Perfusion CT: noninvasive surrogate marker for stratification of pancreatic cancer response to concurrent chemo- and radiation therapy.

PURPOSE To prospectively determine whether perfusion computed tomography (CT) parameters, such as volume transfer constant (K(trans)) between blood plasma and extracellular extravascular space (EES) and blood volume calculated from dynamic CT data, can be used to predict response of pancreatic cancer to concurrent chemotherapy and radiation therapy (CCRT). MATERIALS AND METHODS This prospective study was institutional review board approved, and written informed consent was obtained. Thirty patients with pancreatic cancer underwent perfusion CT with 64-detector row CT before gemcitabine-based CCRT. Two perfusion parameters (K(trans) and blood volume) measured before treatment were compared between patients who responded to treatment and those who did not, as determined with World Health Organization criteria from first and second posttherapeutic follow-up CT examinations, which were performed at 3- and 6-month follow-up. Statistical analysis was performed with the two-sample t test. A receiver operating characteristic curve was used to determine the best cutoff value of perfusion parameters for differentiation of responders from nonresponders. RESULTS Twenty of 30 patients examined at 3-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (50.8 mL/100 mL/min +/- 30.5 [standard deviation] vs 19.0 mL/100 mL/min +/- 10.8, P = .001). The best cutoff value for differentiating between responders and nonresponders was 31.8 mL/100 mL/min, which yielded 75.0% sensitivity and 90.0% specificity. Ten of 18 patients examined at 6-month follow-up responded to therapy. Their pretreatment K(trans) value was significantly higher than that of nonresponders (58.6 mL/100 mL/min +/- 43.2 vs 19.8 mL/100 mL/min +/- 10.9, P = .002). Responders also had higher blood volume values, but this difference was not significant. CONCLUSION Tumors with a high pretreatment K(trans) value tended to respond better to CCRT than did tumors with a low pretreatment K(trans) value. Perfusion CT may be used to predict tumor response to CCRT in patients with pancreatic cancer. This might aid in development of a tailored approach to therapy in these patients.

[1]  Ernst Klotz,et al.  Lung cancer perfusion at multi-detector row CT: reproducibility of whole tumor quantitative measurements. , 2006, Radiology.

[2]  James L Tatum,et al.  Hypoxia: Importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy , 2006, International journal of radiation biology.

[3]  J C Ehrhardt,et al.  Tumor perfusion studies using fast magnetic resonance imaging technique in advanced cervical cancer: a new noninvasive predictive assay. , 1996, International journal of radiation oncology, biology, physics.

[4]  K. Miles,et al.  Perfusion CT: a worthwhile enhancement? , 2003, The British journal of radiology.

[5]  K. Miles,et al.  Functional computed tomography in oncology. , 2002, European journal of cancer.

[6]  I Ezzat,et al.  Role of thallium-201 chloride and Tc-99m methoxy-isobutyl-isonitrite (sestaMIBI) in evaluation of breast masses: correlation with the immunohistochemical characteristic parameters (Ki-67, PCNA, Bcl, and angiogenesis) in malignant lesions. , 1997, Anticancer research.

[7]  A. Levy.  Differentiation between Diverticulitis and Colorectal Cancer: Quantitative CT Perfusion Measurements versus Morphologic Criteria—Initial Experience , 2008 .

[8]  K. Miles.  Functional CT imaging in oncology , 2003, European Radiology.

[9]  Vicky Goh,et al.  Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography. , 2007, International journal of radiation oncology, biology, physics.

[10]  T. Murakami,et al.  Quantitative tissue blood flow evaluation of pancreatic tumor: comparison between xenon CT technique and perfusion CT technique based on deconvolution analysis. , 2005, Radiation medicine.

[11]  R. Labianca,et al.  Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  E. Gehan,et al.  Will there be resistance to the RECIST (Response Evaluation Criteria in Solid Tumors)? , 2000, Journal of the National Cancer Institute.

[13]  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.

[14]  C S Patlak,et al.  Graphical Evaluation of Blood-to-Brain Transfer Constants from Multiple-Time Uptake Data , 1983, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  K. Miles,et al.  CT measurement of perfusion and permeability within lymphoma masses and its ability to assess grade, activity, and chemotherapeutic response. , 1999, Journal of computer assisted tomography.

[16]  K. Miles,et al.  Perfusion CT for the assessment of tumour vascularity: which protocol? , 2003, The British journal of radiology.

[17]  K. Miles,et al.  Tumour angiogenesis and its relation to contrast enhancement on computed tomography: a review. , 1999, European journal of radiology.

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

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

[20]  S. Mukherji,et al.  Can pretreatment CT perfusion predict response of advanced squamous cell carcinoma of the upper aerodigestive tract treated with induction chemotherapy? , 2007, AJNR. American journal of neuroradiology.

[21]  F Frouin,et al.  Early changes in liver perfusion caused by occult metastases in rats: detection with quantitative CT. , 2001, Radiology.

[22]  Christopher G Willett,et al.  Locally advanced pancreatic cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  A. Koong,et al.  Pancreatic tumors show high levels of hypoxia. , 2000, International journal of radiation oncology, biology, physics.

[24]  A. Dennison,et al.  HYPOXIA AND ANGIOGENESIS IN PANCREATIC CANCER , 2006, ANZ journal of surgery.

[25]  Vicky Goh,et al.  Tumor antivascular effects of radiotherapy combined with combretastatin a4 phosphate in human non-small-cell lung cancer. , 2007, International journal of radiation oncology, biology, physics.

[26]  H. Rusinek,et al.  Perfusion imaging of the liver: current challenges and future goals. , 2005, Radiology.

[27]  A. Megibow,et al.  Pancreatic adenocarcinoma: designing the examination to evaluate the clinical questions. , 1992, Radiology.

[28]  I. Fidler,et al.  Hypoxia Increases Resistance of Human Pancreatic Cancer Cells to Apoptosis Induced by Gemcitabine , 2004, Clinical Cancer Research.

[29]  Jeffrey E. Lee,et al.  Borderline Resectable Pancreatic Cancer: Definitions, Management, and Role of Preoperative Therapy , 2006, Annals of Surgical Oncology.

[30]  N. Holalkere,et al.  Advanced hepatocellular carcinoma: CT perfusion of liver and tumor tissue--initial experience. , 2007, Radiology.

[31]  Evis Sala,et al.  Dynamic contrast-enhanced MRI as a predictor of tumour response to radiotherapy. , 2007, The Lancet. Oncology.