These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy.
The WEE1 tyrosine kinase regulates G-M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. Thus, a need arises to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel. We implemented an open-label phase I clinical trial using a 3+3 dose-escalation design for patients with stage III/IVB HNSCC with borderline-resectable or -unresectable disease, but who were candidates for definitive chemoradiation. Escalating AZD1775 was administered orally twice a day over 2.5 days on the first week, then in combination with fixed cisplatin (25 mg/m) and docetaxel (35 mg/m) for 3 additional weeks. The primary outcome measure was adverse events to establish MTD. Secondary measures included response rates, pharmacokinetics (PK), pharmacodynamics, and genomic data. The MTD for AZD1775 was established at 150 mg orally twice per day for 2.5 days. RECISTv1.1 responses were seen in 5 of 10 patients; histologic adjustment revealed three additional responders. The only drug-limiting toxicity was grade 3 diarrhea. The PK C8hr target of 240 nmol/L was achieved on day 4 at all three doses tested. Pharmacodynamic analysis revealed a reduction in pY15-Cdk, and increases in γH2AX, CC3, and RPA32/RPA2 were noted in responders versus nonresponders. The triplet combination of AZD1775, cisplatin, and docetaxel is safe and tolerable. Preliminary results show promising antitumor efficacy in advanced HNSCC, meriting further investigation at the recommended phase II dose. .
The presence of middle ear fluid is a key diagnostic marker for two of the most common pediatric ear diseases: acute otitis media and otitis media with effusion. We present an accessible solution that uses speakers and microphones within existing smartphones to detect middle ear fluid by assessing eardrum mobility. We conducted a clinical study on 98 patient ears at a pediatric surgical center. Using leave-one-out cross-validation to estimate performance on unseen data, we obtained an area under the curve (AUC) of 0.898 for the smartphone-based machine learning algorithm. In comparison, commercial acoustic reflectometry, which requires custom hardware, achieved an AUC of 0.776. Furthermore, we achieved 85% sensitivity and 82% specificity, comparable to published performance measures for tympanometry and pneumatic otoscopy. Similar results were obtained when testing across multiple smartphone platforms. Parents of pediatric patients (n = 25 ears) demonstrated similar performance to trained clinicians when using the smartphone-based system. These results demonstrate the potential for a smartphone to be a low-barrier and effective screening tool for detecting the presence of middle ear fluid.
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