TY  - JOUR
A1  - Hacker, Ulrich T.
A1  - Escalona-Espinosa, Laura
A1  - Consalvo, Nicola
A1  - Goede, Valentin
A1  - Schiffmann, Lars
A1  - Scherer, Stefan J.
A1  - Hedge, Priti
A1  - Van Cutsem, Eric
A1  - Coutelle, Oliver
A1  - Büning, Hildegard
T1  - Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial
JF  - British Journal of Cancer
N2  - Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. 
Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml\(^-\)\(^1\)) vs non-Asian patients (3193 pg ml\(^-\)\(^1\)), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml\(^-\)\(^1\) increase: 1.19; 95% CI 1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13-1.64; P = 0.0010 (Asians). 
Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.
KW  - gastric cancer
KW  - angiogenesis
KW  - Angiopoietin-2
KW  - bevacizumab
KW  - liver metastasis
KW  - biomarker
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189578
VL  - 114
IS  - 8
ER  - 
TY  - JOUR
A1  - Lichthardt, Sven
A1  - Kerscher, Alexander
A1  - Dietz, Ulrich A.
A1  - Jurowich, Christian
A1  - Kunzmann, Volker
A1  - von Rahden, Burkhard H. A.
A1  - Germer, Christoph-Thomas
A1  - Wiegering, Armin
T1  - Original article: role of adjuvant chemotherapy in a perioperative chemotherapy regimen for gastric cancer
JF  - BMC Cancer
N2  - Background

Multimodal treatment strategies – perioperative chemotherapy (CTx) and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer. However, the role of adjuvant postoperative CTx (postCTx) in addition to neoadjuvant preoperative CTx (preCTx) in this setting remains controversial.

Methods

Between 4/2006 and 12/2013, 116 patients with locally advanced gastric cancer were treated with preCTx. 72 patients (62 %), in whom complete tumor resection (R0, subtotal/total gastrectomy with D2-lymphadenectomy) was achieved, were divided into two groups, one of which receiving adjuvant therapy (n = 52) and one without (n = 20). These groups were analyzed with regard to survival and exclusion criteria for adjuvant therapy.

Results

Postoperative complications, as well as their severity grade, did not correlate with fewer postCTx cycles administered (p = n.s.). Long-term survival was shorter in patients receiving postCTx in comparison to patients without postCTx, but did not show statistical significance. In per protocol analysis by excluding two patients with perioperative death, a shorter 3-year survival rate was observed in patients receiving postCTx compared to patients without postCTx (3-year survival: 71.2 % postCTx group vs. 90.0 % non-postCTx group; p = 0.038).

Conclusion

These results appear contradicting to the anticipated outcome. While speculative, they question the value of post-CTx. Prospectively randomized studies are needed to elucidate the role of postCTx.
KW  - gastric cancer
KW  - chemotherapy
KW  - neoadjuvant
KW  - multimodal
KW  - complication
KW  - adjuvant
KW  - risk factor
KW  - survival
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147743
VL  - 16
IS  - 650
ER  -