bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II trial of pralatrexate (P) plus oxaliplatin (O) in advanced esophagogastric cancer (aEGC).
Authors: Malhotra Usha , Miller Austin , Bushunow Peter Walter , Loud Peter , Adjei Araba , Yendamuri Saikrishna S. , Robins Melissa , Iyer Renuka V. , Khushalani Nikhil I.
Published: February 2017

152

Background: Advanced EGC is an aggressive cancer with limited treatment (Rx) options. In preclinical studies P has demonstrated increased cellular uptake and polyglutamylation relative to other anti-folates plus is synergistic with platinum. We evaluated combination P plus O in aEGC and examined pharmacogenomics and tumor microRNA profiling to identify predictive signatures for response and toxicity. Here we report on clinical outcome data for the entire cohort. Methods: Objective response (OR) following P+O was assessed in an exact 2-stage design, including early stopping for futility and a safety lead-in cohort of 6 patients (pts) with provisions for dose de-escalation for dose limiting toxicity (DLT). Eligibility included metastatic/unresectable, therapy-naïve EGC pts with adequate organ and functional status and < G2 neuropathy. Rx consisted of biweekly O (85mg/m2) plus P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). O was stopped after 12 cycles. Secondary endpoints were toxicity, survival and molecular correlates. Results: The study met its interim efficacy threshold and proceeded to full accrual. 35 pts, median age 67 yrs (39-83), 32 males, mostly adenocarcinoma (29) were accrued. 2/4 pts at D1 developed DLTs (1 G3 diarrhea, 1 G3 mucositis). All remaining pts were treated at D-1, which had no DLTs in the safety cohort. G4 toxicity included neutropenia (2) and myocardial infarction (1). The most common G3 events were mucositis (5), dehydration and neutropenia (4 each), anorexia, neuropathy, fatigue and nausea/vomiting (all 3 each). Including G1 and 2 events, myelosuppression, mucositis and neuropathy were the most common toxicities. Median # of P cycles administered at D-1 was 8 (1, 17). In an intent to treat analysis, confirmed OR was 23% (8/35) and 16 pts (46%) had stable disease. 3 pts were non-evaluable for response. Conclusions: Combination O and P administered biweekly at 85mg/m2 and 100 mg/m2 respectively is safe, well-tolerated and has modest efficacy in aEGC. Survival analysis results will be available for the meeting. This study was approved and funded by the NCCN from general research support provided by Allos Therapeutics, a subsidiary of Spectrum Pharmaceuticals, Inc. Clinical trial information: NCT01178944.
Prognostic impact of postoperative morbidity after esophagectomy for esophageal cancer: Supplementary exploratory analysis of JCOG9907.
Authors: Takeuchi Hiroya , Mizusawa Junki , Kato Ken , Kataoka Kozo , Igaki Hiroyasu , Abe Tetsuya , Matsushita Hisayuki , Hayashi Kazuhiko , Nakagawa Satoru , Yoshikawa Takaki , Nozaki Isao , Iwaya Takeshi , Kosugi Shinichi , Hirao Motohiro , Udagawa Harushi , Ozawa Soji , Tsubosa Yasuhiro , Nakamura Kenichi , Ando Nobutoshi , Kitagawa Yuko
Published: February 2017

155

Background: Although the impact of postoperative complications, especially infectious complications (IC), on long-term survival after transthoracic esophagectomy remains controversial to date, we hypothesized that postoperative IC may affect tumor recurrence and survival of the patients (pts) undergoing transthoracic esophagectomy. Methods: The data from JCOG9907 (Ando N; Ann Surg Oncol 2012) was used to estimate the influence of IC on the outcome of current standard preoperative chemotherapy followed by surgery for clinical stage II/III squamous cell carcinoma of the thoracic esophagus. IC were classified into three: pneumonia, anastomotic leakage, and the others. OS and PFS were estimated by landmark method at 6 months from randomization. Univariate and multivariate analyses using Cox proportional hazard model were performed to assess the impact of postoperative complications on the survival after right-transthoracic esophagectomy with extended lymphadenectomy. Results: Among the 152 analyzed pts, the incidence of overall IC was 36%, among which pneumonia and anastomotic leakage were observed both in 14%. OS of pts with any IC (n=54) was shorter than that of pts without IC (HR 1.66, 95%CI [1.02-2.71]) and PFS also tended to be shorter in pts with any IC (HR 1.44, [0.92-2.23]). OS of pts with pneumonia (n=22) was shorter than that of pts without pneumonia (HR 1.82, [1.01-3.29]), and PFS also tended to be shorter in pts with pneumonia (HR 1.50, [0.85-2.62]). OS of pts with anastomotic leakage (n=21) were nearly identical to that for pts without leakage (HR 1.06, [0.52-2.13]) and PFS was slightly shorter in pts with leakage (HR 1.28, [0.71-2.32]). Multivariate analysis revealed that pneumonia tended to compromise OS and PFS (HR 1.66, [0.87-3.17] and HR 1.37, [0.75-2.51]). Conclusions: This study reveals that postoperative morbidity, especially pneumonia may deteriorate the survival of pts undergoing esophagectomy after preoperative chemotherapy. Achieving esophagectomy without postoperative complications might prolong OS and PFS. Clinical trial information: NCT00190554.
The impact of neoadjuvant therapy for gastroesophageal adenocarcinoma on postoperative morbidity and mortality.
Authors: Fuentes Eva , Ahmad Rima , Hong Theodore S. , Clark Jeffrey W. , Kwak Eunice Lee , Rattner David W , Mullen John Thomas
Published: February 2017

156

Background: The effects of neoadjuvant chemotherapy (CTX) or chemoradiotherapy (CTX-RT) on postoperative complications following surgical resection of adenocarcinomas of the stomach and gastroesophageal junction (GEJ) have not been well studied. Methods: We identified 308 patients undergoing a surgery-first approach and 145 patients undergoing neoadjuvant therapy (CTX, n = 73 and CTX-RT, n = 72) followed by curative-intent surgeryfor adenocarcinomas of the stomach and GEJ from 1995-2014. We compared the baseline characteristics and the postoperative outcomes between the two groups using univariate and multivariate analyses. Results: Patients receiving neoadjuvant therapy were significantly more likely to be of younger median age (63 y vs. 71 y), have tumors of the GEJ (37% vs. 17%), to undergo esophagogastrectomy (51% vs. 26%) and D2 lymphadenectomy (39% vs. 27%), and to have more advanced stage disease than patients undergoing surgery first. There were no differences in overall 30-day morbidity or mortality rates between the neoadjuvant therapy and surgery-first groups, respectively (Table). However, patients undergoing surgery first were significantly more likely to have higher-grade complications than those undergoing neoadjuvant therapy. Conclusions: Despite having more advanced disease and undergoing higher-risk surgical procedures, patients with adenocarcinomas of the stomach or GEJ who receive neoadjuvant therapy prior to surgery are less likely to have major post-operative complications than patients treated with a surgery-first approach. Concerns about higher rates of post-operative complications should not deter the use of neoadjuvant therapy for gastroesophageal cancer. [Table: see text]
Phase I study of s-1 plus fractional cisplatin as adjuvant chemotherapy for advanced gastric cancer in an outpatient setting (KOGC-03).
Authors: Ono Taiki , Takahashi Tsunehiro , Nakamura Rieko , Wada Norihito , Kawakubo Hirofumi , Takeuchi Hiroya , Saikawa Yoshiro , Omori Tai , Kitagawa Yuko
Published: February 2017

157

Background: The aim of this phase I study is to confirm the dose of cisplatin as adjuvant combination chemotherapy with S-1 in gastric cancer patients in an outpatient setting. Methods: The first course was initiated with S-1 monotherapy on days 1-28. From the second to sixth course, S-1 was administered on days 1-28 and cisplatin was added on days 1, 15, and 29. Dose level of cisplatin was escalated as follows: 20 mg/m2 (level 1); 25 mg/m2 (level 2); 30 mg/m2 (level 3). Results: Between Sep. 2010 and Feb. 2014, 13 patients were entered into this study. The median age was 65 years. All patients had a performance status of 0. Final stages were: Stage IIIA, 4; Stage IIIB, 8; and Stage IIIC, 1. The first three patients enrolled at level 1 and none of the three patients experienced Dose-limiting toxicity (DLT). However, one patient at level 2 could not complete administration of cisplatin. Therefore, an additional three patients were entered into level 2. Since these patients did not experience any severe adverse events, level 2 was completed. The first patient enrolled at level 3 had experienced leukocytopenia and elevated bilirubin. These toxicities did not resolve to the level of the starting criteria for the next course within 21 days. In the next patient, the third course could not be started within 21 days because of fatigue and anorexia. Based on these results, the Maximum Tolerated Dose and Recommended Dose were confirmed as level 3 and level 2, respectively. The DLT was >21-day delay of starting the next course. Three patients at level 1 completed combination adjuvant chemotherapy between the second and sixth course based on the protocol. During these treatments, no grade >2 hematological or non-hematological toxicities were experienced. At level 2, two out of six patients completed 5 courses of combination chemotherapy without experiencing severe adverse events. Three out of six patients at level 2 had received 4 courses of combination chemotherapy. Conclusions: Although further clinical trials are recommended to evaluate efficacy, this combination S-1 plus cisplatin regimen is expected to become a standard adjuvant treatment for gastric cancer in the outpatient setting. Clinical trial information: 601995.
Postchemoradiotherapy (CRT) pathologic stage classified by American Joint Committee on Cancer (AJCC) staging system to predict prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Guo Jhe-Cyuan , Huang Ta-Chen , Lin Chia-Chi , Hsieh Min-Shu , Chang Chin-Hao , Lee Jang-Ming , Cheng Jason C. , Wang Hsiu-Po , Yeh Kun-Huei , Cheng Ann-Lii , Hsu Chih-Hung
Published: February 2017

158

Background: Preoperative CRT followed by surgery is a curative treatment option for patients with locally advanced ESCC. Whether post-CRT pathologic staging can predict the outcomes of these patients is uncertain. Methods: Among 194 patients enrolled in three phase II clinical trials of preoperative CRT for patients with locally advanced ESCC (clinical T3N0-1M0 or T1-3N1M0 or M1a according to AJCC 6th edition), 140 patients were included. All patients received preoperative CRT comprised with twice weekly paclitaxel/cisplatin-based regimens and radiotherapy 40Gy given in 20 fractions, and esophagectomy. Post-CRT pathologic staging was classified according to AJCC 7thedition. Clinicopathologic factors were analyzed for their impacts on patients' overall survival (OS) and progression-free survival (PFS). Results: One hundred and thirty two men and 8 women were enrolled. The distribution of the post-CRT pathologic stages according to AJCC 7thedition and their median survival times were listed in Table 1. In univariate analysis, gender, performance status (PS), tumor location, pathologic N, pathologic stage, extranodal extension (ENE), and pathologic complete response (pCR) were statistically significant factors associated with PFS; PS, tumor location, pathologic N, pathologic stage, ENE, and pCR were statistically significant factors associated with OS. In multivariate analysis, PS (P < 0.001), tumor location (P = 0.016), and ENE (P = 0.024) were independent prognostic factors for PFS; PS (P < 0.001) and post-CRT pathologic stage (P = 0.027) were independent prognostic factors for OS. Conclusions: Post-CRT pathologic staging classified by AJCC 7thedition could predict the survivals of patients with locally advanced ESCC who underwent preoperative paclitaxel/cisplatin-based CRT followed by esophagectomy. (The work was supported by the Grant of MOST 103-2314-B-002-092.) [Table: see text]
The survival outcome after hepatic resection in patients with liver metastasis from gastric cancer.
Authors: Tatsubayashi Taichi , Miki Yuichiro , Takagi Wataru , Hirata Fumiko , Omori Hayato , Honda Shinsaku , Makuuchi Rie , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: February 2017

161

Background: Optimal treatment strategy for patients with liver metastasis from gastric cancer (LMGC) has not yet been established. Although systemic chemotherapy remains mainstay of treatment for LMGC, complete resection of primary tumor and LMGC may improve survival outcome. Thus, the aim of this study is to investigate survival outcome and prognostic factors of patients who underwent hepatic resection for LMGC. Methods: From September 2002 to February 2014, 30 patients underwent hepatic resection for LMGC in our hospital. Indications of hepatic resection were as follows; (1) hepatic lesion is not more than three, (2) without extrahepatic metastasis other than lymph node metastasis, (3) adequate liver function. We investigated the overall median survival time (MST) and 5-year survival rate of all eligible patients. Univariate and multivariate analyses were performed to assess the association between each clinicopathological features and overall survival time. Results: There were 25 males and 5 females with a median age of 72 (range, 39-86). There were 16 synchronous LMGCs and 14 metachronous LMGCs. With respect to the number of LMGC, 22 patients had 1 lesion, 7 patients had 2 lesions, and 1 patient had 3 lesions. Overall MST and 5 year survival rates after hepatic resection were 2.8 years and 31.0%, respectively. The significant prognostic factors were age (70 years or older, p=0.029) and blood transfusion (p=0.013). Multivariate analysis showed that lymph node metastasis was an only independent indicator of poor prognosis (HR=6.13, p=0.026). Conclusions: Hepatic resection for patients with LMGC might be a promising treatment strategy, with 5-year survival rate of 31.0%. Lymph node metastasis was an only independent prognostic factor. A multi-institutional confirmatory study will be required to evaluate the role of hepatic resection in patients with LMGC.
Long-term survival results of the patients who were enrolled to the feasibility study of laparoscopy-assisted distal gastrectomy for c-stage I gastric cancer.
Authors: Cho Haruhiko , Segami Kenki , Kawabe Taiichi , Hayashi Shigeya , Makuuchi Yousuke , Yamada Takanobu , Hasegawa Shinichi , Tsuchida Kazuhito , Murakami Hitoshi , Yoshida Tatsuya , Sato Tsutomu , Ogata Takashi , Yoshikawa Takaki
Published: February 2017

166

Background: We introduced laparoscopy-assisted distal gastrectomy (LADG) as multi-institutional feasibility study, and already reported that the overall morbidity rate was 1.6% in the study (Gastric Cancer 2012). The aim of this study is to evaluate the long-term survival results of the patients who were enrolled to the study and finished 5-year follow-up. Methods: A total of 165 c-stage I gastric cancer patients who were registered from Kanagawa Cancer Center were included to the study. The Kaplan-Meier method was used to evaluate overall survival and recurrence-free survival. Results: Median follow-up period of the patients was 1901 days. The reconstruction methods were either B-I (n=150), R-Y (n=14), or B-II (n=1). The accuracy for preoperative diagnosis of stage I was 87.2% (144/165). Among 14 patients with p-stage II/III excluding T3N0/T1N2-3, eight patients received postoperative adjuvant chemotherapy. The recurrence rates by pathological stage were 0% (0/123) for stage IA, 4.7% (1/21) for stage IB, 6.2% (1/16) for stage II, and 60% (3/5) for stage III/IV, respectively. The organ of recurrence was mainly observed in liver (n=3), followed by bone, lymph node, peritoneum (n=1). The 5-year recurrence-free survival rates were 94.5% for all patients, 97.2%/92.3%/60% for pT1/pT2/pT3/4, 98.5%/82.4%/71.4%/66.7% for pN0/pN1/pN2/pN3, 97.9%/81.3%/40% for p-stage I/p-stage II/p-stage III/IV. Conclusions: LADG for c-stage I gastric cancer was feasible in long-term result, as well as in short-term outcome.
Weekly nanoparticle albumin-bound paclitaxel(nab-PTX) as second-or later-line treatment for unresectable or recurrent gastric cancer in practice.
Authors: Yagisawa Masataka , Sogabe Susumu , Iwanaga Ichiro , Oshino Tomohiro , Yamamura Takahiro , Hirata Hajime , Nakajima Masahito , Suzuki Kazuharu , Shimono Joji , Takasaka Takuma , Takahashi Kazuhiro , Kobayashi Yoshimitsu , Kudo Taiki , Okada Kohei , Dazai Masayoshi , Oda Hisashi , Miyagishima Takuto
Published: February 2017

168

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel, solvent polyoxyethylated castor oil-free, biologically interactive form of paclitaxel (PTX). Nab-PTX allows shorter infusion schedules and needs no premedication for hypersensitivity reactions, so nab-PTX will be used as the alternative to PTX for more patients. In Japan, nab-PTX was approved as tri-weekly regimen (210mg/m2 every 3weeks) for gastric cancer. On the other hands, weekly PTX (80mg/m2 on day1, 8, and 15, every 4weeks) is mostly used as PTX regimen as 2nd or later line treatment for gastric cancer in Japan. So in practice, nab-PTX would be used by weekly regimen same as weekly PTX. However, the safety and efficacy of weekly nab-PTX for gastric cancer had not been reported yet. Methods: Unresectable or metastatic gastric cancer patients who began receiving weekly nab-PTX as 2nd or later line chemotherapy in our two facilities from February 2013 to August 2014 were retrospectively analyzed for the safety and efficacy. Written informed consent about the treatment of weekly nab-PTX was obtained from all patients before treatment. Results: A total of 32 patients were assessed, retrospectively. The dose and schedule of nab-PTX was 100mg/m2 on day1, 8, and 15, every 4weeks in all patients. Patients characteristics were as follows: median age 67.5(37-84); Male/female: 24/8; PS 0/1/2/3:15/8/7/2; treatment line 2/3/4/5: 12/14/5/1. The overall response rate was 9.3% (CR/PR/SD/PD/NE: 1/2/12/15/2). The median progression-free survival (mPFS) and median overall survival (mOS) were 2.99 months and 5.95 months, in all patients. In 23 patients whose PS were 0 or 1, mPFS and mOS were 4.14 months and 8.44 months. Most common grade 3/4 hematological toxicities were anemia (46.9%), neutropenia (40.6%), febrile neutropenia (15.6%). About the sensory neuropathy, grade 3 was 9.3%, grade2 was 21.9%, and grade1 was 3.1%. There were no treatment-related deaths. Conclusions: Weekly nab-PTX showed promising efficacy against previously treated unresectable or recurrent gastric cancer especially for good PS patients, The Common toxicities of weekly nab-PTX were well-tolerated.
Diagnostic accuracy of multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS) for clinical N staging in early gastric cancer.
Authors: Jin Eun Hyo , Lee Dong Ho , Seo Ji Yeon , Yoon Hyuk , Shin Cheol Min , Kim Nayoung , Park Young Soo , Jung Hyun Chae
Published: February 2017

17

Background: An accurate preoperative assessment of potential lymph node metastasis is useful in the decision for the treatment strategy of early gastric cancer. The aim of this study was to retrospectively evaluate the accuracy of preoperative assessment of lymph node status with multi detector-row computed tomography (MDCT) and endoscopic ultrasound (EUS). Methods: We had analyzed 1,104 patients with early gastric cancer who underwent gastrectomy with lymph-node dissection at Seoul National University Bundang Hospital from May 2003 to July 2011. Patients were underwent preoperative MDCT in 1,104 and EUS in 1,028. Lymph nodes were considered positive for metastasis if they were larger than 8mm in the short axis diameter of MDCT. The criteria of EUS for metastatic lymph nodes are rounded nodes larger than 8 mm diameter with hypoechogenicity. The clinical N staging of preoperative MDCT and EUS was compared to the postoperative pathological finding. Results: The overall diagnostic accuracy of MDCT and EUS for determining lymph node metastasis was 89.1% and 90.5%. In MDCT, the rate of overestimation of lymph node metastasis was 8.20% (91/1104) and underestimation was 8.7% (96/1104). Tumor size (>2cm) was significant related with overestimation (p=0.007). Underestimation of clinical N staging was related with female (p=0.025, OR 2.025), lymphovascular invasion (p<0.0001, OR 7.807), positive EGFR (p=0.015, OR 2.566) and tumor size (>2cm) (p=0.009, OR 3.221). In EUS, overestimated lymph node metastasis was 5.40% (56/1028) and underestimation was 9.6% (99/1028). No factor was significantly related with overestimation. Underestimation of lymph node metastasis was related with female (p=0.020, OR 2.049), lymphovascular invasion (p<0.0001, OR 11.716), positive EGFR (p=0.024, OR 2.489) and tumor size (>2cm) (p=0.020, OR 2.774). Conclusions: For preoperative assessment of lymph node metastasis in early gastric cancer, MDCT and EUS showed high diagnostic accuracy. Both MDCT and EUS, female, lymphovascular invasion, positive EGFR, large tumor size (>2cm) were related to underestimation of clinical N staging. We proposed that careful attention is required to choose treatment based on clinical N staging by MDCT and EUS.
Changes in neutrophil-to-lympocyte and platelet-to-lymphocyte ratios to predict survival and pathologic complete response in esophageal cancer patients who receive trimodality therapy.
Authors: Hyder Jalal , Boggs Drexell , Hanna Andrew , Suntharalingam Mohan , Chuong Michael David
Published: February 2017

170

Background: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict for survival in cancer patients. In patients receiving multi-modality therapy, the effect of each specific therapy on the NLR and PLR is not well understood. We therefore evaluated changes in NLR and PLR among locally advanced esophageal cancer patients who received trimodality therapy. Methods: We performed a retrospective analysis of non-metastatic patients with esophageal cancer who received neoadjuvant chemoradiation (CRT) followed by esophagectomy at our institution between March 2000 and April 2012. NLR and PLR values were obtained the following time points (TP): 1) at diagnosis before CRT, 2) after CRT prior to surgery, and 3) after surgery. We also evaluated change in NLR and PLR using the difference and ratio between TPs. Overall survival (OS) was evaluated by Kaplan-Meier analysis. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of NLR and PLR. Results: 83 patients with stage II-IV esophageal cancer and median age 60 years were included. Median follow up was 29.3 months. Median dose of 50.4 Gy (50.4-59.4) in 28 fractions (28-33) was used. Median NLR and PLR at the each TP: 1) 3.3 and 157.2, 2) 12 and 645, and 11.5 and 391.7, respectively. On multivariate analysis, inferior OS was associated with PLR ≥250 at TP 3 (p=.03), PLR decrease ≥609.2 from TP 2-3 (p=.02), and PLR ratio (TP 1/TP3) ≥1.08 (p=.03). Inferior progression free survival (PFS) was associated with NLR at TP 2 ≥36 (p=.0008), NLR increase ≥28.3 from TP 1-2 (p=.0005), PLR increase from TP 1-3 ≥19 (p=.01), and PLR ratio (TP 2/TP 3) ≥0.34 (p=0.1). Pathologic complete response (pCR) was less likely for adenocarcinoma histology (p=.03), NLR at TP 2 ≥10.6 (p=.04), and NLR increase from TP 1 to TP 2 ≥4.6 (p=.03). Conclusions: This is the first study to demonstrate that changes in NLR and PLR throughout trimodality therapy for esophageal cancer correlate with OS, PFS, and pCR. Further evaluation is warranted to better define which of the identified cut-off values are most clinically significant.
Efficacy and safety of regorafenib in Korean patients with advanced gastrointestinal stromal tumor after failure of imatinib and sunitinib: A multicenter study based on the management access program.
Authors: Son Myoung Kyun , Ryu Min-Hee , Park Joon Oh , Im Seock-Ah , Ryoo Baek-Yeol , Park Sook Ryun , Kang Yoon-Koo
Published: February 2017

175

Background: GRID phase III trial showed that regorafenib improves progression free survival (PFS) in patients (pts) with advanced gastrointestinal stromal tumors (GIST) after failure of imatinib and sunitinib. This study aims to confirm the efficacy and safety of regorafenib for advanced GIST in Korean pts. Methods: Clinical records were reviewed from 57 Korean pts with advanced GIST who failed both imatinib and sunitinib and were treated with regorafenib under MAP between December 2012 and November 2013. Pts received regorafenib 160mg p.o. once daily in a 3 weeks on/1 week off schedule, every 4 weeks until intolerable toxicities or disease progression with no benefit by physician’s discretion. Results: Out of total 57 pts, none achieved a complete or a partial response whereas 25 pts (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 8.6 months (range, 0.2-15.3), median PFS and overall survival (OS) were 4.5 months (95% CI, 3.8-5.3) and 12.2 months (95% CI, 10.1-14.3), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of cancer-related symptoms (abdominal pain in 8 and abdominal distension in 5) during the rest period of regorafenib, which were reduced with resumption of regorafenib. The most common grade 3 or 4 adverse events were hand-foot skin reaction (25%), hypertension (7%), and skin rash (7%). The dose of regorafenib was reduced in 44 patients (77%) because of toxicities, mainly due to hand-foot skin reaction (n=31). There was no treatment-related death. Conclusions: We could confirm the efficacy and safety ofregorafenib for advanced GIST after failure of imatinib and sunitinib reported in GRID trial in Korean pts. Considering exacerbation of cancer-related symptoms during rest periods, continuous dosing schedule of regorafenib needs to be explored in future clinical trials.
The effect of neoadjuvant chemotherapy (NACT) on lymph node retrieval in gastroesophageal carcinoma: A comparison of two cohorts treated at a single institution.
Authors: Felismino Tiago Cordeiro , De Barros E. Silva Milton Jose , Fanelli Marcello Ferretti , Costa Wilson Luiz da , Coimbra Felipe José Fernandez , Mello Celso Lopes
Published: February 2017

182

Background: Surgery for gastric cancer (GC) has evolved over time. D2-lymphademectomy with a minimum of 16 nodes is the current approach in many countries. In locally advanced GC, surgery alone has high rates of recurrence. Hence, adjuvant therapies are needed. Adjuvant chemoradiotherapy (CRT) and perioperative chemotherapy (PCT) are standard. The effect of PCT causing histological changes and tumor regression is clear. However it is unknown if PCT could change the number of dissected nodes due to tumor response and histological modification. Our aim is to evaluate patients treated with gastrectomy followed by CRT or PCT and surgery and define the impact of PCT in the number of nodes dissected. Methods: We retrospectively analyzed two historical cohorts treated at our institution. Cohort 1 (C1) underwent upfront gastrectomy and CRT. Cohort 2 (C2) underwent PCT and gastrectomy. Results: C1 had 51 patients. Median age was 54y. 60.8% male and 39.2% female. There were 88% primary gastric and 12% esophagastric junction (EGJ). Pathologic stages II or III were described in 92.2%. Median follow-up was 65 m. C2 had 66 patients. Median age was 58y. 70.1% male and 29.9% female. There were 71.6% primary gastric and 28.4% EGJ. cT3 was described in 82% and cN+ in 77.4%. Main chemotherapy regimens were DCF in 35.8%, EOX in 23.9% and CF in 13.4%. At surgery, 67.1% had stages II or III. Six patients had pathologic complete response. Three patients died due to toxicity. Median follow-up time was 34 m. Median number of dissected nodes was 35 in C1 and 31 in C2 (p=0.08). 90.2% in C1 and 91% in C2 had more then 16 nodes dissected. Median number of positive nodes was four in C1 and one in C2 (p=0.01). Regarding chemotherapy, DCF or a non-taxane regimen had the same median of 31 nodes dissected. 3-year recurrence free survival was 78.3% for C1 and 66% for C2 (p=0.21). 28.3% of patients recurred in C1 and 35% in C2, mainly in distant sites. Only two patients in each group had local failure. Conclusions: Although NACT induces histological changes, it does not reduce the number of retrieved lymph nodes at surgery. Moreover, PCT is associated with a lower median number of positive nodes, related to tumor downstaging.
Early tumor shrinkage (ETS) and deepness of response (DpR) in patients with metastatic esophageal cancer receiving a first-line treatment with DCF: Exploratory analysis of the JCOG0807.
Authors: Ura Takashi , Hironaka Shuichi , Tsubosa Yasuhiro , Mizusawa Junki , Kataoka Kozo , Kato Ken , Kitagawa Yuko , Kii Takayuki , Tomori Akihisa , Kiyota Naomi , Taniki Toshikatsu , Chin Keisho , Kojima Takashi , Doki Yuichiro
Published: February 2017

183

Background: ETS and DpR have been recognized as favorable prognostic factors of metastatic colorectal cancer. However, the effect of tumor shrinkage on clinical outcomes has not yet been reported for metastatic esophageal cancer (mEC). The purpose of the present study is to determine the associations of ETS and DpR with progression-free survival (PFS), post-progression survival (PPS), and overall survival (OS) in patients (pts) with mEC. Methods: This exploratory analysis included 53 pts, who received triplet chemotherapy with docetaxel (D) plus CF (cisplatin plus 5-fluorouracil) (DCF) as a first-line treatment during the JCOG0807. ETS after 8 weeks was defined as a relative change of 20% in the sum of the longest diameters of target lesions compared with baseline. DpR was defined as a relative change in the sum of the longest diameters of target lesions at the nadir compared with baseline. The cutoff level of DpR was 30%. PPS was calculated as follows: PPS = OS - PFS. Univariate and multivariate analysis using Cox proportional hazard model was performed to identify a predictor of PFS and OS. Results: Thirty-five of the 53 pts achieved ETS ≥ 20% after 8 weeks. Thirty-seven of the 53 pts achieved DpR ≥ 30%. Pts with ETS ≥ 20% showed longer PFS (7.5 vs. 3.4 months (M), p < 0.001, HR: 0.26, 95% CI 0.14–0.49), longer OS (13.8 vs. 6.1 M, p < 0.001, HR 0.20, 95% CI 0.11–0.39), and longer PPS (6.4 vs. 2.8 M, p = 0.002, HR 0.38, 95% CI 0.20–0.72). Further, pts with DpR ≥ 30% showed longer PFS (7.5 vs. 2.9 M, p < 0.001, HR 0.17, 95% CI 0.08–0.34), longer OS (13.8 vs. 6.0 M, p < 0.001, HR 0.14, 95% CI 0.07–0.27), and longer PPS (6.8 vs. 2.8 M, p < 0.001, HR 0.30, 95% CI 0.15–0.57). Multivariate analysis, including the following additional prognostic variables: age, ECOG PS, the lactate dehydrogenase level, and the number of organs with metastases revealed that ETS ≥ 20% and DpR ≥ 30% were predictors of PFS and OS. Conclusions: ETS and DpR were associated with longer PFS, OS, and PPS. They were also strongly prognostic of PFS and OS in mEC pts treated with DCF. These findings support the treatment strategy involving the highly effective triplet chemotherapy as a first-line treatment of mEC. Clinical trial information: UMIN000001737.
Toxicity and efficacy of salvage paclitaxel chemotherapy in Royal Marsden (RM) oesophagogastric adenocarcinoma (OGA) patients (pts).
Authors: TARAZONA NOELIA , Smyth Elizabeth Catherine , Peckitt Clare , Chau Ian , Watkins David J. , Rao Sheela , Starling Naureen , Cunningham David
Published: February 2017

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Background: Paclitaxel is a standard global salvage therapy for pts with advanced refractory OGA. Western pts may differ from Asian pts with respect to chemotherapy metabolism and cancer behaviour, and the benefits associated with paclitaxel in this setting have not been assessed outside of Asia. We examined the efficacy and toxicity associated with salvage paclitaxel for advanced OGA at RM over a 3 year period. Methods: This was a retrospective observational study. We identified all pts with OGA treated with salvage weekly paclitaxel from 01/06/2011 to 21/02/2014 from the electronic pt record at RM. The following data was collected: demographics, metastatic sites, resection status, response/duration of response to prior chemotherapy, ECOG PS, haemoglobin, albumin, alkaline phosphatase (ALP), neutrophil/lymphocyte ratio, CEA, CA19.9, RM prognostic score, CT response and date of progression, death or last follow up. Toxicity was collected as per NCI Common Toxicity Criteria (v4.0). Overall and progression free survival (OS/PFS) were estimated using the Kaplan-Meier method. Multivariate Cox regression analysis examined the association between clinical and laboratory variables with survival. Results: 57 pts were identified. Pts were 74% male; median age 64y; 66% PS 0-1; 91% 2nd line. Median number cycles 3 (range 1-8). Median follow up 13.6m. Response rate was 18.4% in evaluable pts. OS and PFS were 5.8m (95% CI: 4.8 – 6.8m) and 2.6m (95% CI: 1.9 – 3.2m). 2y and 3y survival from start of 1st line treatment were 26% and 13%. In multivariate analyses PS ≥2 [HR 2.28, p = 0.018], and ALP ≥100 U/L, [HR=2.01, p= 0.033] were independent negative prognostic factors for OS. ≥ Grade 3 nausea, diarrhea and neuropathy were uncommon (<2% each), rate of ≥ grade 3 fatigue was 11%. Grade 3-4 neutropenia, leucopenia and thrombocytopenia occurred in 12%, 11% and 2% pts. Conclusions: Advanced OGA pts treated at RM with salvage paclitaxel have an OS equivalent to pts in clinical trials with less hematological toxicity than seen in Asian patients. This may be due to regional pharmacogenetic profiles. As a significant proportion of pts now survive 2-3y with limited toxicity, therapeutic nihilism is unwarranted.
Conversion chemotherapy combined with surgical treatment of unresectable advanced gastric cancer.
Authors: Du Yian , Yu Pengfei
Published: February 2017

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Background: Local advanced gastric cancer which could not receive R0 resection, or gastric cancer with single distant metastasis usually received palliative chemotherapy or entered into various clinical trials, and surgery usually roled as a symptomatic treatment. This study is to investigate the efficacy and safety of PCF chemotherapy combined with surgery in the treatment of these patients. Methods: From 2007.8 to 2012.8, 78 cases of local advanced gastric cancer which can not be treated with R0 resection(T4N2~3M0) or gastric cancer with single distant metastases(M1) were prospectively analysed. Patients were treated with 2~4 cycles of combined chemotherapy with paclitaxel (150mg/m2,d1), cisplatin(25mg/m2, d1~3) and 5-fluorouracil (750 mg/m2, d1~3) ( repeated every 3 weeks), and were then treated with cytoreductive surgery: mainly treated with radical resection of gastric tumor, combined with extended lymph node dissection, pancreaticoduodenal resection, colon resection, ovariectomy, liver resection and tumor radio frequency, followed by another 2~4 cycles of postoperative PCF chemotherapy.The treatment completion rate, patients’ tolerance and overall survival time were analyzed. Results: 56 patients (71.8%) accomplished chemotherapy and surgical resection as planned. 47 cases had R0 resection(60.3%). Grade 3/4 toxic effects included bone marrow suppression(24.4%) and gastrointestinal reaction(37.2%), the overall response rate (CR+PR) was 73.1%(CR 2 cases, PR 55 cases). Survival analysis: the median survival time was 23.4 months. 1-year and 3-year survival rate was 68.1% and 33.5%. The OS of patients with surgical resection was much longer than that of the non-surgery group.(36.1 VS 10.0 months, P<0.01). The OS of local advanced group was 38.6 months, and was significantly longer than 20.7 months of the distant metastasis group (P<0.01), however, it had no significant difference compared to 31.3 months of the distant metastasis group with R0 resection. Conclusions: PCF chemotherapy combined with surgical resection were safe and effective, and can make survival benefits for patients with local advanced gastric cancer or gastric cancer with single distant metastasis.
Risk factors for peritoneal recurrence in serosa-negative gastric cancer.
Authors: Omori Hayato , Miki Yuichiro , Takagi Wataru , Hirata Fumiko , Tatsubayashi Taichi , Honda Shinsaku , Makuuchi Rie , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: February 2017

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Background: Peritoneal recurrence is often observed in gastric cancer patients without serosal invasion. It is difficult for pathologists to evaluate whether tumor cells penetrate serosa or not, because the subserosa layer is very thin. We evaluated the incidence and risk factors of peritoneal recurrence in serosa -negative gastric cancer patients to clarify the mechanism of peritoneal recurrence in these patients. Methods: A total of 1,745 gastric cancer patients underwent R0 resection from 2002 to 2009 were enrolled. The incidence of peritoneal recurrence according to tumor depth was analyzed. In serosa-nagative patients, the univariate and multivariate analysis were performed to identify the risk factors for peritoneal recurrence. Results: Peritoneal recurrence was observed in 64 (3.7 %) out of 1,745 patients. The incidence of peritoneal recurrence according to depth of tumor invasion was in 0 / 466 in T1a, 5 / 567 (0.88 %) in T1b, 4 / 187 (2.1 %) in T2, 31 / 360 (7.9 %) in T3, 20 / 108 (15.9 %) in T4a, and 4 / 12 (25 %) in T4b, respectively (p<0.001). As for the risk factor for peritoneal recurrence in T3 patients, histologically undifferentiated type, negative lymphatic invasion, scirrhous type, invasive infiltrating growth pattern were the significant factors identified by univariate analysis. Only the invasive infiltrating growth pattern (OR3.44 p0.038) was selected as significant independent risk factor for peritoneal recurrence by multivariate analysis. In T1b / T2 patients, massive lymph node metastasis (N3a, 3b), scirrhous type were the significant factor for peritoneal recurrence by univariate analysis. Only massive lymph node metastasis (OR25.1 p<0.001) was selected as the significant independent risk factor by multivariate analysis. Conclusions: The incidence of peritoneal recurrence increases in proportion to the tumor depth. Invasive infiltrating growth pattern was selected as an independent risk factor for peritoneal recurrence in T3 patients, while it was massive lymph node metastasis in T1b / T2 patients. The results suggest the possibility that microscopic serosal invasion in T3 tumor and lymphatic progression in T1b / T2 tumor may contribute to peritoneal recurrence in gastric cancer.
A retrospective review of treatment outcomes following definitive chemoradiotherapy or single modality radical radiotherapy among patients with locally advanced esophageal cancer.
Authors: Fulton Ben A , Gray Joanna , MacLaren Vivienne , McIntosh David , McDonald Alexander , Hennessy Aisling , Grose Derek B
Published: February 2017

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Background: Definitive chemoradiotherapy (CRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemoradiotherapy (CRT) or single modality radical radiotherapy (RT) with curative intent. Methods: Retrospective analysis permitted identification of consecutive pts who underwent contemporary staging prior to non-surgical treatment for oesophageal carcinoma. The primary outcomes were overall (OS) and disease-free survival (DFS), adjusted for baseline differences in age, tumour staging and histological cell type. All patients were treated with either definitive CRT or single modality RT within a single centre treated between 2009 and 2012. Results: We identified 135 pts in total (median age 69.8 yrs, male=130pts, female=105pts, Adenocarcinoma=85pts, Squamous=150pts). 190 pts received CRT and 45pts were treated with RT. All pts were staged with CT of chest, abdomen and pelvis, 226 pts underwent Endoscopic ultrasound (EUS) and 183 pts had PET-CT. Patients treated with CRT demonstrated longer OS (37 versus 25 months, p=0.02) and DFS (31 versus 16 months, p=0.01) compared to those treated with RT. More advanced tumour stage (stage 3 v stage 1-2) at presentation conferred poorer OS (32 versus 38.2 months) and DFS (11 versus 28 months, p=0.013). We demonstrated an acceptable toxicity profile with only 77 pts (32.8%) and 9 pts (4.2%) experiencing grade III or IV CTC toxicities respectively. Conclusions: This retrospective analysis is in keeping with current treatment paradigms emphasising the importance and safety of concurrent CRT in maximising curative potential for pts undergoing non-surgical treatment of oesophageal cancer. Although retrospective, in comparison to similar retrospective series from our centre, our data suggest improvements in OS and DFS, possibly due to improved patient selection through the use of more effective tumour staging.
Long-term follow-up of patients with Barrett esophagus: Progression to high-grade dysplasia and esophageal adenocarcinoma according to histology at presentation.
Authors: Kahn Allon , Kommineni Vishnu , Callaway Jonathan , Pannala Rahul , Fleischer David , Ashman Jonathan Ben , Ross Helen J. , Ramirez Francisco
Published: February 2017

20

Background: Esophageal adenocarcinoma (EAC) incidence is rising and prognosis is uniformly poor, even with early stage disease. Barrett esophagus (BE) serves as a premalignant marker for EAC, with an estimated progression of 0.5% per year. Low-grade (LGD) and high-grade dysplasia (HGD) confer a higher risk of progression, providing an opportunity for intervention and surveillance. Aims: To evaluate a large cohort of patients undergoing endoscopic evaluation of BE and thereby better understand the natural history of BE and dysplasia. Methods: A retrospective review of endoscopic databases was conducted for all patients with the diagnosis of BE undergoing upper endoscopy at a tertiary academic medical center from 1991-2010. All endoscopy and accompanying pathology reports were reviewed. Only those patients with 2 biopsies documenting specialized intestinal metaplasia were analyzed. Results: 848 patients underwent upper endoscopy for evaluation of BE. Of these, 674 patients met inclusion criteria, at a mean follow up of 66.6 months. Table 1 depicts the distribution of patients according to their histology at presentation. 22 (3.2%) patients presented with established EAC, while EAC developed in 51 (7.6%). Of patients with HGD, LGD, or no dysplasia (ND) at presentation, EAC ultimately developed in 30.6%, 6.6%, and 2.7%, respectively. EAC developed in 4 patients despite RFA treatment for ND (2) or LGD (2). HGD developed in 6 such patients after treatment for ND (3) and LGD (3). Only 1 patient in each RFA-treated cohort required esophagectomy, while the others cleared dysplasia or EAC with continuous treatment. Conclusions: In this large cohort of patients with Barrett’s esophagus, higher grade of dysplasia at first endoscopy was associated with development of EAC. Continuous surveillance during and after endoscopic treatment is necessary and often results in clearance of dysplasia and EAC. [Table: see text]
Neoadjuvant or adjuvant chemoradiation therapy for stage II-III esophageal squamous cell carcinoma.
Authors: Chen Yongshun , Hao Daxuan , Wu Xiaoyuan , Yang Yuanyuan , He Chunyu , Wang Wen , Liu Jinsong , Wang Jianhua
Published: February 2017

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Background: Esophageal cancer is the eighth most common cancer worldwide, and especially in China is the fourth most common cause of death. Clinical trials have explored the value of neoadjuvant or adjuvant chemoradiation in potentially resectable esophageal squamous cell carcinoma (ESCC); however, these studies have produced conflicting results. This retrospective study was performed to investigate whether patients with resectable stage II/III ESCC should receive neoadjuvant or adjuvant therapy in addition to surgery. Methods: A review of stage II/III ESCC patients who underwent esophagectomy and either neoadjuvant or adjuvant chemoradiation was performed. Patients who underwent neoadjuvant therapy were treated with one cycle of chemotherapy consisted of cisplatin and fluorouracil concurrently with radiotherapy (40Gy/20f), adjuvant therapy consisted of two cycles of chemotherapy concurrently with radiotherapy (46-50Gy/23-25f, 5 days/week). Results: A total of 122 patients met inclusion criteria, of which 49 underwent neoadjuvant chemoradiation and 73 underwent adjuvant chemoradiation. Median follow up was 36.5 months. The median survival times and 3, 5-year OS rates for the neoadjuvant and adjuvant groups were 39.3 vs 31.5 months, and 53.0%, 45.7% vs 42.9%, 29.7% respectively (p = 0.091). For the patients with stage III ESCC, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant group were 39.3 vs 21.2 months, and 43.4% vs 15.4% respectively (p = 0.005). Among lymph node-positive patients, the median survival times and 5-year OS rates for the neoadjuvant and adjuvant groups were 55.6 vs 23.7 months, and 43.0% vs 25.7% respectively (p = 0.085). The incidence of postoperative complications was 26.5% (13/49) in the neoadjuvant group and 20.5% (15/73) in the adjuvant group (p = 0.212). Conclusions: Neoadjuvant chemoradiation does not increase postoperative complications, and is associated with better OS when compared to adjuvant chemoradiation. OS in stage III patients is significantly improved with the use of neoadjuvant chemoradiation.
Effects of a planned preoperative exercise program on body composition in early gastric cancer patients with metabolic syndrome.
Authors: Kawabe Taiichi , Cho Haruhiko , Segami Kenki , Hayashi Shigeya , Makuuchi Yousuke , Sato Tsutomu , Aoyama Toru , Hayashi Tsutomu , Yamada Takanobu , Fujikawa Hirohito , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Yoshikawa Takaki
Published: February 2017

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Background: Visceral fat obesity and skeletal muscle depletion were reported to be both risk factors for complications in abdominal cancers surgery. Preoperative exercise may reduce morbidity by modifying body composition. Methods: We conducted an exploratory study attached to a prospective study (AEGES) to examine the effects of a 4-weeks exercise in stage I gastric cancer patients with metabolic syndrome. The AEGES enrolled 50 patients between 2007 and 2013, of which 18 were assigned to the exercise arm. The exercise program consisted of aerobic training 3-7 days a week, resistance training once or twice a week, and stretching. The expected energy expenditure of exercise was set at 30 kcal/kg/week. The total energy expenditure was measured using a calorie counter. After completion of the exercise, the patients received CT and endoscopy for re-staging, then underwent curative gastrectomy. Total skeletal muscle cross-sectional area (cm2) was evaluated on the average of two adjacent axial images at L3. Muscle area was expressed as lumber skeletal muscle index (cm2/m2). Total visceral fat volume was evaluated at the level of umbilicus. The changes of parameters before and after the exercise were assessed by paired Wilcoxon sign test. Results: A total of 15 patients with evaluable CT image were examined. Body weight, body mass index, and abdominal circumference were significantly decreased (-1.5 kg, -0.52 kg/m2, and -3.3 cm, respectively). The median skeletal muscle index was 48.06 cm2/m2 before and 46.85 cm2/m2 after the exercise, which was not statistically significant (p=0.41), while the median visceral fat volume was 205.2 cm2 before and 169.0 cm2 after the exercise, which was statistically significant (p=0.001). There was a weak correlation between total energy expenditure and amount of skeletal muscle index change (r=0.22 by Spearman’s correlation and p=0.427). No patient demonstrated progression of clinical cancer stage during 4 weeks. Conclusions: Preoperative exercise for 4 weeks could significantly modify body composition without progression of gastric cancer. More intensive or personalized exercise would be required to increase skeletal muscle.