bluuebunny/crossref_metadata_2025 huggingface dataset:
Formulating a surveillance strategy following surgery for oesophagogastric cancer.
Authors: Moorcraft Sing Yu , Fontana Elisa , Cunningham David , Peckitt Clare , Waddell Tom Samuel , Smyth Elizabeth Catherine , Allum William H. , Thompson Jeremy , Rao Sheela , Watkins David , Starling Naureen , Chau Ian
Published: February 2017

153

Background: Oesophagogastric adenocarcinoma (OGA) has a poor prognosis, even for patients (pts) with operable disease. We conducted a retrospective study to assess relapse characteristics to see if these could influence follow-up strategies. Methods: We performed a retrospective review of all pts with OGA who had surgery with radical intent at the Royal Marsden between January 2001 – December 2010. Details of first relapse, including date, site, symptoms, method of relapse detection, tumour markers and treatment were recorded. Association of survival outcomes with relapse characteristics was determined by Cox regression univariate analysis. Results: 360 pts with OGA had surgery and 72.8% received neoadjuvant or peri-operative chemotherapy. After a median follow-up of 61.7 months, the median disease-free survival (DFS) was 35.6 months (95% CI 27.0 – 65.4) and median overall survival (OS) was 59.6 months (95% CI 40.7 – 81.2). 147 pts (40.8%) had disease recurrence. 51.0%, 78.9% and 91.8% of relapses occurred within 1, 2 and 3 years respectively. 78.9% of pts had distant relapse only, 7.5% had anastomotic recurrence and 13.6% had both. R1/2 resection was associated with a shorter time to distant relapse (p <0.001) and OS (13.8 months vs 77.7 months, HR 2.76, 95% CI 1.97 – 3.88, p < 0.001). At relapse, 101 pts (68.7%) were symptomatic. The 46 asymptomatic relapses were detected by tumour markers (n = 30, 65.2%), routine CT (n = 10, 21.7%) and endoscopy (n = 3, 6.5%). Symptomatic pts were less likely to receive further treatment than asymptomatic pts (55.5% vs 82.6%, p = 0.001), had worse OS from the time of surgery (18.9 months vs 26.3 months, HR 1.57, 95% CI 1.07 – 2.30, p = 0.02) and worse survival beyond relapse (5.1 months vs 14.6 months, HR 2.05, 95% CI 1.40 – 3.00, p < 0.001). There was no difference in DFS between these two groups (HR 0.90, 95% CI 0.63 – 1.27, p = 0.539), thus excluding a lead time bias. Conclusions: In pts undergoing surgery for localised OGA, over 90% of relapses occurred within the first 3 years. Pts with asymptomatic relapses were more likely to receive further treatment with resultant prolonged OS. A more intensive surveillance program with regular tumour marker measurement should be considered for the first 3 years post surgery.
Clinical study on harvesting lymph nodes with carbon nanoparticles for advanced gastric cancer: A prospective randomized trail.
Authors: Li Ziyu , Ao Sheng , Ji Jiafu
Published: February 2017

159

Background: There were no ideal materials nor quantizing regime for surgeons’ training on harvesting lymph nodes in advanced gastric cancer(AGC). A prospective randomized trial on Carbon Nanoparticles (CNP),a kind of lymphatic tracers, was designed to find a solution. Methods: Patients with previously untreated resectable AGC were eligible for inclusion in this study. All patients were randomly allocated to two subgroups. In experimental group, total of 1.0 mL CNP was injected into the subserosa of stomach around the tumor before gastrectomy with D2 dissection performed. On the contrary, the same procedure was performed directly without any coloring materials in control arm. Following surgery,the investigator harvested lymph nodes (LNs), counted colored LNs and measured the diameters with pathologist. Results: 30 patients were enrolled in the study. We observed no serious adverse effects related to CNP injection. The rate of stained LNs was 46.6%. The mean number of harvested LNs was larger in experimental than control group (38.33 vs. 28.27, p=0.041). Smaller diameter was recorded in experimental arm (3.32vs4.30mm,p=0.023), which might clarify the reason why the number of LNs was larger with CNP. In addition, we set up a model for predicting total number of LNs based on the data of CNP-staining LNs and metastatic LNs(MLNs), which might help the surgeons review their work of removing LNs so as to improve their surgical skills. Conclusions: CNP was a kind of safe materials and surgeons could harvest more LNs with it in AGC, which might benefit from the harvest of more smaller ones. Further study was needed to prove the model’s practicability. Clinical trial information: NCT02123407.
The impact of persistent dysphagia (PD) after induction chemotherapy in patients with locoregionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastroesophageal junction (E/GEJ) receiving a trimodality treatment regimen.
Authors: McNamara Michael J. , Rybicki Lisa A. , Rodriguez Cristina P. , Videtic Gregory M.M. , Stephans Kevin L. , Greskovich John , Sohal Davendra , Murthy Sudish C. , Raja Siva , Ives Denise I. , Bodmann Joanna , Adelstein David J.
Published: February 2017

160

Background: For patients with LRA ACA of the E/GEJ who receive pre-operative therapy, advanced pathologic stage at surgery is strongly associated with recurrence and death. Identification of such patients prior to resection, however, is problematic. Given the morbidity of esophageal resection, alternative treatment strategies may be desirable in this patient population. Methods: Between 2/08 and 1/12, 60 evaluable patients with LRA ACA of the E/GEJ enrolled in single arm phase II trial of induction chemotherapy, surgery, and post-operative chemoradiotherapy. A clinical stage of T3, N1 or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50mg/m2 d1, oxaliplatin 130mg/m2 d1, and fluorouracil 200mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55Gy @ 1.8-2.0 Gy/d and 2 courses of cisplatin (20mg/m2/d) and fluorouracil (1000mg/m2/d) given as 96 hour infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. Updated results as of March 2014 are presented. Results: Of the 60 evaluable patients enrolled, 54 completed induction therapy and underwent surgery. Of these 54 patients, 44 patients experienced complete resolution of dysphagia, while 10 patients had persistent symptoms. PD was associated with worse distant metastatic control [HR 3.48 (1.43 – 8.43), p=0.006], recurrence free survival [HR 3.04 (1.34 – 6.92), p=0.008], and overall survival [HR 3.31 (1.43 – 7.66), p=0.005]. PD was associated with more advanced pathologic T-descriptor (pT) (p=0.048) and N-descriptor (pN) (p=0.002), a greater median number of involved lymph nodes (3 v 1, p=0.003), and greater residual tumor viability (p=0.05). No patients with PD had pT0-T2 or pN0 disease. Of the 9 patients with pN3 disease, 5 (56%) had PD. Conclusions: PD after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes. These patients may require alternative treatment strategies. Clinical trial information: NCT00601705.
Trends in resected oesophageal and gastric adenocarcinoma (OGA) outcomes: Royal Marsden (RM) experience 2001-2010.
Authors: Fontana Elisa , Smyth Elizabeth Catherine , Cunningham David , Rao Sheela , Watkins David J. , Allum William H. , Thompson Jeremy , Waddell Tom Samuel , Peckitt Clare , Chau Ian , Starling Naureen
Published: February 2017

169

Background: OGA is a lethal cancer globally. Overall survival (OS) has improved in the last decade, potentially due to stage migration and changes in management of early stage cancer. To examine this hypothesis we assessed outcomes of resected OGA patients (pts) at RM over 10 years (y), comparing 2 time periods, 2001-2005 (A) and 2006-2010 (B). Methods: Electronic records of all pts who had undergone surgery with radical intent for OGA between 01/2001 and 12/2010 were reviewed. Pt age, sex, ECOG PS, pre-operative staging investigations (CT, EUS, PET-CT), perioperative therapy, pathological stage, dates of death, last follow up and treatment for recurrent disease were recorded. Disease-free (DFS), OS and survival beyond relapse (SBR) were estimated using the Kaplan Meier method; co-variates were compared using the log rank test and Hazard ratios calculated using cox regression within the 2 time periods. Results: 367 pts were identified; 151 (A) and 216 (B). Median age was 67y (A) and 66y (B). Gender distribution, PS, site of primary and pre-intervention lymph node status were comparable. PET-CT use increased from 9% (A) to 37% (B), p<0.001, (84% in 2010). >75% pts in both groups were treated with chemotherapy; use of perioperative therapy increased over time (19% of treated pts in A vs 52% in B). Conversely use of pre-operative therapy alone decreased over time (75% of treated pts A vs. 45% in B). Rates of R0 resection increased from 75% (A) to 89 % (B) (p=0.001). Median number of resected lymph nodes was 20 (A) and 31 (B). ≥T3 tumours (46% vs 33%) and ≥N1 lymph nodes (53% vs 48%) were more common in A. After a median follow-up of 95 (A) and 59 (B) months, relapse occurred in 47% (A) and 38% (B). 5y DFS for A and B was 34% vs. 51% [HR 0.59, (0.45-0.78), p<0.001]. 5y OS for A and B was 40% vs. 55% [HR 0.58, (0.43-0.77), p<0.001]. Median SBR was 7.6 months in both groups (p=0.713). Conclusions: During 2001-2010 survival of pts with resected OGA improved. Relevant factors may include improved preoperative staging by PET, increased numbers of R0 resections and higher lymph node yield. Pattern of chemotherapy usage as a surgical adjunct may also be contributory. However survival for relapsed pts was unchanged.
Outcomes associated with minimally invasive esophagectomy techniques.
Authors: Abbott Andrea M. , Doepker Matthew , Shridhar Ravi , Hoffe Sarah E. , Almhanna Khaldoun , Meredith Kenneth L.
Published: February 2017

171

Background: Surgery is pivotal in the management of patients with esophageal cancer. Recent prospective data demonstrates advantages of minimally invasive techniques. However, varying surgical techniques precludes the recommendation of a standard approach. We sought to examine our outcomes with differing approaches to minimally invasive esophagectomy. Methods: We queried a prospective esophageal database to identify patients who underwent minimally invasive esophagectomy (MIE) from 1994 and 2014. Surgical approaches included trans-hiatal (TH), Ivor Lewis (IVL), and robotic assisted Ivor Lewis (RAIL). Demographics, operative variables and post-operative complications were all compared. Results: We identified 280 patients who underwent MIE with a mean age of 65.65 ± 10.5 and a median follow-up of 48 months. Fifty-seven patients underwent IVL, 78 underwent TH, and 145 underwent RAIL. The length of operation was significantly longer in IVL and RAIL approaches compared to TH (TH=242, IVL=320, RAIL=415, p=0.001). Estimated blood loss did not differ between cohorts (TH=150, IVL=125, RAIL=158, p=0.8). Anastomotic leakage, stricture, pneumonia, and wound infections were all higher in the TH compared to the trans-thoracic approaches p=0.04, p=0.02, p=0.01, and p<0.001 respectively. Operative mortality was low for each cohort and did not differ between approaches (TH=2.6%, IVL=0%, RAIL=2%, p=0.2). The median length of hospitalization also did not differ between groups (TH=10 days, IVL=8.5 days, and RAIL=9 days, p=0.15). Adequacy of oncologic resection was measured by margins and nodal harvest. There was decreased R1 resections in both the IVL and RAIL compared to TH (TH=8%, IVL=0%, and RAIL=0% p=0.04). Additionally, the mean number of lymph nodes harvested was lower in patients undergoing TH compared to IVL and RAIL groups (TH=9.2, IVL=12.8, and RAIL=20.6, p=0.05). Conclusions: In our large series comparing minimally invasive approaches to esophageal resection we have demonstrated improved operative outcomes and oncologic outcomes in trans-thoracic approaches compared to trans-hiatal approaches. We recommend that patients undergoing minimally invasive esophagectomy be strongly considered for a trans-thoracic approach.
Does capecitabine plus cisplatin (XP) give advanced or recurrent gastric cancer (AGC) patients higher early tumor shrinkage (ETS) rate than S1 plus cisplatin (SP) with safety?
Authors: Sugimoto Naotoshi , Yoshinami Tetsuhiro , Yamamoto Sachiko , Yagi Toshinari , Imamura Fumio
Published: February 2017

172

Background: Capecitabine plus cisplatin (XP) is defined as the platform regimen in many global trials (ex: ToGA, AVAGAST) for AGC in first-line setting. But in the Japanese Gastric Cancer Treatment Guideline (4th edition), S-1 plus cisplatin (SP) is mentioned the standard (recommendation 1), XP is considered as recommendation 2. Few reports were existed about the comparison between XP and SP. So we retrospectively compared the efficacy and toxicity of XP and SP for patients with AGC in our hospital. Methods: The selection criteria were pathologically proven AGC (HER2 negative or unknown); no previous chemotherapy; performance status 0-2; able to oral intake; and adequate organ functions. The patients in XP group, capecitabine 1,000mg/m2 was given orally twice daily for 14days followed by a 7-day rest; cisplatin 80mg/m2 on day1 was given by intravenous infusion. In SP group, S1 40mg/m2 was given orally twice daily for 21 days followed by a 14-day rest and cisplatin 60mg/m2 intravenous infusion on day8. Results: The analysis covered 115 patients over the period from May 2008 to June 2014. The median age was 64 years (range 22-81); 76 males and 39 females; PS 0/1/2 score 85/29/1; 31 patients were treated XP and 84 patients were treated SP. Progression-free survival and overall survival were 6.6 and 16.4 months with XP and 6.1 and 13.3 months with SP (no significant difference). The response rates were XP/SP 61%/50%. The ETS (over 20% tumor shrinkage in 6-8weeks) rate were 83% in XP and 61% in SP (p=0.09). The rate of grade 3-4 toxicity in XP/SP were; neutropenia 23%/15%, anemia 16%/20%, nausea 0%/3%, anorexia 3%/ 8%, fatigue 0%/ 4%, hyponatremia 3%/ 0%. There was no treatment death in both groups. Conclusions: It is suggested that XP give AGC patients high ETS rate with safety.
The effect of curative surgery in Borrmann type IV advanced gastric cancer.
Authors: Song Kyo Young , Kim Eun Young
Published: February 2017

176

Background: The aims of the present study are to know the significance of curative surgery in Borrmann type IV and prove the causes related with poor prognosis by analyzing the recurrence patterns and unique diagnostic characteristics. Methods: We analyzed 168 patients with Borrmann type IV undergoing surgery at Seoul St. Mary Hospital from 1989 to 2010. We categorized the patients into curative (R0) and non-curative (R1, R2 and no-resection) group. Results: The numbers of curative and non-curative group were 91 and 77. The 3- and 5-yr OSRs of patients in curative group were significantly higher than those in non-curative group (curative: 52.4% and 33.0%, non-curative: 18.6% and 7.0%; p<0.001). In multivariate analysis, the curability was not a significant prognostic factor for survival (p=0.527). The most frequent recurrence site was peritoneum (64.7%). Most of recurrences were presented within early 2 years. The preoperative diagnostic rate of Borrmann type IV was only 50.5%. The reasons for non-curative surgery were unexpected peritoneal seeding (28.4%) and resection margin involvement (6.4%). Conclusions: The role of surgery for Borrmann type IV is quite limited. It has poor prognosis even after curative surgery, because it is very difficult to diagnose preoperatively and make curative surgery. [Table: see text]
FOLFIRINOX as first-line therapy in patients with metastatic gastroesophageal cancers (GEC).
Authors: Lockhart Albert C. , Krajewski Kenneth Anthony , Wang-Gillam Andrea , Amin Manik , Sorscher Steven , Lim Kian-Huat , Tan Benjamin R. , Picus Joel , Hecky Anne , Allen Kenisha , Peterson Jaclyn D , O'Day Emily , Marsh Robert de Wilton , Kozloff Mark , Polite Blase N. , Kindler Hedy Lee , Sharma Manish , Catenacci Daniel Virgil Thomas
Published: February 2017

177

Background: Adenocarcinomas of the distal esophagus, gastroesophageal junction and stomach (GEC) remain challenging cancers to treat. Unfortunately, 80-90% of newly diagnosed patients (pts) present with advanced disease where the overall median survival (mOS) is less than 1 year. Discouragingly, various common first-line metastatic regimens have similar overall response rates (ORR) (30-40%; and 47% for HER2+ with trastuzumab). Given results within other GI tumors, FOLFIRINOX was administered to pts with newly diagnosed advanced GEC. Methods: A pooled analysis from two independent ongoing clinical trials was conducted from: 1) the University of Chicago UC (NCT01643499) where pts received modified ‘mFOLFIRINOX’ with irinotecan dosing based on UGT1A1*28 genotyping; and 2) Washington University (WU) (NCT01928290) where pts received standard ‘sFOLFIRINOX’ as previously described, and HER2+ pts also received trastuzumab (sFOLFIRINOX-T). Both studies administered therapy every 14 days. Trastuzumab was administered as 6 mg/kg loading dose then 4 mg/kg every 14 days. mFOLFIRINOX used UGT1A1 genotype *1/*1, *1/*28, and *28/*28 to assign initial irinotecan doses of 180, 135, and 90 mg/m2, respectively. The mFOLFIRINOX 5-FU dose was 2400 mg/m2 over 46 hours (no bolus) with leucovorin 400 mg/m2, and oxaliplatin 85 mg/m2. Outcomes included ORR, tolerability/safety, mPFS, and mOS for both trials. Results: In the pooled analysis, 18 pts with GEC were enrolled to date (11 at WU and 7 at UC), and 16 evaluable for response. ORR was 62.5% (10/16), (HER2- 58% (7/12), HER2+ 75% (3/4)). One HER2+ pt experienced a CR. mPFS was 8 months (range 1.5-18 months), however 10/16 pts have not progressed on first-line therapy to date. There were no unexpected toxicities for any of the regimens. Conclusions: ORR and PFS with first-line FOLFIRINOX were encouraging for metastatic GEC. sFOLFIRINOX was well tolerated in these patients, and sFOLFIRINOX-T was safely administered.mFOLFIRINOX consisting of genotype-directed irinotecan dose reductions and no 5FU bolus may limit toxicity yet retain similar benefit to sFOLFIRINOX. Continued investigation of this regimen is warranted given these encouraging preliminary results. Clinical trial information: 01928290.
Outcomes of recurrence after complete response to definitive chemoradiotherapy for stage II/III (non–T4) esophageal squamous cell carcinoma.
Authors: Kuwabara Hiroki , Kato Ken , Sasaki Yusuke , Takahashi Naoki , Shoji Hirokazu , Okita Natsuko T. , Takashima Atsuo , Honma Yoshitaka , Iwasa Satoru , Hamaguchi Tetsuya , Yamada Yasuhide , Boku Narikazu , Ito Yoshinori , Itami Jun
Published: February 2017

179

Background: Recurrence after definitive chemoradiotherapy (dCRT) for locally advanced esophageal cancer is associated with poor outcome. We examined patterns of recurrence and clinical outcomes in patients with recurrence after complete response (CR) to dCRT. Methods: We retrospectively investigated 238 patients who had achieved initial CR after dCRT for locally advanced esophageal cancer between January 2000 and December 2010. From among these patients we selected 95 who had developed disease recurrence after CR. Overall survival was defined as survival time from recurrence to death and was calculated by using the Kaplan-Meier method. Univariate and multivariate analyses were performed with the Cox regression model to determine prognostic factors for survival. Results: The characteristics of the 95 patients were as follows: male: female = 84:11; median age = 64 years (range 46 to 80); clinical stage at diagnosis (UICC 6th edition) IIA/IIB/III = 20/31/44; and performance status at recurrence (0/1) = (51/44). Primary CRT consisted of 5-FU+cisplatin (n = 87), 5-FU+nedaplatin (n = 3), S-1+cisplatin (n = 3), 5-FU+cisplatin+ nimotuzumab (n = 1), or docetaxel (n = 1). The pattern of recurrence was locoregional failure (n = 53) or any distant failure (n = 42). Median time from the start of dCRT to recurrence was 13.0 months, and median survival time from recurrence to death was 19.6 months. Median survival time according to the pattern of failure was 34.7 months (locoregional failure) or 17.0 months (any distant failure). Application of the Cox regression model, including the additional prognostic variables of age, ECOG performance status, number of organs in which metastases were present, and LDH, revealed that any distant failure (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.2 to 4.1; P = 0.01) and recurrence before 13.0 months (HR 2.1; 95% CI 1.2 to 3.6; P = 0.01) were predictors of poor overall survival. Conclusions: Early recurrence and any distant failure were associated with poor prognosis after CR to dCRT for locally advanced esophageal cancer.
Acetaldehyde/ethanol breath test for identifying people at high risk of upper aerodigestive tract cancer.
Authors: Aoyama Ikuo , Tsurumaki Mihoko , Nakai Yukie , Ohashi Shinya , Muto Manabu
Published: February 2017

18

Background: Alcohol drinking increases the risk of upper aerodigestive tract cancer, and acetaldehyde (a metabolite of alcohol) is a definite carcinogen for this type of cancer. Acetaldehyde is formed mainly by the oxidation of ethanol by alcohol dehydrogenase 1B (ADH1B) and is eliminated by aldehyde dehydrogenase 2 (ALDH2) in the liver. About 50% of Asian people have the ALDH2*2 variant allele, which encodes an inactive enzyme. Those with the ALDH2*2 allele and an alcohol drinking habit are at definite risk of esophageal and head and neck cancers. Genetic testing is the most reliable method for identifying the ALDH2 genotype, but it is not practical for mass screening because of the cost and time. Therefore, we have established a simple method to identify the ALDH2 genotype by analyzing breath samples. Methods: One hundred seven consecutive healthy Japanese volunteers participated in this study. After providing informed consent, participants drank 100 ml of 0.5% ethanol in a single gulp. Breath samples were collected with originally developed simple gasbags before the alcohol was consumed, and 1, 2, and 5 minutes later. The concentrations of acetaldehyde and ethanol in the bag were measured by high-sensitivity gas chromatography. The ALDH2 and ADH1B genotypes of all participants were confirmed using blood DNA. The relationships between acetaldehyde level and genotypes were determined. Results: The frequencies of ALDH2*1/*1, ALDH2*1/*2, and ALDH2*2/*2 were 46.7%, 43.9%, and 9.3%, respectively. The breath acetaldehyde levels at 1 minute after alcohol ingestion were 89.2 (18.1–399.0) ppb in those with ALDH2*1/*1, 346.3 (78.4–1218.4) ppb in those with ALDH2*1/*2, and 537.1 (213.2–1353.8) ppb in those with ALDH2*2/*2. The breath acetaldehyde level was significantly higher in the ALDH2*2 carrier group regardless of the ADH1B genotype (P<0.001). Setting the cutoff for the acetaldehyde/ethanol ratio at 22.3×10–3 to include ALDH2*2 carriers yielded an accuracy for the detection of ALDH2*2 carriers of 96.3% (95% CI: 91.5–96.9%), sensitivity of 100%, and specificity of 92%. Conclusions: Our breath test may be a convenient screening tool for identifying those at high risk of upper aerodigestive tract cancer.
Docetaxel plus FOLFOX4 compared with FOLFOX4 as adjuvant chemotherapy for gastric cancer.
Authors: Du Chun-Xia , Liu Xiao-Yan , Zhang Hong-Gang , Zhou Ai-Ping
Published: February 2017

181

Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.
Second primary malignancies in gastric cancer: A U.S. population-based study.
Authors: Shah Binay Kumar , Khanal Amit
Published: February 2017

191

Background: Risk of second primary malignancies (SPM) is not known in gastric cancer. In this population based study, we analyzed rates of SPM in gastric cancer. Methods: We selected adult (≥18 years) patients with gastric cancer as first primary malignancy diagnosed from January 1992 to December 2011 from Surveillance, Epidemiology and End Result 13 database. We used SEER*stat’s multiple primary standardized incidence ratio (MP-SIR) session to calculate the risk of SPM diagnosed 6 months after the diagnosis of index gastric cancer. Results: Among 31,818 patients with first primary gastric cancer, 1674 (5.26%) developed 1,839 SPM with observed/expected (O/E) ratio of 1.09 (95% CI = 1.05-1.15, p<0.0001) and excess risk of 16.15 per 10,000 population. The median time to first SPM from the time of diagnosis of stomach cancer was 49 months (range 6 months to 19.08 years). There was significantly increased risk of gastrointestinal malignancies [O/E ratio 1.65 (CI=1.53-1.79, p<0.001)], thyroid cancer [O/E ratio 1.98 (CI=1.32-2.84, p<0.01)] and myeloid leukemia [O/E ratio 1.47(CI=1-2.09, p<0.05)]. Interestingly, there was significantly decreased risk of melanoma, breast cancer and prostate cancer. Conclusions: Our study showed that patients with gastric cancer are at higher risk of gastrointestinal malignancies, thyroid cancer and myeloid leukemia. Similarly, risk of melanoma, breast cancer and prostate cancer in patients with gastric cancer is lower than general population.
The treatment for unresectable advanced gastric cancer with pyloric stenosis.
Authors: Watanabe Ryohei , Nakamura Yoichi , Nagaoka Yasushi , Asai Koji , Enomoto Toshiyuki , Watanabe Manabu , Saida Yoshihisa , Kusachi Shinya , Nagao Jiro
Published: February 2017

194

Background: Inability of oral intake due to advanced gastric cancer with pyloric stenosis (AGCPS) should be avoided, because the key drug of chemotherapy for gastric cancer is S-1 in Japan. We have performed palliative gastrectomy (PG), gastrojejunostomy (GJ) or stent placement (SP) for unresectable AGCPS. We investigated therapeutic outcomes (gastric outlet obstruction scoring system: GOOSS, chemotherapy introduction rate: CIR and median survival time: MST) of each therapy retrospectively. Methods: Between April 1999 and April 2013, 42 patients with unresectable AGCPS were included in this study (PG/GJ/SP, 13/10/19). We compared therapeutic outcomes (GOOSS, CIR and MST) between the 3 groups. Results: The demographic characteristics of patients were similar across the three groups. We evaluated the Glasgow Prognostic Score (GPS) of all cases before treatment. GPS tended to be 1 in the PG group, 0 in the GJ group and 2 in the SP group. The proportion of GPS 2 in the SP group was higher than in PG or GJ group significantly (p=0.0056 for SP vs. PG, p=0.0191 for SP vs. GJ and p=0.007 for SP vs. Surgery). GOOSS scores of all patients were improved. GOOSS score 3 of PG/GJ/SP groups after treatment were 84.6 / 90 / 68.4% respectively. CIR, MST and post-operative complication rate of PG/GJ/SP groups were 53.8 / 90 / 42.1%, 222.5 / 435.5 / 74 days and 46.2 / 10 / 0%, respectively. The proportion of patients receiving chemotherapy was higher in the GJ group than in the PG group, and survival was longer in the GJ group than in the PG group. Post-operative complication rate was lower in GJ group than in PG group. Conclusions: GJ is well tolerated and offers improved survival compared with PG and SP in the patients with AGCPS. High CIR improved MST. Success of chemotherapy introduction might improve survival. Enabling oral intake is important for chemotherapy. However, it is very difficult to select a treatment method that suits the patient individually. GPS might be an important predictor in the selection of the treatment method for unresectable AGCPS.
Paclitaxel, carboplatin, and capecitabine (TCX) with and without radiation in locally advanced and metastatic distal esophageal and esophagogastric junction cancer: A single-center retrospective review.
Authors: Hosein Peter Joel , Ray Neha , Anthony Lowell Brian , Tzeng Ching-Wei David , Kudrimoti Mahesh R. , McGarry Ronald , Martin Jeremiah Thomas , Long Katie E , Overly Colleen , DeSimone Philip A.
Published: February 2017

197

Background: Toxicities of the active triple-drug DCF regimen (docetaxel, cisplatin and 5-FU) in gastric cancer limit its broad use and general acceptance as first-line therapy. To improve the toxicity profile of triple-drug therapy, distal esophageal and esophagogastric junction (DE-EGJ) poorly differentiated and moderately differentiated adenocarcinoma patients were treated with TCX. This single-center retrospective review is reported for patients treated between 2005 and 2013. Methods: Patients with DE-EGJ adenocarcinoma were treated with capecitabine (850 mg/m2 5 out of 7 or 14 out of 21 days), carboplatin (AUC 5) and paclitaxel (175 mg/m2) every 3 weeks. Those with locally advanced disease received concomitant radiation therapy (50.4 Gy using 3D approach) during the first 2 cycles. Dose reductions (25-50%), delay of therapy and hospitalizations for disease and treatment-related Grades 3/4 toxicities were recorded. Growth factors were prescribed reactively. Kaplan-Meier statistics were used for survival analyses. The institutional tumor registry data provided the historical median survival. Results: Thirty-one males and 3 females (median age 56, range 37-82) with locally advanced (N=17) and metastatic (N=17) disease were included. Median overall survivals are shown below. Two patients were admitted for neutropenic fever and 7 total hospitalizations occurred. Conclusions: A triple-drug combination first-line regimen (TCX) with and without radiation in DE-EGJ cancer is active, and associated with a manageable toxicity profile. The median survival of 15.8 months in patients with metastatic disease treated with TCX compares favorably with the DCF regimen (9.2 mos), the EOX regimen (11.2 mos) as well as institutional historical controls. Our data suggests that future prospective trials evaluating triple-drug regimens in combination with targeted therapy may be feasible in patients with esophageal and gastric adenocarcinoma. [Table: see text]
Prognostic factors in advanced gastric cancer after second-line treatment.
Authors: LONGO FEDERICO , Pachon Vanessa , Guillen Carmen , Ferreiro Reyes , Rodriguez Garrote Mercedes , Puertas Pablo Reguera , Madariaga Ainhoa , Gion Maria , Lopez Hervas Pedro , Galindo Julio , Gonzalez Lizarbe Eva , Varona Constantino , Montans Jose , Earl Julie , Grande Enrique , Olmedo Garcia Maria Eugenia , Garrido Pilar , Lobo Eduardo , Palacios José , Carrato Alfredo
Published: February 2017

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Background: Advanced gastric cancer (AGC) is a highly lethal disease worldwide with a median overall survival (OS) of less than 12 months. Ramucirumab was the first targeted agent to show survival benefit in the second-line (2L) treatment of AGD. From the REGARD trial, women exhibited a trend towards a worse survival when compared to men. Methods: We retrospectively analyzed the outcome of a Spanish cohort of 55 AGC patients who had received at least two consecutive chemotherapy lines of treatment at our institution. We preselected some clinical parameters (age, gender, Lauren subtype, Her-2 status, grade of differentiation, primary tumor localization and resection, TNM stage, neoadjuvant/adjuvant administration, mono/polychemotherapy in 2L, irinotecan- or taxane-based 2L, Trastuzumab treatment, and administration of third-lines [3L]) to be tested as potential prognostic factors. We focused our analysis on the gender effect in OS after 2L treatment in AGC. The SPSS software package was used for all statistical analyses (Mann-Whitney U test, Chi Square, Kaplan-Meier, Cox regression). Results: Women, diffuse subtype, poorly differentiated tumors, sub-cardia location, single-agent 2L and 3L administration were the clinical characteristics with a significant shorter OS by the univariable analysis. Median OS of women (5 months, 95%CI 3.9-6.0) was significant lower than that in men (13 months, 95%CI 7.9-18.0) by both Log-Rank and Breslow tests (p 0.002). We found no significant differences in age, progression-free survival or time-on-treatment between men and women. Female gender was significantly associated with more taxane-based 2L and with less 3L treatment administration. When 3L treatment administration was excluded in the multivariable analysis, female gender was the only independent prognostic factor of all the clinical parameters included in our review (HR 0.33, 95%CI 0.15-0.75, p 0.008). Conclusions: Our retrospective study found that gender, Lauren subtype, grade of differentiation, primary tumor location, polychemotherapy and 3L administration may be potential prognostic factors in AGC after 2L treatment. Female gender was an independent prognostic factor in our Spanish cohort.
A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in patients with metastatic or recurrent esophageal squamous cell carcinoma.
Authors: Hiramoto Shuji , Kato Ken , Shoji Hirokazu , Okita Natsuko T. , Takashima Atsuo , Honma Yoshitaka , Iwasa Satoru , Hamaguchi Tetsuya , Yamada Yasuhide , Shimada Yasuhiro
Published: February 2017

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Background: Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, 5-fluorouracil /Cisplatin (FP) have been mostly used for these patients as first line chemotherapy. But there were few reports which reveal the reality containing the efficacy of FP regimen for ESCC. We conduct this retrospective study to reveal the efficacy and prognostic factors of the patients treated with FP as first line chemotherapy for ESCC. Methods: Patients with metastatic or recurrent ESCC after esophagectomy were enrolled. FP comprised of CDDP at a dose of 80mg/m2 on day1, and 5-FU at a dose of 800mg/m2given by continuous on days 1-5 every 4 weeks. Cox-proportional hazard model was used for multivariate analysis to evaluate prognostic factors. Results: Between April 2001 and March 2012 in the National Cancer Center Hospital, data of 187 patients were collected by medical records. Characteristics of 187 patients were as follows; the median age (range) 62 (34-84); (male/female) 163/24; (performance status: 0/1/2) 69/110/8; (metastatic/recurrent) 116/71; median number of metastasis 1(range1-4); median cycles of FP 2(range1-10). Overall response rate was 31.6% (95%CI: 25.0-38.7%). Median progression free and overall survival time was 4.9 month and 10.5 month, respectively. In multivariate analysis, serum CRP (≥2 vs <2 mg/dl) (HR=2.61, p<0.001), serum albumin (<3.5 vs >3.5 mg/dl) (HR=1.85, p=0.001) at the time of diagnosis and number of metastatic site (≥2 vs <2) (HR=1.563, p=0.01) were remaining independent prognostic factor for survival. Survival time of the patients who had no these poor prognostic factors was 17.9 month, while survival time who had all poor prognostic factors was only 4.0 month. Conclusions: Number of metastatic site, CRP, and serum albumin are independent prognostic factor on metastatic or recurrent ESCC patients treated with FP. Information from this analysis can be used to aid clinical decision-making and help individual patient risk stratification.
A study of cell-free and concentrated ascites reinfusion therapy (CART) for intractable ascites associated with cancerous ascites.
Authors: Ueda Yuki , Katayama Kanji , Fujimoto Daisuke , Murakami Makoto , Hirono Yasuo , Goi Takanori , Yamaguchi Akio
Published: February 2017

205

Background: Intractable ascites associated with cancerous ascites causes severe abdominal distention, loss of appetite, poor nutritional condition and reduce the quality of life. We treat patients suffering from cancerous ascites by Cell-free and Concentrated Ascites Reinfusion Therapy (CART). But, cancerous ascites contains a lot of cellular components, and it easily cause filter obstruction. So we applied new method of CART: KM-CART in cancerous ascites patients. This CART system has a filter cleaning function, so the system has less incidence of filter obstruction. We report on our experience on CART for patients with cancerous ascites. Methods: Since November 2009 to August 2014, we applied CART in 31 cases of cancerous ascites (gastric cancer, 13; colorectal cancer, 6; pancreatic cancer, 10; others, 2). Results: On average, 3.8kg (range 1.2-7.5kg) of ascites were filtrated and concentrated to 440g (70-1110g). In all cases abdominal distention disappeared and abdominal girth decreased. Side effect was only mild fever on 11 cases. Conclusions: CART is safe and effective treatment for patients with cancerous ascites. This treatment may be able to improve quality of life with peritoneal dissemination.
Optimal indications for palliative chemotherapy in elderly patients with metastatic or recurrent gastric cancer.
Authors: Hasegawa Hiroko , Fujitani Kazumasa , Sugimoto Aya , Nakazuru Shoichi , Hirao Motohiro , Tsujinaka Toshimasa , Mita Eiji
Published: February 2017

207

Background: Gastric cancer is the second causes of cancer-related deaths in the world and its incidence of advanced gastric cancer (AGC) in the elderly is increasing as a result of increased life expectancy. However, elderly patients have been underrepresented in many kinds of chemotherapy clinical trials. Therefore it is difficult to evaluate the efficacy and safety of chemotherapy for elderly patients and select the appropriate patients aged 70 years or older who are likely to benefit from the chemotherapy. Methods: There were 265 patients with primary unresectable or recurrent gastric cancer treated at our institution between April 2007 and March 2014. Of all, 90 patients aged 70 years or older were retrospectively identified. We evaluated the efficacy of the chemotherapy and prognostic significance of clinico-pathologic factors to identify the optimal indications for chemotherapy. Univariate and multivariate analyses were perfomed on the base-line characteristics such as patient’s performance status (PS), gender, chemotherapy regimens, history of gastrectomy, presense of co-morbidity, serum LDH level, serum C reactive protein, and nutritional status, at the initiation of the first-line chemotherapy. Results: The median overall survival time (OS) was 343 days and the median TTF on first-line chemotherapy was 111 days. The toxicity was mild and tolerable. There were no significant difference in overall survival between patients receiving monotherapy and combination therapy. On multivariate analyses, PS 1 or 2 (hazard ratio (HR), 1.883; 95% confidence interval (CI), 1.047–3.390), presence of primary tumor (HR, 1.916; 95% CI, 1.063–3.448) at the initiation of the first- line chemotherapy were identified as significant independent poor prognostic factors for overall survival. Especially in patients aged 75 years or older, only PS was an independent prognostic factor for OS (HR, 3.703; 95% CI, 1.314–9.900). Conclusions: Analysis of our results shows that patients aged 70 years or older with good performance status and absence of primary tumor might achieve clinical benefit from chemotherapy.
Effect of neoadjuvant therapy on the risk for atrial fibrillation in patients undergoing esophagectomy.
Authors: Doepker Matthew , Abbott Andrea M. , Shridhar Ravi , Hoffe Sarah E. , Almhanna Khaldoun , Meredith Kenneth L.
Published: February 2017

210

Background: Neoadjuvant chemoradiation (NT) has become the standard for patients with locally advanced esophageal cancer. Thirty percent of patients who undergo esophagectomy will develop atrial fibrillation (AF). NT may contribute to patients developing AF and this may be a surrogate for anastomotic dehiscence (AD). Methods: We queried a prospective esophageal database to identify patients who underwent esophagectomy with or without NT. Demographics and post-operative complications were all compared with fisher exact test and considered significant at p<0.05. Results: We identified 811 patients who underwent esophagectomy with a mean age of 68 +/- 12 years. Five-hundred and fifteen (63.5%) were treated with NT and 296 (36.5%) were not. Eighty-nine (11%) of patients developed AF, 59 (11.5%) in the NT group, and 30 (10.1%) in the non NT group. There was no significant differences noted in the incidence of AF in those that were treated with NT and those that were not (p=0.64). A total of 54 (6.7%) patients were identified as having AD, 27 (5.2%) in the NT cohort and 27 (9.1%) in the non NT cohort. The NT group had lower incidence of AD compared to their non NT counterparts (p=0.04). Of the 54 patients who experienced AD, 6 (11%) had concomitant AF, and 48 (89%) did not and the remaining 83 patients who developed AF did not develop AD (p=1). Conclusions: NT prior to esophagectomy does not increase patient’s risk for developing postoperative AF. Moreover, the presence of AF in the post esophagectomy patient, did not serve as a surrogate for identifying AD.
Clinical outcomes in 66 patients with advanced gastric cancer treated in phase I trials: The NCCHE experience.
Authors: Kawazoe Akihito , Shitara Kohei , Fukuoka Shota , Kuboki Yasutoshi , Bando Hideaki , Okamoto Wataru , Kojima Takashi , Yoshino Takayuki , Doi Toshihiko , Ohtsu Atsushi
Published: February 2017

213

Background: Patients with advanced gastric cancer (AGC) have a poor prognosis once standard therapies fail. Phase I trial of investigational drugs might be one of the treatment options for patients with sufficient general status. But, the clinical outcome of patients with AGC treated in phase I trials has not yet been reported in detail. Methods: We retrospectively reviewed the clinical outcomes in 66 consecutive patients with AGC who were treated in phase I trials after standard chemotherapies between March 2008 and July 2014. Results: Median age was 66 years (range, 28-78 years) and all had performance status ECOG 0 or 1. The median number of previous systemic chemotherapy was 3 (range, 1-6) with the median interval from beginning of first-line chemotherapy to enrollment for phase I trials of 18 months. Twenty-three patients were enrolled for two or more phase I trials. Objective response was observed in 5 patients (8%) and additional 8 patients (12%) achieved stable disease >3 months. Although the median time to treatment failure (TTF) of the best phase I treatment was shorter than those of the last line of systemic chemotherapy (1.5 vs. 2.3 months; HR 1.80; P=0.002), the median TTF of best phase I trial was longer than the last line of systemic chemotherapy in 21 patients (32%). Severe adverse events and grade >3 toxicities were reported in 8 patients (12%) and 12 patients (18%), respectively. No treatment related death was observed. Median survival time after enrollment for phase I trials was 7.5 months and 4 death (6%) within 30 days after last administration was observed. Conclusions: The clinical outcome for patients with AGC treated in phase I trials was comparable to that of other malignancies previously reported. These results of our study suggest phase I trial might be one treatment option for patients with AGC after failure of standard chemotherapy.
Retrospective analysis of preoperative chemoradiation therapy for esophageal and gastroesophageal junction (GEJ) cancer: Lessons to be learned from expanding inclusion criteria in this patient population.
Authors: Iafolla Marco Adelmo James , Spratlin Jennifer L. , Ghosh Sunita , Mulder Karen E.
Published: February 2017

214

Background: Preoperative chemoradiation therapy utilizing paclitaxel, carboplatin and radiation as per the CROSS Group increased survival rates among patients with potentially curable esophageal or GEJ cancer. A retrospective chart review was performed to determine: 1) the frequency of patients meeting the original trial inclusion/exclusion criteria 2) overall survival (OS), disease free survival (DFS), and pathological response rates (RR) of this patient population. Methods: Data was collected on 89 patients who received preoperative chemoradiation therapy (CROSS protocol) in Edmonton, Alberta between June 1, 2010 and April 11, 2014. Mean and standard deviation were calculated for continuous data and frequency (proportion) for categorical data. Time to event was presented using Kaplan-Meier estimates and log rank tests were used to compare the KM curves. Results: The median age of the entire patient population was 62 years with 77 (86.5%) of the patients being male. Twenty-three (26%) patients met inclusion criteria (MIC), whereas 66 (74%) patients failed to meet inclusion criteria (FMIC). Reasons for FMIC included: clinical stage (39.3%); weight loss > 10% (39.0%); previous cancer history (22.5%); tumor length (9.0%); and age (5.6%). Pathological complete response (CR) occurred in 24% of all patients with a trend to increased CR in MIC vs FMIC (35% vs 20%; p=0.18). Significant improvement in DFS was observed in the MIC group compared to FMIC (p=0.004). Although a trend to improvement was seen for OS in the MIC group, it is not yet significant at this early analysis (p=0.12). Conclusions: A significant proportion of patients treated with neoadjuvant chemoradiation therapy for esophageal and GEJ cancer at our center did not meet the inclusion/exclusion criteria utilized in the CROSS trial. This had a detrimental impact on FMIC patients questioning its benefit and utility in a broader patient population. [Table: see text]