Squamous cell carcinoma of the head and neck is a complex group of diseases that presents a challenge to the clinician. The prognosis in the recurrent/metastatic disease is particularly dismal, with a median survival of approximately 12 months. Recently, the personalized and multimodal approach has increased prognosis by integrating locoregional strategies (salvage surgery and stereotactic radiotherapy) and systemic treatments (chemotherapy, immunotherapy, and target therapy). Malnutrition is a significant clinical problem that interferes with dose intensity, and thus, feeding supplementation is critical not only to increase the quality of life but also to improve overall survival. With this review, we want to emphasize the importance of the multidisciplinary approach, quality of life, and nutritional supportive care and to integrate the latest updates of predictive biomarkers for immunotherapy and future therapeutic strategies.

Head and neck squamous cell carcinoma (HNSCC) develops within a biologically complex niche shaped by epithelial, immune, environmental, and microbial interactions. Growing evidence indicates that microbial communities influence HNSCC initiation, progression, therapeutic response, and toxicity. This narrative review synthesizes current knowledge on microbiome composition in healthy mucosa, oral potentially malignant disorders, and established HNSCC, emphasizing how dysbiosis characterized by enrichment of periodontitis-associated taxa such as Fusobacterium and Porphyromonas and depletion of protective genera including Corynebacterium and Kingella may drive carcinogenesis through inflammation, genotoxic metabolites, immune modulation, and metabolic alterations. We also examine microbiome-mediated effects on systemic treatments, including chemotherapy, radiotherapy-induced mucositis, and immune checkpoint inhibitor (ICI) response, and review emerging approaches to therapeutically modulate microbial communities. Although several microbial signatures show potential as biomarkers or therapeutic targets, no reproducible microbiome-based tools are yet ready for clinical implementation. Standardized methodologies and prospective interventional studies will be essential to translate these findings into precision oncology for HNSCC.

RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary.