Background: Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi‐modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of care in management of recurrent/metastatic HNSCC. However, its role in the definitive and neoadjuvant setting remains unclear.Methods: A literature search was conducted that included all articles investigating ICI in untreated locally advanced (LA) HNSCC. Data was extracted and summarised and rated for quality using the Cochrane risk of bias tool.Results: Of 1086 records, 29 met the final inclusion criteria. In both concurrent and neoadjuvant settings, the addition of ICI was safe and did not delay surgery or reduce chemoradiotherapy completion. In the concurrent setting, although ICI use demonstrates objective responses in all published trials, there has not yet been published data to with PFS or OS benefit. In the neoadjuvant setting, combination ICI resulted in superior major pathological response rates compared to ICI monotherapy without a significant increase adverse event profiles, but its value in improving survival is not clear. ICI efficacy appears to be affected by tumour characteristics, in particular PD‐L1 combined positive score, HPV status and the tumour microenvironment.Conclusions: There is significant heterogeneity of ICI use in untreated LA HNSCC with multiple definitive concurrent and neoadjuvant protocols used. Resultantly, conclusions regarding the survival benefits of adding ICI to standard‐of‐care regimens cannot be made. Further trials and translational studies are required to elucidate optimal ICI sequencing in the definitive setting as well as better define populations more suited for neoadjuvant protocols.

Antibody–drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy, and targeted agents are occurring.

Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancers, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development [1]. Therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options [1-4]. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection [5-7]. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy and targeted agents are occurring.

This study tested if intelligently suspending cell phone conversationsduring demanding driving situations would improve driver’s performance andlessen subjective workload. Using a simulator, drivers followed a lead carapproximately 2 secs ahead and braking randomly. The drivers engaged inspontaneous “Neutral,” “Intense,” or “No” cell phone conversations with theexperimenter, who sustained all conversations with scripted non-directiveutterances. When the lead car started to decelerate, the conversations weresuspended or not for the duration of the event. Objective driving performance andsubjective “workload” estimates showed significant differences betweenconversation topic types. Engaging in an “Intense” conversation duringdeceleration produced (1) smaller decreases in forward velocity, and (2) delays inreleasing the accelerator, applying the brake and decelerating. Suspending“Intense” conversations counteracted these effects, producing larger decreases inforward velocity, and speeding up drivers’ responses on the vehicle controls.Furthermore, suspending conversations clearly increased drivers’ headways andtemporal distances with the lead car. The results show that cell phoneconversation intensity has significant effects on both performance and workload.The results also show positive effects of suspending cell phone conversationsduring critical driving situations on driver performance, thus perhapscounteracting the negative effects of the workload imposed by the conversations.Subjective ratings and value judgments for this system indicate generally positiveassessments of the system.