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CT Perfusion for the Monitoring of Neoadjuvant Chemotherapy and Radiation Therapy in Rectal Carcinoma: Initial Experience¹

¹ From the School of Medicine, University of Milan, Milan, Italy (M.B., G.P.); and the Departments of Radiology (M.B., G.P.), Pathology and Laboratory Medicine (A.S.), and Medical Oncology (M.G.Z., A.R.), European Institute of Oncology, 435 Via Ripamonti, 20141 Milan, Italy. Received July 11, 2006; revision requested September 6; revision received October 9; accepted November 3; final version accepted January 10, 2007. Address correspondence to M.B. (e-mail: massimo.bellomi{at}ieo.it).

	ABSTRACT

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Purpose: To prospectively monitor changes in rectal cancer perfusion after combined neoadjuvant chemotherapy and radiation therapy with perfusion computed tomography (CT) and to evaluate whether perfusion CT findings correlate with response to therapy.

Materials and Methods: The study was approved by the institutional ethics committee of the European Institute of Oncology; written informed consent was obtained from all participants before the study. Twenty-five patients with rectal adenocarcinoma (18 men, seven women; age range, 42–72 years; mean age, 61.3 years) underwent perfusion CT; all of them underwent neoadjuvant chemotherapy and radiation therapy, followed by surgery. In 19 patients, perfusion CT was repeated after chemotherapy and radiation therapy. Dynamic perfusion CT was performed for 50 seconds after intravenous injection of contrast medium (40 mL, 370 mg iodine per milliliter, 4 mL/sec). Blood flow (BF), blood volume (BV), mean transit time, and permeability–surface area product (PS) were computed in the tumor and in normal rectal wall by two independent blinded radiologists. Microvessel density was evaluated in pretreatment biopsy specimens in nine patients and in surgical specimens in seven patients. Wilcoxon signed-rank and rank sum tests were used for paired and independent comparisons, respectively.

Results: BF, BV, and PS were significantly higher in rectal cancer than in normal rectal wall (P < .001). BF, BV, and PS significantly decreased after combined chemotherapy and radiation therapy (P < .009). No correlation was found between perfusion parameters and microvessel density, neither in baseline values nor in posttherapy changes. Baseline BF and BV in the seven patients who failed to respond to treatment were significantly lower than in the 17 responders (P = .02 for BF and < .001 for BV).

Conclusion: Perfusion CT has potential for monitoring the effects of combined neoadjuvant chemotherapy and radiation therapy and predicting the response of rectal cancer to such therapy.

© RSNA, 2007

	INTRODUCTION

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Despite the advances in rectal cancer treatment, imaging, and screening programs (1), 5-year overall survival in patients with rectal cancer is still below 50% (2). Innovative treatments are required to improve these outcomes. Some researchers have selected angiogenesis as a promising target of therapies (3–5) for rectal cancer, since high values of tumor microvessel density (MVD) (6,7) and high vascular endothelial growth factor expression (8,9) have been correlated with poor outcome (6,7). An in vivo marker of rectal cancer angiogenesis may therefore be extremely useful for diagnosis, risk stratification, and monitoring of therapeutic success in patients with rectal cancer.

The serial monitoring of MVD to assess changes in rectal cancer angiogenic activity induced by treatment requires multiple biopsies for tissue sampling and is limited because of its invasiveness. Moreover, MVD count may not reflect the effectiveness of the treatment, because it does not independently measure vascular inhibition but rather reflects many different changes occurring in tumor vasculature over time (10).

Functional imaging techniques that can help monitor treatment effects on tumor angiogenic activity noninvasively are highly desirable; there is, therefore, great interest in the integration of functional imaging into trials of chemotherapy and radiation therapy. Functional imaging has conventionally been the domain of nuclear medicine. However, radionuclide techniques have limitations, such as spatial resolution and cost (11). Both magnetic resonance (MR) imaging and computed tomography (CT) have shown potential as functional imaging tools (12–15). Thus, the purpose of our study was to monitor changes in rectal cancer perfusion prospectively with perfusion CT after combined neoadjuvant chemotherapy and radiation therapy (hereafter, chemoradiation therapy) and to evaluate whether findings of perfusion CT correlate with response to therapy.

	MATERIALS AND METHODS

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Patients
The study was approved by the institutional ethics committee of the European Institute of Oncology; written informed consent was obtained from all participants. Untreated patients with biopsy-confirmed nonmucinous rectal adenocarcinoma were included in the study if the tumor extended beyond the rectal wall (T3 or T4), with or without nodal involvement (N0, N1, or N2) and with no distant metastases (M0). Patients with stage T1 or T2 rectal cancer and distant metastases or patients with high serum creatinine levels (>2 mg/dL [>176.8 µmol/L]) were excluded.

From June 2003 to March 2005, 25 consecutive patients who met the inclusion criteria (18 men and seven women; mean age, 61.3 years; range, 42–72 years) were enrolled in the study: 13 patients had stage T3N0M0 disease and 12 patients had stage T3N1M0 disease at the time of presentation.

Local tumor staging was based on findings at endorectal ultrasonography (US), according to the TNM classification given by the International Union against Cancer (16). US was performed by a single operator with 7 years of experience in endorectal US; the operator used a linear-array echoendoscope (FG 36 UX; Pentax, Tokyo, Japan) with a convex transducer (120°), set at 5–10 MHz and connected to a US console (EUB-525; Hitachi, Wiesbaden, Germany) with color Doppler capabilities. Distant metastases were investigated with contrast material–enhanced multidetector CT (LightSpeed 16; GE Healthcare, Milwaukee, Wis) of the chest and abdomen.

Treatment and Surgery
All patients underwent neoadjuvant chemoradiation therapy. Dimensional conformal radiation therapy was given at a dose of 1.8 Gy per day, 5 days per week, for 28 sessions, with a total radiation dose of 50.4 Gy given over a period of 38 days. Capecitabine (825 mg/m²) was administered orally twice daily, concomitant to radiation therapy for 38 days, 7 days per week. After a rest period of 10–14 days, intermittent capecitabine (1250 mg/m²) was then administered twice daily for 14 days, every 3 weeks for two cycles. Two weeks after the completion of neoadjuvant chemoradiation therapy, all patients underwent total mesorectal excision, and the surgical specimens were evaluated by a single pathologist (A.S.), who had 11 years of experience in the postoperative staging of rectal cancer.

Patients who had local downstaging (T or N) at pathologic analysis of the surgical specimen, as compared with the stage at endorectal US before therapy, were considered responders; patients with no local downstaging or increase in local tumor stage were considered nonresponders.

Perfusion CT Technique
All 25 patients underwent baseline perfusion CT 1–11 days before the beginning of therapy. Nineteen patients underwent follow-up with a second perfusion CT study, within 1 week after completion of neoadjuvant therapy (7–8 weeks after completion of radiation therapy), at a mean interval of 91.2 days after baseline perfusion CT. Of the other six patients, two had no visible tumor identified at posttherapy CT, one was unavailable for follow-up, one was excluded owing to motion artifacts, and two refused the second examination.

All patients observed a standard preparation the day before the study, including a cleansing enema, an oral laxative, and a low-fiber diet to reduce the discomfort caused by the water enema and avoid fecal retention above the tumor. No oral contrast material was administered. Once the patient was on the CT bed, a water enema (2000 mL) was administered through a 24-F Foley catheter, to obtain homogeneous, reproducible, and persistent rectal wall distention, including the proximal rectal segments lying anteriorly, with the patient in supine position: the enema was stopped whenever the patient complained of discomfort. Hyoscine butylbromide (1 mL) was injected intravenously immediately before scanning.

Perfusion CT was performed with a 16-section multidetector CT scanner (LightSpeed 16; GE Healthcare). Preliminary noncontrast CT of the pelvis (2.5-mm section thickness) was performed to localize the tumor. An expert radiologist (M.B.) with 2 years of experience in rectal cancer perfusion studies then selected a 20-mm scanning range for dynamic CT; the range was chosen to include the maximum tumor area visible. Dynamic study of this volume was performed with the following parameters: two contiguous 10 mm reconstructed sections at the same table position, 1-second gantry rotation time, 120 kVp, 300 mA, and 50-second acquisition time (to avoid tube overheating). CT was performed with no scanning delay after injection of 40 mL of nonionic iodinated contrast material (iopromide, Ultravist [370 mg iodine per milliliter]; Schering, Berlin, Germany), followed by 40 mL of saline solution, injected at a rate of 4 mL/sec via an 18–20-gauge cannula in the antecubital vein.

Image and Data Analysis
The images and data obtained were transferred to an image processing workstation (Advantage Windows 4.2; GE Healthcare) and analyzed by two independent readers, who were blinded to results of pathologic evaluation and the patient's clinical response to treatment. At the start of the study, one reader (M.B.) had 2 years of experience with perfusion CT studies; the other (G.P.) was a radiologist who had 10 weeks of experience with perfusion CT. The expert reader (M.B.) repeated the perfusion CT analysis on the same data set 4–8 weeks after the first reading, to allow evaluation of intraobserver variability.

Commercially available software (CT Perfusion 3; GE Healthcare) was used to calculate perfusion parameters. The arterial input was obtained from a 2–6-pixel region of interest (ROI) placed in the first (cranial) of the two sections on the left external iliac artery, which is always shown in the field of view.

Functional maps were generated, representing in a color scale pixel values of the following perfusion parameters: blood flow (BF) (in milliliters per 100 g of wet tissue per minute), blood volume (BV) (in milliliters per 100 g of wet tissue), mean transit time (MTT) (in seconds) and permeability–surface area product (PS) (in milliliters per 100 g of wet tissue per minute). ROIs were manually drawn along the visible margins of the rectal cancer (area range, 266–1860 mm² for baseline perfusion CT, 120–1246 mm² for follow-up perfusion CT) and along the normal rectal wall, in both the anatomic section locations available, for each functional map type (BF, BV, MTT, and PS). Perfusion parameters obtained from the ROIs of the two sections were averaged. A circular ROI (area range, 400–500 mm²) was placed in the same region of the left gluteus maximus muscle, as a control.

Pathologic Evaluation
A single operator performed endorectal US–guided biopsies with standard biopsy forceps (Pentax) and obtained multiple samples from each tumor. A single pathologist (A.S.), who had 11 years of experience in gastrointestinal pathology and was blinded to perfusion CT results, examined formalin-fixed and paraffin-embedded tumor samples.

Material for MVD counts was available in nine of the biopsy samples obtained at the time of diagnosis and in seven of the posttherapy surgical specimens from the nine patients who had baseline MVD counts. Sections 3 µm thick were cut. MVD counts were evaluated after CD34 immunostaining of endothelial cells with a mouse monoclonal antibody (clone QBEnd/10) in formalin-fixed and paraffin-embedded tumor samples; the mean count was calculated by analyzing three different x250 microscopic fields, chosen in the tumor area with the highest vascularization.

Statistical Analysis
Most perfusion parameters did not fit a normal distribution. Therefore, nonparametric tests were used. Data are summarized as median and 95% confidence intervals (CIs) for the population median, calculated with the binomial-based method. Interobserver and intraobserver agreement of perfusion CT analysis were assessed by means of the Spearman rank correlation coefficient.

Baseline perfusion parameters of rectal cancer were compared with those of the normal rectal wall and with those of the left gluteus muscle, by means of the Wilcoxon signed rank test. Perfusion parameters of the rectal cancer before therapy were compared between responders and nonresponders by means of the Wilcoxon rank sum test. Perfusion parameters before and after therapy were compared by means of the Wilcoxon signed-rank test. All tests were two sided.

Baseline perfusion parameters of rectal cancer were correlated with baseline MVD, and differences between baseline and posttherapy perfusion parameters for rectal cancer were correlated with differences in MVD, by means of the Spearman correlation coefficient. Differences between medians were calculated with the Hodges-Lehmann estimator, and CIs were based on the Wilcoxon test critical values. P values of less than .05 were considered to indicate statistically significant differences. No adjustment was made for the performance of multiple tests. Statistical analysis was performed with R, version 2.1 (R Foundation for Statistical Computing, Vienna, Austria) (17).

The sample size was defined according to the main clinical objective of the study, which was the activity of the regimen, measured in terms of pathologic complete remission rate. With an optimal two-stage phase II design, for a .05 significance level and 0.9 power in a two-sided test, if a pathologic complete remission rate of 10% or less is considered unacceptable and a pathologic complete remission rate of 30% or higher is considered acceptable, 18 patients must be enrolled in the first stage. If a pathologic complete remission is achieved in three or more, 17 more patients are enrolled in the second stage, for a total of 35, accepting treatment as active if pathologic complete remission occurs in at least seven patients overall. Of the 35 patients enrolled, 25 underwent baseline perfusion CT; the other 10 did not undergo the examination for logistic reasons. No formal power analysis was conducted a priori for the end points related to the perfusion CT study, because of the lack of previous data on the distribution and standard deviation of the perfusion variables, needed for sample size calculation.

	RESULTS

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Inter- and Intraobserver Agreement
Interobserver agreement was assessed by comparing the two sets of perfusion parameters for rectal cancer calculated from the two readers, for a total of 176 paired measurements; this comparison showed a significant correlation (Spearman R = 0.98, P < .001).

Intraobserver variability was evaluated from two different readings of the perfusion parameters, for a total of 176 paired measurements, made by the experienced radiologist at intervals of more than 4 weeks; this comparison showed a highly significant correlation (Spearman R = 0.998, P < .001).

Perfusion Parameters at Baseline
Comparison of rectal cancer perfusion parameters with those of the normal rectal wall in the 25 enrolled patients, at the baseline perfusion CT study, showed that BF, BV, and PS were significantly higher (P < .001) in rectal cancer than in normal wall; MTTs were not significantly different (P = .06) (Table 1). Baseline BF, BV, and PS were also significantly higher (P < .001) in rectal cancer than in gluteus muscle; baseline MTTs were not significantly different (P = .14).

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure a: Rectal cancer, stage T3N1 (staged with endorectal US). (a) One section of the dynamic CT scan obtained before neoadjuvant chemoradiation therapy shows the tumor as thickening of the right lateral rectal wall. An 869-mm2 ROI was manually drawn along the margins of the rectal cancer for perfusion parameters calculation. (b) On the same section shown in a, a functional map of BF is designed by the software, showing the BF value calculated in each pixel of the image on a color scale. (c) CT scan obtained in the same patient after completion of neoadjuvant chemoradiation therapy shows a great reduction in the tumor; only a mild thickening of rectal wall can be seen and is outlined by the ROI, which is used to calculate perfusion CT values. (d) On the same section shown in c, the functional map of BF shows in a color scale the reduction in BF compared with b. (e) Pathologic surgical specimen shows thickening of the right lateral rectal wall due to inflammatory and cicatritial changes induced by therapy; no tumor cells were found at histologic examination, and the final pathologic stage was T0N0.

View larger version (176K): [in this window] [in a new window] [Download PPT slide]   Figure b: Rectal cancer, stage T3N1 (staged with endorectal US). (a) One section of the dynamic CT scan obtained before neoadjuvant chemoradiation therapy shows the tumor as thickening of the right lateral rectal wall. An 869-mm2 ROI was manually drawn along the margins of the rectal cancer for perfusion parameters calculation. (b) On the same section shown in a, a functional map of BF is designed by the software, showing the BF value calculated in each pixel of the image on a color scale. (c) CT scan obtained in the same patient after completion of neoadjuvant chemoradiation therapy shows a great reduction in the tumor; only a mild thickening of rectal wall can be seen and is outlined by the ROI, which is used to calculate perfusion CT values. (d) On the same section shown in c, the functional map of BF shows in a color scale the reduction in BF compared with b. (e) Pathologic surgical specimen shows thickening of the right lateral rectal wall due to inflammatory and cicatritial changes induced by therapy; no tumor cells were found at histologic examination, and the final pathologic stage was T0N0.

View larger version (101K): [in this window] [in a new window] [Download PPT slide]   Figure c: Rectal cancer, stage T3N1 (staged with endorectal US). (a) One section of the dynamic CT scan obtained before neoadjuvant chemoradiation therapy shows the tumor as thickening of the right lateral rectal wall. An 869-mm2 ROI was manually drawn along the margins of the rectal cancer for perfusion parameters calculation. (b) On the same section shown in a, a functional map of BF is designed by the software, showing the BF value calculated in each pixel of the image on a color scale. (c) CT scan obtained in the same patient after completion of neoadjuvant chemoradiation therapy shows a great reduction in the tumor; only a mild thickening of rectal wall can be seen and is outlined by the ROI, which is used to calculate perfusion CT values. (d) On the same section shown in c, the functional map of BF shows in a color scale the reduction in BF compared with b. (e) Pathologic surgical specimen shows thickening of the right lateral rectal wall due to inflammatory and cicatritial changes induced by therapy; no tumor cells were found at histologic examination, and the final pathologic stage was T0N0.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure d: Rectal cancer, stage T3N1 (staged with endorectal US). (a) One section of the dynamic CT scan obtained before neoadjuvant chemoradiation therapy shows the tumor as thickening of the right lateral rectal wall. An 869-mm2 ROI was manually drawn along the margins of the rectal cancer for perfusion parameters calculation. (b) On the same section shown in a, a functional map of BF is designed by the software, showing the BF value calculated in each pixel of the image on a color scale. (c) CT scan obtained in the same patient after completion of neoadjuvant chemoradiation therapy shows a great reduction in the tumor; only a mild thickening of rectal wall can be seen and is outlined by the ROI, which is used to calculate perfusion CT values. (d) On the same section shown in c, the functional map of BF shows in a color scale the reduction in BF compared with b. (e) Pathologic surgical specimen shows thickening of the right lateral rectal wall due to inflammatory and cicatritial changes induced by therapy; no tumor cells were found at histologic examination, and the final pathologic stage was T0N0.

View larger version (188K): [in this window] [in a new window] [Download PPT slide]   Figure e: Rectal cancer, stage T3N1 (staged with endorectal US). (a) One section of the dynamic CT scan obtained before neoadjuvant chemoradiation therapy shows the tumor as thickening of the right lateral rectal wall. An 869-mm2 ROI was manually drawn along the margins of the rectal cancer for perfusion parameters calculation. (b) On the same section shown in a, a functional map of BF is designed by the software, showing the BF value calculated in each pixel of the image on a color scale. (c) CT scan obtained in the same patient after completion of neoadjuvant chemoradiation therapy shows a great reduction in the tumor; only a mild thickening of rectal wall can be seen and is outlined by the ROI, which is used to calculate perfusion CT values. (d) On the same section shown in c, the functional map of BF shows in a color scale the reduction in BF compared with b. (e) Pathologic surgical specimen shows thickening of the right lateral rectal wall due to inflammatory and cicatritial changes induced by therapy; no tumor cells were found at histologic examination, and the final pathologic stage was T0N0.

Perfusion Parameters at Baseline in Responders and Nonresponders
Responses could be assessed in 24 patients; one was unavailable for follow-up. Seven patients were nonresponders (six T3N0 and one T3N1 at baseline endorectal US): six had no local downstaging, and one had upstaging from N0 to N1. Seventeen patients (six T3N0 and 11 T3N1 at baseline endorectal US) were classified as responders (71%; 95% CI: 48%, 89%), including four patients (two T3N0 and two T3N1 at baseline endorectal US) with pathologic complete response at the postoperative staging and 13 with local downstaging (T and/or N).

The baseline BF and BV of nonresponders were significantly lower (P = .02 and < .001, respectively) and the baseline MTT significantly higher (P = .03) than those of responders; no significant difference was found in PS (P = .4) (Table 3).

Changes in MVD after treatment did not correlate with changes in any perfusion parameter, for either percentage or absolute differences, except for a negative correlation with absolute difference in PS (Spearman R = –0.86, P = .02) (Table 4).

	DISCUSSION

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We found very high interobserver and intraobserver agreement in perfusion parameter measurements, thanks to the easy-to-use software interface, which automatically calculates perfusion parameters. The repeatability of perfusion CT studies was confirmed by our study findings; equivalent perfusion measurements (P = .73–.99) were obtained for the same untreated area (left gluteus muscle) in the same patients, after 12 weeks.

The only published report of which we are aware concerning the use of perfusion CT to monitor the treatment response of rectal cancer (22) noted significantly higher BF and significantly shorter MTT in rectal cancer compared with normal rectal wall. Our data partially agree with those findings, showing that not only BF but also BV and PS were significantly higher in rectal cancer than in the normal rectal wall. MTT, though showing shorter mean values, did not differ significantly between tumor and normal wall.

Perfusion CT seems able to differentiate rectal cancer from normal rectal wall and to reflect reliably changes occurring in neoplastic tissue, changes probably related to the angiogenic process. Angiogenesis causes the formation of a number of arteriovenous shunts with low resistance, which may determine increased BF. Moreover, angiogenesis increases the vascular bed, owing to the growth of new vessels from preexisting ones, thereby increasing the BV. In our series PS was also significantly higher in rectal cancer than in normal rectal wall. PS is expected to be high in tumors, due to the higher permeability of the capillary endothelial membranes of newly developed tumor vessels compared with normal vessels. However, our PS values may not be reliable, because contrast medium extravasation, measured by means of PS, is affected by the duration of data collection. We used a 50-second scanning time, but a minimum scanning duration of at least 65 seconds is generally recommended (22,23).

The only published study of which we are aware on perfusion CT for monitoring neoadjuvant chemoradiation therapy in rectal cancer found a significant decrease in BF and increase in MTT after treatment (22). In partial agreement with those findings, we observed a significant decrease in BF and BV after therapy, which may reflect, respectively, a decreased number of arteriovenous shunts and a reduced volume of the vascular bed. The PS also decreased significantly after therapy, possibly related to reduced leakage from neoplastic vessels after therapy, but PS values may not be reliable in our study because of the short scanning time.

We observed tumor downstaging in 54% (13 of 24) of patients and pathologic complete response in 17% (four of 24), and these values are in agreement with published results (24). In our series no significant difference in MVD before and after therapy was demonstrated and no significant correlation was found between changes in MVD and changes in any perfusion parameter. MVD is considered unreliable for monitoring response to treatment (10).

Published results of several studies (25–29) that assessed contrast material enhancement with either dynamic MR imaging or CT have shown the potential of dynamic imaging in predicting rectal cancer response to therapy. High perfusion index (25) and tumor permeability (26), assessed with dynamic MR imaging, were reported in those rectal cancers responsive to neoadjuvant chemoradiation therapy. Similar dynamic MR imaging or CT results for other tumors are reported in the literature. Mayr et al (27), using dynamic contrast-enhanced MR imaging to examine 17 patients with cervical carcinoma undergoing radiation therapy, found that patients with high tumor perfusion values had a low incidence of local recurrence. Hermans et al (28,29) evaluated perfusion CT findings in 105 head-and-neck squamous cell carcinomas and found that patients with lower perfusion values had a significantly higher local failure rate.

These results of earlier studies, even if they were obtained with different techniques and included different tumors, suggest that highly perfused tumors may have better access for chemotherapy, better oxygenation, and higher radiosensitivity compared with poorly perfused tumors. On the contrary, what is to our knowledge the only published study (22) on perfusion CT in patients with rectal cancer undergoing neoadjuvant chemoradiation therapy showed that patients with high BF and low MTT had poor response to therapy. The authors attributed the high perfusion values of nonresponders to high intratumoral arteriovenous shunts, to an intrinsically high angiogenic activity of tumor, or to a secondary response to tissue hypoxia.

In our series baseline BF and BV were significantly higher in responders than in nonresponders, and baseline MTT was significantly lower; the differences between our results and those reported by Sahani et al (22) may reflect differences in patient selection and differences in perfusion CT technique. We used fixed, higher peak voltage values and thicker sections to reduce noise, which result in overestimation of enhancement rates and miscalculation of perfusion values (30). According to previous reports (28–30) we administered a relatively small bolus (40 mL, 370 mg iodine per milliliter) injected at a high flow rate, followed by saline solution injection (instead of 125 mL at 300 mg iodine per milliliter) to reach the arterial peak concentration before the maximal increase in tissue enhancement. Finally, rectal wall distention and hypotonia increase confidence in the visualization of tumor margins for manual drawing of ROIs and reduce peristaltic artifacts, which may interfere with calculation of perfusion values. We believe that differences in duration of scanning are not relevant.

There are limitations to our study. A 50-second duration of scanning after the start of contrast medium injection, which means an effective scanning duration of about 30 seconds, is too short to allow reliable assessment of PS (23,30). The measurement of perfusion parameters could be somewhat variable due to the technique used (10 mm section thickness, two sections per rotation). Our results are specific to the analytic methods and software used in our study and might not necessarily apply to other methods.

The assessment of rectal cancer response to neoadjuvant therapy is based on a comparison between initial local staging with endorectal US and postoperative pathologic staging. This method of comparison could have caused an inadvertent bias, as some rectal cancers might have been under- or overstaged with endorectal US, which has 90% sensitivity and 75% specificity for mesorectal tissue invasion assessment and 67% sensitivity and 78% specificity for lymph node involvement (31). The size of the nonresponder group was too small to allow a proper analysis of the value of perfusion CT in predicting the response to neoadjuvant chemoradiation therapy.

The manual drawing of ROIs along rectal cancer margins is critical, especially when relevant tumor shrinkage occurs after therapy and tumor margins may be more ill-defined than at pretherapy CT. We did not evaluate baseline rectal cancer volume, which may predict response to therapy (32), nor did we evaluate changes in rectal cancer volume after therapy, since we did not perform additional contrast-enhanced thin-section scanning of the pelvis. Finally, the radiation dose of perfusion CT, although less than that of radiation therapy, may limit its applications in nonradiotherapy patient assessment.

In conclusion, perfusion CT may have an important clinical application in rectal cancer management; monitoring the response to therapy may lead clinicians to customize treatment to the response of the individual patient, and reliable prediction of the response may improve patient selection and avoid nonproductive, costly treatments. However, larger studies are needed to confirm our results.

	ADVANCES IN KNOWLEDGE

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• The blood flow (BF), blood volume (BV), and permeability–surface area product (PS) are significantly higher (P < .001) and the mean transit time is lower (P = .06) in rectal cancer than in normal rectal wall, results that confirm those of a prior study.
  
• The BF and BV of rectal cancer in patients who respond well to chemoradiation therapy are significantly higher (P = .02 and < .001, respectively) than in those who have a poor response to treatment.
  
• The BF, BV, and PS of rectal cancer decrease significantly (P < .009) after chemoradiation therapy, results that confirm those of a prior study.
  

	IMPLICATION FOR PATIENT CARE

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 

• Perfusion CT, when added to the routine CT examination of patients with rectal cancer undergoing neoadjuvant chemoradiation therapy, has potential for monitoring the response to treatment.
  

	FOOTNOTES

 

Abbreviations: BF = blood flow • BV = blood volume • CI = confidence interval • MTT = mean transit time • MVD = microvessel density • PS = permeability–surface area product • ROI = region of interest

Authors stated no financial relationship to disclose.

Author contributions: Guarantors of integrity of entire study, M.B., A.R.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, M.B., G.P.; clinical studies, G.P., A.S., M.G.Z.; statistical analysis, A.R.; and manuscript editing, M.B., G.P., M.G.Z., A.R.

	References

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION ADVANCES IN KNOWLEDGE IMPLICATION FOR PATIENT CARE References

 

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