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Published in: Annals of Surgical Oncology 5/2017

Open Access 01-05-2017 | Colorectal Cancer

The Pretreatment Systemic Inflammatory Response is an Important Determinant of Poor Pathologic Response for Patients Undergoing Neoadjuvant Therapy for Rectal Cancer

Authors: Stephan B. Dreyer, MBChB, Arfon G. M. T. Powell, MSc, Stephen T. McSorley, MBChB, Ashita Waterston, PhD, James J. Going, PhD, Joanne Edwards, PhD, Donald C. McMillan, PhD, Paul G. Horgan, PhD

Published in: Annals of Surgical Oncology | Issue 5/2017

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Abstract

Background

Not all patients respond equally to neoadjuvant chemoradiotherapy (nCRT), with subsequent effects on survival. The systemic inflammatory response has been shown to predict long-term outcomes in colorectal cancer. The current study examined the association between systemic inflammation and nCRT in patients with rectal cancer.

Methods

Between 1999 and 2010, patients who underwent nCRT were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow prognostic score (mGPS), and differential white cell counts were obtained before and after nCRT. The Rödel scoring system measured pathologic tumor regression, and magnetic resonance imaging and computed tomography determined radiologic staging.

Results

The study included 79 patients. Of these patients, 37% were radiologically downstaged, and 44% were categorized as showing a good pathologic response (Rödel scores 3 and 4). As a validated measure of the systemic inflammatory response, mGPS (P = 0.022) was associated with a poor pathologic response to nCRT. A radiologic response was associated with a good pathologic response to treatment (P = 0.003). A binary logistic regression model identified mGPS (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.07–0.96; P = 0.043) and radiologic response (OR 0.43; 95% CI 0.18–0.99; P = 0.048) as strong independent predictors of a pathologic response to treatment.

Conclusion

The current study showed that a systemic inflammatory response before nCRT is associated with a poor pathologic response. Further study in a prospective controlled trial setting is warranted.
Literature
1.
go back to reference Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg. 2009;249:788–93.CrossRefPubMed Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Comparison of the prognostic value of inflammation-based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Ann Surg. 2009;249:788–93.CrossRefPubMed
2.
go back to reference Powell AG, Wallace R, McKee RF, Anderson J, Going JJ, Edwards J, et al. The relationship between tumour site, clinicopathological characteristics, and cancer-specific survival in patients undergoing surgery for colorectal cancer. Colorectal Dis. 2012;14:1493–9.CrossRefPubMed Powell AG, Wallace R, McKee RF, Anderson J, Going JJ, Edwards J, et al. The relationship between tumour site, clinicopathological characteristics, and cancer-specific survival in patients undergoing surgery for colorectal cancer. Colorectal Dis. 2012;14:1493–9.CrossRefPubMed
3.
go back to reference Fleming FJ, Pahlman L, Monson JR. Neoadjuvant therapy in rectal cancer. Dis Colon Rectum. 2011;54:901–12.CrossRefPubMed Fleming FJ, Pahlman L, Monson JR. Neoadjuvant therapy in rectal cancer. Dis Colon Rectum. 2011;54:901–12.CrossRefPubMed
4.
go back to reference Verdecchia A, Guzzinati S, Francisci S, de Angelis R, Bray F, Allemani C, et al. Survival trends in European cancer patients diagnosed from 1988 to 1999. Eur J Cancer. 2009;45:1042–66.CrossRefPubMed Verdecchia A, Guzzinati S, Francisci S, de Angelis R, Bray F, Allemani C, et al. Survival trends in European cancer patients diagnosed from 1988 to 1999. Eur J Cancer. 2009;45:1042–66.CrossRefPubMed
5.
go back to reference Roh MS, Colangelo LH, O’Connell MJ, Yothers G, Deutsch M, Allegra CJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.CrossRefPubMedPubMedCentral Roh MS, Colangelo LH, O’Connell MJ, Yothers G, Deutsch M, Allegra CJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.CrossRefPubMedPubMedCentral
6.
go back to reference Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMed Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.CrossRefPubMed
7.
go back to reference Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–20.CrossRefPubMedPubMedCentral Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–20.CrossRefPubMedPubMedCentral
8.
go back to reference Quirke P. Training and quality assurance for rectal cancer: 20 years of data is enough. Lancet Oncol. 2003;4:695–702.CrossRefPubMed Quirke P. Training and quality assurance for rectal cancer: 20 years of data is enough. Lancet Oncol. 2003;4:695–702.CrossRefPubMed
9.
go back to reference Group MS. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333:779.CrossRef Group MS. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333:779.CrossRef
10.
go back to reference Carruthers R, Tho LM, Brown J, Kakumanu S, McCartney E, McDonald E. Systemic inflammatory response is a predictor of outcome in patients undergoing preoperative chemoradiation for locally advanced rectal cancer. Colorectal Dis. 2012;14:e701–7.CrossRefPubMed Carruthers R, Tho LM, Brown J, Kakumanu S, McCartney E, McDonald E. Systemic inflammatory response is a predictor of outcome in patients undergoing preoperative chemoradiation for locally advanced rectal cancer. Colorectal Dis. 2012;14:e701–7.CrossRefPubMed
11.
go back to reference Rödel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.CrossRefPubMed Rödel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.CrossRefPubMed
12.
go back to reference Jamieson NB, Mohamed M, Oien KA, Foulis AK, Dickson EJ, Imrie CW, et al. The relationship between tumor inflammatory cell infiltrate and outcome in patients with pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2012;19:3581–90.CrossRefPubMed Jamieson NB, Mohamed M, Oien KA, Foulis AK, Dickson EJ, Imrie CW, et al. The relationship between tumor inflammatory cell infiltrate and outcome in patients with pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2012;19:3581–90.CrossRefPubMed
13.
go back to reference Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.CrossRef Roxburgh CS, McMillan DC. Role of systemic inflammatory response in predicting survival in patients with primary operable cancer. Future Oncol. 2010;6:149–63.CrossRef
14.
go back to reference Toiyama Y, Inoue Y, Saigusa S, et al. C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery. Anticancer Res. 2013;33:5065–74.PubMed Toiyama Y, Inoue Y, Saigusa S, et al. C-reactive protein as predictor of recurrence in patients with rectal cancer undergoing chemoradiotherapy followed by surgery. Anticancer Res. 2013;33:5065–74.PubMed
15.
go back to reference Watt DG, Proctor MJ, Park JH, Horgan PG, McMillan DC. The neutrophil-platelet score (NPS) predicts survival in primary operable colorectal cancer and a variety of common cancers. PLoS ONE. 2015;10:e0142159.CrossRefPubMedPubMedCentral Watt DG, Proctor MJ, Park JH, Horgan PG, McMillan DC. The neutrophil-platelet score (NPS) predicts survival in primary operable colorectal cancer and a variety of common cancers. PLoS ONE. 2015;10:e0142159.CrossRefPubMedPubMedCentral
16.
go back to reference Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil-to-lymphocyte ratio predicts survival in patients with cancer. Br J Cancer. 2012;107:695–9.CrossRefPubMedPubMedCentral Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ. A derived neutrophil-to-lymphocyte ratio predicts survival in patients with cancer. Br J Cancer. 2012;107:695–9.CrossRefPubMedPubMedCentral
17.
go back to reference Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol. 2014;32:1554–62.CrossRefPubMed Fokas E, Liersch T, Fietkau R, Hohenberger W, Beissbarth T, Hess C, et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol. 2014;32:1554–62.CrossRefPubMed
18.
go back to reference Park JH, McMillan DC, Horgan PG, Roxburgh CS. The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer. Cancer Treat Rev. 2014;40:68–77.CrossRefPubMed Park JH, McMillan DC, Horgan PG, Roxburgh CS. The impact of anti-inflammatory agents on the outcome of patients with colorectal cancer. Cancer Treat Rev. 2014;40:68–77.CrossRefPubMed
20.
go back to reference Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.CrossRefPubMed Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12:19–23.CrossRefPubMed
21.
go back to reference Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRefPubMed Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer. 1994;73:2680–6.CrossRefPubMed
22.
go back to reference Huh JW, Kim HC, Lee SJ, Yun SH, Lee WY, Park YA, et al. Diagnostic accuracy and prognostic impact of restaging by magnetic resonance imaging after preoperative chemoradiotherapy in patients with rectal cancer. Radiother Oncol. 2014;113:24–8.CrossRefPubMed Huh JW, Kim HC, Lee SJ, Yun SH, Lee WY, Park YA, et al. Diagnostic accuracy and prognostic impact of restaging by magnetic resonance imaging after preoperative chemoradiotherapy in patients with rectal cancer. Radiother Oncol. 2014;113:24–8.CrossRefPubMed
23.
go back to reference Seierstad T, Hole KH, Groholt KK, Dueland S, Ree AH, Flatmark K, et al. MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer. Br J Radiol. 2015;88:20150097.CrossRefPubMedPubMedCentral Seierstad T, Hole KH, Groholt KK, Dueland S, Ree AH, Flatmark K, et al. MRI volumetry for prediction of tumour response to neoadjuvant chemotherapy followed by chemoradiotherapy in locally advanced rectal cancer. Br J Radiol. 2015;88:20150097.CrossRefPubMedPubMedCentral
24.
go back to reference Suppiah A, Hunter IA, Cowley J, Garimella V, Cast J, Hartley JE, et al. Magnetic resonance imaging accuracy in assessing tumour down-staging following chemoradiation in rectal cancer. Colorectal Dis. 2009;11:249–53.CrossRefPubMed Suppiah A, Hunter IA, Cowley J, Garimella V, Cast J, Hartley JE, et al. Magnetic resonance imaging accuracy in assessing tumour down-staging following chemoradiation in rectal cancer. Colorectal Dis. 2009;11:249–53.CrossRefPubMed
25.
go back to reference Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011;29:3753–60.CrossRefPubMed Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011;29:3753–60.CrossRefPubMed
26.
go back to reference Nougaret S, Fujii S, Addley HC, Bibeau F, Pandey H, Mikhael H, et al. Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience. J Magn Reson Imaging. 2013;38:726–32.CrossRefPubMed Nougaret S, Fujii S, Addley HC, Bibeau F, Pandey H, Mikhael H, et al. Neoadjuvant chemotherapy evaluation by MRI volumetry in rectal cancer followed by chemoradiation and total mesorectal excision: Initial experience. J Magn Reson Imaging. 2013;38:726–32.CrossRefPubMed
27.
go back to reference Aiba T, Uehara K, Nihashi T, Tsuzuki T, Yatsuya H, Yoshioka Y, et al. MRI and FDG-PET for assessment of response to neoadjuvant chemotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2014;21:1801–8.CrossRefPubMed Aiba T, Uehara K, Nihashi T, Tsuzuki T, Yatsuya H, Yoshioka Y, et al. MRI and FDG-PET for assessment of response to neoadjuvant chemotherapy in locally advanced rectal cancer. Ann Surg Oncol. 2014;21:1801–8.CrossRefPubMed
28.
go back to reference Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. 2008:109502, 2008.CrossRefPubMed Mathur N, Pedersen BK. Exercise as a mean to control low-grade systemic inflammation. Mediators Inflamm. 2008:109502, 2008.CrossRefPubMed
29.
go back to reference Sattar N, Gaw A, Scherbakova O, Ford I, O’Reilly DS, Haffner SM, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003;108:414–9.CrossRefPubMed Sattar N, Gaw A, Scherbakova O, Ford I, O’Reilly DS, Haffner SM, et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation. 2003;108:414–9.CrossRefPubMed
30.
go back to reference O’Reilly DS, Upton MN, Caslake MJ, Robertson M, Norrie J, McConnachie A, et al. Plasma C reactive protein concentration indicates a direct relation between systemic inflammation and social deprivation. Heart. 2006;92:533–5.PubMedPubMedCentral O’Reilly DS, Upton MN, Caslake MJ, Robertson M, Norrie J, McConnachie A, et al. Plasma C reactive protein concentration indicates a direct relation between systemic inflammation and social deprivation. Heart. 2006;92:533–5.PubMedPubMedCentral
31.
go back to reference Guthrie GJ, Roxburgh CS, Horgan PG, McMillan DC. Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses, and outcome in patients with colorectal cancer? Cancer Treat Rev. 2013;39:89–96.CrossRefPubMed Guthrie GJ, Roxburgh CS, Horgan PG, McMillan DC. Does interleukin-6 link explain the link between tumour necrosis, local and systemic inflammatory responses, and outcome in patients with colorectal cancer? Cancer Treat Rev. 2013;39:89–96.CrossRefPubMed
33.
go back to reference Kim IY, You SH, Kim YW. Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer. BMC Surg. 2014;14:94.CrossRefPubMedPubMedCentral Kim IY, You SH, Kim YW. Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer. BMC Surg. 2014;14:94.CrossRefPubMedPubMedCentral
34.
go back to reference Toiyama Y, Inoue Y, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, et al. Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery. Int Surg. 2015;100:199–207.CrossRefPubMedPubMedCentral Toiyama Y, Inoue Y, Kawamura M, Kawamoto A, Okugawa Y, Hiro J, et al. Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery. Int Surg. 2015;100:199–207.CrossRefPubMedPubMedCentral
35.
go back to reference Garcia-Florez LJ, Gomez-Alvarez G, Frunza AM, Barneo-Serra L, Martínez-Alonso C, Fresno-Forcelledo MF, et al. Predictive markers of response to neoadjuvant therapy in rectal cancer. J Surg Res. 2015;194:120–6.CrossRefPubMed Garcia-Florez LJ, Gomez-Alvarez G, Frunza AM, Barneo-Serra L, Martínez-Alonso C, Fresno-Forcelledo MF, et al. Predictive markers of response to neoadjuvant therapy in rectal cancer. J Surg Res. 2015;194:120–6.CrossRefPubMed
36.
go back to reference Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.CrossRefPubMed Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–90.CrossRefPubMed
Metadata
Title
The Pretreatment Systemic Inflammatory Response is an Important Determinant of Poor Pathologic Response for Patients Undergoing Neoadjuvant Therapy for Rectal Cancer
Authors
Stephan B. Dreyer, MBChB
Arfon G. M. T. Powell, MSc
Stephen T. McSorley, MBChB
Ashita Waterston, PhD
James J. Going, PhD
Joanne Edwards, PhD
Donald C. McMillan, PhD
Paul G. Horgan, PhD
Publication date
01-05-2017
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 5/2017
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5684-3

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