RESUMEN
The use of immunotherapy in head and neck squamous cell carcinoma (HNSCC)has increased treatment options for patients who may not be candidates for traditional cytotoxic chemotherapy. Recent studies have resulted in the approval of immunotherapy in the first and second line setting for recurrent/metastatic disease. Various combinations of immunotherapy with targeted therapies, monoclonal antibodies, or human papilloma virus vaccines are also being studied in recurrent/metastatic disease. Currently, programmed death-ligand 1 status is the main marker utilized to assess potential response to immunotherapy. Studies are focused on identifying additional markers, which may help better predict response to immunotherapy for HNSCC patients.
Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Humanos , Inmunoterapia/métodos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunologíaRESUMEN
BACKGROUND: Radiotherapy (RT) is used in head and neck squamous cell carcinoma (HNSCC) with excellent effectiveness, but it is burdened by important side effects, which may negatively impact patients' quality of life (QoL). In particular when associated with chemotherapy (CT), that has a radiosensitising effect (and its own toxicities), it is responsible for several adverse events, causing social discomfort and lower QoL, in patients who are already experiencing several tumor-related discomforts. Prehabilitation is a healthcare intervention consisting of several specialist visits prior to the start of treatment, with the aim of improving the patient's health status, resolving symptoms that interfere with treatment and impact QoL, and finally to better avoid or overcome complications. Of all cancer patients, HNSCC patients are among those who could benefit most from prehabilitation, both because of the high number of symptoms and toxicities and their difficult management. Despite this and the emerging data, prehabilitation is not often considered for the majority of patients undergoing (C)RT. In this review, we tried to understand what are the main areas in which interventions can be made prior to the (C)RT start, the possible side effects of the treatment, the effectiveness in their prevention and management, and the impact that prehabilitation may have in adherence to therapy and on the principal survival outcomes, providing important guidance for the planning of future studies. EVIDENCES AND CONCLUSIONS: Although there is no strong data evaluating multidisciplinary prehabilitation strategies, evidence shows that optimizing the patient's health status and preventing possible complications improve the QoL, reduce the incidence and severity of adverse events, and improve treatment adherence. While cardiology prehabilitation is of paramount importance for all patients undergoing concomitant CRT in the prevention of possible side effects, the remaining interventions are useful independently of the type of treatment proposed. Geriatricians have a key role in both elderly patients and younger patients characterized by many comorbidities to comprehensively assess health status and indicate which treatment may be the best in terms of risk/benefit ratio. Collaboration between nutritionists and phoniatrics, on the other hand, ensures adequate nutritional intake for the patient, where possible orally. This is because optimizing both body weight and muscle mass and qualities has been shown to impact key survival outcomes. Finally, HNSCC patients have the second highest suicide rate, and the disease has side effects such as pain, dysfiguration, and sialorrhea that can reduce the patient's social life and create shame and embarrassment: A psychological intake, in addition to the usefulness to the patient, can also provide current support to caregivers and family members. Therefore clinicians must define a personalized pathway for patients, considering the characteristics of the disease and the type of treatment proposed, to optimize health status and prevent possible side effects while also improving QoL and treatment adherence.
Asunto(s)
Quimioradioterapia , Neoplasias de Cabeza y Cuello , Calidad de Vida , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Quimioradioterapia/métodos , Quimioradioterapia/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Ejercicio Preoperatorio , Carcinoma de Células Escamosas/terapiaRESUMEN
The interplay between immune components and the epithelium plays a crucial role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Natural killer (NK) cells, one of the main tumor-killing immune cell populations, have received increasing attention in HNSCC immunotherapy. In this review, we explore the mechanism underlying the interplay between NK cells and HNSCC. A series of immune evasion strategies utilized by cancer cells restrict HNSCC infiltration of NK cells. Overcoming these limitations can fully exploit the antineoplastic potential of NK cells. We also investigated the tumor-killing efficacy of NK cell-based immunotherapies, immunotherapeutic strategies, and new results from clinical trials. Notably, cetuximab, the most essential component of NK cell-based immunotherapy, inhibits the epidermal growth factor receptor (EGFR) signaling pathway and activates the immune system in conjunction with NK cells, inducing innate effector functions and improving patient prognosis. In addition, we compiled information on other areas for the improvement of patient prognosis using anti-EGFR receptor-based monoclonal antibody drugs and the underlying mechanisms and prognoses of new immunotherapeutic strategies for the treatment of HNSCC.
Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Células Asesinas Naturales , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Células Asesinas Naturales/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Inmunoterapia/métodos , Animales , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/inmunología , Escape del Tumor/efectos de los fármacos , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Transducción de Señal , Cetuximab/uso terapéutico , Cetuximab/farmacologíaRESUMEN
Background: Immune checkpoint inhibitors have demonstrated promising therapeutic outcomes in recurrent/metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC), prompting numerous clinical trials to investigate the safety and efficacy of this approach in neoadjuvant therapy. This systematic review aims to consolidate and analyze the findings from various clinical trials combining neoadjuvant immunotherapy for HNSCC, with the goal of identifying the most effective neoadjuvant immunotherapy regimen. Methods: The system conducted searches across electronic databases including PubMed, Embase, the Cochrane Library and Web of science from their inception to July 1, 2024. The primary focus was on evaluating efficacy (particularly pathological complete response (pCR), major pathological response (MPR), and overall response rate (ORR)) and safety (primarily assessed by grade 3-4 treatment-related adverse reactions). Results: A total of 1943 patients from 32 studies were analyzed. Combining neoadjuvant immunotherapy with chemotherapy or radiotherapy demonstrated superiority over neoadjuvant immunotherapy alone in terms of the MPR rate, while showing no statistically significant difference in the pCR rate. Furthermore, the combination of neoadjuvant immunotherapy with chemotherapy or radiotherapy exhibited a lower CR rate compared to neoadjuvant immunotherapy with radiotherapy alone, but a higher PR rate and SD rate. Apart from the neoadjuvant immunotherapy group in isolation, there were no statistically significant differences in grade ≥3 treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs) among the other three combination therapy groups. Conclusion: This systematic review and meta-analysis indicate that patients with locally advanced HNSCC might benefit from neoadjuvant immunotherapy, particularly when used in conjunction with chemotherapy or radiotherapy. Nonetheless, additional data is required to definitively confirm its efficacy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=553753, identifier CRD42024553753.
Asunto(s)
Neoplasias de Cabeza y Cuello , Inmunoterapia , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Terapia Neoadyuvante/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Resultado del Tratamiento , Terapia Combinada , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95%CI: 74.0% to 94.8%) and 50.3% (95%CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95%CI: 88.9% to 100.0%) and 58.2% (95%CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95%CI: 74.2% to 94.9%) and 53.5% (95%CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Neoplasias Hipofaríngeas , Terapia Neoadyuvante , Paclitaxel , Humanos , Masculino , Persona de Mediana Edad , Femenino , Cisplatino/uso terapéutico , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Adulto , Anciano , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios Retrospectivos , Albúminas/uso terapéutico , Albúminas/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidoresRESUMEN
BACKGROUND AND AIMS: Oral squamous cell carcinoma (OSCC) is among the most malignant cancers in the world and has a high mortality rate. MicroRNAs (miRNAs) have progressively gained attention due to their roles in the pathogenesis and maintenance of various kinds of cancers, including OSCC. In this research, we carried out a scoping review to analyze the role of miRNA and therapeutic response in OSCC and focus on target axes associated with miRNA that inhibit metastasis and cell proliferation in OSCC. METHODS: This review adhered to a six-stage methodology framework and PRISMA guidelines. Three databases were systematically searched to find eligible articles until July 2024. Two reviewers conducted publication screening and data extraction independently. 54 articles meeting the predefined inclusion criteria were successfully identified. Quality assessment was done using the QUIN checklist specified for dental in vitro studies. RESULTS: Studies with different designs reported 53 miRNAs that were experimentally validated to act as therapeutic targets in OSCC in vivo and in vitro studies. The study found that 25 miRNAs were up-regulated in OSCC patients and cell lines, while another 25 were down-regulated. Mir-186 was also found to be up- and down-regulated in two different investigations. The study highlights the potential of six microRNAs (miR-32-5p, miR-195-5p, miR-3529-3p, miR-191, miR-146b-5p, and miR-377-3p) as anti-proliferation, migration, and invasion therapeutics for OSCC treatment. Two miRNAs (miR-302b and miR-18a) are identified as anti-metastatic therapeutics, while four miRNAs (miR-617, miR-23a-3p, miR-105, miR-101) are anti-proliferation therapeutics. CONCLUSION: The study recommends that restoring the expression of tumor suppressor miRNAs may be a suitable cancer therapy. Utilizing this technology does present certain difficulties, and resolving them will improve the methods for miRNA transfer to target cells. With more research and the resolution of associated issues, miRNA can be employed as an efficient therapeutic method for OSCC.
Asunto(s)
Proliferación Celular , MicroARNs , Neoplasias de la Boca , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proliferación Celular/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/terapia , Regulación Neoplásica de la Expresión Génica , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Metástasis de la NeoplasiaRESUMEN
Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.
Asunto(s)
Neoplasias de Cabeza y Cuello , Recurrencia Local de Neoplasia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Portugal , Persona de Mediana Edad , Anciano , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Estudios Retrospectivos , Metástasis de la Neoplasia , Recursos en Salud/estadística & datos numéricosRESUMEN
Macrophages played an important role in the progression and treatment of head and neck squamous cell carcinoma (HNSCC). We employed weighted gene co-expression network analysis (WGCNA) to identify macrophage-related genes (MRGs) and classify patients with HNSCC into two distinct subtypes. A macrophage-related risk signature (MRS) model, comprising nine genes: IGF2BP2, PPP1R14C, SLC7A5, KRT9, RAC2, NTN4, CTLA4, APOC1, and CYP27A1, was formulated by integrating 101 machine learning algorithm combinations. We observed lower overall survival (OS) in the high-risk group and the high-risk group showed elevated expression levels in most of the immune checkpoint and human leukocyte antigen (HLA) genes, suggesting a strong immune evasion capacity. Correspondingly, TIDE score positively correlated with risk score, implying that high-risk tumors may resist immunotherapy more effectively. At the single-cell level, we noted macrophages in the tumor microenvironment (TME) predominantly stalled in the G2/M phase, potentially hindering epithelial-mesenchymal transition and playing a crucial role in the inhibition of tumor progression. Finally, the proliferation and migration abilities of HNSCC cells significantly decreased after the expression of IGF2BP2 and SLC7A5 reduced. It also decreased migration ability of macrophages and facilitated their polarization towards the M1 direction. Our study constructed a novel MRS for HNSCC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy for HNSCC patients.
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Neoplasias de Cabeza y Cuello , Inmunoterapia , Aprendizaje Automático , Macrófagos , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Inmunoterapia/métodos , Pronóstico , Macrófagos/inmunología , Macrófagos/metabolismo , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Masculino , Línea Celular TumoralAsunto(s)
Neoplasias de Cabeza y Cuello , Terapia Neoadyuvante , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Quimioterapia Adyuvante/métodos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Terapia Neoadyuvante/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Head and neck squamous cell carcinomas are characterized by a high incidence of recurrence, especially in patients with locally advanced disease. Standard treatment strategies can be associated with severe side effects to healthy tissues that can negatively impact the patient's quality of life. Hyperthermia (HT) is a noninvasive treatment modality that has improved the effectiveness of chemotherapy (CT) and/or radiotherapy (RT) for the management of some solid neoplasms. In this context, the association of this approach with rationally designed nanomaterials may further enhance the treatment outcome. In this study, we demonstrate the enhanced effect of neoadjuvant HT in combination with hybrid nanoarchitectures enclosing a cisplatin prodrug (NAs-CisPt) and RT. All the treatments and their combinations have been fully evaluated by employing standardized chorioallantoic membrane tumor models of HPV-negative head and neck carcinoma. An improved tumor-shrinking effect was observed by the administration of the trimodal treatment (HT/NAs-CisPt/RT), which also highlighted a significant increase in apoptosis. Our findings demonstrate that the combination of HT with nanotechnology-based CT and RT in a certain order enhances the in vivo treatment outcome. On a broader basis, this study paves the way for the next exploration of noninvasive treatment approaches for the clinical management of oral cancer based on innovative strategies.
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Quimioradioterapia , Neoplasias de Cabeza y Cuello , Hipertermia Inducida , Nanoestructuras , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Humanos , Hipertermia Inducida/métodos , Animales , Quimioradioterapia/métodos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Terapia Neoadyuvante/métodos , Cisplatino/uso terapéutico , Línea Celular Tumoral , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéuticoRESUMEN
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.
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Proteínas de la Ataxia Telangiectasia Mutada , Antígeno B7-H1 , Inmunoterapia , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Animales , Femenino , Humanos , Ratones , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/antagonistas & inhibidores , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de la radiación , Antígenos CD40/metabolismo , Antígenos CD40/inmunología , Antígenos CD40/antagonistas & inhibidores , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/radioterapia , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Ratones Endogámicos C57BL , Subfamília C de Receptores Similares a Lectina de Células NK/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Linfocitos T Citotóxicos/inmunología , Microambiente Tumoral/efectos de la radiaciónRESUMEN
BACKGROUND/AIM: Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment modality that selectively kills cancer cells and may induce a therapeutic host immune response. The aim of this study was to determine the feasibility of combining NIR-PIT with immune checkpoint inhibitor (ICI) therapy for unresectable recurrent head and neck cancer. PATIENTS AND METHODS: Five patients underwent NIR-PIT at Ryukyu University Hospital between January 2022 and April 2024. These patients had unresectable recurrent head and neck squamous cell carcinoma. Among these five patients, four received a combination NIR-PIT and pembrolizumab administration. RESULTS: A total of seven lesions in the oropharynx and oral cavity were targeted. One patient was treated for three different target lesions. The best observed response (BOR) rate was 100%, with three complete responses and four partial responses. The most common treatment-related adverse event was Grade 1 or 2 local pain lasting one to two days postoperatively, which occurred in all patients. Grade 3 adverse events occurred in three cases (42.9%), including pneumonia, pharynx-cutaneous fistula, and trismus. Three patients received ICI therapy following NIR-PIT, achieving a 60% BOR rate. No immune-related adverse events were noted, and the aforementioned Grade 3 adverse events did not worsen during ICI therapy. At a median follow-up of 376 days (range=157-845 days), four target lesions showed no recurrence, while three had recurred. All five patients were alive, including three with no evidence of disease. CONCLUSION: The combination of NIR-PIT and ICI therapy for unresectable recurrent head and neck cancer was feasible.
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Estudios de Factibilidad , Neoplasias de Cabeza y Cuello , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Humanos , Masculino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Anciano , Persona de Mediana Edad , Femenino , Inmunoterapia/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Terapia Combinada , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Fototerapia/métodos , Resultado del Tratamiento , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversosRESUMEN
BACKGROUND/AIM: Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Programmed death-ligand 1 (PD-L1) is clinically assessed before initiating ICIs; however, there are no established biomarkers for predicting the response to immunotherapy. In this study, inflammatory and nutritional parameters were examined to determine the therapeutic outcomes of ICIs for HNSCC. PATIENTS AND METHODS: Sixty-five patients with metastatic or recurrent HNSCC who received programmed death-1 (PD-1) blockade were enrolled. Inflammatory and nutritional indices were correlated with patient outcomes, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and prognostic nutritional index (PNI). RESULTS: Patients aged <70 years were significantly associated with a high NLR, whereas those with a performance status of 2 or 3 were closely related to a high NLR, high SII, and low PNI. Although all patients achieved an objective response rate of 24.6% and a disease control rate of 36.9%, the NLR, PLR, SII, and PNI values were not significantly different between responders and non-responders. Univariate analysis showed that the NLR, PLR, SII, and PNI were significant predictors of progression-free survival (PFS) and overall survival (OS). Multivariate analysis identified PNI as an independent predictor of PFS and OS. CONCLUSION: PNI, as a nutritional marker, was identified as a significant predictor of outcomes following PD-1 blockade administration in patients with advanced HNSCC, compared to inflammatory markers, such as NLR, PLR, and SII.
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Neoplasias de Cabeza y Cuello , Inmunoterapia , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Persona de Mediana Edad , Anciano , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/sangre , Inmunoterapia/métodos , Adulto , Neutrófilos/inmunología , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Linfocitos/inmunología , Evaluación Nutricional , Estado NutricionalRESUMEN
BACKGROUND: Concomitant high-dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy, is known for causing irreversible sensorineural hearing loss, with individual variability suggesting a genetic component. This study aims to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in HNSCC patients, as outlined in Theunissen et al., by incorporating significant genetic variants. METHODS: Conducted at the Netherlands Cancer Institute, this retrospective study included 74 patients treated between 1997 and 2011. Thirty-one SNPs that were previously associated with CIHL or other cisplatin-induced toxicities were identified and incorporated into the model. The primary outcome measured was the change in decibels at posttreatment 1-2-4 kHz hearing levels per additional minor allele of these SNPs, evaluated using linear mixed-effects regression models. The model's predictive accuracy was determined by the area under the curve (AUC) using 10-fold cross-validation. RESULTS: The rs2289669 SNP in the SLC47A1/MATE1 gene was linked to a significant 2.67 dB increase in hearing loss per allele (95% CI 0.49-4.86, p = 0.017). Incorporating rs2289669 improved the model's AUC from 0.78 to 0.83, a borderline significant improvement (p = 0.073). CONCLUSIONS: This study underscores the importance of the rs2289669 SNP in CIHL and demonstrates the potential of combining genetic and clinical data for enhanced predictive models in personalized treatment strategies.
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Quimioradioterapia , Cisplatino , Polimorfismo de Nucleótido Simple , Humanos , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Estudios Retrospectivos , Anciano , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Adulto , Pérdida Auditiva/genética , Pérdida Auditiva/inducido químicamente , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapiaRESUMEN
BACKGROUND: Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes. METHODS: Patients were recruited from an institutional database. Semi-structured interviews were conducted according to the Model of Pathways to Treatment. Thematic analysis was based on the four main intervals in the framework using a data-driven analytical method. RESULTS: Seventeen participants were interviewed. Facilitators included patients' past experiences, symptom progression, trust in healthcare professionals (HCPs), and capacity to leverage relationships. Barriers included difficult diagnoses, limited access to cancer services, lack of care coordination, and lack of awareness of PNS among primary health care providers. CONCLUSION: These findings emphasise the complexity early diagnosis and treatment of PNS. Interventions like clinical practice guidelines, education for HCPs, and telehealth could facilitate timely detection and management.
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Neoplasias de Cabeza y Cuello , Neoplasias Cutáneas , Humanos , Masculino , Femenino , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Anciano , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Investigación Cualitativa , Anciano de 80 o más Años , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologíaRESUMEN
PURPOSE: There is no agreed-upon standard option for patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) unfit for cisplatin-based regimens. Therefore, we performed a systematic review to explore alternative options for this population. METHODS: We searched PubMed, Cochrane, and Embase databases for observational studies and clinical trials (CTs) assessing treatment options for LA HNSCC cisplatin-ineligible patients. This study was registered in PROSPERO under the number CRD42023483156. RESULTS: This systematic review included 24 studies (18 observational studies and 6 CTs), comprising 4450 LA HNSCC cisplatin-ineligible patients. Most patients were treated with cetuximab-radiotherapy [RT] (50.3%), followed by carboplatin-RT (31.7%). In seven studies reporting median overall survival (OS) in patients treated with cetuximab-RT, it ranged from 12.8 to 46 months. The median OS was superior to 40 months in two studies assessing carboplatin-RT, and superior to 15 months in two studies assessing RT alone. For other regimens such as nimotuzumab-RT, docetaxel-RT, and carboplatin-RT plus paclitaxel the median OS was 21, 25.5, and 28 months, respectively. CONCLUSIONS: Our systematic review supports the use of a variety of therapy combinations for LA HNSCC cisplatin-ineligible patients. We highlight the urgent need for clinical studies assessing treatment approaches in this population.
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Cisplatino , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Cetuximab/uso terapéutico , Cetuximab/administración & dosificación , Carboplatino/administración & dosificación , Antineoplásicos/uso terapéuticoRESUMEN
Oral squamous cell carcinoma (OSCC) is considered the most common type of head and neck squamous cell carcinoma (HNSCC) as it holds 90â¯% of HNSCC cases that arise from multiple locations in the oral cavity. The last three decades witnessed little progress in the diagnosis and treatment of OSCC the aggressive tumor. However, in-depth knowledge about OSCC's pathogenesis, staging & grading, hallmarks, and causative factors is a prime requirement in advanced diagnosis and treatment for OSCC patients. Therefore present review was intended to comprehend the OSCCs' prevalence, staging & grading, molecular pathogenesis including premalignant stages, various hallmarks, etiology, diagnostic methods, treatment (including FDA-approved drugs with the mechanism of action and side effects), and theranostic agents. The current review updates that for a better understanding of OSCC progress tumor-promoting inflammation, sustained proliferative signaling, and growth-suppressive signals/apoptosis capacity evasion are the three most important hallmarks to be considered. This review suggests that among all the etiology factors the consumption of tobacco is the major contributor to the high incidence rate of OSCC. In OSCC diagnosis biopsy is considered the gold standard, however, toluidine blue staining is the easiest and non-invasive method with high accuracy. Although there are various therapeutic agents available for cancer treatment, however, a few only are approved by the FDA specifically for OSCC treatment. The present review recommends that among all available OSCC treatments, the antibody-based CAR-NK is a promising therapeutic approach for future cancer treatment. Presently review also suggests that theranostics have boosted the advancement of cancer diagnosis and treatment, however, additional work is required to refine the role of theranostics in combination with different modalities in cancer treatment.
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Neoplasias de la Boca , Humanos , Neoplasias de la Boca/patología , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologíaRESUMEN
BACKGROUND: T2N0 glottic squamous cell carcinoma (SCC) typically responds well to radiotherapy (RT); however, achieving local control remains challenging. In cases of RT failure, total laryngectomy may be necessary. Improved local control and preservation of the larynx directly enhances patients' quality of life. Our retrospective analysis using the Japan Head and Neck Cancer Registry (JHNCR) aimed to compare the clinical benefits of RT and chemoradiotherapy (CRT) in patients with T2N0 glottic SCC. METHODS: Using data from the JHNCR (2011-2015), we included 1,231 patients with T2N0 glottic SCC. Among them, 346 received curative RT and 425 underwent curative CRT. The CRT group was further divided into the oral CRT (Oral CRT, N=120) and intravenous CRT (DIV CRT, N=305) groups. This study assessed local control rate (LCR), progression-free survival (PFS), and overall survival (OS). A 1:1 propensity score-matching analysis was used to adjust for patient characteristics. RESULTS: After matching, 105 pairs compared RT with Oral CRT, and 224 pairs compared RT with DIV CRT. The variables were well-balanced in the matched populations. In the matched populations, the Oral CRT group had significantly better 5-year LCR and PFS than the RT group (LCR, 89.4 % vs. 80.6 %, P=0.043; and PFS, 85.5 % vs. 72.3 %, P=0.025, respectively), while the DIV RT group had significantly better 5-year PFS than the RT group (80.1 % vs. 68.6 %, P=0.026). CONCLUSIONS: The clinical benefits of better local and disease controls were observed when oral chemotherapy was added to RT in patients with T2N0 glottic SCC. Thus, the significance of adding oral chemotherapeutic agents to RT in the treatment of T2N0 glottic SCC requires further prospective investigation.
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Quimioradioterapia , Glotis , Neoplasias Laríngeas , Sistema de Registros , Humanos , Masculino , Femenino , Japón , Anciano , Persona de Mediana Edad , Quimioradioterapia/métodos , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/mortalidad , Glotis/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Administración Oral , Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Adulto , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Response to immunotherapy is the main challenge of head and neck squamous cancer (HNSCC) treatment. Previous studies have indicated that tumor mutational burden (TMB) is associated with prognosis, but it is not always a precise index. Hence, investigating specific genetic mutations and tumor microenvironment (TME) changes in TMB-high patients is essential for precision therapy of HNSCC. METHODS: A total of 33 HNSCC patients were enrolled in this study. We calculated the TMB score based on next-generation sequencing (NGS) sequencing and grouped these patients based on TMB score. Then, we examined the immune microenvironment of HNSCC using assessments of the bulk transcriptome and the single-cell RNA sequence (scRNA-seq) focusing on the molecular nature of TMB and mutations in HNSCC from our cohort. The association of the mutation pattern and TMB was analyzed in The Cancer Genome Atlas (TCGA) and validated by our cohort. RESULTS: 33 HNSCC patients were divided into three groups (TMB-low, -medium, and -high) based on TMB score. In the result of 520-gene panel sequencing data, we found that FAT1 and LRP1B mutations were highly prevalent in TMB-high patients. FAT1 mutations are associated with resistance to immunotherapy in HNSCC patients. This involves many metabolism-related pathways like RERE, AIRE, HOMER1, etc. In the scRNA-seq data, regulatory T cells (Tregs), monocytes, and DCs were found mainly enriched in TMB-high samples. CONCLUSION: Our analysis unraveled the FAT1 gene as an assistant predictor when we use TMB as a biomarker of drug resistance in HNSCC. Tregs, monocytes, and dendritic cells (DCs) were found mainly enriched in TMB-high samples.
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Neoplasias de Cabeza y Cuello , Inmunoterapia , Mutación , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Inmunoterapia/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Anciano , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Pronóstico , Proteínas de la Membrana/genética , CadherinasRESUMEN
OBJECTIVES: To propose a radiomics-based prediction model for head and neck squamous cell carcinoma (HSNCC) recurrence after radiation therapy using a novel data imbalance correction method known as Gaussian noise upsampling (GNUS). MATERIALS AND METHODS: The dataset includes 97 HNSCC patients treated with definitive radiotherapy alone or concurrent chemoradiotherapy at two institutions. We performed radiomics analysis using nine segmentations created on pretreatment positron emission tomography and computed tomography images. Feature selection was performed by the least absolute shrinkage and selection operator analysis via five-fold cross-validation. The proposed GNUS was compared with seven conventional data-imbalance correction methods. Classification models of HNSCC recurrence were constructed on oversampled features using the machine learning algorithms of linear regression. Their predictive performance was evaluated based on accuracy, sensitivity, specificity, and the area under the curve (AUC) of the receiver operating performance characteristic curve via five-fold cross-validation using the same combinations as for feature selection. RESULT: The prediction model without data imbalance correction shows sensitivity, specificity, accuracy, and AUC values of 83 %, 96 %, 92 %, and 0.96, respectively. The conventional model with the best performance is the random over-sampler model, which shows sensitivity, specificity, accuracy, and AUC values of 93 %, 91 %, 92 %, 0.97, respectively, whereas the GNUS model shows values of 93 %, 94 %, 94 %, 0.98, respectively. CONCLUSION: Oversampling methods can reduce sensitivity and specificity bias. The proposed GNUS can improve accuracy as well as reduce sensitivity and specificity bias.