Objectives: Our aim was to assess FDG-PET/CT as a surrogate biomarker of the pathological complete response in locally advanced rectal cancer treated with neoadjuvant chemoradiation. Methods: T3–4 and/or N+ rectal cancer patients were treated prospectively with capecitabine-based chemoradiation and total mesorectal excision 7–8 weeks later. FDG-PET/CT uptake was obtained at baseline, after 2 weeks, and 6 weeks following treatment completion, calculating the maximum standardized uptake value (SUV) and percentage difference to identify the early and late metabolic ‘response index’. Results: Thirty-one patients were treated from January 2009 to January 2012 at the Istituto Nazionale dei Tumori of Milan. One patient was excluded due to surgery refusal. The pathological complete response rate was 30%. Early FDG-PET/CT was performed in 24 consenting patients and failed to show predictive utility. On the contrary, significant differences in late SUV value and response index were observed between complete and noncomplete pathological responders (p = 0.0006 and 0.03). In multivariate analysis including most relevant SUV parameters, none of them was independently associated with a pathological complete response. With receiver operating characteristic curve analysis, a late SUV threshold <5.4 had 81% sensitivity and 100% specificity, with 90% overall accuracy. Conclusions: We evidenced a possible predictive role of late FDG-PET/CT for the assessment of pathological response in locally advanced rectal cancer following neoadjuvant chemoradiation.

1.
Gunderson LL, Sargent DJ, Tepper JE: Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis. Int J Radiat Oncol Biol Phys 2002;54:386–396.
2.
Sauer R, Becker H, Hohenberger W: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–1740.
3.
Nelson H, Sargent DJ: Refining multimodal therapy for rectal cancer. N Engl J Med 2011;345:690–692.
4.
Kapiteijn E, Marijnen CA, Nagtegaal ID, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–646.
5.
Janjan NA, Khoo VS, Abbruzzese J: Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44:1027–1038.
6.
Glynne-Jones R, Harrison M: Locally advanced rectal cancer: what is the evidence for induction chemoradiation? Oncologist 2007;12:1309–1318.
7.
Crane CH, Skibber JM, Feig BW: Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 2003;97:517–524.
8.
Gavioli M, Bagni A, Piccagli I: Usefulness of endorectal ultrasound after preoperative radiotherapy in rectal cancer: comparison between sonographic and histopathologic changes. Dis Colon Rectum 2000;43:1075–1083.
9.
Suppiah A, Hunter IA, Cowley J: Magnetic resonance imaging accuracy in assessing tumor down-staging following chemoradiation in rectal cancer. Colorectal Dis 2009;11:249–253.
10.
Bipat S, Glas AS, Slors FJ: Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging – a meta-analysis. Radiology 2004;232:773–783.
11.
Ciccocioppo A, Stephens JH, Hewett PJ: Complete pathologic response after preoperative rectal cancer chemoradiotherapy. ANZ J Surg 2009;79:481–484.
12.
Rodel C, Martus P, Papadoupolos T: Prognostic significance of tumor regression after preoperative chemoradiation for rectal cancer. J Clin Oncol 2006;23:8688–8696.
13.
Capirci C, Valentini V, Cionini L: Prognostic value of pathologic complete response after neoadjuvant therapy for locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 2008;72:99–107.
14.
Habr-Gama A, Perez RO, Nadalin W: Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 2004;240:711–718.
15.
Glynne-Jones R, Wallace M, Livingstone JI: Complete clinical response after preoperative chemoradiation in rectal cancer: is a ‘wait and see’ policy justified? Dis Colon Rectum 2008;51:10–20.
16.
O’Neill BD, Brown G, Heald RJ: Nonoperative treatment after neoadjuvant chemoradiotherapy for rectal cancer. Lancet Oncol 2007;8:625–633.
17.
Maas M, Beets-Tan RG, Lambregts DM: Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 2011;29:4633–4640.
18.
Chavaudra J: Last ICRU recommendations for the prescription, recording and reporting of external bean therapy. Cancer Radiother 1998;2:607–614.
19.
Kim JS, Kim JS, Cho MJ: Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002;54:403–408.
20.
Mandard AM, Dalibard F, Mandard JC: Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma: clinicopathologic correlations. Cancer 1994;73:2680–2686.
21.
Kinahan PE, Fletcher JW: Positron emission tomography-computed tomography standardized uptake values in clinical practice and assessing response to therapy. Semin Ultrasound CT MR 2010;31:496–505.
22.
Young H, Baum R, Cremerius U: Measurement of clinical and subclinical tumour response using [18 F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations – European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999;35:1773–1782.
23.
Roh MS, Colangelo LH, O’Connell MJ: Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 2009;27:5124–5130.
24.
Valentini V, Coco C, Picciocchi A: 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.
25.
Bouzourene H, Bosman FT, Seelentag W: 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.
26.
Hiotis SP, Weber SM, Cohen AM: Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg 2002;194:131–135.
27.
Guillem J, Chessin D, Shia J: Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol 2005;23:3475–3479.
28.
Kahn H, Alexander A, Rakinic J: Preoperative staging of irradiated rectal cancers using digital rectal examination, computed tomography, endorectal ultrasound, and magnetic resonance imaging does not accurately predict T0, N0 pathology. Dis Colon Rectum 1997;40:140–144.
29.
de Geus-Oei LF, Vriens D, van Laarhoven HW: Monitoring and predicting response to therapy with 18F-FDG PET in colorectal cancer: a systematic review. J Nucl Med 2009;50(suppl 1):43S–54S.
30.
Capirci C, Rubello D, Chierichetti F: Restaging after neoadjuvant chemoradiotherapy for rectal adenocarcinoma: role of F18-FDG PET. Biomed Pharmacother 2004;58:451–457.
31.
Capirci C, Rubello D, Chierichetti F: Long-term prognostic value of 18-F-FDG PET in patients with locally advanced rectal cancer previously treated with neoadjuvant radiochemotherapy. Am J Roentgenol 2006;187:202–208.
32.
Capirci C, Rubello D, Pasini F: The role of dual-time combined 18-fluorideoxyglucose 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 Radiation Biol Phys 2009;74:1461–1469.
33.
Martoni AA, Di Fabio F, Pinto C: Prospective study on the FDG-PET/TC predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer. Ann Oncol 2011;22:650–656.
34.
Yeung JMC, Kalff V, Hicks RJ: Metabolic response of rectal cancer assessed by 18-FDG PET following chemoradiotherapy is prognostic for patient outcome. Dis Colon Rectum 2011;54:518–525.
35.
Kalff V, Duong C, Drummond EG: Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. J Nucl Med 2006;47:14–22.
36.
Janssen MHM, Öllers MC, van Stiphout RGPM: PET-based treatment response evaluation in rectal cancer: prediction and validation. Int J Radiation Biol Phys 2012;82:871–876.
37.
Rosenberg R, Herrmann K, Gertler R: The predictive value of metabolic response to preoperative radiochemotherapy in locally advanced rectal cancer measured by PET/CT. Int J Colorectal Dis 2009;24:191–200.
38.
Zhang C, Tong J, Sun X: 18F-FDG-PET evaluation of treatment response to neo-adjuvant therapy in patients with locally advanced rectal cancer: a meta-analysis. Int J Cancer 2012;131:2604–2611.
39.
Sawada N, Ishikawa T, Sekiguchi F: X-ray irradiation induces thymidine phosphorilase and enhance the efficacy of capecitabine in human cancer xenograft. Clin Cancer Res 1999;5:2948–2953.
40.
Hofheinz R, Wenz F, Post S: Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): long-term results of a randomized, phase III trial (abstract 3504). 2011 ASCO Annu Meet, Chicago, 2011.
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