Multicentre cohort study to define and validate pathological assessment of response to neoadjuvant therapy in oesophagogastric adenocarcinoma

Background This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. Methods A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assess...

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Veröffentlicht in:	British journal of surgery Jg. 104; H. 13; S. 1816 - 1828
Hauptverfasser:	Noble, F., Lloyd, M. A., Turkington, R., Griffiths, E., O'Donovan, M., O'Neill, J. R., Mercer, S., Parsons, S. L., Fitzgerald, R. C., Underwood, T. J., Noorani, A., Fels Elliott, R., Abdullahi, Z., de la Rue, R., Bornschein, J., MacRae, S., Nutzinger, B., Grehan, N., Contino, G., Crawte, J., Edwards, P. A. W., Miremadi, A., Malhotra, S., Hayden, A., Walker, R., Peters, C., Hannah, G., Hardwick, R., Davies, J., Ford, H., Gilligan, D., Safranek, P., Hindmarsh, A., Sujendran, V., Carroll, N., McManus, D., Hayes, S. J., Ang, Y., Preston, S. R., Oakes, S., Bagwan, I., Skipworth, R. J. E., Save, V., Hupp, T. R., Puig, S., Bedford, M., Taniere, P., Whiting, J., Byrne, J., Kelly, J., Owsley, J., Crichton, C., Barr, H., Shepherd, N., Old, O., Lagergren, J., Gossage, J., Davies, A., Chang, F., Zylstra, J., Sanders, G., Berrisford, R., Harden, C., Bunting, D., Lewis, M., Cheong, E., Kumar, B., Saunders, J. H., Soomro, I. N., Vohra, R., Duffy, J., Kaye, P., Grabowska, A., Lovat, L., Haidry, R., Eneh, V., Igali, L., Welch, I., Scott, M., Sothi, S., Suortamo, S., Lishman, S., Beardsmore, D., Sutaria, R., Secrier, M., Eldridge, M.D., Bower, L., Lynch, A. G., Tavaré, S.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Chichester, UK John Wiley & Sons, Ltd 01.12.2017 Oxford University Press
Schlagworte:	Adenocarcinoma - mortality Adenocarcinoma - pathology Adenocarcinoma - therapy Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biopsy Chemotherapy Chemotherapy, Adjuvant Cisplatin - administration & dosage Cohort analysis Cohort Studies Digital divide Epirubicin - administration & dosage Esophageal cancer Esophageal Neoplasms - mortality Esophageal Neoplasms - pathology Esophageal Neoplasms - therapy Female Fluorouracil - administration & dosage Humans Lymph Nodes - pathology Lymphatic Metastasis - pathology Lymphatic system Male Middle Aged Neoadjuvant Therapy Neoplasm Grading Neoplasm Staging Original Stomach Neoplasms - mortality Stomach Neoplasms - pathology Stomach Neoplasms - therapy Toxicity
ISSN:	0007-1323, 1365-2168, 1365-2168
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Zusammenfassung:	Background This multicentre cohort study sought to define a robust pathological indicator of clinically meaningful response to neoadjuvant chemotherapy in oesophageal adenocarcinoma. Methods A questionnaire was distributed to 11 UK upper gastrointestinal cancer centres to determine the use of assessment of response to neoadjuvant chemotherapy. Records of consecutive patients undergoing oesophagogastric resection at seven centres between January 2000 and December 2013 were reviewed. Pathological response to neoadjuvant chemotherapy was assessed using the Mandard Tumour Regression Grade (TRG) and lymph node downstaging. Results TRG (8 of 11 centres) was the most widely used system to assess response to neoadjuvant chemotherapy, but there was discordance on how it was used in practice. Of 1392 patients, 1293 had TRG assessment; data were available for clinical and pathological nodal status (cN and pN) in 981 patients, and TRG, cN and pN in 885. There was a significant difference in survival between responders (TRG 1–2; median overall survival (OS) not reached) and non‐responders (TRG 3–5; median OS 2·22 (95 per cent c.i. 1·94 to 2·51) years; P < 0·001); the hazard ratio was 2·46 (95 per cent c.i. 1·22 to 4·95; P = 0·012). Among local non‐responders, the presence of lymph node downstaging was associated with significantly improved OS compared with that of patients without lymph node downstaging (median OS not reached versus 1·92 (1·68 to 2·16) years; P < 0·001). Conclusion A clinically meaningful local response to neoadjuvant chemotherapy was restricted to the small minority of patients (14·8 per cent) with TRG 1–2. Among local non‐responders, a subset of patients (21·3 per cent) derived benefit from neoadjuvant chemotherapy by lymph node downstaging and their survival mirrored that of local responders. Response associated with survival
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Members of the OCCAMS consortium are co-authors of this article and can be found under the heading Collaborators.
ISSN:	0007-1323 1365-2168 1365-2168
DOI:	10.1002/bjs.10627