabine in patients with metastatic PDAC that have progressed after a gemcitabine-based regimen. The phase I part will be conducted in a dose de-escalation fashion, with two planned dose levels of tosedostat (120mg or 60mg) p.o. daily on days 1 to 21 with capecitabine 1000 mg/m2 p.o. BID on days 1 to 14 of a 21-day cycle. If more than one patient in the tosedostat (120 mg) cohort experiences a dose limiting toxicity (DLT), then 6 more patient will be enrolled to the tosedostat (60 mg) cohort. A total of 36 patients will be enrolled in the phase II portion. Primary objective of the phase I portion is to determine the maximum tolerated dose and DLTs of tosedostat and capecitabine combination therapy. Primary objective of the phase II portion is to determine the progression-free survival at 3 months. Secondary objectives are to determine the overall response rate, time-to-progression, overall survival and CA 19-9 response. Exploratory objectives are to explore the predictive molecular biomarkers for treatment response and to explore the prognostic biomarkers. Clinical trial: NCT02352831. Clinical trial information: NCT02352831.
A randomized, double-blind, placebo-controlled phase III study of ramucirumab versus placebo as second-line treatment in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein following first-line sorafenib (REACH-2).
Authors: Zhu Andrew X. , Galle Peter R. , Kudo Masatoshi , Finn Richard S. , Yang Ling , Abada Paolo , Chang Shao-Chun , Llovet Josep M. 
Published: February 2017

TPS478 Background: Ramucirumab (Ram) is a human IgG1 monoclonal antibody that inhibits ligand activation of the vascular endothelial growth factor receptor 2 (VEGFR2). The Phase 3 REACH study assessed Ram in the treatment of patients with advanced hepatocellular carcinoma (HCC) after prior sorafenib. Ram was well tolerated. A significant improvement in overall survival (OS) in the overall population (N = 565) was not demonstrated (Hazard Ratio [HR] = 0.866; p = 0.1391). However, a meaningful improvement in OS was observed in the pre-specified subgroup of patients with baseline alpha-fetoprotein (AFP) ≥ 400 ng/mL (N = 250)(HR = 0.674; p = 0.0059) and warrants confirmation. Methods: REACH-2 is a randomized, double-blind, placebo-controlled phase III study of Ram and best supportive care (BSC) versus placebo and BSC in patients with HCC and elevated baseline AFP following prior therapy with sorafenib. Eligible patients will be randomized 2:1 to receive Ram (8mg/kg, IV) or placebo on Day 1 of each 14-day cycle until disease progression or other discontinuation criteria. Eligible patients must have a diagnosis of HCC (tissue or tumor with classical imaging characteristics); prior sorafenib; Child-Pugh score < 7; Barcelona Clinic Liver Cancer Stage C or Stage B disease not amenable/refractory to locoregional therapy; AFP ≥ 400 ng/mL; ECOG performance status < 2. Patients with history of encephalopathy, ongoing clinically meaningful ascites, liver transplant, or hepatic locoregional therapy after sorafenib are not eligible. The primary objective is to assess the OS for patients treated with Ram versus placebo, and assumes an OS HR of 0.7 (85% power; 2 sided type I error 0.05). Target enrollment is 399 patients with the primary analysis at 318 events (20% censoring). Secondary objectives include progression free survival, objective response rate, safety, and patient focused outcomes. Additional objectives include assessment of biomarkers relevant to angiogenesis and HCC. Clinical trial information: NCT02435433.
Prospective phase I study of nab-paclitaxel plus gemcitabine with concurrent MR-guided IMRT in patients with locally advanced or borderline resectable pancreatic cancer.
Authors: Olsen Jeffrey R. , Parikh Parag J. , DeWees Todd A. , Olsen Lindsey , Hawkins William G. , Strasberg Steven M. , Lim Kian-Huat , Singh Preet Paul , Suresh Rama , Tan Benjamin R. , Ratner Lee , Fields Ryan C. , Amin Manik A. , Wang-Gillam Andrea 
Published: February 2017

TPS480 Background: Radiotherapy (RT) for locally advanced and borderline resectable pancreatic cancer (LABPC) is controversial as potential local control benefits are often obscured by high rates of distant progression. However, local failure remains a significant cause of morbidity among patients without distant progression after initial chemotherapy, although toxicity concerns may limit delivery of optimal systemic therapy concurrent with RT. Given known systemic efficacy and radiosensitization effects of nab-paclitaxel (A) with gemcitabine (G), we initiated a phase I study of nab-paclitaxel with gemcitabine (AG) and concurrent intensity modulated radiation therapy with magnetic resonance guidance (MR-IMRT) for LABPC. Methods: A planned 24 patients with LABPC will be enrolled to a phase I dose escalation trial using the Time-to-Event Continual Reassessment Method (TITE-CRM) design. Following one lead-in cycle of GA, MR-IMRT is administered daily with concurrent weekly GA for a total of 25 fractions in 5 weeks. The initial dose levels for RT and AG, respectively, are: 40 Gy MR-IMRT, 75 mg/m2 A and 600mg/m2 G. The maximum possible dose level is 60 Gy MR-IMRT, 100mg/m2 A and 1000mg/m2 G. To reduce toxicity risk, MR-IMRT volumes include the primary tumor only, with cine-MR used for intra-fraction tumor tracking in place of fiducial markers. The primary endpoint is determination of the maximum tolerated dose level, with secondary endpoints including rate of conversion to resectable disease, progression- free survival, overall survival, and patient reported quality of life. Clinical trial information: NCT02283372.
Cisplatin plus irinotecan in the treatment of gallbladder or biliary tract cancer: A randomized phase II trial (NCT01859728).
Authors: dos Santos Lucas Vieira , Ferraz MauriÂcio Wagner Souto , Lima Joao Paulo , Abdalla Kathia Cristina 
Published: February 2017

TPS485 Background: Gallbladder and biliary tract cancer (GBTC) have an aggressive behavior and gemcitabine-platinum chemotherapy emerged as the new standard of care for advanced or metastatic GBTC. Despite optimal management, prognosis is still poor. This randomized trial aims to compare irinotecan plus cisplatin versus gembitabine plus cisplatin in advanced or metastatic GBTC. Methods: Patients with biopsy-proven, chemo-naïve, unresectable or metastatic carcinoma of GBTC (gallbladder, intrahepatic biliary tract, extrahepatic biliary tract, or ampulla of Vater), ECOG 0-2, measurable disease per RECIST 1.1, adequate organ function and written informed consent are stratified by ECOG (0 or 1 vs 2) and hematogenic metastases (yes vs no) and randomized to receive Irinotecan 65mg/m² D1 and D8 q21 days plus Cisplatin 60mg/m² D1 q 21 days (IP) or Gemcitabine 1000mg/m² D1 and D8 every 21 days plus cisplatin 25mg/m² D1 and D8 every 21 days (GC), until disease progression or unacceptable toxicity, with standard hydration and antiemetics. Computed tomography for response evaluation is undertaken every 6 weeks. The primary end-point is overall response rate (ORR). Assuming p0 = 25%, p1 = 50%, alpha = 5% and beta = 20% in an optimal Simon’s two stage design, 24 patients per arm will be recruited (N1 = 9; R1 = 2; Ntot = 24; Rtot = 9). The sample size for each arm was calculated separately. Secondary end-points are progression-free survival (PFS), overall survival (OS), disease control rate (DCR), quality of life and safety. This clinical trial was activated in January 2013 and the accrual period is expected to end by December 2017. This protocol was approved by institutional review board. Clinical trial information: NCT01859728.