Skip to main content
Erschienen in: Journal of Gastrointestinal Cancer 2/2020

10.06.2019 | Original Research

Primary Tumor Location Is a Predictor of Poor Prognosis in Patients with Locally Advanced Esophagogastric Cancer Treated with Perioperative Chemotherapy

verfasst von: Tiago Cordeiro Felismino, Audrey Cabral Ferreira de Oliveira, Ana Caroline Fonseca Alves, Wilson Luiz da Costa Junior, Felipe José Fernadez Coimbra, Maria Dirlei Ferreira de Souza Begnami, Rachel P. Riechelmann, Victor Hugo Fonseca de Jesus, Celso Abdon Lopes de Mello

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 2/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

Esophagogastric cancer (EGC) is a leading neoplasm worldwide. Perioperative chemotherapy (periCT) is currently a standard of care for most patients (pts). Prevalence of esophagogastric junction (EGJ) tumors is increasing over the last years.

Methods

The aim of this study was to retrospectively search for prognostic factors in pts. with locally advanced EGC treated with periCT. Three-year overall survival (OS) and Event-Free Survival (EFS) were main end-points. HER-2 positive tumors were defined by immunohistochemistry or FISH.

Results

Between June/2007 and November/2015, 128 pts. started periCT for esophagogastric junction (EGJ) or gastric adenocarcinoma (GC). Median age was 59.5 y and 64% were male. Primary site was EGJ in 27% and 65% were cN+. Diffuse subtype was seen in 42%. Ninety-seven pts. were assessed for HER-2; 14 (14.4%) were positive. After median follow-up time of 45 m, 48 deaths occurred. The 3-year OS and EFS rate was 61.3% and 51.2%, respectively. Main prognostic factors were: AJCC ypT3-T4yN1-N3 (HR 6.75 p 0.002) and EGJ primary (HR 2.64, p 0.004). Overall HER-2 was not prognostic. Still, a difference in 3-year OS was observed for GC/HER2+ compared to EGJ/HER2+ (88.9% versus 20%, p = 0.002). This difference is greater for 3-year EFS with no patient with EGJ/HER2+ free-of-event against 62.5% for GC/HER+ (p = 0.011).

Conclusion

In our analysis, pathological staging and primary site were main prognostic factors. Moreover, a small group of EGJ/HER2+ had very poor survival.
Literatur
1.
Zurück zum Zitat Bray F, Ren JS, Masuyer E, Ferlay J. Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–45.CrossRef Bray F, Ren JS, Masuyer E, Ferlay J. Estimates of global cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013;132:1133–45.CrossRef
2.
Zurück zum Zitat Al-Batran S, Lorenzen S. Management of locally advanced gastroesophageal cancer: still a multidisciplinary global challenge? Hematol Oncol Clin North Am. 2013;31:441–52.CrossRef Al-Batran S, Lorenzen S. Management of locally advanced gastroesophageal cancer: still a multidisciplinary global challenge? Hematol Oncol Clin North Am. 2013;31:441–52.CrossRef
3.
Zurück zum Zitat Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRef Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345:725–30.CrossRef
4.
Zurück zum Zitat Cunningham D, Allum WH, Stenning SP, Allum WH, Stenning SP, Thompson JN, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef Cunningham D, Allum WH, Stenning SP, Allum WH, Stenning SP, Thompson JN, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef
5.
Zurück zum Zitat Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.CrossRef Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21.CrossRef
6.
Zurück zum Zitat Al Batran S-E, Homann N, Schmalenberg H, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial (abstract). J Clin Oncol 2017 (suppl; abstr 4004). Al Batran S-E, Homann N, Schmalenberg H, et al. Perioperative chemotherapy with docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) versus epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) for resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma (FLOT4-AIO): a multicenter, randomized phase 3 trial (abstract). J Clin Oncol 2017 (suppl; abstr 4004).
7.
Zurück zum Zitat Talamonti MS, Kim SP, Yao KA, Wayne JD, Feinglass J, Bennett CL, et al. Surgical outcomes of patients with gastric carcinoma: the importance of primary tumor location and microvessel invasion. Surgery. 2003;134:720–7.CrossRef Talamonti MS, Kim SP, Yao KA, Wayne JD, Feinglass J, Bennett CL, et al. Surgical outcomes of patients with gastric carcinoma: the importance of primary tumor location and microvessel invasion. Surgery. 2003;134:720–7.CrossRef
8.
Zurück zum Zitat Bruno L, Nesi G, Montinaro F, Carassale G, Lassig R, Boddi V, et al. Clinicopathologic findings and results of surgical treatment in cardiac adenocarcinoma. J Surg Oncol. 2000;74:33–5.CrossRef Bruno L, Nesi G, Montinaro F, Carassale G, Lassig R, Boddi V, et al. Clinicopathologic findings and results of surgical treatment in cardiac adenocarcinoma. J Surg Oncol. 2000;74:33–5.CrossRef
9.
Zurück zum Zitat Costa L, Toneto M, Moreira L. Do proximal and distal gastric turmors behave differently? Arquivos Brasileiros de Cirurgia Digestiva:ABCD. 2016;29:232–5.CrossRef Costa L, Toneto M, Moreira L. Do proximal and distal gastric turmors behave differently? Arquivos Brasileiros de Cirurgia Digestiva:ABCD. 2016;29:232–5.CrossRef
10.
Zurück zum Zitat Ychou M, Boige V, Pignon J-P, Conroy T, Bouché O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.CrossRef Ychou M, Boige V, Pignon J-P, Conroy T, Bouché O, Lebreton G, et al. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011;29:1715–21.CrossRef
11.
Zurück zum Zitat Ajani JA, In H, Sano T, et al. Stomach. In: Amin MB, editor. AJCC cancer staging manual, 8th. Chicago: AJCC; 2017. p. 203.CrossRef Ajani JA, In H, Sano T, et al. Stomach. In: Amin MB, editor. AJCC cancer staging manual, 8th. Chicago: AJCC; 2017. p. 203.CrossRef
12.
Zurück zum Zitat Smyth E, Fassan M, Cunningham D, et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol. 2016;34:2721–7.CrossRef Smyth E, Fassan M, Cunningham D, et al. Effect of pathologic tumor response and nodal status on survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. J Clin Oncol. 2016;34:2721–7.CrossRef
13.
Zurück zum Zitat Marchet A, Mocellin S, Ambrosi A, de Manzoni G, Di Leo A, Marrelli D, et al. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series. Eur J Surg Oncol. 2008;34:159–65.CrossRef Marchet A, Mocellin S, Ambrosi A, de Manzoni G, Di Leo A, Marrelli D, et al. The prognostic value of N-ratio in patients with gastric cancer: validation in a large, multicenter series. Eur J Surg Oncol. 2008;34:159–65.CrossRef
14.
Zurück zum Zitat Han DS, Suh YS, Kong SH, Lee HJ, Choi Y, Aikou S, et al. Nomogram predicting long-term survival after d2 gastrectomy for gastric cancer. J Clin Oncol. 2012;30:3834–40.CrossRef Han DS, Suh YS, Kong SH, Lee HJ, Choi Y, Aikou S, et al. Nomogram predicting long-term survival after d2 gastrectomy for gastric cancer. J Clin Oncol. 2012;30:3834–40.CrossRef
15.
Zurück zum Zitat Sohn BH, Hwang JE, Jang HJ, Lee HS, Oh SC, Shim JJ, et al. Clinical significance of four molecular subtypes of gastric cancer identified by the cancer genome atlas project. Clin Cancer Res. 2017;23:4441–9.CrossRef Sohn BH, Hwang JE, Jang HJ, Lee HS, Oh SC, Shim JJ, et al. Clinical significance of four molecular subtypes of gastric cancer identified by the cancer genome atlas project. Clin Cancer Res. 2017;23:4441–9.CrossRef
16.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRef Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.CrossRef
17.
Zurück zum Zitat Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes--a systematic review. Int J Cancer. 2012;130:2845–56.CrossRef Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes--a systematic review. Int J Cancer. 2012;130:2845–56.CrossRef
18.
Zurück zum Zitat Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York: Springer; 2010. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, editors. AJCC cancer staging manual (7th ed). New York: Springer; 2010.
19.
Zurück zum Zitat Kattan M, Karpeh M, Mazumdar M, Brennan M. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003;21:3647–50.CrossRef Kattan M, Karpeh M, Mazumdar M, Brennan M. Postoperative nomogram for disease-specific survival after an R0 resection for gastric carcinoma. J Clin Oncol. 2003;21:3647–50.CrossRef
20.
Zurück zum Zitat Schmidt T, Sicic L, Blank S, Becker K, Weichert W. Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas. Br J Cancer. 2014;110:1712–20.CrossRef Schmidt T, Sicic L, Blank S, Becker K, Weichert W. Prognostic value of histopathological regression in 850 neoadjuvantly treated oesophagogastric adenocarcinomas. Br J Cancer. 2014;110:1712–20.CrossRef
21.
Zurück zum Zitat Siewert J, MD FM, Werner M, Stein H. Adenocarcinoma of the esophagogastric junction results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232:353–61.CrossRef Siewert J, MD FM, Werner M, Stein H. Adenocarcinoma of the esophagogastric junction results of surgical therapy based on anatomical/topographic classification in 1,002 consecutive patients. Ann Surg. 2000;232:353–61.CrossRef
22.
Zurück zum Zitat Amin, MB, Edge, S, Greene, F, Byrd, DR, Brookland, RK, Washington, MK, et al. AJCC cancer staging manual (8th edition). Springer international publishing: American joint commission on Cancer; 2017. Amin, MB, Edge, S, Greene, F, Byrd, DR, Brookland, RK, Washington, MK, et al. AJCC cancer staging manual (8th edition). Springer international publishing: American joint commission on Cancer; 2017.
23.
Zurück zum Zitat Barbour AP, Rizk NP, Gonen M, Tang L, Bains MS, Rusch VW, et al. Adenocarcinoma of the gastroesophageal junction: influence of esophageal resection margin and operative approach on outcome. Ann Surg. 2007;246:1–8.CrossRef Barbour AP, Rizk NP, Gonen M, Tang L, Bains MS, Rusch VW, et al. Adenocarcinoma of the gastroesophageal junction: influence of esophageal resection margin and operative approach on outcome. Ann Surg. 2007;246:1–8.CrossRef
24.
Zurück zum Zitat van Hagen P, Hulshof MC, van Lanschot JJ, et al. CROSS group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;31(366):2074–84.CrossRef van Hagen P, Hulshof MC, van Lanschot JJ, et al. CROSS group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;31(366):2074–84.CrossRef
25.
Zurück zum Zitat Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, et al. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017;81:183–90.CrossRef Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, et al. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017;81:183–90.CrossRef
26.
Zurück zum Zitat Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen AB, Friesland S, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016;27:660–7.CrossRef Klevebro F, Alexandersson von Döbeln G, Wang N, Johnsen G, Jacobsen AB, Friesland S, et al. A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction. Ann Oncol. 2016;27:660–7.CrossRef
27.
Zurück zum Zitat Al-Batran S, Pauligk C, Homann N, et al. Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO). Presented at: ESMO 2017 congress; Madrid, Spain: September 8–12, 2017. Abstract LBA27. Al-Batran S, Pauligk C, Homann N, et al. Docetaxel, oxaliplatin, and fluorouracil/leucovorin (FLOT) for resectable esophagogastric cancer: updated results from multicenter, randomized phase 3 FLOT4-AIO trial (German Gastric Group at AIO). Presented at: ESMO 2017 congress; Madrid, Spain: September 8–12, 2017. Abstract LBA27.
28.
Zurück zum Zitat Gordon MA, Gundacker HM, Benedetti J, Macdonald JS, Baranda JC, Levin WJ, et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol. 2013;24:1754–61.CrossRef Gordon MA, Gundacker HM, Benedetti J, Macdonald JS, Baranda JC, Levin WJ, et al. Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. Ann Oncol. 2013;24:1754–61.CrossRef
29.
Zurück zum Zitat Okines AF, Thompson LC, Cunningham D, et al. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol. 2013;24:1253–61.CrossRef Okines AF, Thompson LC, Cunningham D, et al. Effect of HER2 on prognosis and benefit from peri-operative chemotherapy in early oesophago-gastric adenocarcinoma in the MAGIC trial. Ann Oncol. 2013;24:1253–61.CrossRef
30.
Zurück zum Zitat Maresch J, Schoppmann S, Thallinger C, Zielinski C, et al. Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: from pathology to treatment. Crit Rev Oncol Hematol. 2012;82:310–22.CrossRef Maresch J, Schoppmann S, Thallinger C, Zielinski C, et al. Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: from pathology to treatment. Crit Rev Oncol Hematol. 2012;82:310–22.CrossRef
31.
Zurück zum Zitat Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res. 2012;18:5992–6000.CrossRef Terashima M, Kitada K, Ochiai A, Ichikawa W, Kurahashi I, Sakuramoto S, et al. Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res. 2012;18:5992–6000.CrossRef
32.
Zurück zum Zitat Begnami MD, Fukuda E, Fregnani JH, et al. Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol. 2011;29:3030–6.CrossRef Begnami MD, Fukuda E, Fregnani JH, et al. Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol. 2011;29:3030–6.CrossRef
Metadaten
Titel
Primary Tumor Location Is a Predictor of Poor Prognosis in Patients with Locally Advanced Esophagogastric Cancer Treated with Perioperative Chemotherapy
verfasst von
Tiago Cordeiro Felismino
Audrey Cabral Ferreira de Oliveira
Ana Caroline Fonseca Alves
Wilson Luiz da Costa Junior
Felipe José Fernadez Coimbra
Maria Dirlei Ferreira de Souza Begnami
Rachel P. Riechelmann
Victor Hugo Fonseca de Jesus
Celso Abdon Lopes de Mello
Publikationsdatum
10.06.2019
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 2/2020
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-019-00258-1

Weitere Artikel der Ausgabe 2/2020

Journal of Gastrointestinal Cancer 2/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.