Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552.

^99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: −19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

The authors report on a patient suffering from acute Lyme borreliosis who underwent two consecutive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) studies demonstrating the course of the disease. The first FDG-PET study revealed markedly increased glucose metabolism in the brainstem, matching exactly the signal abnormalities exhibited on magnetic resonance images and indicating a brainstem tumor. A second PET scan demonstrated no abnormality in this region, thus reflecting clinical remission following antibiotic therapy. Data in the present case indicate that hypermetabolic findings on FDG-PET studies in the brainstem region should be regarded with caution and that neuroborreliosis must be considered as a possible differential diagnosis.