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Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

ABSTRACT: Oesophageal junctional adenocarcinoma is a challenging and increasingly common disease. Optimisation of pre-operative staging and consolidation of surgery in large volume centres have improved outcomes, however the preferred adjunctive treatment approach remains a matter of debate. This review examines the benefits of neoadjuvant, peri-operative, and post-operative chemotherapy and chemoradiotherapy in this setting in an attempt to reach an evidence based conclusion. Recent findings relating to the molecular characterisation of oesophagogastric cancer and their impact on therapeutics are explored, in addition to the potential benefits of fluoro-deoxyglucose positron emission tomography (FDG-PET) directed therapy. Finally, efforts to decrease the incidence of junctional adenocarcinoma using early intervention in Barrett's oesophagus are discussed, including the roles of screening, endoscopic mucosal resection, ablative therapies and chemoprevention.

SUBMITTER: Smyth EC

PROVIDER: S-EPMC4058722 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

Smyth Elizabeth C EC Cunningham David D

World journal of gastrointestinal oncology 20140601 6

Oesophageal junctional adenocarcinoma is a challenging and increasingly common disease. Optimisation of pre-operative staging and consolidation of surgery in large volume centres have improved outcomes, however the preferred adjunctive treatment approach remains a matter of debate. This review examines the benefits of neoadjuvant, peri-operative, and post-operative chemotherapy and chemoradiotherapy in this setting in an attempt to reach an evidence based conclusion. Recent findings relating to ...[more]

PMID: 24936225

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Project description:ObjectiveTo assess the incidence rate of oesophageal adenocarcinoma among patients with non-erosive gastro-oesophageal reflux disease compared with the general population.DesignPopulation based cohort study.SettingAll patients in hospital and specialised outpatient healthcare in Denmark, Finland, and Sweden from 1 January 1987 to 31 December 2019.Participants486 556 adults (>18 years) who underwent endoscopy were eligible for inclusion: 285 811 patients were included in the non-erosive gastro-oesophageal reflux disease cohort and 200 745 patients in the validation cohort with erosive gastro-oesophageal reflux disease.ExposuresNon-erosive gastro-oesophageal reflux disease was defined by an absence of oesophagitis and any other oesophageal diagnosis at endoscopy. Erosive gastro-oesophageal reflux disease was examined for comparison reasons and was defined by the presence of oesophagitis at endoscopy.Main outcome measuresThe incidence rate of oesophageal adenocarcinoma was assessed for up to 31 years of follow-up. Standardised incidence ratios with 95% confidence intervals were calculated by dividing the observed number of oesophageal adenocarcinomas in each of the gastro-oesophageal reflux disease cohorts by the expected number, derived from the general populations in Denmark, Finland, and Sweden of the corresponding age, sex, and calendar period.ResultsAmong 285 811 patients with non-erosive gastro-oesophageal reflux disease, 228 developed oesophageal adenocarcinomas during 2 081 051 person-years of follow-up. The incidence rate of oesophageal adenocarcinoma in patients with non-erosive gastro-oesophageal reflux disease was 11.0/100 000 person-years. The incidence was similar to that of the general population (standardised incidence ratio 1.04 (95% confidence interval 0.91 to 1.18)), and did not increase with longer follow-up (1.07 (0.65 to 1.65) for 15-31 years of follow-up). For validity reasons, we also analysed people with erosive oesophagitis at endoscopy (200 745 patients, 1 750 249 person-years, and 542 oesophageal adenocarcinomas, corresponding to an incidence rate of 31.0/100 000 person-years) showing an increased overall standardised incidence ratio of oesophageal adenocarcinoma (2.36 (2.17 to 2.57)), which became more pronounced with longer follow-up.ConclusionsPatients with non-erosive gastro-oesophageal reflux disease seem to have a similar incidence of oesophageal adenocarcinoma as the general population. This finding suggests that endoscopically confirmed non-erosive gastro-oesophageal reflux disease does not require additional endoscopic monitoring for oesophageal adenocarcinoma.

Project description:BACKGROUND:TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. METHODS:Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. RESULTS:In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40?-?82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1?-?5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6?-?4.9]), median time to progression (TTP) was 2.9 months (CI [1.4?-?4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. CONCLUSIONS:This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. TRIAL REGISTRATION:EU-CTR 2009-012097-12 2009-09-03.

Project description:IntroductionPerioperative chemotherapy is the gold standard treatment of the resectable gastro-oesophageal adenocarcinoma. However, 70% of patients cannot receive the complete sequence because of a postoperative complication or a decrease in functional and nutritional reserves. Recently, a new concept appeared in digestive surgery: prehabilitation. This interventional process consists of patient preparation, between surgical consultation and surgery, and is based on 3 components: (1) physical management, (2) nutritional care and (3) psychological care. Prehabilitation should decrease postoperative complications and improve nutritional and physical status during the preoperative and postoperative periods. Therefore, it is becoming essential to evaluate the effect of prehabilitation, compared to conventional care, on the percentage of patients reaching the complete oncological treatment.Methods and analysisThe PREHAB trial aimed to evaluate the efficacy of prehabilitation compared to conventional care, in patients with gastro-oesophageal cancer with perioperative chemotherapy. This trial is a prospective, randomised, controlled, open-blind and interventional study in 4 centres. Patients (n=60 per group) will be randomly assigned for management with either prehabilitation or conventional care. The primary outcome is the percentage of patients reaching the complete oncological treatment decided in a multidisciplinary tumour board. The secondary outcomes are the postoperative morbidity, disease-free survival, overall survival, feasibility of the protocol, length of stay, variation of the functional reserve after the preoperative chemotherapy (defined by the VO2peak, ventilatory threshold and 6-min walk test), preoperative and postoperative nutritional status, preoperative anxiety, quality of life, 30-day and 90-day mortality and cumulative dose of cytotoxic treatment received.Ethics and disseminationThe study was approved by an independent medical ethics committee (IRB00008526, CPP Sud-Est VI, Clermont-Ferrand, France) and by the competent French authority (ANSM, Saint Denis, France) and registered on Clinicaltrial.gov. The results will be disseminated in a peer-reviewed journal.Trial registration numberNCT02780921.

Project description:Background18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) may improve cancer staging by combining sensitive cancer detection with high-contrast resolution and detail. We compared the diagnostic performance of 18F-FDG PET/MRI to 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging oesophageal/gastro-oesophageal cancer. Following ethical approval and informed consent, participants with newly diagnosed primary oesophageal/gastro-oesophageal cancer were enrolled. Exclusions included prior/concurrent malignancy. Following 324 ± 28 MBq 18F-FDG administration and 60-min uptake, PET/CT was performed, immediately followed by integrated PET/MRI from skull base to mid-thigh. PET/CT was interpreted by two dual-accredited nuclear medicine physicians and PET/MRI by a dual-accredited nuclear medicine physician/radiologist and cancer radiologist in consensus. Per-participant staging was compared with the tumour board consensus staging using the McNemar test, with statistical significance at 5%.ResultsOut of 26 participants, 22 (20 males; mean ± SD age 68.8 ± 8.7 years) completed 18F-FDG PET/CT and PET/MRI. Compared to the tumour board, the primary tumour was staged concordantly in 55% (12/22) with PET/MRI and 36% (8/22) with PET/CT; the nodal stage was concordant in 45% (10/22) with PET/MRI and 50% (11/22) with PET/CT. There was no statistical difference in PET/CT and PET/MRI staging performance (p > 0.05, for T and N staging). The staging of distant metastases was concordant with the tumour board in 95% (21/22) with both PET/MRI and PET/CT. Of participants with distant metastatic disease, PET/MRI detected additional metastases in 30% (3/10).ConclusionIn this preliminary study, compared to 18F-FDG PET/CT, 18F-FDG PET/MRI showed non-significant higher concordance with T-staging, but no difference with N or M-staging. Additional metastases detected by 18F-FDG PET/MRI may be of additive clinical value.

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Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

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Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

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