Pre-treatment predictors of laryngeal preservation (LP) and survival in advanced laryngeal-hypopharyngeal squamous-cell carcinoma (LHSCC) represent an unmet clinical need. A multicentric, international, retrospective series of LHSCC patients undergoing induction chemotherapy (IC) within an LP protocol was analyzed. The primary objective was to develop a predictive model by exploiting multiomics data (clinical, genomics, radiomics). Endpoints were laryngo-esophageal dysfunction (LED), response to IC, overall survival (OS), and progression-free survival (PFS). Patients were divided into three groups: group A (no LED); group B (responders to IC with LED); group C (non-responders to IC with LED). Several algorithms (support vector machine, random forest, C5.0, k-nearest neighbors, XGBoost, and naive Bayes) were run and compared in terms of multiclass area under the curve (AUC) score and classification error. One hundred and ninety-one LHSCC patients were included (median age 60 years, 72% laryngeal, 80% T1-T3, and 58% N+). Responders to IC were 85%, while 66% suffered from LED. The 5-year PFS and OS were 58.4% and 64.7%, respectively. When comparing the three predictive models (clinical, clinical + genomics, clinical + radiomics), the addition of genomics provided the highest AUC. Then, we selected a 64-gene signature and 6 clinical variables (comorbidities, primary site, smoking, T category, N category, performance status) to build up the PRESERVE model. It showed a classification error of 28.9% and an AUC of 87.4%. Risks of major misclassification were low (group A to C, 1.13%; group C to A, 7.38%). Decision analysis confirmed the efficiency of the model. The PRESERVE model proved to be efficient and accurate in predicting LED and response to IC in LHSCC. External validation is needed before clinical application.

Introduction: The concomitant use of antibiotics, especially beta lactams, during acute EBV infection is widely associated with an increased risk of skin manifestations; the actual pathophysiology and prevalence of this phenomenon are still debated. Case report: We present the first reported case of atypical exanthema associated with amoxicillin intake in a patient with EBV-related nasopharyngeal carcinoma. We recorded a pattern in the plasma EBV-DNA load consisting of a significant increase at the onset of the rash with a sudden remission after its resolution. The patient recovered without sequelae. Discussion/Conclusions: The temporal relationship and the reported data on rash morphology, clinical findings and triggering factors support a possible correlation between the intake of beta-lactam antibiotics, particularly amoxicillin, and the onset of cutaneous manifestations in a patient with nasopharyngeal carcinoma. Such reactions can be a challenging differential diagnosis and may warrant increased provider consideration when choosing to prescribe beta lactams in patients affected by nasopharyngeal cancer.

Head and neck squamous cell carcinomas (HNSCCs) develop from the mucosa of the oral cavity, pharynx, and larynx. The methylation levels of Septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in ccfDNA are considered pan-cancer biomarkers and have shown prognostic value in preliminary reports in HNSCC. Liquid biopsy is a non-invasive procedure that collects tumor-derived molecules including circulating cell-free DNA (ccfDNA). Here, we developed a ddPCR-based assay to detect the DNA methylation levels of plasma circulating SEPT9 and SHOX2 in patients with HNSCC. We first set up the assay on commercial methylated and un-methylated DNA. Then, the dynamic changes of the methylation levels of SEPT9 and SHOX2 were quantified in 20 patients during the follow-up. The results highlighted: i) the capability of the ddPCR-based assay in detecting very low copies of methylated molecules; ii) the significant decrease in methylation levels of SEPT9 and SHOX2 in plasma of HNSCC patients at the first time points of follow-up respect to T0; iii) a different trend of longitudinally DNA methylation variations associable to the clinicopathological features of the patients. The absolute quantification of the methylation levels of SEPT9 and SHOX2 in HNSCC may be used for risk stratification and disease monitoring.

Background Drug-drug interactions (DDIs) are an emerging issue in oncological patients, given the risk of increased toxicities and reduced efficacy from oncological treatments. This is particularly relevant in recurrent-metastatic (RM) head and neck cancer (HNC), where patients are often older, multimorbid, and receiving multiple home medications. While most DDIs are known for chemotherapy and targeted therapies, data on immune checkpoint inhibitors (ICIs) remain limited. Therefore, RM HNC patients represent a target population to investigate DDIs effects on ICIs. Material and Methods We conducted a retrospective, multicenter study to evaluate if polypharmacy affected safety and efficacy in RM HNC patients treated with ICIs, given alone (pembrolizumab or nivolumab) or in combination (combo) with chemotherapy (pembrolizumab-platinum-5-fluoruracil). DDIs were assessed using the Drug-PIN® platform, which provides for each patient two parameters: a Drug-PIN score, i.e. a continuous variable - the greater the number, the greater the likelihood of DDI; and a Drug-PIN level, with 5 levels ranging from green, meaning no interaction found, to red, meaning high potential for interaction. The relationship between Drug-PIN parameters and immune-related adverse events (irAEs) was tested using Student’s t-test. The correlation between Drug-PIN parameters and patients’ survival was assessed with the Kaplan-Meier method. Results We analysed 180 RM HNC (128 males) patients treated between June 2017 and July 2022 with ICIs (49 pembrolizumab alone, 89 nivolumab alone, 42 combo) at three different institutions. The median age was 65 years old (range: 33-89). Every patient took a median of 5 medications (0-15). Median Charlson Comorbidity Index score was 8 (2-14). IrAEs of any grade were observed in 55 patients (31%). Median PFS and OS were 5.9 and 6.5 months for pembrolizumab alone, 7.8 and 11.1 months for combo, 5 and 11.4 months for nivolumab. Median Drug-PIN score was 39.4 (0-214,3); Drug-PIN levels were green, light yellow, dark yellow, orange and red in 56, 27, 32, 9, 56 pts, respectively. Dichotomizing patients according to median Drug-PIN score, no difference was found in irAEs incidence (p 0.48), PFS (p. 0.82), or OS (p 0.89). No differences in irAEs incidence or in survival outcomes could be elucidated by stratifying patients according to Drug-PIN levels. Conclusions ICIs safety and efficacy in the treatment of RM HNC seem not to be affected by polypharmacy and DDIs.