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The significance of molecular analysis of peritoneal fluid in staging laparoscopy of oesophagogastric junction (EGJ) and gastric cancer is still controversial. METHODS: A retrospective analysis of prospective data collection of all patients diagnosed with locally advanced gastric neoplasia or Siewert II-III EGJ cancer from July 2009 to October 2019 who underwent staging peritoneal lavage prior to neoadjuvant treatment was performed. Cytology studies and molecular analysis of peritoneal lavage were performed by real-time reverse transcriptase polymerase chain reaction (RT_PCR) of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) as tumor makers. RESULTS: 168 patients were operated. Citology and molecular analysis were performed in 138 patients. Macroscopic carcinomatosis (P+) was evidenced in 12.3% (17 patients). Of the remaining 87.7% (121 patients), 9.9% (12 patients) had positive cytology. In 21% (29 patients) disseminated macroscopic or microscopic disease (P + or Cyt+) was identified. 11.6% (16 patients) were P0Cyt- but RT-PCR+. Of these, 9 responded to chemotherapy before salvage surgery. The sensitivity of cytology and molecular analysis was 0.70 and 0.76, respectively (p = 0.67). The survival of Cyt-RT_PCR + vs. Cyt + RT_PCR + patients was similar (p = 0.1). However, there were no differences in the survival curves between Cyt-RT_PCR- patients vs Cyt-RT_PCR + patients who underwent salvage surgery (p = 0.69). CONCLUSION: Molecular analysis showed a sensitivity of 76%. In our study, the survival of P0 Cyt-RT_PCR + patients responding to chemotherapy and undergoing surgery was similar to that of P0 Cyt-RT_PCR- patients but less disease free survival.

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II–IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7–22.8). Median overall survival was 23.4 months (95% CI 12.2–36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1–11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting.Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on days 1 and 8 every 21 days) followed by IC/RT (daily radiotherapy-45 Gy-with concurrent IC: irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2), on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment.Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon's optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30 days after resection. The median survival was 10.5 months, and the actuarial 2-year survival rate was 27%.Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC.

Purpose To determine in a Phase II trial whether preoperative irinotecan–cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). Patients and Methods Patients with resectable Stage II–IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65mg/m 2 ; cisplatin, 30mg/m 2 on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65mg/m 2 ; cisplatin, 30mg/m 2 on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5–8 weeks after the end of radiotherapy. Results Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3–4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. Conclusions Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.

Chemotherapy has improved the overall survival (OS) in patients (pts) with advanced gastric cancer (AGC). Docetaxel (D), oxaliplatin (O) and capecitabine (C) have shown interesting activity in this setting. We defined “suboptimal” pts as those with PS ECOG = 2, weight loss 10–25 % and/or age ≥70 years. This population is usually underrepresented in AGC clinical trials. We explored in 43 previously untreated “suboptimal” AGC pts the effect of “miniDOX” regimen (D: 40 mg/m2 iv, day 1; O: 80 mg/m2 iv, day 1; C: 625 mg/m2 po bid, day 1 to day 21, every 21 days; after six courses, only C was maintained). Primary end point was response rate (RR), and secondary end points were adverse events (AE), progression-free survival (PFS) and overall survival (OS). Patients characteristics: PS ECOG = 2: 12 pts; weight loss 10–25 %: 23 pts; median age 73.3 years (range 40–87; 28 pts were ≥70 years); 32 males; locally advanced: 8 pts/metastatic: 35 pts; primary site: gastric 32 pts/EGJ 11. Worst AE per pt (grade 3–4): neutropenia: 5 pts (febrile neutropenia: 3); pulmonary embolism (PE): 4 pts (3 of them suffered sudden death); diarrhea: 9 pts; paronychia: 2 pts; ictus: 1 pt; renal failure: 1 pt (this pt suffered infection/bacteriemia without neutropenia and died); hand-foot syndrome: 4 pts and asthenia: 5 pts. Response: CR: 1 pt, PR: 23 pts (RR: 56 %), SD: 12 pts, progression: 3 pts, no determined: 4 pts. Median and 1 year actuarial PFS and OS were 5.5 months/18 % and 13.3 months/52 %, respectively. Although miniDOX’s toxicity (mainly PE)has been important, its activity has been promising in “suboptimal” pts with AGC, and this combination should be further investigated in this setting.

Skin rash is an adverse event which might be associated with longer survival in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors. The aim of this nonrandomised phase II clinical trial is to prospectively evaluate the relationship between skin rash and overall survival (OS) in advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.Patients were given gemcitabine (1000 mg/m2/week, 3 weeks every 4 weeks) plus erlotinib (100 mg/day orally continuously) until disease progression/unacceptable toxicity. The primary end point was OS.A total of 153 eligible patients were enrolled (grade≥2 rash, 25%; grade2 rash, 75%). OS was longer in patients with grade≥2 rash versus grade2 (11 versus 5 months; P0.001). Progression-free survival was longer in patients with grade≥2 rash versus grade2 (6 versus 3 months; P0.001) and shorter in those without rash versus grade 1 (2 versus 4 months; P=0.005) or grade≥2 (2 versus 6 months; P0.001). Patients with grade≥2 rash showed higher rates of overall response (21% versus 7%; P0.05) and disease control (84% versus 43%; P0.05) versus grade2.This study prospectively confirms the relationship between rash and longer OS in unresectable locally advanced/metastatic pancreatic cancer treated with erlotinib plus gemcitabine.

4098 Background: Perioperative chemotherapy has demonstrated better OS and DFS than surgery alone in resectable stomach or EGJ adenocarcinoma. Trastuzumab has improved OS when added to chemotherapy in pts with HER-2 + metastatic gastric cancer and is interesting to explore its role in the perioperative setting. Methods: A Spanish, multicenter, open-label phase II study evaluated the efficacy and toxicity profile of perioperative XELOX-T (capecitabine 1000 mg/m2/12h po days 1-14, oxaliplatin 130 mg/m2 day 1, trastuzumab 8 mg/kg→ mg/kg day 1, q3w ; 3 preoperative cycles and 3 postsurgery cycles followed by 12 cycles of trastuzumab monotherapy) in patients with T1-2N+M0 or T3-4NxM0 resectable stomach or EGJ adenocarcinoma, HER-2+ ( IHQ3+ or IHQ2+/FISH+). The primary endpoint was 18 months DFS, secondary endpoint included pCR, R0 resection rate, ORR and toxicity of preoperative treatment (NCI CTC v3.0 criteria). Results: From June 2010 to March 2012, 36 pts were included: median age 65 (39-85); ECOG 0/1/2: 16/19/1 pts; localization: stomach 21 pts, EGJ 15 pts; histologic type: intestinal: 23 pts, diffuse: 4 pts, mixed: 1pt, not specified 8 pts; TNM: T 4: 7 pts; N+: 31 pts. Preoperative XELOX-T: Response: PR: 14 pts (39%), SD: 18 pts, PD: 0 pts, NE: 4 pts. G-3-4 toxicity (≥ 5% of pts): diarrhea 22% and asthenia 5%. Surgery was performed in 31 pts: R0: 28 pts (78%, 95% CI: 61-90%), R1: 1 pt, R2: 2 pts (1 had peritoneal carcinomatosis); pCR was observed in 7 pts (19 %; 95% CI: 8-36%) and 22 pts (61%) were pN0. Two pts died due to surgical complications,. We do not have mature data about postoperative XELOX-T yet. Follow-up is still too short for DFS and OS. Conclusions: This preliminary analysis suggests that perioperative XELOX+T in HER-2 positive resectable stomach or esophagogastric junction adenocarcinoma is feasible and has interesting activity. Clinical trial information: NCT01130337.

e15111 Background: Modern management of Oesophageal and oesophagogastric junction (OGJ) cancers requires a multidisciplinary approach, which was implemented at our health centre in 2005. This study aimed to assess the impact of this change on clinical outcomes. Methods: A retrospective cohort study was conducted, covering all patients treated for oesophageal and OGJ cancer at the cancer centre established by the Bellvitge University Hospital and Catalonian Institute of Oncology, over two time periods, i.e., 2000-2004 and 2005-2008. Descriptive and multivariate analyses were performed using survival at 1 and 3 years as dependent variables. Results: Between 1 January 2000 and 31 December 2008, 586 patients were included. Number of patients with unknown stage at diagnosis was significantly reduced. Neoadjuvant strategies at the oesophageal location clearly increased in the recent period. A multidisciplinary approach resulted in a significant reduction in surgical mortality (11.8% vs. 2%) in the period 2005-2008. Analysis restricted to patients undergoing surgery with curative intent indicated a significant increase in 1- and 3-year survival in the latter period (68.4% vs. 89.8% and 38.2% vs. 57.1% respectively). Multivariate analysis showed that variables associated with improved survival were: age; tumour stage; radical intent of treatment (surgery and radical combined chemoradiotherapy); and therapeutic strategy. Conclusions: Better selection of patients for therapy together with improved staging resulted in a significant improvement in 1- and 3-year survival in cases undergoing surgery with curative intent. These changes would support the adoption of a multidisciplinary approach to clinical decision-making in cases of oesophageal and OGJ cancer.

Introduction Since 2006, the results of MAGIC trial demonstrated that a perioperative regimen of Epirrubicin-cisplatin-5FU (ECF) decreases tumour size and stage, with significantly improvement in overall survival (OS) and progression-free survival (PFS). However, the survival rate of patients (pts) with locally advanced resectable gastric cancer (LARGC) remains poor. Our aim was to identify prognostic factors and their correlation with a more aggressive disease in our area. Methods We retrospectively reviewed 65 pts with LARGC who were planned to receive perioperative chemotherapy followed by surgery at our institution, between May 2008 and February 2012. We analysed the correlation between mOS and recurrence free survival (RFS) with patient characteristics, sex and age, and some tumour characteristics, as histology, tumour localization, both clinical and pathological stage, and tumour regression rate (TRR). OS and RFS was analysed using Kaplan-Meier curves and the differences with Log-Rank test. Results 16 women and 49 men were analysed, with a median age of 63 years (range 38-78). 41% pts had a diffuse type, 49% an intestinal type and 10% a mixt type adenocarcinoma. 30% of tumours were proximal and 70% were distal. There were clinically 1.6% stage I, 49.2% stage II and 49.2% stage III pts. 58 pts (98%) completed 3 cycles of neoadjuvant chemotherapy. 42 pts received ECF, whereas 23 pts received other schemes (13 pts carboplatin+5FU, 8 pts cisplatin+5FU, 2 pts other combinations). Radiological downstaging was observed in 59% pts. 40 total gastrectomy, 14 partial gastrectomy and 9 Ivor-Lewis were conducted. There was 1 pt who underwent a palliative derivation. We found 1 surgery-related death. Adjuvant chemotherapy was delivered in 45 pts. There were pathologically 22% stage I, 47% stage II, 22% stage III and 9% stage IV pts. Pathological downstaging in terms of TRR (RG1+RG2+RG3) was obtained in 42% pts, achieving 3 complete responses (RG1). 4 pts had marked regression (RG2) and 19 pts had 10-50% viable tumour remaining (RG3), meanwhile 36 pts did not respond (RG4). The median follow-up of the whole group was 24 months. We did not reach nor the mOS neither the mRFS, given that 70% pts were alive after 2 years. 2 year OS was 72% (95 CI, 60.3%-83.6%) and 2 year RFS was 52.5% (95 CI, 39.8%-65.3%). Age Conclusion Preoperative chemotherapy contributes to pathological downstaging and histologic tumour regression in less than 50% pts. Age>60 years, minor pathological downstaging and tumour regression rate have been objectively correlated to poor outcomes. New patient and tumour characteristics must be identified as prognostic and predictive factors. The development of targeted therapies should provide new possibilities in the treatment of LARGC.

Introduction The long term survival of patients with resectable pancreatic cancer (PC) is appalling, so data regarding what factors may influence outcome, following attempted curative resection is essential in order to optimize the treatment options for patients. Our aims were to analyze prognostic factors influencing survival in patients with resected PC in our institution. Methods Eligible participants included all persons diagnosed with pancreatic cancer from June 2004 to August 2008 that underwent pancreaticoduodenectomy for adenocarcinoma of only pancreatic head at the Surgical Department in Bellvitge Hospital. Risk factors associated with overall survival (OS) and Progression Free Survival (PFS) were assessed with the Kaplan-Meier survival method and the log-rank test. Demographic, tumour, and clinical variables were assessed using the Cox proportional hazards model. We also examined plasmatic VEGF (pVEGF) levels in these patients to evaluate the prognostic significance of these levels and correlate the results with the clinic- pathological features, microvascular density and K-RAS gene status. Results The median follow-up was 17.8 months for all patients. The median follow-up for living patients was 40 months (range 3-83 months). The median survival time for all patients was 21.26 months (95% confidence interval 13.29-29.24 months).The median Progression Free Survival for all patients was 15.76 months (95% confidence interval 4.99-26.54 months). Pathological stage was unfavorable prognostic factor in our pancreas cancer patients by univariate and multivariate analysis for OS and PFS. Perineural and vascular invasion as well as R1 resection were also negative prognostic factors for PFS. There was no survival correlation between high levels of p-VEGF and the remaining clinico-pathological features (including the number of resected nodes, microvascular density or K-RAS gene status). Conclusion Our results are consistent with the most important published studies and tumor characteristics remain the best significant features influencing survival after pancreatic cancer surgery.

Introduction Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used as a first-line treatment of advanced gastric cancer (AGC). Docetaxel has been considerable promise against this disease. We want to investigate the efficacy and safety of docetaxel monotherapy as salvage chemotherapy for AGC in clinical practice and determine the prognostic factors in these patients. Methods We retrospectively reviewed the medical records of patients with AGC for whom fluoropyrimidine and platinum had previously failed and who had received docetaxel salvage monotherapy between March 2005 and December 2011. Docetaxel was administered at a dose of 75 mg/m(2) intravenously every 3 weeks with dexamethasone prophylaxis. Results A total of 40 patients received 133 cycles of docetaxel with a median of three cycles per patient (range 1-6). The median age was 63 years (range 38-78 years). The objective response rate was 10%, with 4 partial responses, with response duration of 1.1, 2.2, 2.6 and 7.1 months respectively. An additional 4 patients achieved stable disease. The median time to progression (TTP) for all patients was 1.9 months [95% confidence interval (CI), 1.2-2.7] and the median overall survival (OS) from the start of docetaxel chemotherapy was 4.1 months (95% CI, 3.6-4.6). Grade 3/4 neutropenia and febrile neutropenia occurred in 15% of patients and anemia occurred in 12.5%. The incidence of non-hematologic toxicities of grade 3 or worse was asthenia 25%, anorexia 12.5%, diarrhea 2.5% and stomatitis 2.5%. Multivariate analysis showed that the Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 versus 2) was an independent prognostic factor for both TTP and OS. Number of metastatic sites was a predictor for better TTP. Conclusion Docetaxel 75 mg/m(2) is relatively active against AGC as a second-line salvage treatment after failure of fluoropyrimidine and platinum combination chemotherapy in general clinical practice. The toxicity profile is moderate. Further investigation in salvage therapy is needed, in order to improve survival and provide palliation of symptoms.

4094 Background: Skin rash is a common adverse event associated with HER1/EGFR-targeted agents. Clinical trials suggest a relationship between the development of rash and response and/or survival. ...

e14573 Background: Chemoradiotherapy is an effective treatment in esophageal cancer p; however, there are no reliable pretreatment clinical parameters to predict the efficacy of this multimodal app...

12031 Background: Human tumor xenografts in mice can be remarkably predictive of response in humans to cytotoxic chemotherapeutic drugs. Tumor endothelial cells are sensitive to the action of conventional cytotoxic drugs when they are regularly administrated at low doses. This concept, known as metronomic chemotherapy, has been demonstrated in preclinical studies using transplanted tumor models. We aim to investigate the potential anti-tumoral activity of Gemcitabine (G) when administered in a low-dose schedule in an ortothopic implantation model of human pancreatic carcinomas. Methods: Standard gemcitabine schedule: NP18 tumor orthotopically implanted nude mices were randomly distributed to experimental (n = 13, G100 mg/kg intraperitoneally on days 0, 3, 6 and 9 post-implantation) and control group (n = 13, saline). Animal were sacrificed after 4 weeks and we compared weigths (grams) and volume (cm3) of tumors betwen the two groups by the Mann-Whitney U test. Metronomic schedule: After a toxicological study an optimal metronomic dose of 1 mg G /kg per day was chosen. Thirty xenografted mices were randomly distributed to experimental group (n = 15, intraperitoneal G1 mg/kg) and control group (n = 15, saline) and treated for 30 days. Animal were analysed as described before. Results: Standard schedule: Tumor weight mean of treatment group was 0.01 grams ± 0.01 versus 0.54 grams ± 0.48 of the control group. Tumor volume mean in G group was 0.01 cm 3 ± 0.01 versus 0.51 cm 3 ± 0.67) in the control group.Treatment significantly inhibited NP18 tumour growth (p < 0.001). No differences in mice weight were observed between both groups. Metronomic schedule: Tumor weight mean in the treatment group was 0.04 grams ± 0.08 versus 0.53 grams ± 0.46 in control group. Tumor volume mean in G group was 011 cm 3 ± 0.19 versus 0.37 cm 3. Treatment with low-dose of G significantly inhibited NP18 tumour growth (p < 0.003). There were no differences in mice weight between the two groups. Conclusions: Our data show that G administered in a metronomic schedule is effective in inhibiting the growth of NP18 tumor orthotopically implanted in the nude mice. We now aim to study the angiogenic profile of tumors receiving the standard and metronomic schedule and to set up a new experiment to compare survival benefit in the animal model. No significant financial relationships to disclose.

Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action toward proliferative cells. In this article, we aim to investigate the potential antitumor and antiangiogenic effect of gemcitabine following a metronomic schedule that involves the regular administration of cytotoxic drugs at doses lower than standard treatment. In vitro results showed that human endothelial cells are more sensitive to gemcitabine (IC50 3 nmol/L) than pancreatic tumor cells (IC50 20 nmol/L). For in vivo studies, we used an orthotopic implantation model of human pancreatic carcinoma in nude mice. Gemcitabine was administered i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation). Metronomic treatment effect on established tumor was equivalent to standard administration. The measure of CD31 endothelial marked area allowed us to show an in vivo antiangiogenic effect of this drug that was further enhanced by using metronomic administration. This effect correlated with an induction of thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to hypothesize that, in addition to a direct antiproliferative or cytotoxic antiendothelial cell effect, a secondary effect involving thrombospondin-1 induction might provide an explanation for the specificity of the effects of metronomic gemcitabine treatment. [Mol Cancer Ther 2008;7(3):638–47]