Skip to main content
Top
Published in: Current Colorectal Cancer Reports 4/2017

01-08-2017 | Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer (JY Wo, Section Editor)

Biomarkers that Predict Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

Authors: Philmo Oh, Kevin L. Du

Published in: Current Colorectal Cancer Reports | Issue 4/2017

Login to get access

Abstract

Neoadjuvant chemoradiation has been a standard of care for locally advanced rectal cancers. Recent reports suggest that a pathologic complete response to neoadjuvant treatment correlates to improved overall survival. In addition, some series suggest that patients who have a complete response to neoadjuvant therapy may safely defer surgery in favor of a “watch and wait” approach, therefore avoiding the potential complications and adverse bowel function associated with surgery. It is therefore important to understand the clinical and biologic factors which affect the response of rectal cancers to chemoradiation. This review highlights the current literature examining the biomarkers of tumor response to chemoradiation.
Literature
3.
go back to reference • Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. doi:10.1200/JCO.2011.40.1836. This trial established the use of neoadjuvant chemoradiation in locally advanced rectal cancer. CrossRefPubMed • Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012;30(16):1926–33. doi:10.​1200/​JCO.​2011.​40.​1836. This trial established the use of neoadjuvant chemoradiation in locally advanced rectal cancer. CrossRefPubMed
4.
go back to reference Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30(31):3827–33. doi:10.1200/JCO.2012.42.9597.CrossRefPubMed Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012;30(31):3827–33. doi:10.​1200/​JCO.​2012.​42.​9597.CrossRefPubMed
5.
go back to reference Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23. doi:10.1002/bjs.5506.CrossRefPubMed Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. 2006;93(10):1215–23. doi:10.​1002/​bjs.​5506.CrossRefPubMed
6.
go back to reference • Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, Proscurshim I, Sabbagh C, Lynn PB, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88(4):822–8. doi:10.1016/j.ijrobp.2013.12.012. A key study demonstrating the feasibility of the watch and wait approach with early salvage surgery. CrossRefPubMed • Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP, Proscurshim I, Sabbagh C, Lynn PB, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88(4):822–8. doi:10.​1016/​j.​ijrobp.​2013.​12.​012. A key study demonstrating the feasibility of the watch and wait approach with early salvage surgery. CrossRefPubMed
7.
go back to reference Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44. doi:10.1016/S1470-2045(10)70172-8.CrossRefPubMed Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835–44. doi:10.​1016/​S1470-2045(10)70172-8.CrossRefPubMed
8.
go back to reference Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99(7):918–28. doi:10.1002/bjs.8702.CrossRefPubMed Martin ST, Heneghan HM, Winter DC. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer. Br J Surg. 2012;99(7):918–28. doi:10.​1002/​bjs.​8702.CrossRefPubMed
9.
go back to reference • Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16(8):979–89. doi:10.1016/S1470-2045(15)00159-X. The addition of oxaliplatin increased preoperative acute grade 3–4 toxicities but also increased 3 year DFS. CrossRefPubMed • Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16(8):979–89. doi:10.​1016/​S1470-2045(15)00159-X. The addition of oxaliplatin increased preoperative acute grade 3–4 toxicities but also increased 3 year DFS. CrossRefPubMed
10.
go back to reference • Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957–66. doi:10.1016/S1470-2045(15)00004-2. This study demonstrates increased pCR with intensification of neoadjuvant therapy at the expense of increased toxicities. CrossRefPubMedPubMedCentral • Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957–66. doi:10.​1016/​S1470-2045(15)00004-2. This study demonstrates increased pCR with intensification of neoadjuvant therapy at the expense of increased toxicities. CrossRefPubMedPubMedCentral
11.
go back to reference van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, 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;12(6):575–82. doi:10.1016/S1470-2045(11)70097-3.CrossRefPubMed van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, 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;12(6):575–82. doi:10.​1016/​S1470-2045(11)70097-3.CrossRefPubMed
14.
go back to reference Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10(10):1319–1328; discussion 28–9. doi:10.1016/j.gassur.2006.09.005.CrossRefPubMed Habr-Gama A, Perez RO, Proscurshim I, Campos FG, Nadalin W, Kiss D, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10(10):1319–1328; discussion 28–9. doi:10.​1016/​j.​gassur.​2006.​09.​005.CrossRefPubMed
15.
go back to reference •• Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711–7. discussion 7–8 This is the demonstration with long term follow up demonstrating excellent results without surgery in patients with a complete clinical response. PubMedPubMedCentral •• Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U Jr, Silva e Sousa AH Jr, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711–7. discussion 7–8 This is the demonstration with long term follow up demonstrating excellent results without surgery in patients with a complete clinical response. PubMedPubMedCentral
16.
go back to reference • Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40. doi:10.1200/JCO.2011.37.7176. A series from MSKCC also demonstrating the potential of non-operative management after a complete response to neoadjuvant therapy in locally advanced rectal cancer. CrossRefPubMed • Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29(35):4633–40. doi:10.​1200/​JCO.​2011.​37.​7176. A series from MSKCC also demonstrating the potential of non-operative management after a complete response to neoadjuvant therapy in locally advanced rectal cancer. CrossRefPubMed
18.
go back to reference van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6. doi:10.1038/415530a.CrossRef van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6. doi:10.​1038/​415530a.CrossRef
19.
20.
go back to reference Kim IJ, Lim SB, Kang HC, Chang HJ, Ahn SA, Park HW, et al. Microarray gene expression profiling for predicting complete response to preoperative chemoradiotherapy in patients with advanced rectal cancer. Dis Colon Rectum. 2007;50(9):1342–53. doi:10.1007/s10350-007-277-7.CrossRefPubMed Kim IJ, Lim SB, Kang HC, Chang HJ, Ahn SA, Park HW, et al. Microarray gene expression profiling for predicting complete response to preoperative chemoradiotherapy in patients with advanced rectal cancer. Dis Colon Rectum. 2007;50(9):1342–53. doi:10.​1007/​s10350-007-277-7.CrossRefPubMed
21.
go back to reference Brettingham-Moore KH, Duong CP, Greenawalt DM, Heriot AG, Ellul J, Dow CA, et al. Pretreatment transcriptional profiling for predicting response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma. Clin Cancer Res. 2011;17(9):3039–47. doi:10.1158/1078-0432.CCR-10-2915.CrossRefPubMed Brettingham-Moore KH, Duong CP, Greenawalt DM, Heriot AG, Ellul J, Dow CA, et al. Pretreatment transcriptional profiling for predicting response to neoadjuvant chemoradiotherapy in rectal adenocarcinoma. Clin Cancer Res. 2011;17(9):3039–47. doi:10.​1158/​1078-0432.​CCR-10-2915.CrossRefPubMed
22.
go back to reference • Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, et al. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol. 2005;23(9):1826–38. doi:10.1200/JCO.2005.00.406. This study identified a gene set from pretreatment biopsies collected in the German Rectal Cancer Trial. CrossRefPubMedPubMedCentral • Ghadimi BM, Grade M, Difilippantonio MJ, Varma S, Simon R, Montagna C, et al. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol. 2005;23(9):1826–38. doi:10.​1200/​JCO.​2005.​00.​406. This study identified a gene set from pretreatment biopsies collected in the German Rectal Cancer Trial. CrossRefPubMedPubMedCentral
23.
go back to reference Rimkus C, Friederichs J, Boulesteix AL, Theisen J, Mages J, Becker K, et al. Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol. 2008;6(1):53–61. doi:10.1016/j.cgh.2007.10.022.CrossRefPubMed Rimkus C, Friederichs J, Boulesteix AL, Theisen J, Mages J, Becker K, et al. Microarray-based prediction of tumor response to neoadjuvant radiochemotherapy of patients with locally advanced rectal cancer. Clin Gastroenterol Hepatol. 2008;6(1):53–61. doi:10.​1016/​j.​cgh.​2007.​10.​022.CrossRefPubMed
24.
go back to reference Lopes-Ramos C, Koyama FC, Habr-Gama A, Salim AC, Bettoni F, Asprino PF, et al. Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer. Cancer Genet. 2015;208(6):319–26. doi:10.1016/j.cancergen.2015.03.010.CrossRefPubMed Lopes-Ramos C, Koyama FC, Habr-Gama A, Salim AC, Bettoni F, Asprino PF, et al. Comprehensive evaluation of the effectiveness of gene expression signatures to predict complete response to neoadjuvant chemoradiotherapy and guide surgical intervention in rectal cancer. Cancer Genet. 2015;208(6):319–26. doi:10.​1016/​j.​cancergen.​2015.​03.​010.CrossRefPubMed
25.
go back to reference •• Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6. doi:10.1038/nm.3967. This is an excellent resource that for the first time pooled several large datasets to generate consensus molecular subtypes in colorectal cancer. CrossRefPubMedPubMedCentral •• Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, et al. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015;21(11):1350–6. doi:10.​1038/​nm.​3967. This is an excellent resource that for the first time pooled several large datasets to generate consensus molecular subtypes in colorectal cancer. CrossRefPubMedPubMedCentral
26.
go back to reference Nicholson BD, Shinkins B, Pathiraja I, Roberts NW, James TJ, Mallett S, et al. Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev. 2015;12:CD011134. doi:10.1002/14651858.CD011134.pub2. Nicholson BD, Shinkins B, Pathiraja I, Roberts NW, James TJ, Mallett S, et al. Blood CEA levels for detecting recurrent colorectal cancer. Cochrane Database Syst Rev. 2015;12:CD011134. doi:10.​1002/​14651858.​CD011134.​pub2.
28.
go back to reference Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750–5. doi:10.1002/cncr.22625.CrossRefPubMed Das P, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Wolff RA, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer. 2007;109(9):1750–5. doi:10.​1002/​cncr.​22625.CrossRefPubMed
29.
go back to reference Zeng WG, Liang JW, Wang Z, Zhang XM, Hu JJ, Hou HR, et al. Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Chin J Cancer. 2015;34(10):468–74. doi:10.1186/s40880-015-0033-7.PubMed Zeng WG, Liang JW, Wang Z, Zhang XM, Hu JJ, Hou HR, et al. Clinical parameters predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer. Chin J Cancer. 2015;34(10):468–74. doi:10.​1186/​s40880-015-0033-7.PubMed
30.
go back to reference Kleiman A, Al-Khamis A, Farsi A, Kezouh A, Vuong T, Gordon PH, et al. Normalization of CEA levels post-neoadjuvant therapy is a strong predictor of pathologic complete response in rectal cancer. J Gastrointest Surg. 2015;19(6):1106–12. doi:10.1007/s11605-015-2814-3.CrossRefPubMed Kleiman A, Al-Khamis A, Farsi A, Kezouh A, Vuong T, Gordon PH, et al. Normalization of CEA levels post-neoadjuvant therapy is a strong predictor of pathologic complete response in rectal cancer. J Gastrointest Surg. 2015;19(6):1106–12. doi:10.​1007/​s11605-015-2814-3.CrossRefPubMed
32.
go back to reference Agostini M, Pucciarelli S, Enzo MV, Del Bianco P, Briarava M, Bedin C, et al. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol. 2011;18(9):2461–8. doi:10.1245/s10434-011-1638-y.CrossRefPubMed Agostini M, Pucciarelli S, Enzo MV, Del Bianco P, Briarava M, Bedin C, et al. Circulating cell-free DNA: a promising marker of pathologic tumor response in rectal cancer patients receiving preoperative chemoradiotherapy. Ann Surg Oncol. 2011;18(9):2461–8. doi:10.​1245/​s10434-011-1638-y.CrossRefPubMed
33.
go back to reference Pucciarelli S, Rampazzo E, Briarava M, Maretto I, Agostini M, Digito M, et al. Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as predictors of pathologic tumor response in rectal cancer patients receiving neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2012;19(9):3089–96. doi:10.1245/s10434-012-2272-z.CrossRefPubMed Pucciarelli S, Rampazzo E, Briarava M, Maretto I, Agostini M, Digito M, et al. Telomere-specific reverse transcriptase (hTERT) and cell-free RNA in plasma as predictors of pathologic tumor response in rectal cancer patients receiving neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2012;19(9):3089–96. doi:10.​1245/​s10434-012-2272-z.CrossRefPubMed
34.
go back to reference •• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4. doi:10.1126/science.1129139. This is the first publication demonstrating the potential of using characteristics of the immune microenvironment to predict outcomes. CrossRefPubMed •• Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4. doi:10.​1126/​science.​1129139. This is the first publication demonstrating the potential of using characteristics of the immune microenvironment to predict outcomes. CrossRefPubMed
35.
go back to reference Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29(6):610–8. doi:10.1200/JCO.2010.30.5425.CrossRefPubMed Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, et al. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011;29(6):610–8. doi:10.​1200/​JCO.​2010.​30.​5425.CrossRefPubMed
36.
37.
go back to reference •• Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N, Todosi AM, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res. 2014;20(7):1891–9. doi:10.1158/1078-0432.CCR-13-2830. The authors demonstrate that the pretreatment density of T cell infiltrate is predictive of response to neoadjuvant chemoradiation. CrossRefPubMed •• Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N, Todosi AM, et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res. 2014;20(7):1891–9. doi:10.​1158/​1078-0432.​CCR-13-2830. The authors demonstrate that the pretreatment density of T cell infiltrate is predictive of response to neoadjuvant chemoradiation. CrossRefPubMed
39.
go back to reference Saigusa S, Toiyama Y, Tanaka K, Inoue Y, Mori K, Ide S, et al. Implication of programmed cell death ligand 1 expression in tumor recurrence and prognosis in rectal cancer with neoadjuvant chemoradiotherapy. Int J Clin Oncol. 2016;21(5):946–52. doi:10.1007/s10147-016-0962-4.CrossRefPubMed Saigusa S, Toiyama Y, Tanaka K, Inoue Y, Mori K, Ide S, et al. Implication of programmed cell death ligand 1 expression in tumor recurrence and prognosis in rectal cancer with neoadjuvant chemoradiotherapy. Int J Clin Oncol. 2016;21(5):946–52. doi:10.​1007/​s10147-016-0962-4.CrossRefPubMed
40.
go back to reference Shinto E, Hase K, Hashiguchi Y, Sekizawa A, Ueno H, Shikina A, et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2014;21(Suppl 3):S414–21. doi:10.1245/s10434-014-3584-y.CrossRefPubMed Shinto E, Hase K, Hashiguchi Y, Sekizawa A, Ueno H, Shikina A, et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer. Ann Surg Oncol. 2014;21(Suppl 3):S414–21. doi:10.​1245/​s10434-014-3584-y.CrossRefPubMed
41.
go back to reference McCoy MJ, Hemmings C, Anyaegbu CC, Austin SJ, Lee-Pullen TF, Miller TJ, et al. Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response. Oncotarget. 2017; doi:10.18632/oncotarget.15048. McCoy MJ, Hemmings C, Anyaegbu CC, Austin SJ, Lee-Pullen TF, Miller TJ, et al. Tumour-infiltrating regulatory T cell density before neoadjuvant chemoradiotherapy for rectal cancer does not predict treatment response. Oncotarget. 2017; doi:10.​18632/​oncotarget.​15048.​
42.
45.
go back to reference Dou X, Wang RB, Yan HJ, Jiang SM, Meng XJ, Zhu KL, et al. Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases. Asian Pac J Cancer Prev. 2013;14(6):3881–5.CrossRefPubMed Dou X, Wang RB, Yan HJ, Jiang SM, Meng XJ, Zhu KL, et al. Circulating lymphocytes as predictors of sensitivity to preoperative chemoradiotherapy in rectal cancer cases. Asian Pac J Cancer Prev. 2013;14(6):3881–5.CrossRefPubMed
46.
go back to reference Hasegawa S, Eguchi H, Tomokuni A, Tomimaru Y, Asaoka T, Wada H, et al. Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer. Oncol Lett. 2016;11(2):1560–6. doi:10.3892/ol.2015.4057.PubMed Hasegawa S, Eguchi H, Tomokuni A, Tomimaru Y, Asaoka T, Wada H, et al. Pre-treatment neutrophil to lymphocyte ratio as a predictive marker for pathological response to preoperative chemoradiotherapy in pancreatic cancer. Oncol Lett. 2016;11(2):1560–6. doi:10.​3892/​ol.​2015.​4057.PubMed
49.
go back to reference Shen J, Zhu Y, Wu W, Zhang L, Ju H, Fan Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Med Sci Monit. 2017;23:315–24.CrossRefPubMedPubMedCentral Shen J, Zhu Y, Wu W, Zhang L, Ju H, Fan Y, et al. Prognostic role of neutrophil-to-lymphocyte ratio in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Med Sci Monit. 2017;23:315–24.CrossRefPubMedPubMedCentral
51.
go back to reference •• Taylor FG, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol. 2014;32(1):34–43. doi:10.1200/JCO.2012.45.3258. This is a well-designed clinical trial designed to assess accuracy of MRI in predicting the pathologic surgical margin. CrossRefPubMed •• Taylor FG, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol. 2014;32(1):34–43. doi:10.​1200/​JCO.​2012.​45.​3258. This is a well-designed clinical trial designed to assess accuracy of MRI in predicting the pathologic surgical margin. CrossRefPubMed
52.
go back to reference Lambrecht M, Vandecaveye V, De Keyzer F, Roels S, Penninckx F, Van Cutsem E, et al. Value of diffusion-weighted magnetic resonance imaging for prediction and early assessment of response to neoadjuvant radiochemotherapy in rectal cancer: preliminary results. Int J Radiat Oncol Biol Phys. 2012;82(2):863–70. doi:10.1016/j.ijrobp.2010.12.063.CrossRefPubMed Lambrecht M, Vandecaveye V, De Keyzer F, Roels S, Penninckx F, Van Cutsem E, et al. Value of diffusion-weighted magnetic resonance imaging for prediction and early assessment of response to neoadjuvant radiochemotherapy in rectal cancer: preliminary results. Int J Radiat Oncol Biol Phys. 2012;82(2):863–70. doi:10.​1016/​j.​ijrobp.​2010.​12.​063.CrossRefPubMed
53.
go back to reference Genovesi D, Filippone A, Ausili Cefaro G, Trignani M, Vinciguerra A, Augurio A, et al. Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study. Eur J Surg Oncol. 2013;39(10):1071–8. doi:10.1016/j.ejso.2013.07.090.CrossRefPubMed Genovesi D, Filippone A, Ausili Cefaro G, Trignani M, Vinciguerra A, Augurio A, et al. Diffusion-weighted magnetic resonance for prediction of response after neoadjuvant chemoradiation therapy for locally advanced rectal cancer: preliminary results of a monoinstitutional prospective study. Eur J Surg Oncol. 2013;39(10):1071–8. doi:10.​1016/​j.​ejso.​2013.​07.​090.CrossRefPubMed
54.
go back to reference Sun YS, Zhang XP, Tang L, Ji JF, Gu J, Cai Y, et al. Locally advanced rectal carcinoma treated with preoperative chemotherapy and radiation therapy: preliminary analysis of diffusion-weighted MR imaging for early detection of tumor histopathologic downstaging. Radiology. 2010;254(1):170–8. doi:10.1148/radiol.2541082230.CrossRefPubMed Sun YS, Zhang XP, Tang L, Ji JF, Gu J, Cai Y, et al. Locally advanced rectal carcinoma treated with preoperative chemotherapy and radiation therapy: preliminary analysis of diffusion-weighted MR imaging for early detection of tumor histopathologic downstaging. Radiology. 2010;254(1):170–8. doi:10.​1148/​radiol.​2541082230.CrossRefPubMed
55.
go back to reference Tong T, Sun Y, Gollub MJ, Peng W, Cai S, Zhang Z, et al. Dynamic contrast-enhanced MRI: use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer. J Magn Reson Imaging. 2015;42(3):673–80. doi:10.1002/jmri.24835.CrossRefPubMed Tong T, Sun Y, Gollub MJ, Peng W, Cai S, Zhang Z, et al. Dynamic contrast-enhanced MRI: use in predicting pathological complete response to neoadjuvant chemoradiation in locally advanced rectal cancer. J Magn Reson Imaging. 2015;42(3):673–80. doi:10.​1002/​jmri.​24835.CrossRefPubMed
57.
go back to reference Intven M, Reerink O, Philippens ME. Dynamic contrast enhanced MR imaging for rectal cancer response assessment after neo-adjuvant chemoradiation. J Magn Reson Imaging. 2015;41(6):1646–53. doi:10.1002/jmri.24718.CrossRefPubMed Intven M, Reerink O, Philippens ME. Dynamic contrast enhanced MR imaging for rectal cancer response assessment after neo-adjuvant chemoradiation. J Magn Reson Imaging. 2015;41(6):1646–53. doi:10.​1002/​jmri.​24718.CrossRefPubMed
58.
go back to reference Martoni AA, Di Fabio F, Pinto C, Castellucci P, Pini S, Ceccarelli C, et al. Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol. 2011;22(3):650–6. doi:10.1093/annonc/mdq433.CrossRefPubMed Martoni AA, Di Fabio F, Pinto C, Castellucci P, Pini S, Ceccarelli C, et al. Prospective study on the FDG-PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol. 2011;22(3):650–6. doi:10.​1093/​annonc/​mdq433.CrossRefPubMed
60.
go back to reference Niccoli-Asabella A, Altini C, De Luca R, Fanelli M, Rubini D, Caliandro C, et al. Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery. Biomed Res Int. 2014;2014:952843. doi:10.1155/2014/952843.PubMedPubMedCentral Niccoli-Asabella A, Altini C, De Luca R, Fanelli M, Rubini D, Caliandro C, et al. Prospective analysis of 18F-FDG PET/CT predictive value in patients with low rectal cancer treated with neoadjuvant chemoradiotherapy and conservative surgery. Biomed Res Int. 2014;2014:952843. doi:10.​1155/​2014/​952843.PubMedPubMedCentral
61.
go back to reference Capirci C, Rubello D, Pasini F, Galeotti F, Bianchini E, Del Favero G, et al. The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery. Int J Radiat Oncol Biol Phys. 2009;74(5):1461–9. doi:10.1016/j.ijrobp.2008.10.064.CrossRefPubMed Capirci C, Rubello D, Pasini F, Galeotti F, Bianchini E, Del Favero G, et al. The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery. Int J Radiat Oncol Biol Phys. 2009;74(5):1461–9. doi:10.​1016/​j.​ijrobp.​2008.​10.​064.CrossRefPubMed
62.
go back to reference • Dunne PD, McArt DG, Bradley CA, O'Reilly PG, Barrett HL, Cummins R, et al. Challenging the cancer molecular stratification dogma: intratumoral heterogeneity undermines consensus molecular subtypes and potential diagnostic value in colorectal cancer. Clin Cancer Res. 2016;22(16):4095–104. doi:10.1158/1078-0432.CCR-16-0032. This work highlights the caveats of using the CMS subtypes and potential source of variability as a result of intratumor heterogeneity. CrossRefPubMed • Dunne PD, McArt DG, Bradley CA, O'Reilly PG, Barrett HL, Cummins R, et al. Challenging the cancer molecular stratification dogma: intratumoral heterogeneity undermines consensus molecular subtypes and potential diagnostic value in colorectal cancer. Clin Cancer Res. 2016;22(16):4095–104. doi:10.​1158/​1078-0432.​CCR-16-0032. This work highlights the caveats of using the CMS subtypes and potential source of variability as a result of intratumor heterogeneity. CrossRefPubMed
64.
go back to reference Kalady MF, de Campos-Lobato LF, Stocchi L, Geisler DP, Dietz D, Lavery IC, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250(4):582–9. doi:10.1097/SLA.0b013e3181b91e63.PubMed Kalady MF, de Campos-Lobato LF, Stocchi L, Geisler DP, Dietz D, Lavery IC, et al. Predictive factors of pathologic complete response after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250(4):582–9. doi:10.​1097/​SLA.​0b013e3181b91e63​.PubMed
65.
go back to reference Wolthuis AM, Penninckx F, Haustermans K, De Hertogh G, Fieuws S, Van Cutsem E, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 2012;19(9):2833–41. doi:10.1245/s10434-012-2327-1.CrossRefPubMed Wolthuis AM, Penninckx F, Haustermans K, De Hertogh G, Fieuws S, Van Cutsem E, et al. Impact of interval between neoadjuvant chemoradiotherapy and TME for locally advanced rectal cancer on pathologic response and oncologic outcome. Ann Surg Oncol. 2012;19(9):2833–41. doi:10.​1245/​s10434-012-2327-1.CrossRefPubMed
66.
Metadata
Title
Biomarkers that Predict Response to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer
Authors
Philmo Oh
Kevin L. Du
Publication date
01-08-2017
Publisher
Springer US
Published in
Current Colorectal Cancer Reports / Issue 4/2017
Print ISSN: 1556-3790
Electronic ISSN: 1556-3804
DOI
https://doi.org/10.1007/s11888-017-0376-3

Other articles of this Issue 4/2017

Current Colorectal Cancer Reports 4/2017 Go to the issue

Genetic Syndromes, Screening, and Surveillance in Colorectal Cancer (N Kubiliun, Section Editor)

Adenomatous Polyposis Syndromes: Familial Adenomatous Polyposis and MutYH-Associated Polyposis

Genetic Syndromes, Screening, and Surveillance in Colorectal Cancer (N Kubiliun, Section Editor)

The Role of CT Colonography as a Screening Tool for Colorectal Cancer

Genetic Syndromes, Screening, and Surveillance in Colorectal Cancer (N Kubiliun, Section Editor)

Colorectal Cancer Surveillance: What Is the Optimal Frequency of Follow-up and Which Tools Best Predict Recurrence?

Genetic Syndromes, Screening, and Surveillance in Colorectal Cancer (N Kubiliun, Section Editor)

Quality Colorectal Cancer Screening: Endoscopic Performance Measures and Beyond

Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer (JY Wo, Section Editor)

Clinical Target Volume Definition in Preoperative Radiotherapy of Rectal Carcinoma: a Systematic Review

Systemic Therapies in Colorectal Cancer (RD Kim, Section Editor)

Treatment of Refractory Colorectal Cancer: Regorafenib vs. TAS-102

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine