Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin

R. K. Bott; K. Beckmann; J. Zylstra; M. J. Wilkinson; W. R.C. Knight; C. R. Baker; M. Kelly; N. Maisey; A. Qureshi; T. Sevitt; M. Van Hemelrijck; E. C. Smyth; W. H. Allum; J. Lagergren; J. A. Gossage; D. Cunningham; A. R. Davies; R. McEwan; A. Jacques; N. Griffin; V. Goh; S. Ngan; K. Owczarczyk; H. Deere; M. Green; F. Chang; U. Mahadeva; B. Gill-Barman; S. George; J. Meenan; M. Hill; J. Waters; M. Cominos; O. Hynes; A. Coombes; G. Tham; C. Iezzi; A. Reyhani; J. M. Dunn; S. S. Zeki

doi:10.1002/bjs.11864

Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin

R. K. Bott, K. Beckmann, J. Zylstra, M. J. Wilkinson, W. R.C. Knight, C. R. Baker, M. Kelly, N. Maisey, A. Qureshi, T. Sevitt, M. Van Hemelrijck, E. C. Smyth, W. H. Allum, J. Lagergren, J. A. Gossage, D. Cunningham, A. R. Davies^*, R. McEwan, A. Jacques, N. GriffinV. Goh, S. Ngan, K. Owczarczyk, H. Deere, M. Green, F. Chang, U. Mahadeva, B. Gill-Barman, S. George, J. Meenan, M. Hill, J. Waters, M. Cominos, O. Hynes, A. Coombes, G. Tham, C. Iezzi, A. Reyhani, J. M. Dunn, S. S. Zeki

^*Corresponding author for this work

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Abstract

Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. Methods: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. Results: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4–5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. Conclusion: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

Original language	English
Pages (from-to)	1801-1810
Number of pages	10
Journal	British Journal of Surgery
Volume	107
Issue number	13
DOIs	https://doi.org/10.1002/bjs.11864
Publication status	Published - Dec 2020

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Bott, R. K., Beckmann, K., Zylstra, J., Wilkinson, M. J., Knight, W. R. C., Baker, C. R., Kelly, M., Maisey, N., Qureshi, A., Sevitt, T., Van Hemelrijck, M., Smyth, E. C., Allum, W. H., Lagergren, J., Gossage, J. A., Cunningham, D., Davies, A. R., McEwan, R., Jacques, A., ... Zeki, S. S. (2020). Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin. British Journal of Surgery, 107(13), 1801-1810. https://doi.org/10.1002/bjs.11864

@article{e1f6050e30e5400dafeac107d6faffd8,

title = "Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin",

abstract = "Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. Methods: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. Results: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4–5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. Conclusion: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.",

author = "Bott, {R. K.} and K. Beckmann and J. Zylstra and Wilkinson, {M. J.} and Knight, {W. R.C.} and Baker, {C. R.} and M. Kelly and N. Maisey and A. Qureshi and T. Sevitt and {Van Hemelrijck}, M. and Smyth, {E. C.} and Allum, {W. H.} and J. Lagergren and Gossage, {J. A.} and D. Cunningham and Davies, {A. R.} and R. McEwan and A. Jacques and N. Griffin and V. Goh and S. Ngan and K. Owczarczyk and H. Deere and M. Green and F. Chang and U. Mahadeva and B. Gill-Barman and S. George and J. Meenan and M. Hill and J. Waters and M. Cominos and O. Hynes and A. Coombes and G. Tham and C. Iezzi and A. Reyhani and Dunn, {J. M.} and Zeki, {S. S.}",

year = "2020",

month = dec,

doi = "10.1002/bjs.11864",

language = "English",

volume = "107",

pages = "1801--1810",

journal = "British Journal of Surgery",

issn = "0007-1323",

publisher = "John Wiley & Sons, Ltd",

number = "13",

}

Bott, RK, Beckmann, K , Zylstra, J, Wilkinson, MJ, Knight, WRC, Baker, CR, Kelly, M, Maisey, N, Qureshi, A, Sevitt, T, Van Hemelrijck, M, Smyth, EC, Allum, WH, Lagergren, J, Gossage, JA, Cunningham, D, Davies, AR, McEwan, R, Jacques, A, Griffin, N , Goh, V , Ngan, S , Owczarczyk, K , Deere, H , Green, M , Chang, F , Mahadeva, U , Gill-Barman, B , George, S, Meenan, J, Hill, M, Waters, J, Cominos, M, Hynes, O, Coombes, A, Tham, G, Iezzi, C, Reyhani, A, Dunn, JM & Zeki, SS 2020, 'Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin', British Journal of Surgery, vol. 107, no. 13, pp. 1801-1810. https://doi.org/10.1002/bjs.11864

TY - JOUR

T1 - Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin

AU - Bott, R. K.

AU - Beckmann, K.

AU - Zylstra, J.

AU - Wilkinson, M. J.

AU - Knight, W. R.C.

AU - Baker, C. R.

AU - Kelly, M.

AU - Maisey, N.

AU - Qureshi, A.

AU - Sevitt, T.

AU - Van Hemelrijck, M.

AU - Smyth, E. C.

AU - Allum, W. H.

AU - Lagergren, J.

AU - Gossage, J. A.

AU - Cunningham, D.

AU - Davies, A. R.

AU - McEwan, R.

AU - Jacques, A.

AU - Griffin, N.

AU - Goh, V.

AU - Ngan, S.

AU - Owczarczyk, K.

AU - Deere, H.

AU - Green, M.

AU - Chang, F.

AU - Mahadeva, U.

AU - Gill-Barman, B.

AU - George, S.

AU - Meenan, J.

AU - Hill, M.

AU - Waters, J.

AU - Cominos, M.

AU - Hynes, O.

AU - Coombes, A.

AU - Tham, G.

AU - Iezzi, C.

AU - Reyhani, A.

AU - Dunn, J. M.

AU - Zeki, S. S.

PY - 2020/12

Y1 - 2020/12

N2 - Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. Methods: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. Results: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4–5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. Conclusion: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

AB - Background: The role of adjuvant therapy in patients with oesophagogastric adenocarcinoma treated by neoadjuvant chemotherapy is contentious. In UK practice, surgical resection margin status is often used to classify patients for receiving adjuvant treatment. The aim of this study was to assess the survival benefit of adjuvant therapy in patients with positive (R1) resection margins. Methods: Two prospectively collected UK institutional databases were combined to identify eligible patients. Adjusted Cox regression analyses were used to compare overall and recurrence-free survival according to adjuvant treatment. Recurrence patterns were assessed as a secondary outcome. Propensity score-matched analysis was also performed. Results: Of 616 patients included in the combined database, 242 patients who had an R1 resection were included in the study. Of these, 112 patients (46·3 per cent) received adjuvant chemoradiotherapy, 46 (19·0 per cent) were treated with adjuvant chemotherapy and 84 (34·7 per cent) had no adjuvant treatment. In adjusted analysis, adjuvant chemoradiotherapy improved recurrence-free survival (hazard ratio (HR) 0·59, 95 per cent c.i. 0·38 to 0·94; P = 0·026), with a benefit in terms of both local (HR 0·48, 0·24 to 0·99; P = 0·047) and systemic (HR 0·56, 0·33 to 0·94; P = 0·027) recurrence. In analyses stratified by tumour response to neoadjuvant chemotherapy, non-responders (Mandard tumour regression grade 4–5) treated with adjuvant chemoradiotherapy had an overall survival benefit (HR 0·61, 0·38 to 0·97; P = 0·037). In propensity score-matched analysis, an overall survival benefit (HR 0·62, 0·39 to 0·98; P = 0·042) and recurrence-free survival benefit (HR 0·51, 0·30 to 0·87; P = 0·004) were observed for adjuvant chemoradiotherapy versus no adjuvant treatment. Conclusion: Adjuvant therapy may improve overall survival and recurrence-free survival after margin-positive resection. This pattern seems most pronounced with adjuvant chemoradiotherapy in non-responders to neoadjuvant chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=85091613484&partnerID=8YFLogxK

U2 - 10.1002/bjs.11864

DO - 10.1002/bjs.11864

M3 - Article

AN - SCOPUS:85091613484

SN - 0007-1323

VL - 107

SP - 1801

EP - 1810

JO - British Journal of Surgery

JF - British Journal of Surgery

IS - 13

ER -

Adjuvant therapy following oesophagectomy for adenocarcinoma in patients with a positive resection margin

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