Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with longterm (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%.

The principle of information coding by the brain seems to be based on the golden mean. For decades psychologists have claimed memory span to be the missing link between psychometric intelligence and cognition. By applying BoseEinstein-statistics to learning experiments, Pascual-Leone obtained a fit between predicted and tested span. Multiplying span by mental speed (bits processed per unit time) and using the entropy formula for bosons, we obtain the same result. If we understand span as the quantum number n of a harmonic oscillator, we obtain this result from the EEG. The metric of brain waves can always be understood as a superposition of n harmonics times 2U, where half of the fundamental is the golden mean U ( ¼ 1.618) as the point of resonance. Such wave packets scaled in powers of the golden mean have to be understood as numbers with directions, where bifurcations occur at the edge of chaos, i.e. 2U ¼ 3 þ / 3 . Similarities with El NaschieÕs theory for high energy particleÕs physics are also discussed.

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