Association between tumor response and postoperative morbidity after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma?

Ronellenfitsch, Ulrich; Liodaki, Eirini; Trunk, Marcus J.; Hahn, M; Liodakis, E.; Hofheinz, Ralf–Dieter; Post, Stefan; Kienle, Peter

doi:10.20517/2572-8180.2016.01

Cited by 2 publications

(1 citation statement)

References 36 publications

(42 reference statements)

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“…However, not all patients benefit from this still very standardized treatment routines, developing only significant toxic side effects. This is the case in 35% of patients undergoing chemoradiation and 39% of patients under chemotherapy (Ronellenfitsch et al 2016 ; den Bakker et al 2017 ). This clinical dilemma is due to the fact that EAC is a genetic extremely heterogenous disease.…”

Section: Introductionmentioning

confidence: 99%

GATA binding protein 6 (GATA6) is co-amplified with PIK3CA in patients with esophageal adenocarcinoma and is linked to neoadjuvant therapy

Plum

Löser²,

Zander

et al. 2020

J Cancer Res Clin Oncol

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Purpose Driver mutations are typically absent in esophageal adenocarcinoma (EAC). Mostly, oncogenes are amplified as driving molecular events (including GATA6-amplification in 14% of cases). However, only little is known about its biological function and clinical relevance. Methods We examined a large number of EAC (n = 496) for their GATA6 amplification by fluorescence in situ hybridization (FISH) analyzing both primary resected (n = 219) and neoadjuvant treated EAC (n = 277). Results were correlated to clinicopathological data and known mutations/amplifications in our EAC-cohort. Results GATA6 amplification was detectable in 49 (9.9%) EACs of our cohort. We observed an enrichment of GATA6-positive tumors among patients after neoadjuvant treatment (12,3% amplified tumors versus 6,8% in the primary resected group; p = 0.044). Additionally, there was a simultaneous amplification of PIK3CA and GATA6 (p < 0.001) not detectable when analyzing other genes such as EGFR, ERBB2, KRAS or MDM2. Although we did not identify a survival difference depending on GATA6 in the entire cohort (p = 0.212), GATA6 amplification was associated with prolonged overall survival among patients with primary surgery (median overall-survival 121.1 vs. 41.4 months, p = 0.032). Multivariate cox-regression analysis did not confirm GATA6 as an independent prognostic marker, neither in the entire cohort (p = 0.210), nor in the subgroup with (p = 0.655) or without pretreatment (p = 0.961). Conclusions Our study investigates the relevance of GATA6 amplification on a large tumor collective, which includes primary resected tumors and the clinically relevant group of neoadjuvant treated EACs. Especially in the pretreated group, we found an accumulation of GATA6-amplified tumors (12.3%) and a frequent co-amplification of PIK3CA. Our data suggest an increased resistance to radio-chemotherapy in GATA6-amplified tumors.

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Section: Introductionmentioning

confidence: 99%