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Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Background Head and neck squamous cell carcinoma (HNSCC) affects health-related quality of life (HRQoL); few treatments have demonstrated clinically meaningful HRQoL benefit. KEYNOTE-040 evaluated pembrolizumab versus standard of care (SOC) in patients with recurrent/metastatic (R/M) HNSCC whose disease recurred/progressed after platinum-containing regimen. Methods Patients received pembrolizumab 200 mg or SOC (methotrexate, docetaxel, or cetuximab). Exploratory HRQoL analyses used European Organisation for Research and Treatment of Cancer (EORTC) 30 quality-of-life, EORTC 35-question quality-of-life head and neck cancer-specific module, and EuroQoL 5-dimensions questionnaires. Results HRQoL population comprised 469 patients (pembrolizumab=241, SOC=228). HRQoL compliance for patients on study at week 15 was 75.3% (116/154) for pembrolizumab and 74.6% (85/114) for SOC. Median time to deterioration in global health status (GHS)/QoL score was 4.8 months and 2.8 months, respectively (HR, 0.79; 95% CI: 0.59, 1.05). At week 15, GHS/QoL scores were stable for pembrolizumab (least squares mean [LSM], 0.39; 95% CI: –3.00, 3.78) but worsened for SOC (LSM, –5.86; 95% CI: –9.68, –2.04); LSM between-group difference was 6.25 points (95% CI: 1.32, 11.18; nominal 2-sided P=.01). Greater difference in LSM score for GHS/QoL occurred with pembrolizumab versus docetaxel (10.23; 95% CI: 3.15, 17.30) compared with pembrolizumab versus methotrexate (6.21; 95% CI: -4.57, 16.99) or pembrolizumab versus cetuximab (–1.44; 95% CI: -11.43, 8.56). Pembrolizumab-treated patients had stable functioning and symptoms at week 15, with no notable differences from SOC. Conclusions GHS/QoL was stable with pembrolizumab but declined with SOC in patients at week 15, supporting the clinically meaningful benefit of pembrolizumab in R/M HNSCC.

Immune checkpoint inhibitors have entailed a change of paradigm in the management of multiple malignant diseases and are acquiring a key role in an increasing number of clinical sceneries. However, since their mechanism of action is not limited to the tumor microenvironment, their systemic activity may lead to a wide spectrum of immune-related side effects. Although neurological adverse events are much less frequent than gastrointestinal, hepatic, or lung toxicity, with an incidence of <5%, their potential severity and consequent interruptions to cancer treatment make them of particular importance. Despite them mainly implying peripheral neuropathies, immunotherapy has also been associated with an increased risk of encephalitis and paraneoplastic disorders affecting the central nervous system, often appearing in a clinical context where the appropriate diagnosis and early management of neuropsychiatric symptoms can be challenging. Although the pathogenesis of these complications is not fully understood yet, the blockade of tumoral inhibitory signals, and therefore the elicitation of cytotoxic T-cell-mediated response, seems to play a decisive role. The aim of this review was to summarize the current knowledge about the pathogenic mechanisms, clinical manifestations, and therapeutic recommendations regarding the main forms of neurotoxicity related to checkpoint inhibitors.