Thomas F. Hany

Does the novel PET/CT imaging modality impact on the treatment of patients with metastatic colorectal cancer of the liver?

Objective:To compare the diagnostic value of contrast-enhanced CT (ceCT) and 2-[18-F]-fluoro-2-deoxyglucose-PET/CT in patients with metastatic colorectal cancer to the liver. Background:Despite preoperative evaluation with ceCT, the tumor load in patients with metastatic colorectal cancer to the liver is often underestimated. Positron emission tomography (PET) has been used in combination with the ceCT to improve identification of intra- and extrahepatic tumors in these patients. We compared ceCT and a novel fused PET/CT technique in patients evaluated for liver resection for metastatic colorectal cancer. Methods:Patients evaluated for resection of liver metastases from colorectal cancer were entered into a prospective database. Each patient received a ceCT and a PET/CT, and both examinations were evaluated independently by a radiologist/nuclear medicine physician without the knowledge of the results of other diagnostic techniques. The sensitivity and the specificity of both tests regarding the detection of intrahepatic tumor load, extra/hepatic metastases, and local recurrence at the colorectal site were determined. The main end point of the study was to assess the impact of the PET/CT findings on the therapeutic strategy. Results:Seventy-six patients with a median age of 63 years were included in the study. ceCT and PET/CT provided comparable findings for the detection of intrahepatic metastases with a sensitivity of 95% and 91%, respectively. However, PET/CT was superior in establishing the diagnosis of intrahepatic recurrences in patients with prior hepatectomy (specificity 50% vs. 100%, P = 0.04). Local recurrences at the primary colo-rectal resection site were detected by ceCT and PET/CT with a sensitivity of 53% and 93%, respectively (P = 0.03). Extrahepatic disease was missed in the ceCT in one third of the cases (sensitivity 64%), whereas PET/CT failed to detect extrahepatic lesions in only 11% of the cases (sensitivity 89%) (P = 0.02). New findings in the PET/CT resulted in a change in the therapeutic strategy in 21% of the patients. Conclusion:PET/CT and ceCT provide similar information regarding hepatic metastases of colorectal cancer, whereas PET/CT is superior to ceCT for the detection of recurrent intrahepatic tumors after hepatectomy, extrahepatic metastases, and local recurrence at the site of the initial colorectal surgery. We now routinely perform PET/CT on all patients being evaluated for liver resection for metastatic colorectal cancer.

Positron emission tomography/computed tomography influences on the management of resectable pancreatic cancer and its cost-effectiveness.

Objective:We sought to determine the impact of positron emission tomography/computed tomography (PET/CT) on the management of presumed resectable pancreatic cancer and to assess the cost of this new staging procedure. Summary Background Data:PET using 18F-fluorodeoxyglucose (FDG) is increasingly used for the staging of pancreatic cancer, but anatomic information is limited. Integrated PET/CT enables optimal anatomic delineation of PET findings and identification of FDG-negative lesions on computed tomography (CT) images and might improve preoperative staging. Material and Methods:Patients with suspected pancreatic cancer who had a PET/CT between June 2001 to April 2004 were entered into a prospective database. Routine staging included abdominal CT, chest x-ray, and CA 19-9 measurement. FDG-PET/CT was conducted according to a standardized protocol, and findings were confirmed by histology. Cost benefit analysis was performed based on charged cost of PET/CT and pancreatic resection and included the time frame of staging and surgery. Results:Fifty-nine patients with a median age of 61 years (range, 40–80 years) were included in this analysis. Fifty-one patients had lesions in the head and 8 in the tail of the pancreas. The positive and negative predictive values for pancreatic cancer were 91% and 64%, respectively. PET/CT detected additional distant metastases in 5 and synchronous rectal cancer in 2 patients. PET/CT findings changed the management in 16% of patients with pancreatic cancer deemed resectable after routine staging (P = 0.031) and was cost saving. Conclusions:PET/CT represents an important staging procedure prior to pancreatic resection for cancer, since it significantly improvespatient selection and is cost-effective.

The Role of 11C-Choline and 18F-Fluorocholine Positron Emission Tomography (PET) and PET/CT in Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT The role of positron emission tomography (PET) and PET/computed tomography (PET/CT) in prostate cancer (PCa) imaging is still debated, although guidelines for their use have emerged over the last few years. OBJECTIVE To systematically review and conduct a meta-analysis of the available evidence of PET and PET/CT using 11C-choline and 18F-fluorocholine as tracers in imaging PCa patients in staging and restaging settings. EVIDENCE ACQUISITION PubMed, Embase, and Web of Science (by citation of reference) were searched. Reference lists of review articles and included articles were checked to complement electronic searches. EVIDENCE SYNTHESIS In staging patients with proven but untreated PCa, the results of the meta-analysis on a per-patient basis (10 studies, n = 637) showed pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of 84% (95% confidence interval [CI], 68-93%), 79% (95% CI, 53-93%), and 20.4 (95% CI, 9.9-42.0), respectively. The positive and negative likelihood ratios were 4.02 (95% CI, 1.73-9.31) and 0.20 (95% CI, 0.11-0.37), respectively. On a per-lesion basis (11 studies, n = 5117), these values were 66% (95% CI, 56-75%), 92% (95% CI, 78-97%), and 22.7 (95% CI, 8.9-58.0), respectively, for pooled sensitivity, specificity, and DOR; and 8.29 (95% CI, 3.05-22.54) and 0.36 (95% CI, 0.29-0.46), respectively, for positive and negative likelihood ratios. In restaging patients with biochemical failure after local treatment with curative intent, the meta-analysis results on a per-patient basis (12 studies, n = 1055) showed pooled sensitivity, specificity, and DOR of 85% (95% CI, 79-89%), 88% (95% CI, 73-95%), and 41.4 (95% CI, 19.7-86.8), respectively; the positive and negative likelihood ratios were 7.06 (95% CI, 3.06-16.27) and 0.17 (95% CI, 0.13-0.22), respectively. CONCLUSIONS PET and PET/CT imaging with 11C-choline and 18F-fluorocholine in restaging of patients with biochemical failure after local treatment for PCa might help guide further treatment decisions. In staging of patients with proven but untreated, high-risk PCa, there is limited but promising evidence warranting further studies. However, the current evidence shows crucial limitations in terms of its applicability in common clinical scenarios.

18F-choline and/or 11C-acetate positron emission tomography : detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/ml) after radical prostatectomy

To assess the value of positron emission tomography (PET)/computed tomography (CT) with either 18F‐choline and/or 11C‐acetate, of residual or recurrent tumour after radical prostatectomy (RP) in patients with a prostate‐specific antigen (PSA) level of <1 ng/mL and referred for adjuvant or salvage radiotherapy.

The value of PET, CT and in-line PET/CT in patients with gastrointestinal stromal tumours: long-term outcome of treatment with imatinib mesylate

PurposeGastrointestinal stromal tumours (GIST) are mesenchymal neoplasms of the gastrointestinal tract that are unresponsive to standard sarcoma chemotherapy. Imaging of GIST patients is done with structural and functional methods such as contrast-enhanced helical computed tomography (ceCT) and positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG). The aim of this study was to compare the prognostic power of PET and ceCT and to evaluate the clinical role of PET/CT imaging.MethodsAll patients with GIST undergoing PET or PET/CT examinations were prospectively included in this study, and the median overall survival, time to progression and treatment duration were documented. The prognostic significance of PET and ceCT criteria of treatment response was assessed and PET/CT was compared with PET and ceCT imaging. Data for 34 patients (19 male, 15 female, 21–76 years) undergoing PET or PET/CT for staging or restaging were analysed.ResultsIn 28 patients, PET/CT and ceCT were available after introduction of treatment with the tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis, Basel, Switzerland). Patients without FDG uptake after the start of treatment had a better prognosis than patients with residual activity. In contrast, ceCT criteria provided insufficient prognostic power. However, more lesions were found on ceCT images than on PET images, and FDG uptake was sometimes very variable. PET/CT delineated active lesions better than did the combination of PET and ceCT imaging.ConclusionBoth PET and PET/CT provide important prognostic information and have an impact on clinical decision-making in GIST patients. PET/CT precisely delineates lesions and thus allows for the correct planning of surgical interventions.

Head and neck imaging with PET and PET/CT: artefacts from dental metallic implants

Abstract. Germanium-68 based attenuation correction (PETGe68) is performed in positron emission tomography (PET) imaging for quantitative measurements. With the recent introduction of combined in-line PET/CT scanners, CT data can be used for attenuation correction. Since dental implants can cause artefacts in CT images, CT-based attenuation correction (PETCT) may induce artefacts in PET images. The purpose of this study was to evaluate the influence of dental metallic artwork on the quality of PET images by comparing non-corrected images and images attenuation corrected by PETGe68 and PETCT. Imaging was performed on a novel in-line PET/CT system using a 40-mAs scan for PETCT in 41 consecutive patients with high suspicion of malignant or inflammatory disease. In 17 patients, additional PETGe68 images were acquired in the same imaging session. Visual analysis of fluorine-18 fluorodeoxyglucose (FDG) distribution in several regions of the head and neck was scored on a 4-point scale in comparison with normal grey matter of the brain in the corresponding PET images. In addition, artefacts adjacent to dental metallic artwork were evaluated. A significant difference in image quality scoring was found only for the lips and the tip of the nose, which appeared darker on non-corrected than on corrected PET images. In 33 patients, artefacts were seen on CT, and in 28 of these patients, artefacts were also seen on PET imaging. In eight patients without implants, artefacts were seen neither on CT nor on PET images. Direct comparison of PETGe68 and PETCT images showed a different appearance of artefacts in 3 of 17 patients. Malignant lesions were equally well visible using both transmission correction methods. Dental implants, non-removable bridgework etc. can cause artefacts in attenuation-corrected images using either a conventional 68Ge transmission source or the CT scan obtained with a combined PET/CT camera. We recommend that the non-attenuation-corrected PET images also be evaluated in patients undergoing PET of the head and neck.

Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial

Objective:To evaluate the morbidity of pancreaticoduodenectomy after neoadjuvant chemotherapy for resectable pancreatic cancer and to assess its histologic and metabolic response. Background:Adjuvant chemotherapy improves the outcome of pancreatic cancer, but 25% of patients remain unfit after surgery. Neoadjuvant chemotherapy can be offered to all patients in a multimodality approach, but its efficacy and surgical morbidity are unknown. Methods:Patients with resectable, cytologically proven adenocarcinoma of the pancreatic head received 4 bi-weekly cycles of gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) in this prospective phase II trial. Staging and restaging included chest x-ray, abdominal computed tomography (CT), positron emission tomography (PET)/CT, endoscopic ultrasound, and laparoscopy. Fluorodeoxyglucose uptake was quantified by the standard-uptake value (SUV) on baseline and restaging PET/CT. Immunohistochemistry for GLUT-1 and Ki-67 was performed. The histologic response, cytopathic effects, and surgical complications were graded by respective scores. Results:Twenty-four of 28 patients had resection for histologically confirmed adenocarcinoma. The surgical morbidity was low without perioperative death and one pancreatic fistula. Histologic response was documented in 54% and cytopathic effects in 83% of the patients. A significant SUV decrease occurred during chemotherapy (P = 0.031), which correlated with the baseline SUV (P = 0.001), Ki-67 expression (P = 0.016), and histologic response (P = 0.01). Neither the metabolic nor the histologic response was predictive of the median disease-free (9.2 months) or overall survival (26.5 months). Conclusion:Neoadjuvant chemotherapy induced a significant metabolic and histologic response, which was best predicted by PET. Most importantly, surgery after neoadjuvant chemotherapy for pancreatic cancer was safe.

Contrast-Enhanced 18F-FDG PET/CT: 1-Stop-Shop Imaging for Assessing the Resectability of Pancreatic Cancer

Patients with pancreatic cancer continue to have a poor prognosis, with a 5-y survival rate of less than 5%. Surgery is the only treatment that offers a potential cure. Determining resectability is the principal goal of staging in pancreatic cancer patients. Our objective was to evaluate the value of combined contrast-enhanced 18F-FDG PET/CT in assessing the resectability of pancreatic cancer and to compare enhanced PET/CT with the performance of PET alone and unenhanced PET/CT. Methods: Fifty patients (25 women and 25 men; mean age, 64.3 y; range, 39–84 y) with biopsy-proven pancreatic adenocarcinoma underwent enhanced 18F-FDG PET/CT for the evaluation of resectability. Criteria for unresectability were distant metastases, peritoneal carcinomatosis, arterial infiltration, or invasion of neighboring organs other than the duodenum. The performance of enhanced PET/CT regarding resectability was compared with that of PET alone and unenhanced PET/CT. Histology, intraoperative findings, and follow-up CT with clinical investigations were used as the reference standard. Results: According to the reference standard, 27 patients had disease that was not resectable because of distant metastases (n = 17), peritoneal carcinomatosis (n = 5), or local infiltration (n = 5). In the assessment of resectability, PET alone had a sensitivity of 100%, specificity of 44%, accuracy of 70%, positive predictive value of 61%, and negative predictive value of 100%; unenhanced PET/CT had respective values of 100%, 56%, 76%, 66%, and 100%; and enhanced PET/CT, 96%, 82%, 88%, 82%, and 96%. In 5 patients, unresectability was missed by all imaging methods and was diagnosed intraoperatively. Enhanced PET/CT was significantly superior to PET alone (P = 0.035), and there was a trend for enhanced PET/CT to be superior to unenhanced PET/CT (P = 0.070). Conclusion: The use of enhanced PET/CT as a 1-stop-shop imaging protocol for assessing the resectability of pancreatic cancer is feasible and accurate. Enhanced PET/CT is significantly superior to PET alone.

Value of Retrospective Fusion of PET and MR Images in Detection of Hepatic Metastases: Comparison with 18F-FDG PET/CT and Gd-EOB-DTPA–Enhanced MRI

The purpose of this study was to compare the accuracy of lesion detection and diagnostic confidence between 18F-FDG PET/CT, gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)–enhanced MRI, and retrospectively fused PET and MRI (PET/MRI). Methods: Thirty-seven patients (mean age ± SD, 60.2 ± 12 y) with suspected liver metastases underwent PET/CT and Gd-EOB-DTPA–enhanced MRI within 0–30 d (mean, 11.9 ± 9 d). PET and Gd-EOB-DTPA–enhanced MR image data were retrospectively fused. Images were reviewed independently by 2 readers who identified and characterized liver lesions using PET/CT, Gd-EOB-DTPA–enhanced MRI, and PET/MRI. Each liver lesion was graded on a 5-point confidence scale ranging from definitely benign (grade of 1) to definitely malignant (grade of 5). The accuracy of each technique was determined by receiver-operating-characteristic analysis. Histopathology served as the standard of reference for all patients with malignant lesions. Results: A total of 85 liver lesions (55 liver metastases [65%] and 30 benign lesions [35%]) were present in 29 (78%) of the 37 patients. Twenty-four (65%) of the 37 patients had liver metastases. The detection rate of liver lesions was significantly lower for PET/CT than for Gd-EOB-DTPA–enhanced MRI (64% and 85%; P = 0.002). Sensitivity in the detection and characterization of liver metastases for PET/CT, Gd-EOB-DTPA–enhanced MRI, PET/MRI in reader 1, and PET/MRI in reader 2 was 76%, 91%, 93%, and 93%, respectively; the respective specificity values were 90%, 100%, 87%, and 97%. The difference in sensitivity between PET/CT and PET/MRI was significant (P = 0.023). The level of confidence regarding liver lesions larger than 1 cm in diameter was significantly higher in PET/MRI than in PET/CT (P = 0.046). Accuracy values (area under the receiver-operating-characteristic curve) for PET/CT, Gd-EOB-DTPA–enhanced MRI, PET/MRI in reader 1, and PET/MRI in reader 2 were 0.85, 0.94, 0.92, and 0.96, respectively. Conclusion: The sensitivity of Gd-EOB-DTPA–enhanced MRI and PET/MRI in the detection of liver metastases is higher than that of PET/CT. Diagnostic confidence was significantly better with PET/MRI than with PET/CT regarding lesions larger than 1 cm in diameter. Compared with Gd-EOB-DTPA–enhanced MRI, PET/MRI resulted in a nonsignificant increase in sensitivity and diagnostic confidence.

Absolute quantification of cerebral blood flow with magnetic resonance, reproducibility of the method, and comparison with H215O positron emission tomography

While H215O positron emission tomography (PET) is still the gold standard in the quantitative assessment of cerebral perfusion (rCBF), its technical challenge, limited availability, and radiation exposure are disadvantages of the method. Recent work demonstrated the feasibility of magnetic resonance (MR) for quantitative cerebral perfusion imaging. There remain open questions, however, especially regarding reproducibility. The main purpose of this study was to assess the accuracy and reproducibility of MR-derived flow values to those derived from H215O PET. Positron emission tomography and MR perfusion imaging was performed in 20 healthy male volunteers, who were chronic smokers, on day 1 and day 3 of a 4-day hospitalization. Subjects were randomly assigned to one of two groups, each with 10 subjects. One group was allowed to smoke as usual during the hospitalization, while the other group stopped smoking from day 2. Positron emission tomography and MR images were coregistered and rCBF was determined in two regions of interest, defined over gray matter (gm) and white matter (wm), yielding rCBFPETgm, rCBFMRgm, rCBFPETwm, and rCBFMRwm. Bland-Altman analysis was used to investigate reproducibility by assessing the difference rCBFday3 - rCBFday1 in eight continual-smoker volunteers. The analysis showed a good reproducibility for PET, but not for MR. Mean ± SD of the difference rCBFday3 - rCBFday1 in gray matter was 6.35 ± 21.06 and 0.49 ± 5.27 mL · min−1 · 100 g−1 for MR and PET, respectively; the corresponding values in white matter were 2.60 ± 15.64 and −1.14 ± 4.16 mL · min−1 · 100 g−1. The Bland-Altman analysis was also used to assess MRI and PET agreement comparing rCBF measured on day 1. The analysis demonstrated a reasonably good agreement of MR and PET in white matter (rCBFPETwm - rCBFMRwm; −0.09 ± 7.23 mL · min−1 · 100 g−1), while in gray matter a reasonable agreement was only achieved after removing vascular artifacts in the MR perfusion maps (rCBFPETgm - rCBFMRgm; −11.73 ± 14.52 mL · min−1 · 100 g−1). In line with prior work, these results demonstrate that reproducibility was overall considerably better for PET than for MR. Until reproducibility is improved and vascular artifacts are efficiently removed, MR is not suitable for reliable quantitative perfusion measurements.