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.

PURPOSE To determine whether changes in apparent diffusion coefficients (ADCs) of rectal carcinoma obtained 1 week after the beginning of chemotherapy and radiation therapy (CRT) correlate with tumor histopathologic downstaging after preoperative CRT. MATERIALS AND METHODS This prospective study was approved by an institutional review board; informed consent was obtained from all patients. Thirty-seven patients (mean age, 54.7 years; 13 women, 24 men) with primary rectal carcinoma who were undergoing preoperative CRT were recruited for the study. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed with a 1.5-T MR imager in all patients before therapy, at the end of the 1st and 2nd week of therapy, and before surgery. Tumor ADCs were calculated. Linear mixed-effects modeling was applied to analyze change in ADCs and volumes following treatment. RESULTS Patients were assigned to the tumor downstaged group (n = 17) or the tumor nondownstaged group (n = 20) on the basis of histopathologic examination results following surgery. Before CRT, the mean tumor ADC in the downstaged group was lower than that in the nondownstaged group (1.07 x 10(-3) mm(2)/sec +/- 0.13 [standard deviation] vs 1.19 x 10(-3) mm(2)/sec +/- 0.15, F = 6.91, P = .013). At the end of the 1st week of CRT, the mean tumor ADC increased significantly from 1.07 x 10(-3) mm(2)/sec +/- 0.13 to 1.32 x 10(-3) mm(2)/sec +/- 0.16 (F = 37.63, P <.001) in the downstaged group, but there was no significant ADC increase in the nondownstaged group (F = 1.18, P = .291). The mean percentage of tumor ADC change in the downstaged group was significantly higher than that in the nondownstaged group at each time point (F = 18.39, P < .001). CONCLUSION Early increase of mean tumor ADC and low pretherapy mean ADC in rectal carcinoma correlate with good response to CRT. DW MR imaging is a promising noninvasive technique for helping predict and monitor early therapeutic response in patients with rectal carcinoma who are undergoing CRT.

[1]  R. Kauppinen,et al.  Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging. , 1998, Cancer gene therapy.

[2]  Peter Gibbs,et al.  Diffusion changes precede size reduction in neoadjuvant treatment of breast cancer. , 2006, Magnetic resonance imaging.

[3]  S. Maier,et al.  High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice. , 2004, Radiology.

[4]  Olav Haraldseth,et al.  Measurement of cell density and necrotic fraction in human melanoma xenografts by diffusion weighted magnetic resonance imaging , 2000, Magnetic resonance in medicine.

[5]  R. Kauppinen,et al.  Quantitative 1H nuclear magnetic resonance diffusion spectroscopy of BT4C rat glioma during thymidine kinase-mediated gene therapy in vivo: identification of apoptotic response. , 1998, Cancer research.

[6]  G. Calais,et al.  Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications. , 1997, International journal of radiation oncology, biology, physics.

[7]  J. Monson,et al.  Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial , 2009, The Lancet.

[8]  Jean-Philippe Galons,et al.  Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI. , 2002, Neoplasia.

[9]  E. Espinosa,et al.  Neoadjuvant therapy of rectal carcinoma with UFT-leucovorin plus radiotherapy. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[10]  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.

[11]  Jürgen Griebel,et al.  Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma. , 2003, International journal of radiation oncology, biology, physics.

[12]  D. Collins,et al.  Predicting response of colorectal hepatic metastasis: value of pretreatment apparent diffusion coefficients. , 2007, AJR. American journal of roentgenology.

[13]  Y. Ni,et al.  Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats. , 2005, Radiology.

[14]  Jan Wolber,et al.  Diffusion MRI for prediction of response of rectal cancer to chemoradiation , 2002, The Lancet.

[15]  C. Taylor,et al.  T-Level Downstaging and Complete Pathologic Response After Preoperative Chemoradiation for Advanced Rectal Cancer Result in Decreased Recurrence and Improved Disease-Free Survival , 2002, Diseases of the colon and rectum.

[16]  T L Chenevert,et al.  Monitoring early response of experimental brain tumors to therapy using diffusion magnetic resonance imaging. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  M. Climent,et al.  Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  L. Shen,et al.  Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic metastases. , 2008, Radiology.

[19]  R. Gillies,et al.  Dynamic Contrast-Enhanced and Diffusion MRI Show Rapid and Dramatic Changes in Tumor Microenvironment in Response to Inhibition of HIF-1 A Using PX-4781 , 2005 .

[20]  Alexander de Vries,et al.  Preliminary Results on the Influence of Chemoradiation on Apparent Diffusion Coefficients of Primary Rectal Carcinoma Measured by Magnetic Resonance Imaging , 2003, Strahlentherapie und Onkologie.

[21]  R. Gillies,et al.  Early increases in breast tumor xenograft water mobility in response to paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging. , 1999, Neoplasia.

[22]  A. Rehemtulla,et al.  Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy , 2000, Gene Therapy.

[23]  K. Keum,et al.  A comparative study of volumetric analysis, histopathologic downstaging, and tumor regression grade in evaluating tumor response in locally advanced rectal cancer following preoperative chemoradiation. , 2007, International journal of radiation oncology, biology, physics.

[24]  J. Geschwind,et al.  Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis. , 2000, Journal of vascular and interventional radiology : JVIR.

[25]  Bradford A Moffat,et al.  Therapeutic Efficacy of DTI-015 using Diffusion Magnetic Resonance Imaging as an Early Surrogate Marker , 2004, Clinical Cancer Research.

[26]  A. Padhani,et al.  Rectal carcinoma: MRI with histologic correlation before and after chemoradiation therapy. , 2007, AJR. American journal of roentgenology.

[27]  S E Maier,et al.  Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffusion-weighted magnetic resonance imaging. , 2001, Cancer research.

[28]  J. M. Taylor,et al.  Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors. , 2000, Journal of the National Cancer Institute.

[29]  R. Rosenfeld Strategy , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[30]  R. Gillies,et al.  Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy. , 2004, Neoplasia.

[31]  A. Herneth,et al.  Apparent diffusion coefficient: a quantitative parameter for in vivo tumor characterization. , 2003, European journal of radiology.

[32]  Hoguen Kim,et al.  Oncologic Outcomes After Neoadjuvant Chemoradiation Followed by Curative Resection With Tumor-Specific Mesorectal Excision for Fixed Locally Advanced Rectal Cancer: Impact of Postirradiated Pathologic Downstaging on Local Recurrence and Survival , 2006, Annals of surgery.

[33]  Franklyn A. Howe,et al.  Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient of tissue water as determined by diffusion-weighted 1H-NMR spectroscopy in vivo , 1999 .

[34]  David J Collins,et al.  Technology Insight: water diffusion MRI—a potential new biomarker of response to cancer therapy , 2008, Nature Clinical Practice Oncology.

[35]  J. Pipe,et al.  Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo. , 1996, British Journal of Cancer.

[36]  L. Ellis,et al.  Improved Overall Survival Among Responders to Preoperative Chemoradiation for Locally Advanced Rectal Cancer , 2001, American journal of clinical oncology.