Marcus Ruhlmann

High Level of Agreement Between Pretherapeutic 124I PET and Intratherapeutic 131I Imaging in Detecting Iodine-Positive Thyroid Cancer Metastases

The aim of this retrospective study was to assess the level of agreement between PET and scintigraphy using diagnostic amounts of 124I and therapeutic amounts of 131I, respectively, in detecting iodine-positive metastases in patients with differentiated thyroid carcinoma. Methods: The study included patients who underwent PET/CT 24 and 120 h after administration of approximately 25 MBq of 124I and subsequently underwent imaging 5–10 d after administration of 1–10 GBq of 131I. For each patient, the intratherapeutic 131I imaging comprised a whole-body scintigraphy scan and a SPECT/CT scan of the neck to distinguish between metastatic and thyroid remnant tissues. Iodine uptake was rated as a metastatic focus if located outside the thyroid bed. Lesion- and patient-based analyses were performed. Results: The study included 137 patients with 227 metastases iodine-positive on both functional imaging modalities. In the lesion-based analysis, 124I PET and 131I imaging detected 98% (223/227) and 99% (225/227) of the iodine-positive metastases, respectively; the level of agreement between 124I PET and 131I imaging was 97% (221/227). Four metastases (3 lymph node and 1 bone) in 4 patients were 124I-negative but 131I-positive, and 2 lymph node metastases in 2 patients were 131I-negative but 124I-positive. In the patient-based analysis, 61 of the 137 patients presented with iodine-positive metastases. 124I PET and 131I imaging detected at least one iodine-positive metastasis in 97% (59/61) and 98% (60/61) of the patients, respectively. The level of agreement was 95% (58/61). Both imaging modalities concordantly identified 76 of 137 patients without pathologic iodine uptake. Conclusion: Because of the high level of agreement, pretherapeutic 124I PET/CT is an adequate methodology in the detection of iodine-positive metastases and can be used as a reliable tool for staging of thyroid cancer patients and individualized treatment planning.

Hybrid imaging for detection of carcinoma of unknown primary: A preliminary comparison trial of whole-body PET/MRI versus PET/CT

PURPOSE The aim of this study is to evaluate and compare the diagnostic potential of integrated whole-body [18F]FDG-PET/MRI to [18F]FDG-PET/CT for detection of a potential primary cancer and metastases in patients suspected for cancer of unknown primary (CUP). METHODS A total of 20 patients (15 male, 5 female, age 53±13 years) suspect for CUP underwent a dedicated head and neck & whole-body [18F]FDG-PET/CT (Biograph mCT 128, Siemens Healthcare) and a subsequent simultaneous [18F]FDG-PET/MRI examination (Biograph mMR, Siemens Healthcare). Two readers rated the datasets (PET/CT; PET/MRI) regarding the detection of the primary cancer and metastases, lesion conspicuity (4-point ordinal scale) and diagnostic confidence (3-point ordinal scale). PET analysis comprised the assessment of maximum standardized uptake values (SUVmax) of all PET-positive lesions using volume of interest (VOI) analysis derived from the PET/CT and PET/MR datasets. All available data considering histology and imaging including prior and clinical follow-up examinations served as reference standard. Statistical analysis included comparison of mean values using Mann-Whitney U test and correlation of SUVmax using Pearsons correlation. RESULTS In 14 out of 20 patients 49 malignant lesions were present. The primary cancer could be correctly identified in 11/20 patients with both PET/CT and PET/MRI. PET/CT enabled the detection of a total 38 metastases, PET/MR respectively of 37 metastases (one lung metastasis <5mm was missed). PET/CT and PET/MRI showed comparably high lesion conspicuity (2.6±0.6 each), with superior assessment of cervical lesions in PET/MRI and an indicated superior assessment of pulmonary lesions in PET/CT. Diagnostic confidence was rated comparably high in PET/CT and PET/MRI (2.7±0.5 each). The mean values of SUVmax of all PET-positive lesions (PET/MRT 7.9±4.2 vs. PET/CT 7.2±3.5) showed a strong positive correlation between the SUVs derived from both hybrid imaging systems (Pearsons correlation r=0.927). CONCLUSIONS Both hybrid imaging techniques provide a comparable diagnostic ability for detection of primary cancer and metastases in patients with CUP, with comparably high lesion conspicuity and diagnostic confidence, offering superior assessment of cervical lesions in PET/MRI and potentially of pulmonary lesions in PET/CT. Furthermore, due to the significantly lower dose of ionizing radiation, PET/MRI may serve as a powerful alternative to PET/CT, particularly for therapy monitoring and/or surveillance considering the long-term cumulative dose.

Does diffusion‐weighted imaging improve therapy response evaluation in patients with hepatocellular carcinoma after radioembolization? comparison of MRI using Gd‐EOB‐DTPA with and without DWI

To investigate whether additional diffusion‐weighted imaging (DWI) improves therapy response evaluation by Gd‐EOB magnetic resonance imaging (MRI) in hepatocellular carcinoma (HCC) after radioembolization.

68Ga-DOTATOC-PET/CT in patients with iodine- and 18F-FDG-negative differentiated thyroid carcinoma and elevated serum thyroglobulin

This study evaluated the impact of 68Ga-DOTATOC PET/CT in detecting recurrence or metastases in differentiated thyroid carcinoma (DTC) patients with elevated serum thyroglobulin and both negative radioiodine imaging and negative 18F-FDG PET/CT. Methods: 68Ga-DOTATOC PET/CT (CT without contrast, low-dose) was performed on average 6 wk after negative 18F-FDG PET/CT (CT contrast-enhanced, full-dose) in 15 consecutive radioiodine-negative DTC patients with elevated and rising thyroglobulin. Visual assessment of 68Ga-DOTATOC PET/CT images used a 4-point scale for classification of lesions (0, no pathologic findings; 1, benign; 2, equivocal; 3, malignant). PET findings were correlated with the histologic subtype of tumor, levels of serum thyroglobulin, and morphologic findings on full-dose CT and neck ultrasound. Histology or clinical and imaging follow-up served as a reference standard. Analysis was performed on a patient and lesion basis. Results: 68Ga-DOTATOC PET/CT was true-positive in 5 patients (10 tumor lesions) and was false-positive in 1 patient. The rate of positive 68Ga-DOTATOC PET/CT was significantly higher in poorly differentiated/oxyphilic carcinomas (4/4 patients) than in papillary (1/5) or follicular (0/6) tumors. Thyroglobulin levels tended to be higher in patients with tumor localization on 68Ga-DOTATOC PET/CT, but differences were not significant. In 2 of 5 patients with true-positive findings on 68Ga-DOTATOC PET/CT, CT alone but not ultrasound identified 2 of 10 tumor lesions, but in both patients 68Ga-DOTATOC-PET/CT revealed further tumor lesions not detected on CT alone. Conclusion: 68Ga-DOTATOC PET/CT should be considered in the case of negative 18F-FDG PET/CT in radioiodine-negative DTC patients with elevated and rising thyroglobulin. Imaging with 68Ga-DOTATOC appears promising especially in poorly differentiated and oxyphilic subtypes of DTC.

Assessment of Simplified Blood Dose Protocols for the Estimation of the Maximum Tolerable Activity in Thyroid Cancer Patients Undergoing Radioiodine Therapy Using 124I

In high-activity radioiodine therapies for differentiated thyroid cancer, blood dosimetry has been developed to estimate the maximum tolerable activity (MTA) of 131I that can be safely administered without leading to toxic effects. The reference protocol involves a series of both blood sampling (BS) and whole-body counting (WC) over a period of several days. The aim of this retrospective study was to identify simplified protocols without an appreciable loss of accuracy. Methods: Data from 211 thyroid cancer patients who received 124I blood dosimetries were retrospectively analyzed. BS and WC acquired at approximately 1–2, 4, 24, 48, and 96 h or longer after 124I administration were included. This dataset was used to determine the reference MTA and estimations based on a reduced number of combined data from BS and respective WC. MTA estimates were also determined on the basis of either BS or WC alone using some simplifying assumptions in the dosimetry approach. A simplified protocol was considered equivalent to the reference protocol if the estimates of 95% of the MTAs were within the ±20% range and the absolute maximum percentage deviation did not exceed the limit of 30% in a few cases. Lin’s concordance correlation analysis was applied to assess the protocol’s agreements. Results: Two equivalent protocols were identified that included both BS and respective WC acquired at only 3 time points (1–2, 24 or 48, and ≥96 h). Further equivalent protocols with only 3 blood samples drawn at similar time points were discovered for patients, who had undergone at least 1 radioiodine therapy. For all equivalent protocols, deviations of the mean absolute percentage MTA were below 9% and Lin’s concordance correlation coefficients of 0.95 or greater were found, indicating almost excellent agreement (according to Partik’s criteria). Conclusion: The pretherapy blood dosimetry protocol can be substantially shortened and may be beneficial to patients and patient management while reducing the radiation exposure to medical staff.

A single-center experience in radioembolization as salvage therapy of hepatic metastases of uveal melanoma

Background Overall survival (OS) of patients with hepatic metastases of uveal melanoma is strongly linked with hepatic tumor control. Due to the lack of an effective systemic chemotherapy, locoregional therapies like radioembolization should play an increasingly important role. Purpose To report complications and response rates of radioembolization as salvage therapy for hepatic uveal melanoma metastases. Material and Methods Between October 2006 and January 2014, eight patients (age, 59.1 ± 15.3 years; 5 men) with histologically proven uveal melanoma and hepatic metastases received radioembolization with glass microspheres at a single center. All patients had been heavily pretreated with multiple systemic/locoregional therapies resulting in a long median interval between diagnosis of hepatic metastases and radioembolization (17.1 months; range, 6.4–23.2 months). Follow-up consisted of clinical assessment, laboratory tests and tri-phasic computed tomography (CT) before and 1, 3, 6, 9, and 12 months after radioembolization. Response to therapy was evaluated by CT using RECIST version 1.1 and by survival time. Safety (laboratory and clinical toxicity) was rated according to Common Terminology Criteria for Adverse Events 4.03. Using Kaplan-Meier analysis time to progression of hepatic metastases (hTTP) and OS were calculated. Results One month after radioembolization 50% of patients presented with stable and 50% with progressive disease. Median hTTP and OS after radioembolization were 4.3 weeks (range, 3.4–28.6 weeks) and 12.3 weeks (range, 3.7–62.6 weeks), respectively. Median OS after diagnosis of hepatic metastases was 19.9 months (range, 7.3–31.4 months). Radioembolization was tolerated well in all patients without toxicity higher than grade 2. Conclusion Radioembolization is a safe salvage therapy even in heavily pretreated hepatic metastases of uveal melanoma.

Radioembolization with Y-90 Glass Microspheres: Do We Really Need SPECT-CT to Identify Extrahepatic Shunts?

Purpose Selective Internal Radiation Therapy (SIRT) with 90yttrium (Y-90) is an increasingly used therapeutic option for unresectable liver malignancies. Nontarget embolization of extrahepatic tissue secondary to vascular shunting can lead to SIRT associated complications. Our aim was to assess whether extrahepatic shunts can reliably be diagnosed based on hepatic digital subtraction angiography (DSA) or whether subsequent SPECT/CT data can provide additional information. Materials and Methods 825 patients with hepatocellular carcinoma (n = 636), hepatic metastases (n = 158) or cholangiocellular carcinoma (n = 31) were retrospectively analyzed. During hepatic DSA 128 arteries causing shunt flow to gastrointestinal tissue were coilembolized (right gastric artery n = 63, gastroduodenal artery n = 29; branches to duodenum / pancreas n = 36). Technectium-99m-labeled human serum albumin (HSA) was injected in all 825 patients. SPECT/CT data was used to identify additional or remaining shunts to extrahepatic tissue. Results An unexpected uptake of HSA in extrahepatic tissue was found by SPECT/CT in 54/825 (6.5%) patients (located in stomach n = 13, duodenum n = 26, distal bowel segments n = 12, kidney n = 1, diaphragm n = 2). These patients underwent repeated DSA and newly identified shunt vessels were coilembolized in 22/54 patients, while in 12/54 patients a more distal catheter position for repeat injection of HSA was chosen. In 20/54 patients the repeated SPECT/CT data still revealed an extrahepatic HSA uptake. These patients did not receive SIRT. Conclusion Most extrahepatic shunts can be identified on DSA prior to Y-90 therapy. However, SPECT-CT data helps to identify additional shunts that were initially not seen on DSA.

Therapy Response Assessment after Radioembolization of Patients with Hepatocellular Carcinoma—Comparison of MR Imaging with Gadolinium Ethoxybenzyl Diethylenetriamine Penta-Acetic Acid and Gadobutrol

PURPOSE To compare the utility of gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), a liver-specific magnetic resonance (MR) imaging contrast agent, versus gadobutrol for treatment response evaluation of hepatocellular carcinoma (HCC) after radioembolization. MATERIALS AND METHODS This prospective study included 50 patients with HCC undergoing radioembolization. All patients underwent contrast-enhanced computed tomography (CT) and MR imaging with gadobutrol and Gd-EOB-DTPA on 2 consecutive days before radioembolization and 30 days, 90 days, 180 days, and 270 days after radioembolization. The standard of reference indicating tumor progression was CT combined with either α-fetoprotein or γ-glutamyltransferase. Gadobutrol-enhanced MR imaging, Gd-EOB-DTPA-enhanced MR imaging without late phase imaging (Gd-EOB-DTPA-), and Gd-EOB-DTPA-enhanced MR imaging with late phase imaging (Gd-EOB-DTPA+) were evaluated by 2 radiologists in consensus using a 4-point scale: 1 = definitely no tumor progression; 2 = probably no tumor progression; 3 = probably tumor progression; 4 = definitely tumor progression. Diagnostic accuracy was assessed with receiver operating characteristic analysis. RESULTS Tumor progression was detected in 14 of 82 study visits according to the reference standard. Pairwise comparison of the area under the curve showed a tendency toward a larger area under the curve for Gd-EOB-DTPA+ compared with gadobutrol (P = .056). Sensitivity and specificity were higher in Gd-EOB-DTPA+ (0.929 and 0.971) than in Gd-EOB-DTPA- (0.786 and 0.941) or gadobutrol (0.643 and 0.956). In 2 cases, tumor progression was detected by Gd-EOB-DTPA+ and by an increase in α-fetoprotein, but not by CT, gadobutrol, or Gd-EOB-DTPA-. CONCLUSIONS Gd-EOB-DTPA+ MR imaging was not inferior to gadobutrol-enhanced MR imaging in therapy response evaluation after radioembolization and may allow a more accurate detection of early HCC recurrence in single cases.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography May Exclude Malignancy in Sonographically Suspicious and Scintigraphically Hypofunctional Thyroid Nodules and Reduce Unnecessary Thyroid Surgeries

BACKGROUND The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. METHODS Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (pathological FDG uptake) or follow-up examinations (non-pathological FDG uptake). The endpoints for comparison with the FDG uptake were either histological results or sonographic follow-up examinations of at least five years. RESULTS In 18/65 (28%) patients, PET/CT showed visually pathological FDG uptake in the suspicious thyroid nodules (SUVmax 7.1 ± 4.6). Of these nodules, 3/18 (17%) were sonographically categorized as TIRADS 4a, 11/18 (61%) nodules as TIRADS 4b, 3/18 (17%) nodules as TIRADS 4c, and 1/18 (6%) nodule as TIRADS 5. The other nodules without pathological FDG uptake were categorized as TIRADS 4a in 24/47 (51%) patients, as TIRADS 4b in 18/47 (38%), and as TIRADS 4c in 5/47 (11%) patients. Twenty-three patients (18 FDG positive, 5 FDG negative) underwent surgery. The other patients underwent follow-up examinations with stability on observation over at least five years as a surrogate endpoint. Taking into consideration that FDG-PET/CT was rated as true negative in 42/47 patients with stability on sonographic follow-up, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT in detecting malignancy in the suspicious thyroid nodules were 100%, 87%, 61%, and 100%, respectively. CONCLUSION FDG-PET/CT allows stratification of patients with sonographically suspicious and scintigraphically hypofunctional thyroid nodules with a positive predictive value of 61% and negative predictive value of 100%. The absence of visually pathological FDG uptake in suspicious thyroid nodules may be useful for avoiding unnecessary thyroid surgery.Background: The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. Methods: Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (patholog...

18F-FDG PET/CT may exclude malignancy in sonographically suspicious and scintigraphically hypofunctional thyroid nodules and reduce unnecessary thyroid surgeries

BACKGROUND The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. METHODS Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (pathological FDG uptake) or follow-up examinations (non-pathological FDG uptake). The endpoints for comparison with the FDG uptake were either histological results or sonographic follow-up examinations of at least five years. RESULTS In 18/65 (28%) patients, PET/CT showed visually pathological FDG uptake in the suspicious thyroid nodules (SUVmax 7.1 ± 4.6). Of these nodules, 3/18 (17%) were sonographically categorized as TIRADS 4a, 11/18 (61%) nodules as TIRADS 4b, 3/18 (17%) nodules as TIRADS 4c, and 1/18 (6%) nodule as TIRADS 5. The other nodules without pathological FDG uptake were categorized as TIRADS 4a in 24/47 (51%) patients, as TIRADS 4b in 18/47 (38%), and as TIRADS 4c in 5/47 (11%) patients. Twenty-three patients (18 FDG positive, 5 FDG negative) underwent surgery. The other patients underwent follow-up examinations with stability on observation over at least five years as a surrogate endpoint. Taking into consideration that FDG-PET/CT was rated as true negative in 42/47 patients with stability on sonographic follow-up, sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET/CT in detecting malignancy in the suspicious thyroid nodules were 100%, 87%, 61%, and 100%, respectively. CONCLUSION FDG-PET/CT allows stratification of patients with sonographically suspicious and scintigraphically hypofunctional thyroid nodules with a positive predictive value of 61% and negative predictive value of 100%. The absence of visually pathological FDG uptake in suspicious thyroid nodules may be useful for avoiding unnecessary thyroid surgery.Background: The aim of this study was to evaluate whether 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is useful in the further characterization of sonographically suspicious and scintigraphically hypofunctional thyroid nodules. Methods: Sixty-five patients with sonographically suspicious thyroid nodules that were hypofunctional on 99m-Tc-pertechnetate scintigraphy (diameter >1 cm) were retrospectively analyzed. All patients underwent evaluation with FDG-PET/CT. Thyroid nodules were sonographically categorized by Thyroid Image Reporting and Data System (TIRADS) criteria. FDG uptake in the thyroid nodules was visually compared to the remainder of the thyroid tissue and categorized as pathological or non-pathological. In cases of pathologically increased uptake, maximum standardized uptake values (SUVmax) of the suspicious nodule and the perinodular thyroid tissue were determined. Depending on the results of the FDG-PET/CT, patients underwent thyroid surgery (patholog...