Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma.
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ABSTRACT:
SUBMITTER: Tomita Y
PROVIDER: S-EPMC8094513 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Publications
Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma.
Tomita Yoko Y Moldovan Max M Chang Lee Rachael R Hsieh Amy Hc AH Townsend Amanda A Price Timothy T
The Cochrane database of systematic reviews 20201119
<h4>Background</h4>Salvage systemic therapy has become the new standard of care in patients with advanced gastric and oesophago-gastric junction (OGJ) adenocarcinoma, following disease progression on first-line fluoropyrimidine and platinum-containing chemotherapy. Pharmacological agents proven to be effective in this setting include both chemotherapy and biological therapy, however, the consensus on the best salvage systemic therapy has not been reached.<h4>Objectives</h4>To assess the effects ...[more]
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Project description:Background18-Fluorodeoxyglucose-PET (18F-FDG-PET) can be used for early response assessment in patients with locally advanced adenocarcinomas of the oesophagogastric junction (AEG) undergoing neoadjuvant chemotherapy. It has been recently shown in the MUNICON trials that response-guided treatment algorithms based on early changes of the FDG tumor uptake detected by PET are feasible and that they can be implemented into clinical practice. Only 40%-50% of the patients respond metabolically to therapy. As metabolic non-response is known to be associated with a dismal prognosis, metabolic non-responders are increasingly treated with alternative neoadjuvant chemotherapies or chemoradiation in order to improve their clinical outcome. We plan to investigate whether PET can be used as response assessment during radiochemotherapy given as salvage treatment in early metabolic non-responders to standard chemotherapy.Methods/designThe HICON trial is a prospective, non-randomized, explorative imaging study evaluating the value of PET as a predictor of histopathological response in metabolic non-responders. Patients with resectable AEG type I and II according to Siewerts classification, 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 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 as after the first cycle of salvage docetaxel/cisplatin chemotherapy (PET 1) and at the end of radiochemotherapy (PET2). Tracer uptake will be assessed semiquantitatively using standardized uptake values (SUV). The percentage difference ΔSUV = 100 (SUV Baseline - SUV PET1)/SUV Baseline will be calculated and assessed as an early predictor of histopathological response. In a secondary analysis, the association between the difference SUV PET1 - SUV PET2 and histopathological response will be evaluated.DiscussionThe aim of this study is to investigate the potential of sequential 18FDG-PET in predicting histopathological response in AEG tumors to salvage neoadjuvant radiochemotherapy in patients who do not show metabolic response to standard neoadjuvant chemotherapy.
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Project description:BackgroundThis study aimed to identify microRNAs (miRs) as circulating biomarkers of resistance to first-line trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients.MethodsA high-throughput 1015 Exiqon miRCURY LNA™ microRNA inhibitor library screen was performed in trastuzumab-treated HER2-positive NCI-N87 and HER2-negative FLO-1 oesophago-gastric cancer cell lines. NanoString nCounter® miR analysis was performed in NCI-N87, FLO-1, and MAGIC trial (ISRCTN93793971) formalin-fixed paraffin-embedded (FFPE) oesophago-gastric cancer patient samples. MiR-148a-3p copies in plasma samples were quantified using digital droplet polymerase chain reaction (ddPCR) from HER2-positive oesophago-gastric cancer patients treated with standard-of-care trastuzumab-based therapy within the FOrMAT (NCT02112357) and PLATFORM (NCT02678182) clinical trials. The primary endpoints were overall survival (OS) for plasma miR-148a-3p HIGH (>median) versus LOW (≤median). The secondary endpoints were progression-free survival (PFS) and 3-month progression-free rates (PFRs) miR-148a-3p HIGH versus LOW. PLATFORM sensitivity analysis normalised miR-148a-3p (NmiR-148a-3p).ResultsThe inhibition of miR-148a-3p reduced NCI-N87 relative cell viability (<0.6) and expression was high (>242) in NCI-N87 and HER2-positive MAGIC trial patients (n=5). Normalised-miR-148a-3p (NmiR-148a-3p) LOW versus HIGH demonstrated a statistically significant difference in 3-month PFRs (n=23; OR, 0.11 [0.02-0.78]; p=0.027; aOR, 0.03 [0.001-0.71], p=0.029) but no difference in OS or PFS. There was no statistically significant relationship between miR-148-3p LOW versus HIGH for OS (PLATFORM, n=62; hazard ratio [HR], 0.98 [0.57-1.66]; p=0.933; FOrMAT, n=8; HR, 0.54 [0.13-2.31]; p=0.322), PFS (n=62; HR, 1.08 [0.65-1.81]; p=0.759; FOrMAT, n=8; HR, 1.26 [0.31-5.07]; p=0.714), or PFRs (PLATFORM, n=31; odds ratio [OR], 0.67 [0.2-2.8]; p=0.577).ConclusionNormalised miR-148a-3p may be a relevant biomarker for trastuzumab-based therapy in advanced HER2-positive oesophago-gastric cancer patients.
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