Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer

ObjectiveTo determine the ability of dynamic contrast enhanced (DCE-MRI) to predict pathological complete response (pCR) after preoperative chemotherapy for rectal cancer.MethodsIn a prospective clinical trial, 23/34 enrolled patients underwent pre- and post-treatment DCE-MRI performed at 1.5T. Gadolinium 0.1 mmol/kg was injected at a rate of 2 mL/s. Using a two-compartmental model of vascular space and extravascular extracellular space, Ktrans, kep, ve, AUC90, and AUC180 were calculated. Surgical specimens were the gold standard. Baseline, post-treatment and changes in these quantities were compared with clinico-pathological outcomes. For quantitative variable comparison, Spearman’s Rank correlation was used. For categorical variable comparison, the Kruskal–Wallis test was used. P ≤ 0.05 was considered significant.ResultsPercentage of histological tumour response ranged from 10 to 100%. Six patients showed pCR. Post chemotherapy Ktrans (mean 0.5 min−1 vs. 0.2 min−1, P = 0.04) differed significantly between non-pCR and pCR outcomes, respectively and also correlated with percent tumour response and pathological size. Post-treatment residual abnormal soft tissue noted in some cases of pCR prevented an MR impression of complete response based on morphology alone.ConclusionAfter neoadjuvant chemotherapy in rectal cancer, MR perfusional characteristics have been identified that can aid in the distinction between incomplete response and pCR.Key PointsDynamic contrast enhanced (DCE) MRI provides perfusion characteristics of tumours.These objective quantitative measures may be more helpful than subjective imaging aloneSome parameters differed markedly between completely responding and incompletely responding rectal cancers.Thus DCE-MRI can potentially offer treatment-altering imaging biomarkers.

[1]  Fábio Guilherme Campos,et al.  Operative Versus Nonoperative Treatment for Stage 0 Distal Rectal Cancer Following Chemoradiation Therapy: Long-term Results , 2004, Annals of surgery.

[2]  R. Byhardt Pathologic Stage Is Most Prognostic of Disease-free Survival in Locally Advanced Rectal Cancer Patients After Preoperative Chemoradiation , 2009 .

[3]  Ricky T. Tong,et al.  Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer , 2004, Nature Medicine.

[4]  A. Giaccia,et al.  The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. , 1998, Cancer research.

[5]  D J Collins,et al.  Dynamic contrast‐enhanced magnetic resonance imaging is a poor measure of rectal cancer angiogenesis , 2006, The British journal of surgery.

[6]  J. Hartley,et al.  Magnetic resonance imaging accuracy in assessing tumour down‐staging following chemoradiation in rectal cancer , 2009, Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.

[7]  A. Padhani,et al.  Perfusion MR Imaging of Extracranial Tumor Angiogenesis , 2004, Topics in magnetic resonance imaging : TMRI.

[8]  Philippe Lambin,et al.  Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer. , 2005, International journal of radiation oncology, biology, physics.

[9]  C. Capirci,et al.  Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. , 2008, International journal of radiation oncology, biology, physics.

[10]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[11]  H. Weinmann,et al.  Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. , 1984, Physiological chemistry and physics and medical NMR.

[12]  L. Schwartz,et al.  Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[13]  D. Collins,et al.  Dynamic MRI for imaging tumor microvasculature: Comparison of susceptibility and relaxivity techniques in pelvic tumors , 2007, Journal of magnetic resonance imaging : JMRI.

[14]  Arief Suriawinata,et al.  Patterns of Morphologic Alteration in Residual Rectal Carcinoma Following Preoperative Chemoradiation and Their Association With Long-term Outcome , 2004, The American journal of surgical pathology.

[15]  C. McConkey,et al.  Pathological complete response following pre-operative chemoradiotherapy in rectal cancer: analysis of phase II/III trials. , 2005, The British journal of radiology.

[16]  A. Padhani,et al.  Non‐invasive methods of assessing angiogenesis and their value in predicting response to treatment in colorectal cancer , 2001, The British journal of surgery.

[17]  P. Lambin,et al.  Comparison between perfusion computed tomography and dynamic contrast-enhanced magnetic resonance imaging in rectal cancer. , 2010, International journal of radiation oncology, biology, physics.

[18]  R. Scott,et al.  Long-Term Results , 2001 .

[19]  G Brix,et al.  Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma. , 2001, Cancer research.

[20]  J. Gama-Rodrigues,et al.  Complete Clinical Response After Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Characterization of Clinical and Endoscopic Findings for Standardization , 2010, Diseases of the colon and rectum.

[21]  Vicky Goh,et al.  Functional imaging of colorectal cancer angiogenesis. , 2007, The Lancet. Oncology.

[22]  C Kremser,et al.  Monitoring of tumor microcirculation during fractionated radiation therapy in patients with rectal carcinoma: preliminary results and implications for therapy. , 2000, Radiology.

[23]  J. BotellaLlusiá,et al.  [Long-term results]. , 1983, Anales de la Real Academia Nacional de Medicina.

[24]  S. Kety The theory and applications of the exchange of inert gas at the lungs and tissues. , 1951, Pharmacological reviews.

[25]  Viv Bewick,et al.  Statistics review 10: Further nonparametric methods , 2004, Critical care.

[26]  Rainer Fietkau,et al.  Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  Young Seok Kim,et al.  Phase II study of radiotherapy with three-dimensional conformal boost concurrent with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer. , 2005, International journal of radiation oncology, biology, physics.

[28]  C. Kremser,et al.  Dynamic T1 mapping predicts outcome of chemoradiation therapy in primary rectal carcinoma: Sequence implementation and data analysis , 2007 .

[29]  Tae Hyun Kim,et al.  Usefulness of magnetic resonance volumetric evaluation in predicting response to preoperative concurrent chemoradiotherapy in patients with resectable rectal cancer. , 2005, International journal of radiation oncology, biology, physics.

[30]  D. Sahani,et al.  Assessing tumor perfusion and treatment response in rectal cancer with multisection CT: initial observations. , 2005, Radiology.

[31]  P. Okunieff,et al.  Effect of temperature on blood flow and hypoxic fraction in a murine fibrosarcoma. , 1987, International journal of radiation oncology, biology, physics.

[32]  Lawrence H. Schwartz,et al.  Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  Rodney J Hicks,et al.  Findings on 18F-FDG PET scans after neoadjuvant chemoradiation provides prognostic stratification in patients with locally advanced rectal carcinoma subsequently treated by radical surgery. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[34]  R. Hicks,et al.  Radiation changes do not interfere with postchemoradiation restaging of patients with rectal cancer by FDG PET/CT before curative surgical therapy. , 2009, International journal of radiation oncology, biology, physics.

[35]  P. Tofts,et al.  Measurement of the blood‐brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts , 1991, Magnetic resonance in medicine.