Relevance of shrinkage versus fragmented response patterns in rectal cancer

Sonay Kus Ozturk; Cristina Graham Martinez; Kieran Sheahan; Desmond C Winter; Susan Aherne; Éanna J Ryan; Cornelis Jh van de Velde; Corrie Am Marijnen; Geke AP Hospers; Annet Gh Roodvoets; Michail Doukas; David Mens; Cornelis Verhoef; Rachel S van der Post; Iris D Nagtegaal

doi:10.1111/his.15027

Relevance of shrinkage versus fragmented response patterns in rectal cancer

Sonay Kus Ozturk^*, Cristina Graham Martinez, Kieran Sheahan, Desmond C Winter, Susan Aherne, Éanna J Ryan, Cornelis Jh van de Velde, Corrie Am Marijnen, Geke AP Hospers, Annet Gh Roodvoets, Michail Doukas, David Mens, Cornelis Verhoef, Rachel S van der Post, Iris D Nagtegaal

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.

METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.

CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

Original language	English
Pages (from-to)	870-879
Number of pages	10
Journal	Histopathology
Volume	83
Issue number	6
Early online date	23-Aug-2023
DOIs	https://doi.org/10.1111/his.15027
Publication status	Published - Dec-2023

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Kus Ozturk, S., Graham Martinez, C., Sheahan, K., Winter, D. C., Aherne, S., Ryan, É. J., van de Velde, C. J., Marijnen, C. A., Hospers, G. AP., Roodvoets, A. G., Doukas, M., Mens, D., Verhoef, C., van der Post, R. S., & Nagtegaal, I. D. (2023). Relevance of shrinkage versus fragmented response patterns in rectal cancer. Histopathology, 83(6), 870-879. https://doi.org/10.1111/his.15027

@article{983d2c90548a44df9d12e631902266f5,

title = "Relevance of shrinkage versus fragmented response patterns in rectal cancer",

abstract = "AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.",

author = "{Kus Ozturk}, Sonay and {Graham Martinez}, Cristina and Kieran Sheahan and Winter, {Desmond C} and Susan Aherne and Ryan, {{\'E}anna J} and {van de Velde}, {Cornelis Jh} and Marijnen, {Corrie Am} and Hospers, {Geke AP} and Roodvoets, {Annet Gh} and Michail Doukas and David Mens and Cornelis Verhoef and {van der Post}, {Rachel S} and Nagtegaal, {Iris D}",

note = "{\textcopyright} 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.",

year = "2023",

month = dec,

doi = "10.1111/his.15027",

language = "English",

volume = "83",

pages = "870--879",

journal = "Histopathology",

issn = "0309-0167",

publisher = "Wiley",

number = "6",

}

Kus Ozturk, S, Graham Martinez, C, Sheahan, K, Winter, DC, Aherne, S, Ryan, ÉJ, van de Velde, CJ, Marijnen, CA, Hospers, GAP, Roodvoets, AG, Doukas, M, Mens, D, Verhoef, C, van der Post, RS & Nagtegaal, ID 2023, 'Relevance of shrinkage versus fragmented response patterns in rectal cancer', Histopathology, vol. 83, no. 6, pp. 870-879. https://doi.org/10.1111/his.15027

TY - JOUR

T1 - Relevance of shrinkage versus fragmented response patterns in rectal cancer

AU - Kus Ozturk, Sonay

AU - Graham Martinez, Cristina

AU - Sheahan, Kieran

AU - Winter, Desmond C

AU - Aherne, Susan

AU - Ryan, Éanna J

AU - van de Velde, Cornelis Jh

AU - Marijnen, Corrie Am

AU - Hospers, Geke AP

AU - Roodvoets, Annet Gh

AU - Doukas, Michail

AU - Mens, David

AU - Verhoef, Cornelis

AU - van der Post, Rachel S

AU - Nagtegaal, Iris D

PY - 2023/12

Y1 - 2023/12

N2 - AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

AB - AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

U2 - 10.1111/his.15027

DO - 10.1111/his.15027

M3 - Article

C2 - 37609761

SN - 0309-0167

VL - 83

SP - 870

EP - 879

JO - Histopathology

JF - Histopathology

IS - 6

ER -

Relevance of shrinkage versus fragmented response patterns in rectal cancer

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