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Erschienen in: Virchows Archiv 5/2015

01.05.2015 | Original Article

Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer

verfasst von: Monirath Hav, Louis Libbrecht, Karen Geboes, Liesbeth Ferdinande, Tom Boterberg, Wim Ceelen, Piet Pattyn, Claude Cuvelier

Erschienen in: Virchows Archiv | Ausgabe 5/2015

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Abstract

Most patients with rectal cancer receive neoadjuvant radiochemotherapy (RCT), causing a variable decrease in tumor mass. We evaluated the prognostic impact of pathologic parameters reflecting tumor response to RCT, either directly or indirectly. Seventy-six rectal cancer patients receiving neoadjuvant RCT between 2006 and 2009 were included. We studied the association between disease-free survival (DFS) and the “classical” clinicopathologic features as well as tumor deposits, circumferential resection margin (CRM), Dworak regression grade, and tumor and nodal downstaging. Patients with tumor downstaging had a longer DFS (p = 0.05), indicating a more favorable prognosis when regression was accompanied by a decrease in tumor infiltrative depth, referred to as tumor shrinkage. Moreover, tumor downstaging was significantly associated with larger CRM and nodal downstaging (p = 0.02), suggesting that shrinkage of the primary tumor was associated with a decreased nodal tumor load. Higher Dworak grade did not correlate with tumor downstaging, nor with higher CRM or prolonged DFS. This implies that tumor mass decrease was sometimes due to fragmentation rather than shrinkage of the primary tumor. Lastly, the presence of tumor deposits was clearly associated with reduced DFS (p = 0.01). Assessment of tumor shrinkage after RCT via tumor downstaging and CRM is a good way of predicting DFS in rectal cancer, and shrinkage of the primary tumor is associated with a decreased nodal tumor load. Assessing regression based on the amount of tumor in relation to stromal fibrosis does not accurately discern tumor fragmentation from tumor shrinkage, which is most likely the reason why Dworak grade had less prognostic relevance.
Literatur
1.
Zurück zum Zitat Ceelen W et al (2009) Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis. Int J Cancer 124(12):2966–72CrossRefPubMed Ceelen W et al (2009) Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer: a systematic review and meta-analysis. Int J Cancer 124(12):2966–72CrossRefPubMed
2.
Zurück zum Zitat Kapiteijn E et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345(9):638–46CrossRefPubMed Kapiteijn E et al (2001) Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345(9):638–46CrossRefPubMed
3.
Zurück zum Zitat van Gijn, W., et al., Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol, 2011 van Gijn, W., et al., Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol, 2011
4.
Zurück zum Zitat Rullier A et al (2010) Impact of tumor response on survival after radiochemotherapy in locally advanced rectal carcinoma. Am J Surg Pathol 34(4):562–8CrossRefPubMed Rullier A et al (2010) Impact of tumor response on survival after radiochemotherapy in locally advanced rectal carcinoma. Am J Surg Pathol 34(4):562–8CrossRefPubMed
5.
Zurück zum Zitat Moureau-Zabotto, L., et al., Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys, 2010 Moureau-Zabotto, L., et al., Predictive factors of tumor response after neoadjuvant chemoradiation for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys, 2010
6.
Zurück zum Zitat Valentini V et al (2002) 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 53(3):664–74CrossRefPubMed Valentini V et al (2002) 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 53(3):664–74CrossRefPubMed
7.
Zurück zum Zitat Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Color Dis 12(1):19–23CrossRef Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Color Dis 12(1):19–23CrossRef
8.
Zurück zum Zitat Rödel C et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23(34):8688–96CrossRefPubMed Rödel C et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23(34):8688–96CrossRefPubMed
9.
Zurück zum Zitat Mandard AM et al (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma clinicopathologic correlations. Cancer 73(11):2680–6CrossRefPubMed Mandard AM et al (1994) Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma clinicopathologic correlations. Cancer 73(11):2680–6CrossRefPubMed
10.
Zurück zum Zitat Wheeler J et al (2004) Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade. Dis Colon Rectum 47(12):2025–31CrossRefPubMed Wheeler J et al (2004) Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: correlation with rectal cancer regression grade. Dis Colon Rectum 47(12):2025–31CrossRefPubMed
11.
Zurück zum Zitat Ruo L et al (2002) Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 236(1):75–81CrossRefPubMedCentralPubMed Ruo L et al (2002) Long-term prognostic significance of extent of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg 236(1):75–81CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Bouzourene H et al (2002) Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 94(4):1121–30CrossRefPubMed Bouzourene H et al (2002) Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer 94(4):1121–30CrossRefPubMed
13.
Zurück zum Zitat Debucquoy A et al (2009) Molecular and clinico-pathological markers in rectal cancer: a tissue micro-array study. Int J Color Dis 24(2):129–38CrossRef Debucquoy A et al (2009) Molecular and clinico-pathological markers in rectal cancer: a tissue micro-array study. Int J Color Dis 24(2):129–38CrossRef
14.
Zurück zum Zitat Debucquoy A et al (2008) Morphological features and molecular markers in rectal cancer from 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 trial: prognostic value and effects of preoperative radio (chemo) therapy. Eur J Cancer 44(6):791–7CrossRefPubMedCentralPubMed Debucquoy A et al (2008) Morphological features and molecular markers in rectal cancer from 95 patients included in the European Organisation for Research and Treatment of Cancer 22921 trial: prognostic value and effects of preoperative radio (chemo) therapy. Eur J Cancer 44(6):791–7CrossRefPubMedCentralPubMed
15.
Zurück zum Zitat Topova L et al (2011) Prognostic value of tumor response to neoadjuvant therapy in rectal carcinoma. Dis Colon Rectum 54(4):401–11CrossRefPubMed Topova L et al (2011) Prognostic value of tumor response to neoadjuvant therapy in rectal carcinoma. Dis Colon Rectum 54(4):401–11CrossRefPubMed
16.
Zurück zum Zitat Glynne-Jones R, Mawdsley S, Novell JR (2006) The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language. Color Dis 8(9):800–7CrossRef Glynne-Jones R, Mawdsley S, Novell JR (2006) The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language. Color Dis 8(9):800–7CrossRef
17.
Zurück zum Zitat Nagtegaal I, Quirke P (2008) What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 26(2):303–12CrossRefPubMed Nagtegaal I, Quirke P (2008) What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 26(2):303–12CrossRefPubMed
18.
Zurück zum Zitat Gosens M et al (2007) Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin Cancer Res 13(22 Pt 1):6617–23CrossRefPubMed Gosens M et al (2007) Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma. Clin Cancer Res 13(22 Pt 1):6617–23CrossRefPubMed
19.
Zurück zum Zitat Ueno H, Mochizuki H (1997) Clinical significance of extrabowel skipped cancer infiltration in rectal cancer. Surg Today 27(7):617–22CrossRefPubMed Ueno H, Mochizuki H (1997) Clinical significance of extrabowel skipped cancer infiltration in rectal cancer. Surg Today 27(7):617–22CrossRefPubMed
20.
Zurück zum Zitat Ueno H, Mochizuki H, Tamakuma S (1998) Prognostic significance of extranodal microscopic foci discontinuous with primary lesion in rectal cancer. Dis Colon Rectum 41(1):55–61CrossRefPubMed Ueno H, Mochizuki H, Tamakuma S (1998) Prognostic significance of extranodal microscopic foci discontinuous with primary lesion in rectal cancer. Dis Colon Rectum 41(1):55–61CrossRefPubMed
21.
Zurück zum Zitat Prabhudesai A et al (2003) Impact of microscopic extranodal tumor deposits on the outcome of patients with rectal cancer. Dis Colon Rectum 46(11):1531–7CrossRefPubMed Prabhudesai A et al (2003) Impact of microscopic extranodal tumor deposits on the outcome of patients with rectal cancer. Dis Colon Rectum 46(11):1531–7CrossRefPubMed
22.
Zurück zum Zitat Puppa G et al (2007) Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging. Mod Pathol 20(8):843–55CrossRefPubMed Puppa G et al (2007) Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging. Mod Pathol 20(8):843–55CrossRefPubMed
23.
Zurück zum Zitat Puppa G et al (2009) Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases. Mod Pathol 22(3):410–5CrossRefPubMed Puppa G et al (2009) Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases. Mod Pathol 22(3):410–5CrossRefPubMed
24.
Zurück zum Zitat Nagtegaal ID, Quirke P (2007) Colorectal tumour deposits in the mesorectum and pericolon; a critical review. Histopathology 51(2):141–9CrossRefPubMed Nagtegaal ID, Quirke P (2007) Colorectal tumour deposits in the mesorectum and pericolon; a critical review. Histopathology 51(2):141–9CrossRefPubMed
25.
Zurück zum Zitat Quirke P et al (2007) The future of the TNM staging system in colorectal cancer: time for a debate? Lancet Oncol 8(7):651–7CrossRefPubMed Quirke P et al (2007) The future of the TNM staging system in colorectal cancer: time for a debate? Lancet Oncol 8(7):651–7CrossRefPubMed
26.
Zurück zum Zitat Lindebjerg J et al (2009) The prognostic value of lymph node metastases and tumour regression grade in rectal cancer patients treated with long-course preoperative chemoradiotherapy. Color Dis 11(3):264–9CrossRef Lindebjerg J et al (2009) The prognostic value of lymph node metastases and tumour regression grade in rectal cancer patients treated with long-course preoperative chemoradiotherapy. Color Dis 11(3):264–9CrossRef
27.
Zurück zum Zitat Shia J et al (2011) Significance of acellular mucin pools in rectal carcinoma after neoadjuvant chemoradiotherapy. Am J Surg Pathol 35(1):127–34CrossRefPubMed Shia J et al (2011) Significance of acellular mucin pools in rectal carcinoma after neoadjuvant chemoradiotherapy. Am J Surg Pathol 35(1):127–34CrossRefPubMed
28.
Zurück zum Zitat Quah HM et al (2008) Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer 113(1):57–64CrossRefPubMed Quah HM et al (2008) Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer 113(1):57–64CrossRefPubMed
29.
Zurück zum Zitat Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1(8496):1479–82CrossRefPubMed Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1(8496):1479–82CrossRefPubMed
30.
Zurück zum Zitat Quirke P et al (1986) Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 2(8514):996–9CrossRefPubMed Quirke P et al (1986) Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 2(8514):996–9CrossRefPubMed
31.
Zurück zum Zitat Sobin LH, Fleming ID (1997) TNM classification of malignant tumors, fifth edition. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80(9):1803–4CrossRefPubMed Sobin LH, Fleming ID (1997) TNM classification of malignant tumors, fifth edition. Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer 80(9):1803–4CrossRefPubMed
32.
Zurück zum Zitat Hamilton, S., B. Vogelstein, and S. Kudo, Carcinoma of the colon and rectum., in World Health Organization Classification of Tumors-Pathology and Genetics of Tumors of the Digestive System., S. Hamilton and L. Aaltonen, Editors. 2000, IARC Press: Lyon. p. 105–119 Hamilton, S., B. Vogelstein, and S. Kudo, Carcinoma of the colon and rectum., in World Health Organization Classification of Tumors-Pathology and Genetics of Tumors of the Digestive System., S. Hamilton and L. Aaltonen, Editors. 2000, IARC Press: Lyon. p. 105–119
33.
Zurück zum Zitat Sobin, L., M. Gospodarowicz, and C. Wittekind, TNM Classification of Malignant Tumors. 7th ed, ed. L. Sobin, M. Gospodarowicz, and C. Wittekind. 2009, New York: Wiley-Blackwell Sobin, L., M. Gospodarowicz, and C. Wittekind, TNM Classification of Malignant Tumors. 7th ed, ed. L. Sobin, M. Gospodarowicz, and C. Wittekind. 2009, New York: Wiley-Blackwell
34.
Zurück zum Zitat Quirke P et al (2010) Evidence-based medicine: the time has come to set standards for staging. J Pathol 221(4):357–60PubMed Quirke P et al (2010) Evidence-based medicine: the time has come to set standards for staging. J Pathol 221(4):357–60PubMed
35.
Zurück zum Zitat Ssobin LH, Ch W (1997) TNM classification of malignant tumors. Wiley, New York Ssobin LH, Ch W (1997) TNM classification of malignant tumors. Wiley, New York
36.
Zurück zum Zitat Losi L et al (2006) Prognostic value of Dworak grade of regression (GR) in patients with rectal carcinoma treated with preoperative radiochemotherapy. Int J Color Dis 21(7):645–51CrossRef Losi L et al (2006) Prognostic value of Dworak grade of regression (GR) in patients with rectal carcinoma treated with preoperative radiochemotherapy. Int J Color Dis 21(7):645–51CrossRef
37.
Zurück zum Zitat Ratto C et al (2002) Mesorectal microfoci adversely affect the prognosis of patients with rectal cancer. Dis Colon Rectum 45(6):733–42, discussion 742–3CrossRefPubMed Ratto C et al (2002) Mesorectal microfoci adversely affect the prognosis of patients with rectal cancer. Dis Colon Rectum 45(6):733–42, discussion 742–3CrossRefPubMed
38.
Zurück zum Zitat Ratto C et al (2007) Neoplastic mesorectal microfoci (MMF) following neoadjuvant chemoradiotherapy: clinical and prognostic implications. Ann Surg Oncol 14(2):853–61CrossRefPubMed Ratto C et al (2007) Neoplastic mesorectal microfoci (MMF) following neoadjuvant chemoradiotherapy: clinical and prognostic implications. Ann Surg Oncol 14(2):853–61CrossRefPubMed
Metadaten
Titel
Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer
verfasst von
Monirath Hav
Louis Libbrecht
Karen Geboes
Liesbeth Ferdinande
Tom Boterberg
Wim Ceelen
Piet Pattyn
Claude Cuvelier
Publikationsdatum
01.05.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 5/2015
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-015-1723-x

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