Abstract
The MUNICON I trial confirmed prospectively the usefulness of early response evaluation by FDGPET and showed the feasibility of a PET guided treatment algorithm. Metabolic responders (R) showed initially a higher FDG-uptake compared to nonresponders (NR) (p = 0.018). An association of the VEGF 936C > T polymorphism and FDG-uptake was reported for breast cancer. Therefore we investigated the VEGF 936C > T polymorphism for an association with response and survival.
The study was based on the updated event free survival (EFS) (median EFS 21,1 + 4,6 months (m.)) of the 110 patients included in the MUNCON trial (103 male, 7 female; 75 AEG I, 35 AEG II). Clinical, histopathological and metabolic response were associated with EFS (p = 0.001, p = 0.001, p = 0.008). DNA was isolated from lymphozytes. Genotypes were determined by PCR and subsequent gel electrophoresis.
72 patients showed the CC, 24 the CT and 6 the TT genotype. For further analysis the T-variants (CT/TT), linked to lower VEGF levels were combined. No association of the genotypes (CC or CT/TT) with the SUV (baseline: p = 0.76, day 14: p = 0.53, decrease: p = 0.73) or response (clin: p = 0.24, histopath: p = 0.34, metabol.: p = 0.47) was found. EFS was 29.3 m. for CC, 11.7 m. for CT/TT (p = 0.04). Multivariate analysis revealed histopath. regression (p = 0.005; RR 2.7; 95 % CI 1.3–5.4) and genotype (p = 0.042; RR 0.56; 95 % CI 0.32–0.98) as prognostic factors. A combination of genotype and PET response (Gen-PET) defines 3 prognostic groups (p = 0.003) early in the course of treatment: A: R+CC: EFS 43.0 m.; B: NR+CC: EFS 19.1 m. or R+CT/TT: EFS 20.1 m.; C: NR+CT/TT: EFS 6.7 m. Cox regression analysis including (clin. and histopath. response, Gen-PET) reveals Gen-PET as independent prognostic factor (C: p = 0.004, reference; A: p = 0.001; RR 0.27; 95 % CI 0.13–0.59; B: p = 0.03; RR 0.47; 95 % CI 0.24–0.93).
The 936C>T polymorphism is not associated with FDG-uptake, predicts prognosis, but not response. An early determinable combination allows the definition of 3 groups with different prognosis, which might be used for therapy stratification in future, however needs to be confirmed prospectively.
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Ott, K. et al. (2008). PET basierte neoadjuvante Chemotherapie beim Adenokarzinom des gastroösophgealen Übergangs Typ I und II (MUNICON I): der VEGF 936C>T Polymorphismus ist prädiktiv für die Prognose. In: Arbogast, R., Schackert, H.K., Bauer, H. (eds) Chirurgisches Forum 2008. Deutsche Gesellschaft für Chirurgie, vol 37. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-78833-1_31
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DOI: https://doi.org/10.1007/978-3-540-78833-1_31
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