Original Research| Volume 90, P26-33, February 2018

Histopathological regression predicts treatment outcome in locally advanced esophagogastric adenocarcinoma

Published:December 19, 2017DOI:


      • Histopathological complete/subtotal response is more frequent in intestinal-type esophagogastric adenocarcinoma (EGA).
      • The histological subtype is predictive on histopathological response.
      • Histopathological regression is a prognostic marker in EGA.



      Neoadjuvant chemotherapy (neoCTx) improves survival outcomes of patients with localised esophagogastric adenocarcinoma (EGA). This analysis evaluates the predictive value of histopathological response after neoCTx.


      A total of 461 patients with locally advanced EGA (≥T2 and/or N+) who received neoCTx followed by surgery were analysed: 314 (68.1%) with intestinal, 94 (20.4%) with diffuse and 53 (11.5%) with mixed histological type according to Lauren classification. Histopathological response evaluation was available for 363 patients and performed locally. This analysis evaluates the predictive value of histopathological subtype on histopathological response after neoCTx. Response was correlated with survival.


      Median patients' age was 63 years, 79.8% were male. Tumours were localised in the stomach in 32.5% and EG junction in 67.5% of the patients. With a median follow-up of 49.4 months, median disease-free (DFS) and overall survival (OS) were 38.0 and 66.4 months, respectively.
      Pathological complete response (TRG1a) was 8.8% and combined complete and subtotal regression (TRG1a/b) was 27.3% for all patients. Around 9.2% of patients with intestinal type had a TRG1a compared with 6.2% with diffuse and 10.8% with mixed type. TRG1a/b rate was higher in intestinal (31.0%) than in diffuse (15.4%) and in mixed type (21.6%).
      For patients with intestinal type, 3-year DFS was 78.4% with TRG1a and 54.3% with other regression grades (p = 0.031). All patients with diffuse and mixed type and TRG1a were disease free after 3 years compared with 31.1% (p = 0.056) and 47.7% (p = 0.044) with other regression grades.


      Histopathological subtype is predictive for histopathological response and outcome after neoCTx, with the highest response rates in intestinal differentiated EGA.


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        • Cunningham D.
        • Allum W.H.
        • Stenning S.P.
        • Thompson J.N.
        • VandeVelde C.J.
        • Nicolson M.
        • et al.
        Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.
        N Engl J Med. 2006; 355: 11-20
        • Ychou M.
        • Boige V.
        • Pignon J.P.
        • Conroy T.
        • Bouche 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: 1715-1721
        • Bamboat Z.M.
        • Tang L.H.
        • Vinuela E.
        • Kuk D.
        • Gonen M.
        • Shah M.A.
        • et al.
        Stage-stratified prognosis of signet ring cell histology in patients undergoing curative resection for gastric adenocarcinoma.
        Ann Surg Oncol. 2014; 21: 1678-1685
        • Reim D.
        • Loos M.
        • Vogl F.
        • Novotny A.
        • Schuster T.
        • Langer R.
        • et al.
        Prognostic implications of the seventh edition of the international union against cancer classification for patients with gastric cancer: the Western experience of patients treated in a single-center European institution.
        J Clin Oncol. 2013; 31: 263-271
        • Ronellenfitsch U.
        • Schwarzbach M.
        • Hofheinz R.
        • Kienle P.
        • Kieser M.
        • Slanger T.E.
        • et al.
        Preoperative chemo(radio)therapy versus primary surgery for gastroesophageal adenocarcinoma: systematic review with meta-analysis combining individual patient and aggregate data.
        Eur J Cancer. 2013; 49: 3149-3158
        • Al-Batran S.E.
        • Hofheinz R.D.
        • Pauligk C.
        • Kopp H.G.
        • Haag G.M.
        • Luley K.B.
        • et al.
        Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial.
        Lancet Oncol. 2016; 17: 1697-1708
        • Messager M.
        • Lefevre J.H.
        • Pichot-Delahaye V.
        • Souadka A.
        • Piessen G.
        • Mariette C.
        • et al.
        The impact of perioperative chemotherapy on survival in patients with gastric signet ring cell adenocarcinoma: a multicenter comparative study.
        Ann Surg. 2011; 254 (discussion 693): 684-693
        • Burzikowsky T.
        • Bang Y.
        • on behalf of the GASTRIC project
        Disease-free survival as a surrogate endpoint for overall survival in an adjuvant trial of curatively resected stomach cancer using individual patient data meta-analysis.
        J Clin Oncol. 2009; 27 (15s. suppl; abstr 4517)
        • Lauren P.
        The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification.
        Acta Pathol Microbiol Scand. 1965; 64: 31-49
        • Becker K.
        • Langer R.
        • Reim D.
        • Novotny A.
        • MeyerzumBuschenfelde C.
        • Engel J.
        • et al.
        Significance of histopathological tumor regression after neoadjuvant chemotherapy in gastric adenocarcinomas: a summary of 480 cases.
        Ann Surg. 2011; 253: 934-939
        • Becker K.
        • Mueller J.D.
        • Schulmacher C.
        • Ott K.
        • Fink U.
        • Busch R.
        • et al.
        Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy.
        Cancer. 2003; 98: 1521-1530
        • Homann N.
        • Pauligk C.
        • Luley K.
        • Kraus T.W.
        • Bruch H.P.
        • Atmaca A.
        • et al.
        Pathological complete remission in patients with oesophagogastric cancer receiving preoperative 5-fluorouracil, oxaliplatin and docetaxel.
        Int J Cancer. 2012; 130: 1706-1713
        • Hamada M.
        • Fujiwara T.
        • Hizuta A.
        • Gochi A.
        • Naomoto Y.
        • Takakura N.
        • et al.
        The p53 gene is a potent determinant of chemosensitivity and radiosensitivity in gastric and colorectal cancers.
        J Cancer Res Clin Oncol. 1996; 122: 360-365
        • Ji Q.
        • Hao X.
        • Meng Y.
        • Zhang M.
        • Desano J.
        • Fan D.
        • et al.
        Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres.
        BMC Cancer. 2008; 2008: 266
        • Ajani J.A.
        • Mansfield P.F.
        • Crane C.H.
        • Wu T.T.
        • Lunagomez S.
        • Lynch P.M.
        • et al.
        Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome.
        J Clin Oncol. 2005; 23: 1237-1244
        • Ajani J.A.
        • Mansfield P.F.
        • Janjan N.
        • Morris J.
        • Pisters P.W.
        • Lynch P.M.
        • et al.
        Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma.
        J Clin Oncol. 2004; 22: 2774-2780
        • Lowy A.M.
        • Mansfield P.F.
        • Leach S.D.
        • Pazdur R.
        • Dumas P.
        • Ajani J.
        Response to neoadjuvant chemotherapy best predicts survival after curative resection of gastric cancer.
        Ann Surg. 1999; 229: 303-308
        • Mansour J.C.
        • Tang L.
        • Shah M.
        • Bentrem D.
        • Klimstra D.S.
        • Gonen M.
        • et al.
        Does graded histologic response after neoadjuvant chemotherapy predict survival for completely resected gastric cancer?.
        Ann Surg Oncol. 2007; 14: 3412-3418
        • Alderson D.
        • Langley R.E.
        • Nankivell M.G.
        • Blazeby J.M.
        • Griffin M.
        • et al.
        Neoadjuvant chemotherapy for resectable oesophageal and junctional adenocarcinoma: results from the UK Medical Research Council randomised OEO5 trial (ISRCTN 01852072).
        ASCO Annual Meeting: J Clin Oncol. 2015; 33 (suppl. abstr 4002)
        • Cunningham D.
        • Stenning S.P.
        • Smyth E.C.
        • Okines A.F.
        • Allum W.H.
        • Rowley S.
        • et al.
        Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial.
        Lancet Oncol. 2017 Mar; 18: 357-370
        • Fields R.C.
        • Strong V.E.
        • Gonen M.
        • Goodman K.A.
        • Rizk N.P.
        • Kelsen D.P.
        • et al.
        Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma.
        Br J Cancer. 2011; 104: 1840-1847
        • Lorenzen S.
        • Thuss-Patience P.
        • Al-Batran S.E.
        • Lordick F.
        • Haller B.
        • Schuster T.
        • et al.
        Impact of pathologic complete response on disease-free survival in patients with esophagogastric adenocarcinoma receiving preoperative docetaxel-based chemotherapy.
        Ann Oncol. 2013; 24: 2068-2073
        • Piessen G.
        • Messager M.
        • Malicot K.L.
        • Robb W.
        • Fiore F.D.
        • Guilbert M.
        • et al.
        Phase II/III multicentre randomised controlled trial evaluating a strategy of primary surgery and adjuvant chemotherapy versus peri-operative chemotherapy for resectable gastric signet ring cell adenocarcinomas – PRODIGE 19-FFCD1103-ADCI002.
        BMC Cancer. 2013; 13: 281
        • Bang Y.J.
        • Cutsem E.V.
        • Feyereislova A.
        • Chung H.C.
        • 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: 687-697
        • Smyth E.C.
        • Wotherspoon A.
        • Peckitt C.
        • Gonzalez D.
        • Hulkki-Wilson S.
        • Eltahir Z.
        Mismatch repair deficiency, microsatellite instability, and survival: an exploratory analysis of the medical research council adjuvant gastric infusional chemotherapy (MAGIC) trial.
        JAMA Oncol. 2017 Sep 1; 3: 1197-1203
        • Cancer Genome Atlas Research N
        Comprehensive molecular characterization of gastric adenocarcinoma.
        Nature. 2014; 513: 202-209