Relevance of shrinkage versus fragmented response patterns in rectal cancer.
neoadjuvant chemoradiation treatment
partial response
patterns of response
rectal cancer
Journal
Histopathology
ISSN: 1365-2559
Titre abrégé: Histopathology
Pays: England
ID NLM: 7704136
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
06
07
2023
received:
08
05
2023
accepted:
31
07
2023
medline:
7
11
2023
pubmed:
23
8
2023
entrez:
23
8
2023
Statut:
ppublish
Résumé
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. 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. 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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
870-879Subventions
Organisme : KWF Kankerbestrijding
Informations de copyright
© 2023 The Authors. Histopathology published by John Wiley & Sons Ltd.
Références
Wiegering A, Isbert C, Dietz UA et al. Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence-a retrospective analysis over two decades. BMC Cancer 2014; 14; 816.
Sineshaw HM, Jemal A, Charles R et al. Changes in treatment patterns for patients with locally advanced rectal cancer in the United States over the past decade: an analysis from the National Cancer Database. Cancer 2016; 122; 1996-2003.
Glynne-Jones R, Wyrwicz L, Tiret E et al. Clinical practice guidelines rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2017; 28; 22-40.
Nagtegaal ID, Glynne-Jones R. How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement. Cancer Treat. Rev. 2020; 84; 101964.
Valentini V, Coco C, Picciocchi A et al. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int. J. Radiat. Oncol. Biol. Phys. 2002; 53; 664-674.
Moureau-Zabotto L, Farnault B, De Chaisemartin C et al. Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int. J. Radiat. Oncol. Biol. Phys. 2011; 80; 483-491.
Rullier A, Laurent C, Capdepont M, Vendrely V, Bioulac-Sage P, Rullier E. Impact of tumor response on survival after radiochemotherapy in locally advanced rectal carcinoma. Am. J. Surg. Pathol. 2010; 34; 562-568.
Mandard AM, Dalibard F, Mandard JC et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Cancer 1994; 73; 2680-2686.
Protocol for the Examination of Resection Specimens From Patients With Primary Carcinoma of the Colon and Rectum [Internet]. College of American Pathologists. Version 4.2.0.2. [June 2022]: Available at: https://documents.cap.org/protocols/ColoRectal_4.2.0.2.REL_CAPCP.pdf?_gl=1*1edeqt1*_ga*NDExMzAyNjUyLjE2OTE5MjM2NDc.*_ga_97ZFJSQQ0X*MTY5MTkyMzY0Ny4xLjEuMTY5MTkyNDk2Ny4wLjAuMA
Becker K, Mueller JD, Schulmacher C et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer 2003; 98; 1521-1530.
Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int. J. Colorect. Dis. 1997; 12; 19-23.
Ryan R, Gibbons D, Hyland JMP et al. Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Histopathology 2005; 47; 141-146.
Rödel C, Martus P, Papadoupolos T et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J. Clin. Oncol. 2005; 23; 8688-8696.
Gosens MJEM, Klaassen RA, Tan-Go I et al. Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin. Cancer Res. 2007; 13; 6617-6623.
Chetty R, Gill P, Govender D et al. International study group on rectal cancer regression grading: Interobserver variability with commonly used regression grading systems. Hum. Pathol. 2012; 43; 1917-1923.
Trakarnsanga A, Gonen M, Shia J et al. Comparison of tumor regression grade systems for locally advanced rectal cancer after multimodality treatment. J. Natl. Cancer Inst. 2014; 106; 1-6.
Acenero MJF, Munoz LE, Varela JS et al. Prognostic influence of histopathological regression patterns in rectal adenocarcinoma receiving neoadjuvant therapy. J. Gastrointest. Oncol. 2017; 8; 49-54.
Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 2002; 94; 1121-1130.
Losi L, Luppi G, Gavioli M et al. Prognostic value of Dworak grade of regression (GR) in patients with rectal carcinoma treated with preoperative radiochemotherapy. Int. J. Colorectal Dis. 2006; 21; 645-651.
Bedrosian I, Rodriguez-Bigas MA, Feig B et al. Predicting the node-negative mesorectum after preoperative chemoradiation for locally advanced rectal carcinoma. J. Gastrointestinal. Surg. 2004; 8; 56-63.
Pucciarelli S, Toppan P, Friso ML et al. Complete pathologic response following preoperative chemoradiation therapy for middle to lower rectal cancer is not a prognostic factor for a better outcome. Dis. Colon Rectum 2004; 47; 1798-1807.
Topova L, Hellmich G, Puffer E et al. Prognostic value of tumor response to neoadjuvant therapy in rectal carcinoma. Dis. Colon Rectum 2011; 54; 401-411.
Perez RO, Habr-Gama A, Smith FM et al. Fragmented pattern of tumor regression and lateral intramural spread may influence margin appropriateness after TEM for rectal cancer following neoadjuvant CRT. J. Surg. Oncol. 2014; 109; 853-858.
Hav M, Libbrecht L, Geboes K et al. Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer. Virchows Arch. 2015; 466; 517-523.
Nilsson PJ, van Etten B, Hospers GAP et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer-the RAPIDO trial. BMC Cancer 2013; 13; 279.
Graham Martinez C, Kus Ozturk S, Al-Kaabi A et al. Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance. Histopathology 2022; 80; 982-994.
Swellengrebel HAM, Bosch SL, Cats A et al. Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: a near pathologic complete response does not translate into good clinical outcome. Radiother. Oncol. 2014; 112; 44-51.
Duldulao MP, Lee W, Streja L et al. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer. Dis. Colon Rectum 2013; 56; 142-149.
Lordick F, Mariette C, Hausterman K et al. Oesophageal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2016; 27; 50-57.
Glynne-Jones R, Wyrwicz L, Tiret E et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2017; 28; 22-40.
Graham Martinez C, Barella Y, Kus Ozturk S et al. The immune microenvironment landscape shows treatment-specific differences in rectal cancer patients. Front. Immunol. 2022; 13; 1011498.