For differentiated thyroid cancer (DTC), systemic therapy with radioactive iodine (RAI) is utilized for radiosensitive disease, while for radioiodine refractory (RAIR) disease, current standard of care is treatment with multikinase tyrosine kinase inhibitors (TKI). For BRAF-mutant DTC or anaplastic thyroid cancer (ATC), treatment with inhibitors targeting BRAF and MEK are important advances. RET-inhibitors for RET-mutated medullary thyroid cancer (MTC) recently have been FDA-approved for metastatic disease. Nevertheless, treatment of thyroid cancer resistant to current systemic therapies remains an important area of need. Resistance mechanisms are being elucidated, and novel therapies including combinations of BRAF and MEK inhibitors with RAI or other targeted therapies or TKIs combined with checkpoint inhibition are current areas of exploration.

Background Effective targeted therapy is lacking in head and neck cancer (HNC). The use of next generation sequencing (NGS) has been suggested as a way to potentially expand therapeutic options and improve outcomes. This study was performed in order to further characterize blood sample cell-free circulating tumor DNA (ctDNA) in advanced HNC patients, to determine its ability to identify actionable mutations, and to elucidate its potential role in patient management. Methods Retrospective analysis of 60 patients with recurrent and metastatic (R/M) HNCs who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene ctDNA NGS platform. ctDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures. Results The most common tumor type was oropharyngeal squamous cell carcinoma (n=21). Other cancer types included salivary gland (n=8) and thyroid (n=4). The most common mutations identified by blood analysis were TP53 (68% of patients), PIK3CA (34% of patients), NOTCH1 (20% of patients), and ARID1A (15% of patients). These findings were consistent with results from tumor sequencing data (n=30) where TP53 (48%) and PIK3CA (24%) were also the most common. Seventy-three percent (n=22) of patients had alterations identified in blood that were not present in tumor specimens. In patients with squamous cell carcinoma, 66% had an off-label option identified and 90% had a trial option identified, while 50% of patients with salivary primaries had off-label option identified and 75% had trial options identified. All patients (n=3, 100%) with thyroid primaries had off-label and clinical trial options identified. Of patients with actionable mutations, 13% (n=8) received matched targeted therapy (MTT). Three patients had stable disease (37.5%), 3 had progressive disease (37.5%), and 2 (25%) were not evaluated at the time of follow up. Of those who did not receive targeted therapy (n=21), 11 patients had stable disease (52.4%), 9 had progressive disease (42.9%), and 1 had a complete response (4.8%). Conclusions Alterations identified by ctDNA may help inform management decisions in advanced HNC. The majority of patients had unique mutations identified on ctDNA. The role of NGS of ctDNA should be explored in future studies.

Intracranial abscess is an extremely rare form of central nervous system (CNS) tuberculosis (TB). We describe a case of central nervous system tuberculous abscess in absence of human immunodeficiency virus (HIV) infection. A 82-year-old Middle Eastern male from Yemen was initially brought to the emergency room due to altered mental status and acute renal failure. Cross-sectional imaging revealed multiple ring enhancing lesions located in the left cerebellum and in bilateral frontal lobe as well as in the inferior parietal lobe on the left. The patient was placed on an empiric antibiotic regimen. Preliminary testing for infectious causes was negative. Chest radiography and CT of chest showed no positive findings. He was not on any immunosuppressive medications and human immunodeficiency virus (HIV) enzyme immunoassay (EIA) test was negative. A subsequent MRI one month later showed profound worsening of the lesions with increasing vasogenic edema and newly found mass effect impinging on the fourth ventricle. Brain biopsy showed focal exudative cerebellitis and inflamed granulation tissue consistent with formation of abscesses. The diagnosis of CNS TB was finally confirmed by positive acid-fast bacilli (AFB) cultures. The patient was started on standard tuberculosis therapy but expired due to renal failure and cardiac arrest.

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