bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term outcome of endoscopic submucosal dissection for early gastric cancer compared to surgical resection.
Authors: Sim Eun Hui , Kim Byung-Wook , Kim Ji Hee , Kim Jin-Jo 
Published: February 2017

120 Background: Endoscopic submucosal dissection (ESD) is now accepted as an alternative to surgery for the treatment of early gastric cancer (EGC). However, long-term clinical outcome of ESD for EGC compared to surgical resection has not been evaluated. The aim of this study is to evaluate the clinical outcome of ESD for EGC compared to surgical resection. Methods: A retrospective analysis was performed in 152 patients who underwent ESD or surgical resection for EGC according to Gotoda’s extended criteria from 2006 and 2008 in Incheon St. Mary’s Hospital and Seoul St. Mary’s Hospital, The Catholic University of Korea. Overall survival and recurrence rates were compared between the two groups. Results: A total of 56 patients underwent surgical gastrectomy and 96 patients underwent ESD. The medial follow-up was 76 months in surgical resection group and 71 months in ESD group. Metachronous recurrences including dysplasia were found in 9 patients in ESD group and none in surgical resection group (P=0.001). There was no significant difference between the groups in overall survival. Conclusions: Gotoda’s extended criteria for ESD might be acceptable for the treatment of EGC considering the oval survival. However, meticulous surveillance program should be established because metachronous recurrence is more common after ESD.
A phase II study of weekly nab-paclitaxel in combination with cisplatin as neoadjuvant chemotherapy in patients (pts) with locally advanced esophageal squamous cell carcinoma (SCC).
Authors: Yun Fan , Zhou Xinming , Jiang Youhua , Chen Qixun , Huang Zhiyu , Gong Lei , Yu Haifeng , Yang Haiyan , Liu Jinshi , Mao Weimin 
Published: February 2017

122 Background: This phase II study was aimed to define the pathological response rate and safety of combining weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy in pts with locally advanced esophageal SCC. Methods: Pts with resectable locally advanced thoracic esophageal SCC staged by EUS, CT and/or PET-CTscan. All pts received nab-paclitaxel (100 mg/m2, d1, d8, d22 and d29) and cisplatin (75 mg/m2, d1 and d22) as neoadjuvant chemotherapy, followed by esophagectomy.Postoperation: 2 cycles of adjuvant chemotherapy with same regimen was given in 4-6 weeks after the resection.The primary endpoint was pathological response rate. The second endpoints included R0 resection rate,down-staging rate, 3 years overall survival (OS) and disease-free survival (DFS). Results: From 01/2011 to 10/2012, 35 pts were enrolled. 31 male:4 females; IIA/IIB/IIIA/IIIB/IIIC in 3 (8.6%), 5 (14.3%),10 (28.6%), 8 (22.9%) and 9 (25.7%) pts. 30/35 pts went to surgery (85.7%). 30 had R0 resection (100%). Pathological complete response (pCR) was achieved in 4 pts (13.3%). Near pCR (microfoci of tumor cells on the primary tumor without lymph nodal metastases) in 2 pt (6.7%). Down-staging was observed in 19 of 30 patiens (63.3%). 5 pts did not going to surgery: 2 for progressive disease, 3 for refused. 24/30 pts (80.0%) received adjuvant chemotherapy, 7 pts (23.3%) received adjuvant chemoradiotherapy. Grade 3/4 toxicities in 35 evaluable pts during chemotherapy were as follow: neutropenia (11.4%), anemia (8.6%), thrombocytopenia (5.7%), nausea/vomiting (14.3%), neutropenia fever (8.6%), asthenia (20.0%). Surgical complications: 1 anastomotic leaks (3.3%). No treatment-related death. At a median follow up of 12 months (8~20mos), 29 pts were all disease-free survival. Conclusions: In pts with locally advanced esophageal SCC, weekly nab-paclitaxel and cisplatin as neoadjuvant chemotherapy achieved a high pathological response rate and R0 resection rate. The toxicity was well tolerated. Evaluation of nab-paclitaxel and cisplatin in randomized trials was warranted. Clinical trial information: NCT01258192.
Molecular profiling in gastric cancer: Examining potential targets for chemotherapy.
Authors: Miura John Thomas , Jayakrishnan Thejus T. , Eastwood Daniel , Johnston Fabian McCartney , Tsai Susan , Christians Kathleen K. , Turaga Kiran , Gamblin T. Clark 
Published: February 2017

131 Background: Current NCCN guidelines recommend perioperative epirubicin (E), cisplatin (C), and 5-fluorouracil (F) along with other triple agent derivations as first line therapeutic approaches for operable gastric adenocarcinoma (GC). In this study, we utilized molecular profiling to evaluate expression of chemotherapy targeted biomarkers associated with ECF therapy for GC. Methods: Surgically obtained GC specimens were analyzed by immunohistochemistry for TOP2A, ERCC1, and TS expression (Caris Life Sciences, Phoenix) from 2009-2012. Actionable gene targets were analyzed for mutually exclusive or simultaneous expression. Results: A total of 230 GC specimens were analyzed. The median age of patients was 61 (IQR: 50-72) years with the majority being male (n= 139, 60%). IHC actionable targets included: 60% (n=138) high TOP2A, 55% (n=127) negative ERCC1, and 63% (n=145) negative TS, indicating potential benefit from E, C and F respectively. When analyzing for simultaneous expression profiles of the three genes, only 24 % (n=55) of patients had gene expression levels that suggested sensitivity to all three agents (ECF). Moreover, biomarker results of 6.5% (n=15) of patients demonstrated a potential complete lack of sensitivity to first line ECF therapy. Overall, 61% (n=140) of patients had molecular profiles that indicated sensitivity to two or more agents. Conclusions: Biomarker analysis of GC suggests that there is potential for TOP2A, ERCC1and TS to define patients who have the greatest likelihood of deriving benefit from ECF therapy. 93.5% of patients had the biomarker profile that predicted sensitivity to at least one of these agents. Prospective controlled studies are required to validate the role of TOP2A, TS and ERCC1 in routine management of GC patients.
A prospective observational study on chemotherapy-induced nausea and vomiting for esophageal cancer patients in Japan.
Authors: Yamamoto Sachiko , Ishihara Ryu , Yoshida Naoya , Shimada Hideaki , Noguchi Tsuyoshi , Miyazaki Tatsuya , Yoshikawa Takaki , Yasuda Takushi , Nakajima Yasuaki , Kitagawa Yuko , Baba Hideo , Aiba Keisuke 
Published: February 2017

135 Background: Chemotherapy-induced nausea and vomiting (CINV) is still one of the major problems in cancer treatment. However detailed profile of CINV in patients with esophageal cancer is not known. Prospective multi-center observational study was conducted to assess the current status of CINV in Japan. Methods: Between May 2011 and December 2012, 193 patients with esophageal cancer who underwent systemic chemotherapy with high (HEC) or moderate emetogenic agents (MEC) were registered. Antiemetic drugs (5-HT3 receptor antagonists, dexamethasone and NK1receptor antagonist) were used to suppress CINV. Occurrence and severity of CINV were assessed with a diary provided to the patients prior to chemotherapy. Acute phase (within 24 hours from the start of chemotherapy) and late phase CINV (24 hours or later) were assessed separately. Multivariate logistic regression analysis was conducted to identify the predictive factors for acute and late phase CINV. Results: Of 193 patients 165 were male and 28 were female. Median age was 66 (range 40-84). HEC and MEC were administered in 180 and 13 patients, respectively. Acute phase nausea and vomiting were observed in 9 (4.7%) and 7 (3.6%) of 193 patients, respectively. Late-phase nausea and vomiting were observed in 75 (38.9%) and 18 (9.3%) of 193 patients, respectively. Risk factors for acute phase nausea, acute phase vomiting, late phase nausea and late-phase vomiting were assessed separately. By multivariate analysis for late-phase vomiting, younger age (Odds ratio 0.523 [every 10 years]; 95%CI 0.278-0.986; p=0.045) and male gender (Odds ratio 5.796; 95%CI 1.806-18.603; p=0.003) were independent predictive factors. By multivariate analyses for acute phase nausea, acute phase vomiting and late-phase nausea, no independent predictive factor was identified. Conclusions: Acute phase CINV was effectively suppressed by antiemetic drugs, while late phase CINV was not sufficiently suppressed. Further intervention to suppress late phase CINV should be considered, especially in high-risk patients. Clinical trial information: UMIN000005971.
Comparison of outcomes for the elderly patients treated with single agent versus doublet regimen as first-line chemotherapy for recurrent or metastatic gastric cancer.
Authors: Sun Der Sheng , Ko Yoon Ho , Jeon Eun Kyoung , Won Hye Sung , Shim Byoung Young , Roh Sang Young , Park Ji Chan , KIM Hoon Kyo , Hong Young Seon , Park Suk Young 
Published: February 2017

136 Background: Gastric cancer (GC) is a second leading cause of death in Korean elderly cancer patients. Palliative chemotherapy would be an option of treatment in inoperable elderly GC patients for gaining survival time. We analysed the differences between single and doublet first line palliative chemotherapy in elderly GC patients. Methods: More than 70-year-old GC patients treated in the hospitals of the Catholic university of Korea were analysed. Baseline characteristics, first-line chemotherapy regimen, treatment responses, toxicities, time to progression (TTP) and overall survival (OS) were evaluated. Results: From 2005 to 2012, 178 GC patients above 70 years had been treated with palliative chemotherapy with single or doublet regimen. The median age were 77 years (range 70-89) in single regimen group (SG, 70 patients) and 73 years (range 70-81) in doublet regimen group (DG, 108 patients). TS-1 or capecitabine was used in SG, and platinum combined with 5FU or taxane was the most common regimen in DG. The most common response in both group was stable disease. Median relative dose intensity was 92.4% (range 50~100%) in SG and 83.5% (range 43~100%) in DG. Median TTP in SG was 4.40 months (95% CI, 2.85-5.95) and 4.10 months in DG (95% CI, 2.62-5.57, P=0.295). Median OS was 6.90 months (95% CI, 4.20-9.59) in SG, 8.20 months (95% CI, 5.96-10.43, p=0.918) in DG. Hematologic (P=0.03) and non-hematologic toxicities (p=0.061) were more frequent in DG. The common causes to terminate chemotherapy were disease progression in SG and decreased performance status in DG. Conclusions: No significant differences were observed in TTP and OS in both groups, but treatment related hematologic toxicity of SG was less than DG. Single agent treatment would be considered as the option of first line palliative chemotherapy in the elderly more than 70 years.
Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.
Authors: Prithviraj Gopi Kesaria , Baksh Kathryn Anissa , Fulp William J. , Meredith Ken , Hoffe Sarah E. , Shridhar Ravi , Almhanna Khaldoun 
Published: February 2017

140 Background: Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we present the data of our single center retrospective analysis. Methods: Between 1998-2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly AUC 5 and paclitaxel predominantly 175 mg/m2) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from biopsy to death or last follow-up and progression-free survival was defined at time from cycle 1 to death, progression, or last follow-up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Results: Of the 134 patients evaluated, the median age at diagnosis was 65 years. Overall response rate (ORR) was 62.6% (complete response (CR)- 11%, partial response (PR)- 28%, stable disease (SD)-33%). Median overall survival from date of initial diagnosis was 1.29 years (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 0.44 years (95% CI 0.34-0.5). Grade III toxicity occurred in 18.7% of patients. The most common grade III toxicity was neuropathy, present in 3.7% of total study population. Conclusions: In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.
A phase I dose escalation study to evaluate safety and tolerability of cabazitaxel (Cbz) as a single agent in patients (pts) with advanced gastric adenocarcinoma who have failed prior chemotherapy (CT) regimens (GASTANA).
Authors: Kang Yoon-Koo , Ryoo Baek-Yeol , Yoon Shinkyo , Shen Lin , Lee Jooyun , Wei Chenlu , Zhou Yu , Ryu Min-Hee 
Published: February 2017

141 Background: Cbz showed antitumor activity in a CT-resistant human gastric cancer xenograft model. The Phase I GASTANA study aimed to determine the safety profile of Cbz in pts with advanced gastric adenocarcinoma who failed prior CT regimens. Methods: Asian pts with metastatic gastric adenocarcinoma failing 2 prior CT regimens received Cbz (single agent, Day 1 of every 3-week cycle) in a standard 3+3 dose escalation design. Dose levels (DL) were 20 mg/m2 (DL 1), 25 mg/m2 (DL 2) and 15 mg/m2 (DL -1). Treatment continued until disease progression or unacceptable toxicity. Prophylactic G-CSF was not permitted at cycle 1. Results: Fifteen pts were evaluable for dose-limiting toxicities (DLTs) at cycle 1. All pts were heavily pretreated (median of 2 prior anticancer regimens), and 11 had prior taxane exposure.At DL 1, no DLTs occurred in any of the first 3 pts. At DL 2, 4 pts were enrolled as 1 pt discontinued prematurely, with only 1 DLT (Grade [Gr] 4 febrile neutropenia [FN]) observed. However, all 4 pts at DL 2 experienced FN, and so 3 more pts were enrolled at DL 1 to further explore safety at this lower DL. Two DLTs (Gr 4 neutropenia > 7 days) occurred in these additional 3 pts. In response, DL -1 was opened, with no DLTs observed in the 6 pts enrolled. The median numbers of cycles were 5 (DL 1), 1.5 (DL 2) and 3 (DL -1). Frequent Gr 3/4 toxicities (safety population, N = 16) included neutropenia (63%) and FN (38%). Best overall responses included 1 partial response (6.3%; DL -1) and 8 stable disease (50%). Conclusions: Due to the unexpectedly high incidence of neutropenia-related complications compared with pts with other cancer types, a further Phase II study of Cbz was put on hold pending further data in pts with gastric cancer. The frequent occurrence of neutropenic complications with Cbz in this study may be attributed in part to the heavily pretreated nature of the pts and the accumulated toxicity of prior taxane therapy. Also, prophylactic G-CSF use after cycle 1 was not mandatory in pts with dose interruptions due to neutropenia, which may have increased the rate of neutropenic complications in subsequent cycles. Clinical trial information: NCT01497964.
Adjuvant chemotherapy after trimodality therapy in locally advanced esophageal cancer.
Authors: Yerramilli Divya , Sohal Davendra , Teitelbaum Ursina R. , Wissel Paul Stephen , Damjanov Nevena , Giantonio Bruce J. , O'Dwyer Peter J. , Plastaras John Peter , Ben-Josef Edgar , Metz James M. , Kucharczuk John , Williams Noel , Apisarnthanarax Smith 
Published: February 2017

144 Background: The benefit of adjuvant chemotherapy after preoperative chemoradiation and surgery is unclear in patients with locally advanced esophageal cancer. We studied the toxicities and clinical outcomes in patients treated with or without adjuvant chemotherapy (CTX) after trimodality therapy. Methods: Records of patients with T3+ or N+ esophageal cancer who received preoperative chemoradiation followed by surgical resection from 2003-2013 were reviewed. Patients with postoperative deaths or poor performance status within 3 months after surgery were excluded (n = 13). Tolerability and hematologic toxicities of adjuvant CTX were recorded. Clinical outcomes of patients treated with adjuvant CTX were compared with a cohort of patients who received no further therapy (NFT). Results: Of the 81 trimodality patients included in the study, 53 received CTX and 28 received NFT after surgery. Median follow-up time was 23 months. FOLFOX (34%), cisplatin/5-FU (15%), 5-FU/LV (15%), ECF (13%), and carboplatin/paclitaxel (9%) were the most commonly used adjuvant regimens. Multiple rationales for adjuvant CTX were cited, including pathologic nodal status (32%), favorable pathologic response (61%), and provider preference (51%). Grade III/IV hematologic toxicity occurred in 11% of the CTX group: leukopenia (8%/2%), neutropenia (4%/4%), and thrombocytopenia (2%/0%). Two patients in the CTX group did not complete their prescribed CTX, which was discontinued after 1 cycle. Patient and clinical characteristics between CTX and NFT patients were well-balanced, except for pathologic complete response (pCR) rates (CTX 25% vs. NFT 50%, p=0.03). Three-year OS and DFS were similar between CTX and NFT patients (74% vs 70%, 60% vs. 64%, respectively). In patients who achieved pCR (33% overall), adjuvant CTX was associated with an improved 3-yr OS (86% vs. 62%), but the difference did not reach statistical significance (p=0.22). Distant failures occurred in 11% of the CTX group and 18% of the NFT group. Conclusions: Adjuvant CTX after trimodality therapy in esophageal cancer is feasible and well-tolerated with encouraging clinical outcomes. Further studies are needed to define the role of adjuvant CTX in these patients.
Phase I study of concomitant pemetrexed and cisplatin plus radiation in patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) carcinomas.
Authors: Babiker Hani M. , Kovoor Andrew I. , Green Myke R. , Dragovich Tomislav , Brown Thomas David , Elquza Emad 
Published: February 2017

145 Background: For the treatment of esophageal and GEJ carcinomas, weekly cisplatin (20-30 mg/m2 weekly; total dose approximately 100 mg/m2) has demonstrated efficacy and tolerability. Pemetrexed (PEM) in combination with carboplatin and concomitant radiation has also shown activity for treatment of esophageal or lung carcinomas on a tri-weekly schedule, despite tolerability when administered weekly. This is the first phase I trial sought to establish the MTD of bi-weekly PEM in combination with weekly cisplatin and radiation in patients with locally advanced/metastatic esophageal and GEJ carcinomas. Methods: This is a phase I single institution, open-label dose-escalation trial (Fibonacci 3+3). Patients with stage III/IV esophageal cancer received PEM on weeks 1, 3, and 5 at doses of 300, 500, 750 mg/m2 concurrently with weekly cisplatin (20 mg/m2) and 28 daily fractions of radiation (total 50.4 Gy). If 1 or fewer DLTs were observed, the next cohort of patients received an escalated dose. If two or more patients develop DLTs, then dose escalation halted. Primary endpoint was to determine MTD; secondary endpoints included tolerability and preliminary anti-tumor activity using RECIST (Version 1.0). Results: 8 patients enrolled; median age was 72 (range 56-81); 50% were male; ECOG range was 0-2; 50% of patients had adenocarcinoma (AC), remaining patients had squamous cell carcinoma (SCC); 63% and 37% of patients were stage III and IV, respectively. Dose-escalation proceeded to 750 mg/m2 dose. The MTD was determined to be 500 mg/m2 bi-weekly following grade 4 dehydration and esophagitis at 750 mg/m2. DLTs observed were grade 4 thrombosis and grade 3 neutropenia at 300 and 500 mg/m2, respectively. Complete response was observed in 50% of patients (75% stage III SCC), partial response in 25% of patients (100% Stage IV AC), and disease progression in 1 patient (Stage III AC). 38% of patients proceeded to surgery. Conclusions: The combination of bi-weekly pemetrexed 500 mg/m2 and weekly cisplatin concomitantly with radiation demonstrates efficacy in patients with advanced or metastatic GEJ carcinomas with manageable safety profile. Clinical trial information: NCT00701857.
Can induction chemotherapy improve dysphagia in locally advanced esophageal/GEJ cancer?
Authors: Won Elizabeth , Ilson David H. , Herrera Jessica , Janjigian Yelena Yuriy , Ku Geoffrey Yuyat , Rizk Nabil P. , Sarkaria Inderpal S. , Adusumili Prasad S. , Rusch Valerie W. , Bains Manjit S. 
Published: February 2017

148 Background: Dysphagia is one of the most common presenting symptoms in esophageal cancer (EC) and can lead to significant nutritional decline, which is associated with increased toxicity and poor outcomes. Invasive feeding tubes or endoscopic stents are frequently used to improve nutrition in this setting. We evaluated the role of induction chemotherapy prior to concurrent chemoradiation as presurgical treatment in improving dysphagia. Methods: Retrospective analysis of 4 prospective studies conducted at MSKCC with induction chemotherapy followed by concurrent chemoradiation and surgery in locally advanced esophageal/GEJ cancer. Regimens included cisplatin/paclitaxel, cisplatin/irinotecan, and cisplatin/irinotecan/bevacizumab. Dysphagia was graded prospectively using a validated dysphagia scale. Response of dysphagia and nutritional status to induction chemotherapy was evaluated. Results: Of 161 patients (pts) undergoing induction chemotherapy, [median age 59(21-76), KPS 90 (70-100), 77% adenocarcinoma], 121 (76%) had dysphagia, with 59(37%) having grade 2 dysphagia or higher (20% Stage II, 80% Stage III). 6(4%) required EGD dilatation/stent and none required feeding tube placement prior to treatment. 22% patients had>10% body weight loss prior to treatment and average weight loss in all pts was 4.3kg. After induction chemotherapy, 104 (64%) had improvement in dysphagia. This was associated with a weight gain in 42% of pts. Only 7(4%) had worsening dysphagia after induction chemotherapy: 4/7 required feeding tubes (2% of all pts), 2/7 underwent endoscopic dilatation or stent (1% of all pts). 6/7 of these pts with worsening dysphagia had poor short term outcomes after induction treatment: 2/7 progressive disease, 3/7 unresectable at surgery, 1/7 post-operative death. Conclusions: Induction chemotherapy prior to concurrent chemoradiation for locally advanced esophageal cancer can effectively improve swallowing and nutritional status, while mitigating need for feeding tubes or stents in patients with significant dysphagia. Post-induction dysphagia may be prognostic and merits further investigation.