Antibody-drug conjugates (ADCs) are fusions of therapeutic drugs and antibodies conjugated by a linker, designed to deliver a therapeutic payload to cells expressing the target antigen. By delivering the highly cytotoxic agent directly to cancer cells, ADCs are designed to enhance safety and broaden the therapeutic window. Recently, ADCs have demonstrated promising efficacy in various solid tumors and are rapidly expanding their indications. The prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC) remains poor, with no new therapeutics since the advent of anti-PD-1 antibodies in 2016, highlighting a critical need for innovative therapies. Recent preliminary results suggest that ADCs could be promising treatment options for HNSCC as they explore a variety of target antigens, payloads, and linkers. However, for successful adaptation of ADCs in the treatment of HNSCC, addressing key challenges such as payload toxicities, antigen heterogeneity, and adaptive resistance will be essential. Current research focused on new ADC structures, including multispecific antibodies and noncytotoxic payloads, and diverse combination approaches, show promise for future advancements.

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UNASSIGNED: Definitive concurrent chemoradiotherapy (CRT) is the standard of care in advanced stages of head and neck cancer (HNC). With evident increase in survival rate there is also simultaneous increase in toxicity affecting the quality of life. One of the less researched late toxicity is radiation induced brachial plexopathy (RIBP). In this dosimetric study we intent to contour the brachial plexus (BP) as an organ at risk (OAR) and determine the factors that contribute to dose variations to BP, and clinically evaluate the patients for RIBP during follow-up using a questionnaire.
UNASSIGNED: 30 patients with HNC planned for CRT from September 2020 to June 2022 were accrued. Patients were treated to a dose of 6600 cGy with intensity modulated radiotherapy using the simultaneous integrated boost technique. From the dose-volume histogram (DVH) statistics the BP volume, Dmax and other parameters like V66, V60 were assessed and was correlated with respect to primary tumour and nodal stage.
UNASSIGNED: On corelation, more than the T stage, the N stage and the primary location had a significant impact on the Dmax. With a median follow-up of 17.9 months, the incidence of RIBP was 6.67%. The 2-year disease free survival and the 2-year overall survival were 53.7% and 59.4%, respectively.
UNASSIGNED: In oropharyngeal/hypopharyngeal primaries and in advanced nodal disease, BP receives higher doses contributing to RIBP. Primary tumor and nodal stage also impacted V60 and V66 of BP. Hence, contouring of BP as an OAR becomes imperative, and respecting the DVH parameters is essential.

OBJECTIVE: Cancer related fatigue significantly impairs the ability to undertake sustained physical activity across the domains of daily living, work and recreation. The purpose of this study is to monitor cancer related fatigue and the factors affected or caused by it for 12 months in head and neck cancer patients following their diagnosis. Their perceptions of how fatigue might affect their activity levels in addition to identifying avenues to improve engagement with physical activity will be also explored.
METHODS: A single centre longitudinal mixed-methods study will be conducted. Forty head and neck cancer patients will be recruited over 6 months following the confirmation of their treatment plan, after which fatigue and physical activity will be assessed at four time points over 12 months. Additionally, other factors which influence fatigue such as body composition, blood counts, systemic inflammation levels, haemoglobin concentration, thyroid function, sleep quality, cardiorespiratory fitness and upper and lower extremity strength will be measured to understand how the multifactorial problem of fatigue may evolve over time and influence physical activity levels. Semi-structured interviews will be conducted after treatment completion and at end of twelve months which will analyse the participants fatigue experiences, understand how their perceived fatigue may have impacted physical activity and report the factors which may improve engagement with physical activity during cancer. Quantitative data will be analysed and reported using standard descriptive statistics and post-hoc pairwise comparisons. The changes in outcome measures across time will be analysed using the MIXED procedure in SPSS software. Statistical significance will be accepted at p<0.05. Qualitative data will be analysed using the Interpretative Phenomenological Approach using the NVivo software.
CONCLUSIONS: The results from this study may help inform the planning and delivery of appropriately timed interventions for the management of cancer related fatigue.

We have read the original article titled \"P4HA2 contributes to head and neck squamous carcinoma progression and EMT through PI3K/AKT signaling pathway\" by Yan-Ling Wu et al., which was published in the Medical Oncology journal, with great interest. This study provides valuable insights into the involvement of P4HA2 in the progression of head and neck squamous cell carcinoma (HNSCC), highlighting its potential as an oncogenic factor that promotes epithelial-mesenchymal transition (EMT), motility, invasion, and proliferation of cancer cells through the PI3K/AKT signaling pathway. While this work enhances our understanding of the role of P4HA2 in HNSCC, there are certain aspects that remain unexplored. These areas could be further investigated in future research to obtain a more comprehensive understanding. Specifically, the study did not investigate other signaling pathways or molecular mechanisms through which P4HA2 may impact the development of HNSCC. By exploring these molecular pathways, it may be possible to identify specific targets for pharmaceutical intervention to inhibit the production of P4HA2. Examining these aspects in future research would significantly contribute to our understanding of the role of P4HA2 in HNSCC and its potential as a therapeutic target. We appreciate the authors for their significant contribution and eagerly await future studies that expand upon these findings.

UNASSIGNED: In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC.
UNASSIGNED: The study compared 53 responders and 47 non-responders, analyzing formalin-fixed paraffin-embedded samples using 14-marker multiplex immunohistochemistry and targeted gene sequencing.
UNASSIGNED: Of 100 patients included, responders had significantly lower smoking and alcohol index, higher incidence of immune related adverse events, and higher PD-1 ligand (PD-L1) expression in immune cells as well as PD-L1 combined positive score (CPS) than non-responders. The frequency of natural killer cells was associated with nivolumab response in patients with prior cetuximab use, but not in cetuximab-naïve status. Age-stratified analysis showed nivolumab response was linked to high CPS and lymphoid-inflamed profiles in patients aged ≥ 65. In contrast, lower NLR in peripheral blood counts was associated with response in patients aged < 65. Notably, TP53 mutation-positive group had lower CPS and T cell densities, suggesting an immune-excluded microenvironment. Patients with altered tumor suppressor gene pathways, including TP53, CDKN2A, and SMAD4 mutations, had lower CPS, higher smoking index, and were associated with poor responses.
UNASSIGNED: Nivolumab treatment efficacy in HNSCC is influenced by a combination of clinical factors, age, prior treatment, immune environmental characteristics, and gene mutation profiles.

The combination of radiotherapy/chemoradiotherapy and immune checkpoint blockade can result in poor outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Here, we show that combining ATR inhibition (ATRi) with radiotherapy (RT) increases the frequency of activated NKG2A+PD-1+ T cells in animal models of HNSCC. Compared with the ATRi/RT treatment regimen alone, the addition of simultaneous NKG2A and PD-L1 blockade to ATRi/RT, in the adjuvant, post-radiotherapy setting induces a robust antitumour response driven by higher infiltration and activation of cytotoxic T cells in the tumour microenvironment. The efficacy of this combination relies on CD40/CD40L costimulation and infiltration of activated, proliferating memory CD8+ and CD4+ T cells with persistent or new T cell receptor (TCR) signalling, respectively. We also observe increased richness in the TCR repertoire and emergence of numerous and large TCR clonotypes that cluster based on antigen specificity in response to NKG2A/PD-L1/ATRi/RT. Collectively, our data point towards potential combination approaches for the treatment of HNSCC.

BACKGROUND: The impact of societal factors on the occurrence of head and neck cancers (HNCs) remains understudied, especially in the Nordic countries.
METHODS: To quantify the association between socio-economic status (SES) and the occurrence of HNCs, this cohort study uses data from the Nordic Occupational Cancer project that combine occupational and cancer registry data from 1961 to 2005 of 14.9 million individuals aged between 30 and 64 years. Occupational categories were combined into seven socio-economic categories. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates.
RESULTS: Altogether, 83 997 HNCs-72% in men and 28% in women-were recorded. Among men, a gradient of risk associated with SES was observed for cancers of the tongue, other oral cavity subsites, pharynx, oropharynx and larynx in groups with lower SES. Managers showed decreased SIRs of 0.50 to -0.90 also for cancers of the lip, tongue, other oral cavity subsites, oropharynx, nasopharynx, nose and larynx. In contrast, excess risks of tongue, other oral cavity subsites, pharyngeal, oropharyngeal and laryngeal cancers were observed among clerical (SIRs 1.05-1.16), skilled workers (1.04-1.14), unskilled workers (1.16-1.26) and economically inactive men (1.38-1.87). Among women, no risk gradient similar to that in men was revealed.
CONCLUSIONS: The current study underscores the influence of SES on the incidence of HNCs and highlights the need for targeted interventions, including tobacco and alcohol control policies, and improved access to healthcare services, particularly for socio-economically disadvantaged populations.

The discovery of multiple novel biomarkers in head and neck tumors has led to an increasing interest in utilizing head and neck cytology material as the primary specimens for testing diagnostic and prognostic biomarkers. Although human papillomavirus and programmed death ligand 1 are the most well-established biomarkers tested in cytology specimens, their utilization in cytology is limited by the absence of standardized protocols for specimen collection and fixation. This has led to a quest for innovative techniques to explore the genomic landscape in head and neck tumors and its application in cytology.

BACKGROUND: The principal objective of this study is to ascertain the connections between well-known risk factors of oral cancer, including smoking (cigarette and tobacco), alcohol consumption, betel quid chewing, irritations in the oral cavity, history of head and neck cancer, and history of working outdoor more than 4 days/week, and the presence of OPMDs within the Thai population.
METHODS: 349,318 subjects were recruited for initial screening, then 1,483 subjects who had at least 1 risk factor and a suspicious lesion underwent comprehensive oral examinations followed by a clinical diagnosis and then received initial treatment from either oral surgeons or oral medicine specialists. Among these subjects, individuals with at least 1 risk factor and with a clinical diagnosis of OPMDs were classified as cases, while those with at least 1 risk factor but without OPMDs were categorized as controls. The case group comprised a total of 487 subjects, whereas the control group consisted of 996 subjects. Exclusion criteria were known cases of currently having oral cancer or OPMDs.
RESULTS: The outcomes of the multivariate analysis revealed that among the variables assessed, betel quid (adjusted OR 5.12 [3.93-6.68], p < 0.001) and smoking (adjusted OR 1.46 [1.08-1.97], p = 0.013), there were an association with the presence of OPMDs. Conversely, alcohol drinking, having irritations in the oral cavity, a history of head and neck cancer, and a history of working outdoors more than 4 days/week were not associated with the presence of OPMDs. Furthermore, we also study the synergistic effect of alcohol drinking, irritations in the oral cavity, history of head and neck cancer, and history of working outdoors more than 4 days/week using subgroup analysis. The analysis showed that alcohol consumption combined with smoking or betel quid chewing expressed a significantly increased risk of OPMDs, from 1.46 to 2.03 (OR 2.03 [1.16-3.56], p = 0.014) and from 5.12 to 7.20 (OR 7.20 [3.96-13.09], p < 0.001).
CONCLUSIONS: Smoking and exposure to betel quid were a significant risk factors for the presence of OPMDs. The combination of alcohol with smoking or betel quid chewing was also found to increase the risk of OPMDs in this Thai northeastern population.