Questions and Controversies in the Clinical Application of Tyrosine Kinase Inhibitors to Treat Patients with Radioiodine-Refractory Differentiated Thyroid Carcinoma: Expert Perspectives.

Notwithstanding regulatory approval of lenvatinib and sorafenib to treat radioiodine-refractory differentiated thyroid carcinoma (RAI-R DTC), important questions and controversies persist regarding this use of these tyrosine kinase inhibitors (TKIs). RAI-R DTC experts from German tertiary referral centers convened to identify and explore such issues; this paper summarizes their discussions. One challenge is determining when to start TKI therapy. Decision-making should be shared between patients and multidisciplinary caregivers, and should consider tumor size/burden, growth rate, and site(s), the key drivers of RAI-R DTC morbidity and mortality, along with current and projected tumor-related symptomatology, co-morbidities, and performance status. Another question involves choice of first-line TKIs. Currently, lenvatinib is generally preferred, due to greater increase in progression-free survival versus placebo treatment and higher response rate in its pivotal trial versus that of sorafenib; additionally, in those studies, lenvatinib but not sorafenib showed overall survival benefit in subgroup analysis. Whether recommended maximum or lower TKI starting doses better balance anti-tumor effects versus tolerability is also unresolved. Exploratory analyses of lenvatinib pivotal study data suggest dose-response effects, possibly favoring higher dosing; however, results are awaited of a prospective comparison of lenvatinib starting regimens. Some controversy surrounds determination of net therapeutic benefit, the key criterion for continuing TKI therapy: if tolerability is acceptable, overall disease control may justify further treatment despite limited but manageable progression. Future research should assess potential guideposts for starting TKIs; fine-tune dosing strategies and further characterize antitumor efficacy; and evaluate interventions to prevent and/or treat TKI toxicity, particularly palmar-plantar erythrodysesthesia and fatigue.

Neuroborreliosis and acute encephalopathy: The use of CXCL13 as a biomarker in CNS manifestations of Lyme borreliosis.

We report the case of an 80-year-old patient with acute onset confusion initially suspected to reflect delirium in incipient Alzheimer's disease. Cerebrospinal fluid tests revealed an unusually severe form of neuroborreliosis, which resolved following antibiotic treatment. This was mirrored in the measurement of CXCL13, which is suggested as a complementary biomarker. Clinical implications for screening, differential diagnosis and treatment are discussed.

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PURPOSE OF THE REPORT: The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. PATIENTS AND METHODS: Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of "hot spots" with/without central photopenia and "cold spots" detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. RESULTS: 124I-PET detected significantly more "hot spots" with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more "cold spots" than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). CONCLUSIONS: 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.