Adenocarcinomas of the Esophagogastric Junction
Conditions
Keywords
PET, response evaluation, neoadjuvant, radiochemotherapy, adenocarcinoma of the esophagogastric junction, esophageal carcinoma, evaluation of preoperative (radio)-chemotherapy in patients with adenocarcinomas of the oesophagogastric junction
Brief summary
Prospective, single-center, nonrandomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders Patients with resectable AEG (adenocarcinoma of the esophagogastric junction) type I and II (cT3/4 and/or cN+ and cM0) Metabolic non-responders, showing a \<35% decrease of SUV (standardized uptake value) two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (radiochemotherapy) before surgery. 18FDG-PET scans will be performed before (=Baseline) and after 14 days of standard neoadjuvant therapy as well after the first cycle of Taxotere/Cisplatin chemotherapy (=PET1) and at the end of intensified radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference Delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUVPET1 - SUVPET2 and histopathological response will be evaluated.
Detailed description
The HICON trial is a prospective, single-center, nonrandomized, explorative imaging study evaluating the value of PET (Positron emission tomography) as a predictor of histopathological response in metabolic non-responders Patients with resectable AEG (adenocarcinoma of the esophagogastric junction) type I and II, staged cT3/4 and/or cN+ and cM0 by endoscopic ultrasound, spiral CT or MRI and FDG-PET are eligible. Tumors must be potentially R0 resectable and must have a sufficient FDG-baseline uptake. Only metabolic non-responders, showing a \<35% decrease of SUV (standardized uptake value) two weeks after the start of neoadjuvant chemotherapy are eligible for the study and are taken to intensified taxane-based RCT (chemoradiotherapy (45 Gy) before surgery. 18FDG-PET scans will be performed before (=Baseline) and after 14 days of standard neoadjuvant therapy as well after the first cycle of Taxotere/Cisplatin chemotherapy (=PET1) and at the end of intensified radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference Delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUVPET1 - SUVPET2 and histopathological response will be evaluated..
Interventions
RADIATIONneoadjuvant radiochemotherapy in metabolic non responders
Metabolic non-responders, with a SUV decrease of less than 35%, discontinue induction chemotherapy and proceed to an intensified radiochemotherapy treatment
Sponsors
National Center for Tumor Diseases, Heidelberg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy-proven adenocarcinoma of the distal oesophagus (AEG type I) or cardia (AEG type II) with or without metastases in local lymph nodes (tumor stage cT3/T4, cNX, and cM0 in the tumor-node-metastasis classification) * Staging procedures include endoscopy, endoscopic ultrasound and computed tomography (CT) of the chest and abdomen. * Eligible patients have to be fit for platin-containing chemotherapy * Tumors must be potentially R0 resectable tumors during consecutive operation. * Tumors must have demonstrated a minimal amount of FDG-uptake in the baseline PET-CT, defined as 18FDG-uptake in tumor at first examination \> 1,35 x hepatic-SUV + 2 x standard-deviation of hepatic-SUV, and must be a metabolic non-responder under EOX, defined as a decrease of the SUVmax of \<35% in a second PET on day 14 of chemotherapy.
Exclusion criteria
* Eastern Cooperative Oncology Group score \>1 * Previous or secondary malignancy * Life expectancy of less than 3 months * Uncontrolled bleeding from the tumor * Tumor infiltration of the airways * Pregnancy * Uncontrolled diabetes * Patients are also ineligible if they have undergone previous chemotherapy, radiotherapy, or endoscopic laser therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between change in tumor metabolism (detected by PET) and histopathological response | PET Baseline, PET1 (before RCHT, week 5/6), histological examination of the resected tumor | The primary objective of the study is to evaluate the change in metabolic response - as measured by the relative difference delta SUV=100(SUVBaseline-SUVPET1)/ SUVBaseline in 18F-FDG uptake after 1 cycle of intensified taxan-based chemotherapy (PET1) - relative to the 18F-FDG uptake at the baseline examination, as a predictor of histopathological response in metabolic non-responders (assessed by PET 14 days after the start of neoadjuvant therapy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| distribution of change in tumor metabolism during the treatment in histological responders and non-responders | PET Baseline, PET1 (week 5/6), histological examination of the resected tumor | investigation of the distribution of change in tumor metabolism measured with PET Baseline and PET1(∆SUV = 100 (SUVBaseline - SUVPET1) / SUVBaseline) during the treatment in histological responders and non-responders according to the Becker Score (Histomorphology and grading of regression) |
| accuracy of the binary prediction rule reduction in the tumor metabolism >65% vs. <65% in histopathological responders vs. non-responders | Baseline, PET1 (week 5/6), histological examination of the resected tumor | accuracy of the binary prediction rule delta SUV \>65% vs. \<65% (reduction in the tumor metabolism \>65% vs. \<65 % between PET Baseline and PET1 in correlation with the histopathological regression accoring to the Becker Score |
| association between change in tumor metabolism before/after radiochemotherapy and histopathological response | PET1 (week 5/6), PET2 (before resection), histological examination of the resected tumor | association between tumor metabolism before/after radiochemotherapy (∆SUV = 100 (SUVPET1 - SUVPET2) / SUVPET1) and histopathological response according to the Becker Score (histomorphology and grading of regression) |
| association between change in tumor metabolism between PET Baseline and PET1 and overall survival as well as disease-free survival | Baseline, PET1 (week 5/6), Follow Up (q3 months during the first post-operative year, q6 months during the 2nd/3rd postoperative year) | association between change in tumor metabolism between PET Baseline and PET 1 (∆SUV = 100 (SUVBaseline - SUVPET1) / SUVBaseline)and overall survival as well as disease-free survival |
Countries
Germany
Outcome results
None listed