Nagaraj S. Holalkere

Early Antiangiogenic Activity of Bevacizumab Evaluated by Computed Tomography Perfusion Scan in Patients with Advanced Hepatocellular Carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) is a highly vascularized tumor with a poor prognosis. In a phase II study that combined bevacizumab with gemcitabine and oxaliplatin in advanced HCC, we examined computed tomography perfusion (CTp) scan parameters as surrogate markers of angiogenesis after bevacizumab administration. METHODS HCC patients received bevacizumab alone i.v. at 10 mg/kg on day 1 during cycle 1. CTp scanning was performed at baseline and days 10-12 to assess changes in tissue blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS). RESULTS Compared with baseline, a significant decrease in the estimated tumor perfusion parameters including BF, BV, and PS and an increase in MTT were seen on days 10-12 following bevacizumab administration alone. Patients with progressive disease had lower baseline MTT values and a higher percent increase following bevacizumab administration than those with stable disease or partial responses. CONCLUSIONS Bevacizumab induced a significant decrease in tumor BF, BV, and PS and an increase in MTT by CTp scan in HCC. Baseline and percent change in MTT following bevacizumab administration correlated with clinical outcome, whereas BF, BV, and PS did not.

PET/CT for the Characterization of Adrenal Masses in Patients with Cancer: Qualitative Versus Quantitative Accuracy in 150 Consecutive Patients

OBJECTIVE The objective of our study was to evaluate a large cohort of patients with PET/CT to determine whether qualitative (visual) assessment, quantitative standardized uptake value (SUV), or standardized uptake ratio (SUR) techniques should be used when attempting to characterize adrenal masses in patients with cancer. MATERIALS AND METHODS The study group was composed of 150 consecutive patients (78 men, 72 women; mean age, 60 years; range, 24-88 years) with documented adrenal lesions. All patients were known to have an underlying primary malignancy and were referred for PET/CT to evaluate the underlying primary and metastatic tumor burden. Definitive lesion characterization was determined by evaluating all histologic adrenal specimens and all relevant prior and follow-up CT scans, including unenhanced, contrast-enhanced, and delayed contrast-enhanced washout studies. RESULTS Of the 139 benign lesions, 109 were considered benign by CT densitometry measurements and 135 by qualitative PET data. Qualitative PET characterized 28 of 30 benign lesions that were considered indeterminate by unenhanced CT. All 26 malignant lesions were characterized by PET: All showed qualitative and quantitative signal intensity greater than the liver. By combining unenhanced and qualitative CT data with the retrospective PET data, the analysis yielded a sensitivity of 100% for the detection of malignancy, a specificity of 99%, a positive predictive value (PPV) of 93%, a negative predictive value (NPV) of 100%, and an accuracy of 99% (Table 1). Conversely, for the detection of benignity, the sensitivity, specificity, PPV, NPV, and accuracy were 99%, 100%, 100%, 93%, and 99%, respectively. CONCLUSION PET/CT is a highly accurate method for differentiating benign from malignant adrenal masses particularly when using qualitative, rather than quantitative, PET data. The routine use of quantitative mean or maximal SUV or SUR data may be unnecessary. Occasional benign lesions do show mild to moderate increased FDG uptake compared with that of the liver and may mimic some malignant lesions. Without evidence that these lesions are benign by unenhanced CT densitometry or adrenal mass stability or growth from previous CT scans, we recommend that these lesions be characterized using contrast-enhanced washout tests and that if those tests are inconclusive, using percutaneous biopsy if early lesion characterization is mandatory.

Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation.

PURPOSE We determined whether evaluation of treatment response is feasible by measuring metabolic tumor volume parameters on 18F-FDG (Fluorodeoxyglucose) PET-CT (Positron emission tomography-Computed tomography). We compared the response evaluation based on metabolic tumor volume parameters to a histopathologic and clinical response evaluation (clinical response criteria: RECIST criteria=Response evaluation criteria in solid tumors, and WHO criteria=World health organization). PATIENTS AND METHODS A total of 51 study subjects with adenocarcinomas (Type I due to Siewert classification) of the esophagus underwent PET-CT scans before and after neoadjuvant chemoradiotherapy. Tumor volume, maximum and mean standardized uptake values (SUV) were assessed before and after chemoradiotherapy. Furthermore, the total lesion glycolysis (TLG) was calculated by multiplying the tumor volume by the mean SUV of the volume. Clinical response evaluation was performed with endoscopic ultrasound and CT using RECIST and WHO criteria. The reference standard for treatment response was the postsurgical histopathology. RESULTS The decrease of tumor volume between the pre- and post-treatment PET-CT scans was a better predictor of histopathologic response and survival than the decrease of the SUV and of the clinical response evaluation based on RECIST and WHO criteria. The highest accuracy, however, was achieved when using the TLG for the identification of treatment responders. A decrease of the TLG by > 78% between pre- and post-therapy scans predicted histopathologic response with a sensitivity and specificity of 91% and 93%, respectively. CONCLUSIONS Tumor volume and TLG can be used to assess treatment response and survival in patients with esophageal adenocarcinoma.

Liver Lesion Detection and Characterization in Patients With Colorectal Cancer : A Comparison of Low Radiation Dose Non-enhanced PET/CT, Contrast-enhanced PET/CT, and Liver MRI

Objectives: To compare low-radiation dose nonenhanced fluorine 18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) (NE-PET/CT), contrast-enhanced fluorine 18 fluorodeoxyglucose PET/CT (CE-PET/CT), and gadolinium-enhanced liver magnetic resonance imaging (MRI) for the detection and characterization of liver lesions in patients with colorectal cancer (CRC). Methods: In this retrospective review of imaging database of CRC patients with suspected liver metastases, 33 patients (22 men, 11 women; mean age, 63 years) evaluated with low-radiation dose NE-PET/CT, CE-PET/CT, and liver MRI were studied. The final diagnosis was established either by pathological examination or follow-up imaging over a period of at least 6 months for lesion stability or growth. The liver lesions were characterized on an ordinal scale of 0 to 6 (0 = absent, 1 = definitely benign, and 6 = definitely malignant). Receiver operating characteristic analysis was performed to compare performance of the 3 imaging methods. Results: A total of 110 lesions were present on follow-up. The detection rate on low-radiation dose NE-PET/CT, CE-PET/CT, and MRI was 73.6%, 90.9%, and 95.4%, respectively. Magnetic resonance imaging (P < 0.001) and CE-PET/CT (P < 0.001) had a higher detection rate than low-radiation dose NE-PET/CT. There was no significant statistical difference in lesion detection between MRI and CE-PET/CT (P = 0.11). The sensitivity, specificity, and accuracy for characterization of detected liver lesions on low-radiation dose NE-PET/CT were 67%, 60%, and 66%, respectively; those on CE-PET/CT were 85%, 100%, and 86%, respectively; and those on MRI were 98%, 100%, and 98%, respectively. Comparative receiver operating characteristic analysis showed an area under curve of 0.74 for low-radiation dose NE-PET/CT, 0.86 for CE-PET/CT, and 0.97 for MRI. There were statistically significant differences in the accuracy of MRI, low-radiation dose NE-PET/CT, and CE-PET/CT for lesion characterization. Conclusions When performing PET/CT, optimal detection and characterization of liver lesions require the use of a fused contrast-enhanced CT. Magnetic resonance imaging and CE-PET/CT have similar lesion detection rates. Magnetic resonance imaging is the best test for liver lesion characterization in patients with CRC.

Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume.

Objective: The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. Materials and Methods: Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. Results: The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. Conclusions: In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.

Imaging of Acute Mesenteric Ischemia Using Multidetector CT and CT Angiography in a Porcine Model

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findingsd—compared with pathologic diagnosesd—predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia.