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Gastric Cancer
Published in: Gastric Cancer 3/2014

01-07-2014 | Original Article

Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis

Authors: Ulrike Heger, Franz Bader, Florian Lordick, Maria Burian, Rupert Langer, Martin Dobritz, Susanne Blank, Thomas Bruckner, Karen Becker, Ken Herrmann, Jörg-Rüdiger Siewert, Katja Ott

Published in: Gastric Cancer | Issue 3/2014

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Abstract

Background

Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis.

Methods

Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass.

Results

Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009).

Conclusions

Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.
Literature
1.
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.PubMedCrossRef
2.
Schuhmacher C, Gretschel S, Lordick F, Reichardt P, Hohenberger W, Eisenberger CF, Haag C, Mauer ME, Hasan B, Welch J, et al. Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954. J Clin Oncol. 2010;28(35):5210–8.PubMedCentralPubMedCrossRef
3.
Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, 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(13):1715–21.PubMedCrossRef
4.
Becker K, Reim D, Novotny A, ZumBuschenfelde CM, Engel J, Friess H, Hofler H, Langer R. Proposal for a multifactorial prognostic score that accurately classifies three groups of gastric carcinoma patients with different outcomes after neoadjuvant chemotherapy and surgery. Ann Surg. 2012;256(6):1002–7.PubMedCrossRef
5.
Blank S, Blaker H, Schaible A, Lordick F, Grenacher L, Buechler M, Ott K. Impact of pretherapeutic routine clinical staging for the individualization of treatment in gastric cancer patients. Langenbecks Arch Surg/Dtsch Ges Chir. 2012;397(1):45–55.CrossRef
6.
Ott K, Blank S, Becker K, Langer R, Weichert W, Roth W, Sisic L, Stange A, Jager D, Buchler M, et al. Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10% residual tumor. Langenbecks Arch Surg/Dtsch Ges Chir. 2013;398(2):239–49.CrossRef
7.
Lowy AM, Mansfield PF, Leach SD, Pazdur R, Dumas P, Ajani JA. Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer. Ann Surg. 1999;229(3):303–8.PubMedCentralPubMedCrossRef
8.
Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24(24):3953–8.PubMedCrossRef
9.
Hirakawa M, Sato Y, Ohnuma H, Takayama T, Sagawa T, Nobuoka T, Harada K, Miyamoto H, Sato Y, Takahashi Y, et al. A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker. Cancer Chemother Pharmacol. 2013;71(3):789–97.PubMedCrossRef
10.
Ott K, Sendler A, Becker K, Dittler HJ, Helmberger H, Busch R, Kollmannsberger C, Siewert JR, Fink U. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6(3):159–67.PubMedCrossRef
11.
Weber WA, Petersen V, Schmidt B, Tyndale-Hines L, Link T, Peschel C, Schwaiger M. Positron emission tomography in non-small-cell lung cancer: prediction of response to chemotherapy by quantitative assessment of glucose use. J Clin Oncol. 2003;21(14):2651–7.PubMedCrossRef
12.
Bader FG, Lordick F, Fink U, Becker K, Hofler H, Busch R, Siewert JR, Ott K. Paclitaxel in the neoadjuvant treatment for adenocarcinoma of the distal esophagus (AEG I). A comparison of two phase II trials with long-term follow-up. Onkologie. 2008;31(7):366–72.PubMedCrossRef
13.
Lorenzen S, Blank S, Lordick F, Siewert JR, Ott K. Prediction of response and prognosis by a score including only pretherapeutic parameters in 410 neoadjuvant treated gastric cancer patients. Ann Surg Oncol. 2012;19(7):2119–27.PubMedCrossRef
14.
Stocker G, Ott K, Henningsen N, Becker K, Hapfelmeier A, Lordick F, Hois S, Plaschke S, Hofler H, Keller G. Cyclin D1 and interleukin-1 receptor antagonist polymorphisms are associated with prognosis in neoadjuvant-treated gastric carcinoma. Eur J Cancer. 2009;45(18):3326–35.PubMedCrossRef
15.
Fink U, Schuhmacher C, Stein HJ, Busch R, Feussner H, Dittler HJ, Helmberger A, Bottcher K, Siewert JR. Preoperative chemotherapy for stage III–IV gastric carcinoma: feasibility, response and outcome after complete resection. Br J Surg. 1995;82(9):1248–52.PubMedCrossRef
16.
Schuhmacher CP, Fink U, Becker K, Busch R, Dittler HJ, Mueller J, Siewert JR. Neoadjuvant therapy for patients with locally advanced gastric carcinoma with etoposide, doxorubicin, and cisplatinum. Closing results after 5 years of follow-up. Cancer (Phila). 2001;91(5):918–27.CrossRef
17.
Ott K, Fink U, Becker K, Stahl A, Dittler HJ, Busch R, Stein H, Lordick F, Link T, Schwaiger M, et al. Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial. J Clin Oncol. 2003;21(24):4604–10.PubMedCrossRef
18.
Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, Wieder H, Fink U, Schwaiger M, Siewert JR. Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2006;24(29):4692–8.PubMedCrossRef
19.
Weber WA, Ott K, Becker K, Dittler HJ, Helmberger H, Avril NE, Meisetschlager G, Busch R, Siewert JR, Schwaiger M, et al. Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol. 2001;19(12):3058–65.PubMed
20.
Ott K, Herrmann K, Lordick F, Wieder H, Weber WA, Becker K, Buck AK, Dobritz M, Fink U, Ulm K, et al. Early metabolic response evaluation by fluorine-18 fluorodeoxyglucose positron emission tomography allows in vivo testing of chemosensitivity in gastric cancer: long-term results of a prospective study. Clin Cancer Res. 2008;14(7):2012–8.PubMedCrossRef
21.
Ott K, Herrmann K, Schuster T, Langer R, Becker K, Wieder HA, Wester HJ, Siewert JR, zum Buschenfelde CM, Buck AK, et al. Molecular imaging of proliferation and glucose utilization: utility for monitoring response and prognosis after neoadjuvant therapy in locally advanced gastric cancer. Ann Surg Oncol. 2011;18(12):3316–23.PubMedCrossRef
22.
Blank S, Lordick F, Dobritz M, Grenacher L, Burian M, Langer R, Roth W, Schaible A, Becker K, Blaker H, et al. A reliable risk score for stage IV esophagogastric cancer. Eur J Surg Oncol. 2013;39(8):823–30.PubMedCrossRef
23.
Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, et al. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol. 2007;8(9):797–805.PubMedCrossRef
24.
zum Buschenfelde CM, Herrmann K, Schuster T, Geinitz H, Langer R, Becker K, Ott K, Ebert M, Zimmermann F, Friess H, et al. 18F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J Nucl Med. 2011;52(8):1189–96.PubMedCrossRef
25.
Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma, 2nd English edition. Response assessment of chemotherapy and radiotherapy for gastric carcinoma: clinical criteria. Gastric Cancer. 2001;4(1):1–8.CrossRef
26.
Becker K, Mueller JD, Schulmacher C, Ott K, Fink U, Busch R, Bottcher K, Siewert JR, Hofler H. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer (Phila). 2003;98(7):1521–30.CrossRef
27.
Wilke H, Meyer HJ, Fink U. Preoperative chemotherapy in gastric cancer. Fortschr Krebsforsch (Recent Results Cancer Res). 1996;142:237–48.CrossRef
28.
Ajani JA, Ota DM, Jessup JM, Ames FC, McBride C, Boddie A, Levin B, Jackson DE, Roh M, Hohn D. Resectable gastric carcinoma. An evaluation of preoperative and postoperative chemotherapy. Cancer (Phila). 1991;68(7):1501–6.CrossRef
29.
Homann N, Pauligk C, Luley K, Werner Kraus T, Bruch HP, Atmaca A, Noack F, Altmannsberger HM, Jager E, Al-Batran SE. Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel. Int J Cancer. 2012;130(7):1706–13.PubMedCrossRef
30.
Janunger KG, Hafstrom L, Nygren P, Glimelius B, Care SB-gSCoTAiH. A systematic overview of chemotherapy effects in gastric cancer. Acta Oncol. 2001;40(2):309–26.PubMedCrossRef
31.
Bollschweiler E, Metzger R, Drebber U, Baldus S, Vallbohmer D, Kocher M, Holscher AH. Histological type of esophageal cancer might affect response to neo-adjuvant radiochemotherapy and subsequent prognosis. Ann Oncol. 2009;20(2):231–8.PubMedCrossRef
32.
Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani JA, Kocha W, Minsky BD, Roth JA, et al. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007;25(24):3719–25.PubMedCrossRef
33.
Schneider PM, Metzger R, Schaefer H, Baumgarten F, Vallbohmer D, Brabender J, Wolfgarten E, Bollschweiler E, Baldus SE, Dienes HP, et al. Response evaluation by endoscopy, rebiopsy, and endoscopic ultrasound does not accurately predict histopathologic regression after neoadjuvant chemoradiation for esophageal cancer. Ann Surg. 2008;248(6):902–8.PubMedCrossRef
34.
Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, Komaki R, Macapinlac H, Munden RF, Putnam JB, et al. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg. 2004;78(4):1152–60 (discussion 1152–1160).PubMedCrossRef
35.
Helmberger H 3rd, Baum U, Dittler HJ, Sendler A, Schulte B, Herter B, Fink U, Gerhardt P. Adenocarcinoma of the gastro-esophageal junction: CT for monitoring during neoadjuvant chemotherapy. Eur J Radiol. 1996;23(2):107–10.PubMedCrossRef
36.
Jost C, Binek J, Schuller JC, Bauerfeind P, Metzger U, Werth B, Knuchel J, Frossard J-L, Bertschinger P, Brauchli P, et al. Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02). Gastrointest Endosc. 2010;71(7):1114–21.PubMedCrossRef
37.
Chak A, Canto MI, Cooper GS, Isenberg G, Willis J, Levitan N, Clayman J, Forastiere A, Heath E, Sivak MV Jr. Endosonographic assessment of multimodality therapy predicts survival of esophageal carcinoma patients. Cancer (Phila). 2000;88(8):1788–95.CrossRef
38.
Willis J, Cooper GS, Isenberg G, Sivak MV Jr, Levitan N, Clayman J, Chak A. Correlation of EUS measurement with pathologic assessment of neoadjuvant therapy response in esophageal carcinoma. Gastrointest Endosc. 2002;55(6):655–61.PubMedCrossRef
39.
van Heijl M, Phoa SSKS, van Berge Henegouwen MI, Omloo JMT, Mearadji BM, Sloof GW, Bossuyt PMM, Hulshof MCCM, Richel DJ, Bergman JJGHM, et al. Accuracy and reproducibility of 3D-CT measurements for early response assessment of chemoradiotherapy in patients with oesophageal cancer. Eur J Surg Oncol. 2011;37(12):1064–71.PubMedCrossRef
40.
Hirata N, Kawamoto K, Ueyama T, Masuda K, Utsunomiya T, Kuwano H. Using endosonography to assess the effects of neoadjuvant therapy in patients with advanced esophageal cancer. AJR Am J Roentgenol. 1997;169(2):485–91.PubMedCrossRef
41.
Mesenas S, Vu C, McStay M, Forshaw M, Doig L, Mason R, Boyle N, Meenan J. A large series, resection controlled study to assess the value of radial EUS in restaging gastroesophageal cancer following neoadjuvant chemotherapy. Dis Esophagus. 2008;21(1):37–42.PubMed
42.
Isenberg G, Chak A, Canto MI, Levitan N, Clayman J, Pollack BJ, Sivak MV Jr. Endoscopic ultrasound in restaging of esophageal cancer after neoadjuvant chemoradiation. Gastrointest Endosc. 1998;48(2):158–63.PubMedCrossRef
43.
Shinkai M, Niwa Y, Arisawa T, Ohmiya N, Goto H, Hayakawa T. Evaluation of prognosis of squamous cell carcinoma of the oesophagus by endoscopic ultrasonography. Gut. 2000;47(1):120–5.PubMedCentralPubMedCrossRef
44.
Park SR, Choi IJ, Kim CG, Kim YW, Ryu KW, Lee JH, Lee JS, Bae JM, Kim HK. Use of a combination of computed tomography and endoscopy to assess the response to 5-fluorouracil/cisplatin and predict survival in gastric cancer. J Gastroenterol. 2006;41(4):339–46.PubMedCrossRef
45.
Lim JTW, Truong PT, Berthelet E, Pai H, Joe H, Wai E, Larsson S, Kader HA, Weinerman B, Wilson K, et al. Endoscopic response predicts for survival and organ preservation after primary chemoradiotherapy for esophageal cancer. Int J Radiat Oncol Biol Phys. 2003;57(5):1328–35.PubMedCrossRef
46.
Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer (Phila). 1981;47(1):207–14.CrossRef
47.
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205–16.PubMedCrossRef
48.
Beseth BD, Bedford R, Isacoff WH, Holmes EC, Cameron RB. Endoscopic ultrasound does not accurately assess pathologic stage of esophageal cancer after neoadjuvant chemoradiotherapy. Am Surg. 2000;66(9):827–31.PubMed
49.
Beer AJ, Wieder HA, Lordick F, Ott K, Fischer M, Becker K, Stollfuss J, Rummeny EJ. Adenocarcinomas of esophagogastric junction: multi-detector row CT to evaluate early response to neoadjuvant chemotherapy. Radiology. 2006;239(2):472–80.PubMedCrossRef
Metadata
Title
Interim endoscopy results during neoadjuvant therapy for gastric cancer correlate with histopathological response and prognosis
Authors
Ulrike Heger
Franz Bader
Florian Lordick
Maria Burian
Rupert Langer
Martin Dobritz
Susanne Blank
Thomas Bruckner
Karen Becker
Ken Herrmann
Jörg-Rüdiger Siewert
Katja Ott
Publication date
01-07-2014
Publisher
Springer Japan
Published in
Gastric Cancer / Issue 3/2014
Print ISSN: 1436-3291
Electronic ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-013-0296-0

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