Search Results (99)

Head and neck cancer (HNC) encompasses tumors located within the oral cavity, sinonasal cavity, pharynx, and larynx. It is the sixth most common cancer worldwide. Current treatment methods in HNC patients involve radical surgery, radical radiotherapy, and concomitant chemoradiotherapy, along with adjuvant and induction therapies. Accumulating trials examine the role of immunotherapy in patients with HNC. The results of the CheckMate-141 and KEYNOTE-048 trials demonstrated the benefits of using immunotherapy in patients with metastatic or recurrent HNC. Subsequently, numerous other immunotherapy-based protocols have been evaluated. Then, KEYNOTE-689 successfully implemented immunotherapy in patients with locally advanced disease. This review aims to comprehensively present the landscape of immunotherapy opportunities in patients with HNC. It summarizes completed key clinical trials that led to the approval of immunotherapy in HNC and presents currently performed trials with highly expected results. Furthermore, it discusses methods to improve immunotherapy outcomes in the cohort of HNC patients, describes the current role of immunotherapy in HNC, and presents future perspectives of this type of treatment. Full article

The tumor microenvironment (TME) orchestrates tumor growth, immune evasion, and therapeutic response in head and neck squamous cell carcinoma (HNSCC). Current immune checkpoint inhibitors (ICIs) target the programmed death receptor-1/programmed death-ligand 1 (PD-1/PD-L1) axis and improve survival in recurrent, metastatic, and locally advanced HNSCC. Tumor cells produced exosomes directly suppress cytotoxic T-lymphocytes activity by modulating immune checkpoint pathways and disrupting T-cell receptor signaling. Cancer-associated fibroblast-derived exosomes (CAF-Exos) function indirectly by conditioning immune escape and tumor growth. Together, these exosomal populations cooperate to create an immunosuppressive niche that hinders the efficacy of immunotherapies. CAF-Exos induce TME changes that exclude CD8⁺ T-cells, promote regulatory T-cells (Tregs), and upregulate PD-L1 expression in tumor cells. The bidirectional transfer of microRNAs (miRNAs) between tumor cells and CAFs enhances epithelial–mesenchymal transition (EMT), suppresses cytotoxic lymphocytes, and undermines ICI efficacy. This review article summarizes recent publications about plasma-derived exosomes from HNSCC patients. These exosomes carry tumor and immune checkpoint markers, reflect tumor burden and treatment response, and strongly modulate immune cells by suppressing T- and B-cell activity and promoting immunosuppressive macrophages. We encourage functional and biomechanistic future studies in the field of HNSCC that examine how CAF subtypes exosomes achieve an immunoresistant TME. Full article

The aim of the study was to evaluate the cost-effectiveness of PET/CT in the initial N-staging of head–neck cancer (HNC) and to compare it with alternative strategies using CT or MRI within the Greek National Healthcare System. A cohort of 100 clinically N0 (with no apparent metastatic cervical lymph nodes) HNC patients was simulated over a 10-year time horizon. Initially, a decision tree model was used to simulate the following three different imaging strategies for HNC staging: (a) whole-body FDG-PET/CT, (b) CT of the neck, chest, and abdomen (“CT”), and (c) MRI of the neck plus CT of the chest–abdomen (“MRI”). Subsequently, a Markov model was used to simulate transitions into the health states of recurrence and death. Epidemiological evidence, diagnostic accuracy rates, transition probabilities, and healthcare costs were obtained from the literature and official local tariffs. The estimated total costs per patient were EUR 128,729 for PET/CT, EUR 128,779 for MRI, and EUR 128,585 for CT. The corresponding life years (LYs) were 6.171 LYs for PET/CT, 6.170 LYs for MRI, and 6.170 LYs for CT, respectively. The analysis showed that PET/CT dominates MRI. The incremental cost-effectiveness ratio (ICER) of PET/CT vs. CT was estimated at EUR 144,984 per LY gained. All three imaging strategies had comparable health outcomes and costs, with PET/CT being an appropriate and efficient imaging modality because of its high diagnostic accuracy in the N-staging of HNC. Full article

Background: Recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) after immune checkpoint inhibitor (ICI) progression represents a major clinical challenge. Between 60 and 80% of patients develop resistance, and historical salvage regimens like cytotoxic chemotherapy or chemotherapy plus cetuximab rarely extend median overall survival (mOS) beyond one year. Scope of Review: This review examines systemic therapies evaluated specifically in the post-ICI setting, emphasizing agents advancing to Phase II and III trials. Classes include chemotherapy combinations, ICI-based approaches, small-molecule targeted combinations, bispecific antibodies, antibody-drug conjugates (ADCs), and next-generation vaccines. Results: Promising signals have emerged across multiple therapeutic modalities. Targeted combination strategies have demonstrated encouraging response rates and survival outcomes in difficult-to-treat, PD-1-resistant disease. Antibody-based platforms, including antibody-drug conjugates and bispecific antibodies, continue to show consistent clinical activity across diverse patient populations, offering disease control and prolonged survival. Novel immunotherapies and therapeutic vaccines are also generating durable responses, particularly in biologically defined subgroups, highlighting the potential of immune-based precision treatments in R/M HNSCC. Conclusions: Comparative analysis highlights distinct advantages and limitations: chemotherapy ensures rapid shrinkage but poor durability; biomarker-driven small molecules achieve strong survival gains in narrow niches; ADCs and bispecifics offer balanced efficacy in unselected patients; and vaccine platforms deliver durable benefit in defined subsets. Together, these data signal a paradigm shift toward biomarker-guided, mechanism-driven strategies as the path to closing the post-ICI therapeutic gap in R/M HNSCC. Full article

Background: Head and neck carcinomas represent a heterogeneous group of aggressive malignancies with often poor prognosis and high recurrence rates. In recent years, the identification and characterization of cancer stem cells (CSCs) within these tumors have profoundly reshaped our understanding of tumorigenesis, resistance mechanisms, and metastatic potential in this anatomical district. Cancer stem cells (CSCs) play a central role in therapeutic resistance, recurrence, and metastatic progression in head and neck squamous cell carcinoma (HNSCC), particularly within the anatomically complex maxillofacial region. This review has synthesized recent advances in CSC biology, including marker heterogeneity, stemness-associated pathways, and interactions with the tumor microenvironment. Methods: A narrative review of the available literature was conducted, focusing on studies dealing with cancer stem cells in head and neck carcinoma and their implications for maxillofacial surgery. Results: We have critically examined emerging systemic and locoregional CSC-targeted therapies, highlighting inhibitors of Notch, Wnt/β-catenin, Hedgehog, and Hippo/YAP pathways, ALDH and ABC transporter inhibitors, autophagy modulators, nanoparticle-based delivery systems, and CSC-directed immunotherapies. The implications of these approaches for surgical planning, resection margins, and postoperative disease control in maxillofacial oncology have been discussed. To enhance clarity and analytical value, we have incorporated two comprehensive tables summarizing CSC markers and therapeutic strategies. Collectively, the evidence indicates that integrating CSC-oriented diagnostics and therapeutics into multimodal management may improve long-term outcomes for patients with maxillofacial HNSCC. Conclusions: This review highlights the critical need for integrating CSC-focused research into clinical practice to develop more effective, personalized, and durable treatment strategies. Such an approach could enhance oncologic control, reduce recurrence, and improve functional outcomes for patients undergoing complex oncologic procedures in the maxillofacial region. Full article

Objective: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy, with limited treatment strategies in the recurrent or metastatic cases. Although immune checkpoint inhibitors (ICIs) have shown efficacy in head and neck cancers (HNCs), clinical data specific to SNSCC are scarce. This study aimed to evaluate the therapeutic efficacy and prognosis of ICIs in patients with SNSCC. Methods: We conducted a retrospective review of 18 patients with pathologically confirmed SNSCC treated with nivolumab or pembrolizumab at Gifu University Hospital between May 2017 and December 2024. Treatment response was assessed using RECIST v1.1 criteria. Overall response rate (ORR) and disease control rate (DCR) were evaluated as treatment effects, and overall survival (OS) and progression-free survival (PFS) were evaluated as prognoses. Subgroup analyses were performed according to treatment regimen. Results: The ORR and DCR for all patients were 43.8% and 56.3%, respectively. Pembrolizumab-treated patients showed higher response rates (ORR: 66.7%; DCR: 83.3%) compared to those treated with nivolumab (ORR: 30%; DCR: 40%). Median OS and PFS were 21.5 and 7.9 months, respectively. Long-term durable responses exceeding two years were observed in several cases. Although pembrolizumab tended to result in better outcomes, no statistically significant difference was found between groups. Immune-related adverse events were infrequent and manageable. Conclusions: This study suggests that a subset of patients with SNSCC may benefit from ICI therapy, particularly in combination with chemotherapy. Despite the rarity of SNSCC, accumulating clinical evidence—including prospective studies—is essential to establish standardized treatment strategies for this disease. Full article

Hypopharyngeal carcinoma is a highly aggressive malignancy in the head and neck region with poor prognosis due to challenges in early diagnosis, high invasiveness, recurrence rate, and metastatic potential. Small non-coding RNAs (sncRNAs) play crucial roles in tumorigenesis and progression and hold potential as clinical diagnostic biomarkers and therapeutic targets. However, the ability of traditional RNA-sequencing technologies to detect modified sncRNAs is limited, potentially leading to the failure to accurately identify some functionally relevant sncRNAs. In this study, we employed PANDORA-seq technology for the first time to systematically profile sncRNA expression in cancerous and adjacent normal tissues from five patients with hypopharyngeal carcinoma. Our results revealed dynamic changes in sncRNA expression in hypopharyngeal carcinoma tissues and found 4798 significantly differentially expressed sncRNAs. Among these, differentially expressed miRNAs and tsRNAs were primarily involved in key signaling pathways, including MAPK, FoxO, and TGF-β. Additionally, we validated the differential expression of eight sncRNAs in hypopharyngeal carcinoma tissues, which may represent potential diagnostic biomarkers and therapeutic targets. This study lays the foundation for the application of PANDORA-seq technology in human cancers and offers new directions for exploring the underlying molecular mechanisms of hypopharyngeal carcinoma and potential targets for its clinical diagnosis and treatment. Full article

Background/Objectives: In recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), the overall prognosis is poor, and systemic treatment options remain limited. While precision therapy approaches have revolutionized treatment strategies in several tumor types, molecularly informed therapies in R/M HNSCC are rare, primarily due to the low number of actionable genetic alterations identified through next-generation sequencing (NGS) panels. There is an urgent need to establish precision therapy approaches in R/M HNSCC using innovative predictive testing. Methods: We report the case of a 43-year-old patient with recurrent oral cancer who was extensively pretreated and comprehensively characterized using both descriptive and functional testing. Results: NGS revealed no targetable alterations. A tumor tissue slice radiosensitivity assay suggested radioresistance, arguing against re-irradiation. Kinome profiling identified upregulated Src-family kinases (SFK), and SFK inhibition reduced kinase activity in vitro. Most notably, mRNA analysis demonstrated high Trop-2 overexpression, confirmed by immunohistochemistry (3+ in 100% of tumor cells). Following six cycles of the Trop-2-directed antibody–drug conjugate Sacituzumab govitecan (SG), the patient had an impressive clinical response. Conclusions: Tumor characterization beyond genetic profiling can identify novel treatment options in therapy-refractory HNSCC. This is the first report of “real-world” data on promising antitumor efficacy of SG in a heavily pretreated oral cancer patient with Trop-2 overexpression. Consistent with the findings of the Basket TROPiCS-03 study, SG appears to be a promising novel therapy option for R/M HNSCC after failure of immunotherapy and chemotherapy, particularly in patients with Trop-2 overexpression. Full article

Disease progression and treatment resistance in colorectal and other cancers are driven by a subset of cells within the tumor that have stem-cell-like properties and long-term tumorigenic potential. These stem-cell-like cells express the leucine-rich G repeat-containing protein-coupled receptor 5 (LGR5) and have characteristics similar to tissue-resident stem cells in normal adult tissues such as the colon. Organoid models of murine and human colorectal and other cancers contain LGR5-expressing (LGR5+) stem-cell-like cells and can be used to investigate the underlying mechanisms of cancer development, progression, therapy vulnerability, and resistance. A large biobank of organoids derived from colorectal cancer or adjacent normal tissue was developed. We performed a large-scale unbiased functional screen to identify bispecific antibodies (BsAbs) that preferentially inhibit the growth of colon tumor-derived, as compared to normal tissue-derived, organoids. We identified the most potent BsAb in the screen as petosemtamab, a Biclonics^® BsAb targeting both LGR5 and the epidermal growth factor receptor (EGFR). Petosemtamab employs three distinct mechanisms of action: EGFR ligand blocking, EGFR receptor internalization and degradation in LGR5+ cells, and Fc-mediated activation of the innate immune system by antibody-dependent cellular phagocytosis (ADCP) and enhanced antibody-dependent cellular cytotoxicity (ADCC) (see graphical abstract). Petosemtamab has demonstrated substantial clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC). The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC. Full article

Salivary gland carcinomas (SGCs) represent a rare and heterogeneous group of malignancies accounting for 3–6% of all head and neck cancers. While surgical resection and radiotherapy remain the standard for locoregional control, systemic treatment is indicated for recurrent or metastatic disease. Advances in molecular profiling have identified actionable targets such as NTRK gene fusions, HER2, immune checkpoint regulators, androgen receptors, and RET receptors. These have facilitated the development of targeted therapies, including TRK inhibitors, HER2-directed agents, and androgen receptor modulators, as well as emerging combinations of immunotherapy and chemotherapy. Despite these advancements, challenges such as resistance mechanisms and limited therapeutic efficacy persist. Overall response rates remain relatively low across most systemic therapies, reflecting a persistent unmet clinical need. This review discusses the current landscape of treatment options and explores promising clinical trials and future directions to enhance outcomes for patients with SGCs. Full article

Cutaneous squamous cell carcinoma (cSCC) is a common cancer with increasing incidence and 5% of patients develop incurable disease, often resistant to chemotherapy. The anti-PD-1 therapy cemiplimab has shown high efficacy in clinical trials. This retrospective study evaluated the real-world effectiveness of cemiplimab in incurable cSCC and examined factors influencing response and toxicity. Data from 86 patients across three UK healthcare providers were analysed. Median progression-free survival (PFS) and overall survival (OS) were not reached, with 38% showing durable responses beyond 12 months. The overall response rate was 60.8% (95% CI 49–71), and the clinical benefit rate was 74.3% (95% CI 63–83). A head and neck primary site was associated with improved PFS (p = 0.008) and OS (p = 0.023), while concurrent immunosuppression was associated with worse PFS (p < 0.001). These findings align with clinical trials, suggesting cemiplimab is effective and safe in the recurrent/metastatic setting. Full article

Head and neck cancer (HNC) includes various malignancies and represents the seventh most common cancer worldwide. The early diagnosis of HNC results in a 70–90% five-year survival rate, which declines with locally advanced stages of disease. Current care employs a multimodal strategy encompassing surgery, radiation therapy (RT), chemotherapy, and immunotherapy, while treatment options vary according to the stage, tumor features, and patient characteristics. About 75% of patients with HNC will benefit from RT, either as a primary treatment or as adjuvant therapy following surgical resection. Technological improvements in RT, such as intensity-modulated RT (IMRT) and image-guided RT (IGRT), have enhanced tumor targeting and minimized adjacent healthy tissue irradiation while also expanding RT to the recurrent or metastatic setting. Innovative therapeutic strategies for HNC integrate RT with immunotherapy, gene therapy, molecular targeted therapy, photodynamic therapy, photothermal therapy, and nanoparticles (NPs), with the objective of optimizing tumor control while reducing damage to normal tissues. NPs are emerging as possible radiosensitizers in HNC treatment, enhancing the efficacy of RT, chemotherapy, and immunotherapy. In vivo and in vitro studies on the irradiation of tumors containing gold (Au), gadolinium (Gd), and hafnium oxide (HfO₂) NPs show promising results in enhancing tumor destruction and survival rates, indicating their potential for clinical application. Hyperthermia, investigated as an adjunct treatment, potentially improves outcomes when combined with RT or chemotherapy, with advancements in nanotechnology renewing interest in this approach in HNC. At present, NBTXR3 is the sole NP that is being investigated in clinical trials for the enhancement of HNC RT. Full article

Objectives: The primary aim of this phase 1 trial is to establish the recommended phase 2 dose (RP2D) of tazemetostat given with a fixed dose of pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinomas (RM-HNSCCs). Methods: A 3 + 3 dose-escalation phase 1 design was used to assess three dose-levels of tazemetostat (400, 600, and 800 mg orally, twice daily) with pembrolizumab (200 mg intravenously). Cycle 1 was 35 days (tazemetostat days 1–35; pembrolizumab day 15). Subsequent cycles were 21 days (tazemetostat days 1–21; pembrolizumab day 1). Dose-limiting toxicity (DLT), assessed during cycle 1, was defined as study-drug-related grade 4 neutropenia or thrombocytopenia, grade 3 febrile neutropenia, or grade 3–4 non-hematologic adverse events (AEs). Patients had to have completed cycle 1 to be evaluable for the DLT assessment; otherwise, an equal number of additional patients were enrolled. The RP2D was defined as the highest dose level in which zero of three or less than or equal to one of six patients experienced a DLT. Results: Twelve patients were enrolled: three on 400 mg, three on 600 mg, and six on the 800 mg dose level of tazemetostat. Three patients on the 800 mg dose level did not complete cycle 1 and were not evaluable for DLT. In the other nine patients, DLTs did not occur during cycle 1. In all 12 patients, the most common AEs included anemia (10 patients), fatigue (eight), and hyponatremia (seven). Conclusions: Among the patients with RM-HNSCCs, the RP2D of tazemetostat was 800 mg and administered twice daily when given with pembrolizumab. Full article

Radiation therapy or radiotherapy is a medical treatment that uses high doses of ionizing radiation to eliminate cancer cells and shrink tumors. It works by targeting the DNA within the tumor cells restricting their proliferation. Radiotherapy has been used for treating cancer for more than 100 years. Along with surgery and chemotherapy, it is one of the three main and most common approaches used in cancer therapy. Nowadays, radiotherapy has become a standard treatment option for a wide range of cancers around the world, including lung, breast, cervical, and colorectal cancers. Around 50% of all patients will require radiotherapy, 60% of whom are treated with curative intent. Moreover, it is commonly used for palliative treatment. Radiotherapy provides 5-year local control and overall survival benefit in 10.4% and 2.4% of all cancer patients, respectively. The highest local control benefit is reported for cervical (33%), head and neck (32%), and prostate (26%) cancers. But no benefit is observed in pancreas, ovary, liver, kidney, and colon cancers. Such relatively low efficiency is related to the development of radiation resistance, which results in cancer recurrence, metastatic dissemination, and poor prognosis. The identification of radioresistance biomarkers allows for improving the treatment outcome. These biomarkers mainly include proteins involved in metabolism and cell signaling pathways. Full article

Background/Objectives: The aim of this study is to assess the effectiveness of cetuximab combination therapy in patients with recurrent or metastatic head and neck cancer treated at a hospital in Southern Taiwan. Methods: This study analyzed a retrospective cohort of 67 patients who were treated between January 2020 and May 2024 with two cetuximab regimens, cetuximab combined with cisplatin and 5-Fu, which were administered every four weeks during hospitalization (CPF4) and every two weeks as outpatient treatment (CPF2), respectively. The clinical outcomes, including overall survival and progression-free survival (PFS), were compared across the treatment regimens and age groups using Kaplan–Meier survival curves and Cox proportional hazard models. Results: The median overall survival was 11.1 months (95% confidence interval, 7.8–14.5), with CPF2 showing a potential PFS advantage in patients aged 46–60 years (p = 0.049). No significant differences in overall survival were observed between CPF2 and CPF4. CPF2, which was administered in an outpatient setting, was associated with improved convenience, reduced hospitalization, and potentially lower risks of hospital-acquired infections. Conclusions: CPF2 exhibits practical advantages and comparable effectiveness, making it the preferred treatment regimen for eligible patients. Further studies with larger populations and molecular stratifications are needed to confirm these findings and develop better treatment strategies. Full article