Real-World Data for Lenvatinib in Radioiodine-Refractory Differentiated Thyroid Cancer (RELEVANT): A Retrospective Multicentric Analysis of Clinical Practice in Austria.

BACKGROUND: Lenvatinib has proven efficacy in progressive, radioiodine- (RAI-) refractory thyroid cancer (TC). Dose reductions are commonly performed due to decreased tolerability and adverse effects. This retrospective multicenter study analyzed overall survival (OS) and progression-free survival (PFS) and tolerability in the Austrian patient population treated with lenvatinib. METHODS: Clinical data of 43 patients (25 males and 18 females) with a median age of 70 years (range: 39-91 years) and RAI-refractory TC with metastases to the lymph nodes (74%), lungs (86%), bone (35%), liver (16%), and brain (12%) were analyzed. The mean duration of treatment with lenvatinib was 26.6 ± 15.4 months with dosage reductions required in 39 patients (91%). RESULTS: PFS after 24 months was 71% (95% CI: 56-87), and overall survival (OS) was 74% (95% CI: 60-88), respectively. OS was significantly shorter (p=0.048) in patients with a daily maintenance dosage ≤ 10 mg (63%) (95% CI: 39-86) as compared to patients on ≥ 14 mg lenvatinib (82%) (95% CI: 66-98) daily. Dose reduction was noted in 39 patients (91%). Grade ≥3 toxicities (hypertension, diarrhea, weight loss, and palmar-plantar erythrodysesthesia syndrome) were most common leading to discontinuation of lenvatinib in 7 patients (16%). CONCLUSION: Lenvatinib showed sustained clinical efficacy in patients with metastatic RAI-refractory TC even with reduced maintenance dosages over years. The effects were comparable to the registration trial, although patients had a higher median age and, more commonly, dose reductions.

Quality of life aspects in the management of thyroid cancer.

While there is agreement that quality of life (QoL) is a central aim of medical treatment, the methods of its evaluation as well as its role in the patient's overall treatment experience are under continuous scrutiny. Different perspectives on patients' QoL have emerged; from the treating physician, from the psychologist, and naturally from the patient him/herself. This article provides insights into each of these views within the context of thyroid cancer where, as a consequence of increasing incidence and decreasing mortality rates, QoL aspects deserve close attention. Physicians often find themselves in situations where they perform a balancing act between what they know is best from a somatic point of view and learning about what is best for the individual patient. For psychologists in the field of oncology, a main area of interest is the incorporation of the patient's perspective into research by using patient-reported outcomes (PROs) which include QoL assessment. PROs can also be used in clinical practice as a way to start a conversation about symptoms and QoL aspects that perhaps patients might not volunteer, and this allows physicians to address QoL issues more directly. Patients usually appreciate being asked about all aspects of QoL, and need sound information about how their QoL might be affected by the disease and its treatment. By examining and understanding the different perspectives on QoL, and how QoL differs in patients with thyroid cancer compared with other cancers, it is hoped that the QoL can be enhanced in this particular patient group.

[Treatment of patients with radioiodine refractory, differentiated thyroid carcinoma. A Consensus Statement]. / Therapie des Patienten mit Radioiod-refraktärem, differenziertem Schilddrüsenkarzinom. Ein Konsensusstatement.

There is no clear standard therapy for patients with radioactive iodine (131I)-refractory locally advanced or metastatic differentiated thyroid cancer. The therapeutic options for this indication have expanded with the recently approved multiple kinase inhibitor sorafenib. Recommendations for the definition and the management of iodine refractory patients were worked up by an interdisciplinary expert panel, consisting of endocrine surgeons, medical oncologists and nuclear medicine specialists.

Uptake of (18)F-FLT and (18)F-FDG in primary head and neck cancer correlates with survival.

UNLABELLED: The aim of the study was to determine the practicability of (18)F-FLT in tumours of the head and neck area in terms of visualization, a possible correlation between FLT uptake and proliferation fraction as determined by Ki-67 immunostaining, and if tumoural FLT-uptake has a prognostic meaning, as determined by a correlation to patient survival time. Results were compared to (18)F-FDG. PATIENTS, METHODS: 20 patients with previously untreated lesions of the head and neck area, which were clinically highly suspicious to be malignant, underwent PET scans with (18)F-FLT and (18)F-FDG, a CT of the head and neck area, and a biopsy. Tumour tracer uptake was determined by standardized uptake value (SUV) normalized to body weight and /non-tumor ratios (T/N). (18)F-FDG and (18)F-FLT uptake were compared with histopathologic and immunohistochemical results. RESULTS: 19 patients had malignant tumours; one patient had a benign cystadenoma (so called Warthin's tumour) of the parotid gland. One negative lesion turned out to be a malignant T1 stage squamous cell carcinoma in both PET scans, the Warthin's tumour was false positive with (18)F-FDG but showed only faint uptake with (18)F-FLT, resulting in a sensitivity of 95 % for both tracers. Of all lesions, maximum SUVs of (18)F-FLT ranged from 1.53 to 11.70 (mean +/- SD 5.81 +/- 2.28) those of FDG from 2.63 to 16.50 (mean +/- SD 8.91 +/- 3.58), p < 0.001. (18)F-FLT-T/N ranged from 0.94 to 5.85 (mean +/- SD, 3.18 +/- 1.21), (18)F-FDG-T/N was from 0.92 to 7.50 (mean +/- SD, 3.6 +/- 1.74), n.s. The mean survival time was 18 months in a maximum follow up time of 36 months. A significant correlation between both PET tracers and survival was detected, but no correlation between the amount of Ki-67 positive cells and FLT. CONCLUSION: In head and neck cancer in the primary setting (18)F-FLT does not provide additional visual information in comparison to (18)F-FDG.(18)F-FLT uptake is inversely correlated with patient survival, as well as (18)F-FDG.

Surgical target selection in cerebral glioma surgery: linking methionine (MET) PET image fusion and neuronavigation.

OBJECTIVE: The objective of this study was to investigate the histological correlate of (11)C-methionine (MET) PET uptake of brain gliomas by image fusion for navigated surgery. METHODS: Twenty-seven patients (18 male, 9 female; mean age 42 years; range 11-77 years; 8 low-grade and 11 high-grade astrocytomas or mixed gliomas, 8 oligodendrogliomas) underwent MET PET studies preoperatively. RESULTS: MET PET tumor uptake was detected in 26 of 27 patients (96.3%). The quantitative MET tumor standardized uptake value (SUV) ratio was significantly higher in malignant gliomas and oligodendrogliomas than in low-grade gliomas (2.76/2.62 vs. 1.67, p=0.03). Generally, qualitative visual grading of MET uptake revealed 2 main patterns: focal MET uptake in 12 and uniform global MET uptake in 11 patients. Focal uptake corresponded to malignant glioma histology in 66.7%, and uniform global uptake to oligodendroglial histology in 72.7%. In oligodendrogliomas, global MET uptake constituted 81.5% (range 53.8-135%) of the MRI T(1) tumor volume on average and was limited to the MRI FLAIR tumor volume in 86% (7/8) of patients. Tissue samples of focal MET uptake areas correlated with histological anaplasia in 66.6% (8/12 glioma patients), although 62.5% (5/8 patients) lacked MRI contrast enhancement. CONCLUSION: MET PET image fusion may facilitate the targeting of anaplastic foci in homogeneous MRI non-enhancing gliomas for biopsy, may identify oligodendroglial histology preoperatively as well as characterize biologically active tumor volumes within MRI T(1)/FLAIR tumor areas of candidate patients for resection.

Occlusion of iatrogenic pseudoaneurysms with percutaneous ultrasound guided thrombin injection.

BACKGROUND: Pseudoaneurysm is a common complication of cardiac catheterization and coronary intervention with an incidence of 2% even in experienced centers. PATIENTS AND METHODS: In a feasibility study conducted between December 2004 and February 2006 we enrolled 76 patients consecutively to receive local thrombin injection (mean 329 IU; range 100-800 IU) into the aneurysma sac. RESULTS: Ultrasound guided thrombotic occlusion of pseudoaneurysms was successful after one injection in 83% of the patients, 17% of the patients required more than one injection. The overall success rate of the procedure was 98,9%. No peripheral embolisation of thrombin was noted during any injection and we registered no other complication that needed any further intervention. CONCLUSIONS: We conclude that ultrasound guided occlusion of pseudoaneurysms using thrombin injection with a success rate of the procedure of 98,9% is feasible and safe.

18F-Fluoro-deoxy-glucose positron emission tomography in lymphoma of mucosa-associated lymphoid tissue: histology makes the difference.

BACKGROUND: The usefulness of 2-[fluorine-18]fluoro-2-deoxy-D-glucose Positron emission tomography (18F-FDG-PET) in lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is still a matter of debate, and conflicting results have been reported. We have evaluated whether the histological feature of plasmacytic differentiation (PD) might explain the heterogeneous behavior of MALT lymphoma regarding 18F-FDG uptake. PATIENTS AND METHODS: A total of 35 patients with a diagnosis of MALT lymphoma referred to our PET unit were studied. Whole-body 18F-FDG-PET scans were carried out on a General Electrics advanced PET scanner 40 min after i.v. injection of 300-380 MBq 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake, standard uptake values (SUVs) were calculated. RESULTS: A total of 19 patients had MALT lymphoma with plasmacytic differentiation (pMALT), while MALT lymphoma without plasmacytic features was diagnosed in 16 patients. Sixteen of 19 patients with PD showed significant 18F-FDG uptake in involved sites (SUV: 3.5-11.7). By contrast, 13 of 16 patients with normal MALT lymphoma showed a false-negative 18F-FDG-PET result. Two of these patients disclosed no tracer uptake in the majority of involved sites apart from one single lesions, while three had a true-positive 18F-FDG-PET scan (SUV: 3.4-6.0). CONCLUSIONS: 18F-FDG-PET visualizes pMALT in a high proportion of patients, whereas FDG-PET results are significantly less reliable in typical MALT (P = 0.001). This finding may partly account for the heterogeneous results of 18F-FDG-PET-studies in MALT lymphoma.

Attenuation correction for myocardial perfusion imaging. A comparison between SPECT and PET imaging by polar map analysis.

AIM: We investigated the impact of photon attenuation in myocardial perfusion imaging with SPECT and PET in patients with coronary artery disease. In fact, the regional tracer distribution can be quantitatively assessed by polar map analysis if the effects of photon attenuation are accounted for. PET imaging permits accurate measurement of and correction for photon attenuation, whereas results of attenuation correction in SPECT imaging have been inconsistent. PATIENTS, METHODS: We compared photon attenuation in resting perfusion imaging studies with SPECT ((99m)Tc-sestamibi) and PET ((13)N-ammonia) from 21 patients. Transaxial images were reconstructed with and without attenuation correction and reoriented into short axis images. Polar map analysis was utilized to generate regional tracer uptake in six anatomical segments. RESULTS: Average segmental photon attenuation calculated as the ratio of counts in corrected and uncorrected images was 7.2 +/- 1.4 in SPECT and 14.0 +/- 3.1 in PET imaging (p < 0.01). This attenuation factor was significantly related to body mass index for both methods (p < 0.001). While attenuation correction for SPECT imaging did compensate for attenuation effects in the inferior wall (from -15% to +6% vs. PET), relative tracer uptake in the anterior wall in SPECT images was significantly reduced after attenuation correction (from -2% to -18% vs. PET, p < 0.01). CONCLUSION: Differential effects of attenuation correction for myocardial SPECT perfusion imaging need to be considered when algorithms designed to compensate effects of photon attenuation in SPECT imaging are employed in clinical practice.

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) visualizes follicular lymphoma irrespective of grading.

BACKGROUND: 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) has become a routine measure for staging and follow-up of patients with aggressive lymphoma. By contrast, its usefulness to visualize indolent lymphomas characterized by a lower cellular turnover has not clearly been defined. We have investigated accuracy and clinical usefulness of 18F-FDG-PET in patients with follicular lymphoma (FL). PATIENTS AND METHODS: A total of 64 patients with FL WHO grade I - III (48, 5, and 11 patients) were imaged at our institution to assess the value of 18F-FDG-PET for imaging of FL of different gradings. A total of 115 scans (48 before therapy and 67 for response assessment after treatment) were performed, and findings were compared to conventional staging including CT-scan of thorax and abdomen, sonography of lymph nodes and bone marrow biopsy. RESULTS: Overall, 18F-FDG-PET had a sensitivity of 98%, a specificity of 94%, a positive predictive value of 95% and a negative predictive value of 98%. These results were significantly more accurate (P = 0.023) than the conventional radiology studies. There was no significant difference (P = 0.093) in the accuracy between patients with indolent (WHO grade I and II) versus aggressive FL (WHO grade III). CONCLUSION: 18F-FDG-PET scan is a reliable method for staging and follow up of patients with nodal FL irrespective of tumor grading.

Measurement of renal function in patients with Fabry disease.

UNLABELLED: Appropriate measurement of the glomerular filtration rate (GFR) is important for the assessment of renal function. This paper reviews the methods used to assess GFR in clinical trials of enzyme replacement therapy (ERT) in patients with Fabry disease, which include inulin clearance, 24-hour creatinine clearance, chromium ethylene diamine tetraacetate (51Cr-EDTA) clearance and cystatin C concentrations. GFR has also been estimated using calculations based on creatinine clearance (the Cockcroft-Gault formula) and the Modification of Diet in Renal Disease (MDRD) equation. Analysis of the results of these studies shows that there are striking discrepancies between estimated and measured GFR. For example, the MDRD equation overestimates GFR in patients with Fabry disease who have normal renal function. In addition, cystatin C has been shown to be of limited use for measuring renal function during ERT, because it is influenced by other factors such as age, gender and weight. CONCLUSION: The use of exact methods, such as inulin clearance, 124I-iothalamate, 99mTc-DTPA, 51Cr-EDTA and iohexol, appears to be mandatory for a robust evaluation of the effects of ERT on GFR in patients with Fabry disease.

Value of combined XCT/SPECT technology for avoiding false positive planar (123)I-MIBG scintigraphy.

AIM: The clinical value of combined XCT/SPECT technology in a single device in patients undergoing (123)I-MIBG scintigraphy was analyzed. METHODS: 31 patients (19 men, 12 women; mean age 55 years, range: 31-79 years) demonstrating focal accumulation in planar (123)I-MIBG scan were further investigated with a double headed gamma camera with an X-ray tomograph mounted on the same gantry (GE Medical Systems, Millennium VG with Hawkeye, Milwaukee, USA) for anatomical definition of the focal (123)I-MIBG uptake. The patients were referred to (123)I-MIBG scintigraphy because of biochemically (81%) and/or clinically (19%) suspected pheochromocytoma. RESULTS: In 23 out of 31 patients (74%) the fused images demonstrated physiological accumulation (i. e. intestinal, renal) of (123)I-MIBG. In two patients (6%) suspected adrenal MIBG-accumulation was caused by inhomogeneous liver uptake. In two patients (6%) focal abdominal accumulation was correctly localised in the adrenal glands. Furthermore, the differentiation of bone metastasis from a local recurrence for phaeochromocytoma was accurately possible for two patients (6%). Adrenal lesions mimicking liver foci were correctly localised in the remaining two patients (6%). CONCLUSION: Our study demonstrates the clinical value of XCT/SPECT in a single device in patients demonstrating focal (123)I-MIBG uptake in planar scintigraphy. The combined XCT/SPECT technology provides a higher diagnostic accuracy.

Prognostic value of FDG-PET in malignant lymphoma.

Lymphomas have represented an indication for nuclear medicine investigations for 30 years. Gallium-67 scintigraphy has been shown to be a valuable complementary method in Hodgkin's disease and non-Hodgkin lymphoma for detecting viable residual lesions after chemotherapy and for diagnosis of a relapse. Thallium-201 is of interest in differentiating cerebral lymphomas from infectious lesions in AIDS patients but less useful in extra-cerebral lymphomas. PET with fluorine-18-FDG is more accurate than 67Ga in lymphoma. In patients with a positive PET scan after chemotherapy an early relapse occurs in up to 100%, while more than 80% of patients with a negative PET will have a long-term remission. Most studies show that FDG-PET is significantly correlated with patient outcome whereas there is much weaker or even no correlation for CT. The main reason is that PET is not bound to morphological criteria like lymph node size while CT is often not able to differentiate between residual tumour and post-therapeutic fibrosis. Therefore, based on a considerable number of clinical studies, FDG-PET gains increasing significance for staging, restaging and therapy monitoring in malignant lymphomas.

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

Predictive impact of 2-18fluoro-2-deoxy-D-glucose positron emission tomography for residual postchemotherapy masses in patients with bulky seminoma.

PURPOSE: To establish the predictive potential of 2-18fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) for detecting viable tumor tissue in residual postchemotherapy masses of seminoma patients. PATIENTS AND METHODS: In this prospective multicenter trial, results of FDG PET studies in seminoma patients with postchemotherapy masses > or = 1 cm were correlated with either the histology of the resected lesion or the clinical outcome on follow-up without resection. Negative PET scans of residual lesions that were devoid of viable tumor tissue on resection or disappeared, shrunk, or remained stable in size for at least 2 years were rated as true-negative (TN). Positive scans without histologic or clinical evidence of tumor tissue were classified as false-positive. In patients with histologically positive or progressive lesions, positive PET scans were defined as true-positive (TP) and negative scans, false-negative (FN). RESULTS: Thirty-seven PET scans of 33 patients were assessable at a median follow-up time of 23 months (range, 2 to 46 months). Histologic data were available from nine patients who had undergone resection. Twenty-eight patients were followed-up clinically and radiologically. Twenty-eight scans were TN, eight were TP, and one was FN. All 14 residual lesions more than 3 cm and 22 (96%) of the 23 < or = 3 cm were correctly predicted by FDG PET. The specificity (100%; 95% confidence interval [CI], 87.7% to 100%), sensitivity (89%; 95% CI, 51.7% to 99.7%), positive predictive value (100%), and the negative predictive value (97%) of FDG PET were superior to data obtained by assessing residual tumor size (< or = or > 3 cm). CONCLUSION: FDG PET is a clinically useful predictor of viable tumor in postchemotherapy residuals of pure seminoma, especially those greater than 3 cm.

FDG positron emission tomographic, radioiodine, and MIBI imaging in a patient with poorly differentiated insular thyroid carcinoma.

Poorly differentiated insular thyroid carcinoma is now classified as a separate entity among other tumors of the thyroid gland. Its histologic pattern and its clinical course are regarded as intermediate between well differentiated and anaplastic thyroid cancer. Insular carcinoma accumulates I-131, but no data exist regarding its fluorodeoxyglucose (FDG) positron emission tomographic (PET) uptake. The authors report F-18 FDG PET, Tc-99m MIBI, and radioiodine imaging features in a 63-year-old patient with metastatic insular thyroid carcinoma. After total thyroidectomy (for poorly differentiated insular carcinoma pT3a), the patient was referred for radioiodine ablation. No signs of recurrence were present until 16 months later, when thyroglobulin levels increased. An I-131 scan showed a single lesion in the right lung, and further radioiodine treatment was administered (cumulative dose [530 mCi], 19,610 MBq I-131). Three years after the initial diagnosis, FDG-PET and Tc-99m MIBI scans were performed within 5 days during thyroxine treatment. After that, thyroxine substitution was withdrawn; 6 weeks later, an I-131 whole-body scan was performed. Both radioiodine and MIBI images showed increased tracer uptake in the known lung lesion. However, FDG PET showed a normal tracer distribution. Magnetic resonance and computed tomographic imaging confirmed a 12-mm lesion in the right upper lobe. These findings support the concept of the "flip-flop phenomenon" in insular thyroid carcinoma, an alternating pattern of metastases with either I-131 or FDG-uptake. Despite poorly differentiated histologic findings, glucose metabolism was not increased in this patient with an insular tumor.

Imaging of Primitive Neuroectodermal Tumor (PNET) by Technetium-99m Tetrofosmin.

Purpose. Tc-99m tetrofosmin launched for myocardial studies has recently also shown a good detectability for several tumors. Data on PNET imaging by Tc-99m tetrofosmin are not yet available.Patient and method. In the case of a 21-year-old man suffering from pelvis PNET, Tc-99m tetrofosmin scintigraphy was performed additionally to CT and MRI.Results. The gluteal and iliac tumor masses were visualized by Tc-99m tetrofosmin according to the CT and MRI results.Discussion. Imaging with Tc-99m tetrofosmin could provide additional information to the available conventional radiological imaging modalities for diagnosis of PNET, and could be a useful tool for the restaging of the primary tumor.