Alpelisib and Immunotherapy: A Promising Combination for Recurrent and Metastatic Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND: Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3-kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer. CASES: A 69-year-old woman with locoregional recurrence of PIK3CA-mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono-immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58-year-old man with recurrent metastatic PIK3CA-mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum-based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation. CONCLUSION: Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

Squamous cell carcinoma metastatic to the lymph nodes of the parapharyngeal space: case series and systematic review.

Objective: Parapharyngeal space (PPS) is a rare and unusual site of head and neck squamous cell carcinoma (SCC) metastases. Treatment strategy for PPS metastases is still not well defined. This research aims to investigate the clinical implications and oncological outcomes of SCC metastases in PPS. Material and methods: A systematic review was conducted according to PRISMA criteria. The authors considered only articles reporting the history and treatment of patients with PPS SCC metastases. A retrospective chart review was conducted in two tertiary referral academic centers collecting data of patients with diagnosis of PPS SCC metastases between 2010 and 2023 to study their outcome based on clinical presentation and treatment strategy. Results: The retrospective chart review showed that the oropharynx was the most frequent primary tumour site. The advanced stage at the time of diagnosis was related to poorer survival and higher recurrence rates. A significant difference in 2-year overall survival in the subgroup of patients who experienced PPS metastases within the primary treatment and those who experienced PPS metastases as regional recurrence (66.7 vs 30.8%) was observed. Similar low survival rates were reported in the literature review with a mean overall and disease-free survival of 19.8 and 8.6 months, respectively. Conclusions: PPS metastases are associated with a dismal prognosis, especially when diagnosed as regional recurrence after primary treatment, due to patients' poor general conditions and difficulty of treatment.

Metastasis and cell proliferation inhibition by microRNAs and its potential therapeutic applications in OSCC: A systematic review.

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.

Frequency of use and cost in Japan of first-line palliative chemotherapies for recurrent or metastatic squamous cell carcinoma of the head and neck.

BACKGROUND: Over the last decade, novel anticancer drugs have improved the prognosis for recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN). However, this has increased healthcare expenditures and placed a heavy burden on patients and society. This study investigated the frequency of use and costs of select palliative chemotherapy regimens in Japan. METHODS: From July 2021 to June 2022 in 54 healthcare facilities, we gathered data of patients diagnosed with RM-SCCHN and who had started first-line palliative chemotherapy with one of eight commonly used regimens. Patients with nasopharyngeal carcinomas were excluded. The number of patients receiving each regimen and the costs of each regimen for the first month and per year were tallied. RESULTS: The sample comprised 907 patients (674 were < 75 years old, 233 were ≥ 75 years old). 330 (36.4%) received Pembrolizumab monotherapy, and 202 (22.3%) received Nivolumab monotherapy. Over 90% of patients were treated with immune checkpoint inhibitors as monotherapy or in combination with chemotherapy. Treatment regimens' first-month costs were 612 851-849 241 Japanese yen (JPY). The cost of standard palliative chemotherapy until 2012 was about 20 000 JPY per month. The incremental cost over the past decade is approximately 600 000-800 000 JPY per month, a 30- to 40-fold increase in the cost of palliative chemotherapy for RM-SCCHN. CONCLUSION: First-line palliative chemotherapy for RM-SCCHN exceeds 600 000 JPY monthly. Over the last decade, the prognosis for RM-SCCHN has improved, but the costs of palliative chemotherapy have surged, placing a heavy burden on patients and society.

The Importance of the Time Interval Between Preoperative 18F-FDG PET/CT Imaging and Neck Dissection for the Detection of Nodal Metastases in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Detection of nodal metastasis is critical for the treatment and prognosis of head and neck cancer (HNC). Positron emission tomography/computed tomography (PET/CT) is increasingly being used to detect cervical lymph node involvement. AIM: The purposes of this study were to (1) investigate the diagnostic accuracy of PET/CT for the detection of neck metastasis in patients with HNC and (2) determine the effect of the time interval between surgery and PET/CT. METHODS: Fifty patients with head and neck squamous cell carcinoma who underwent PET/CT before surgery were included in this study. Preoperative PET/CT images that determined lymph node metastasis were compared with the histopathological analysis of neck dissection samples. Neck dissections were divided into three groups according to the time interval between surgery and PET/CT (0-2 weeks, >2-4 weeks, and >4 weeks). The concordance between PET/CT and histopathology was measured using the neck sides at different time intervals. The specificity, sensitivity, accuracy, negative predictive value (NPV), and positive predictive value (PPV) of PET/CT in detecting metastatic lymph nodes in the neck were calculated. RESULTS: A total of 79 neck dissections were included in the study as 29 (58%) of the patients underwent bilateral neck dissection. The overall accuracy of PET/CT in detecting nodal metastasis was highest for the 0-2 weeks interval (95.6%). During this time interval, the sensitivity, specificity, NPV, and PPV of PET/CT were 100%, 90.9%, 100%, and 92.3%, respectively. CONCLUSIONS: Although PET/CT is an important and reliable diagnostic method for detecting nodal metastases in patients with HNC, its reliability decreases as the time between surgeries increases. The optimal interval was 2 weeks; however, up to 4 weeks was acceptable.

Integrating bulk and single-cell sequencing reveals metastasis-associated CAFs in head and neck squamous cell carcinoma.

AIMS: Cancer-associated fibroblasts (CAFs) have been shown to promote the metastasis of head and neck squamous cell carcinoma (HNSCC), but the underlying mechanisms remain unclear. The purpose of this study is to identify gene in CAFs that are associated with metastasis and to preliminarily validate its impact on the metastasis of HNSCC. MATERIALS AND METHODS: Scissor analysis was utilized to process single-cell and bulk RNA sequencing datasets, identifying genes associated with the metastasis of HNSCC through differential gene expression analysis. A risk model was constructed using LASSO regression analysis. Quantitative real time-PCR and Western blot were employed to measure mRNA and protein expressions, respectively. Multiplex immunohistochemistry (mIHC) was used to assess protein expression in CAFs. siRNA was utilized to achieve gene knockdown. CCK-8 and Transwell assays were employed to evaluate the biological characteristics of HNSCC cells. KEY FINDINGS: Compare to the nonmetastatic primary CAFs (nmCAFs), tissue inhibitors of metalloproteinase-1 (TIMP1) was founded to be overexpressed in the cells and tissues of metastatic primary CAFs (mCAFs). Knocking down TIMP1 in CAFs can signifucantly inhibit the proliferation, invasion, and migration of HNSCC cells. SIGNIFICANCE: CAFs facilitate HNSCC cell metastasis by upregulating TIMP1, highlighting TIMP1 as a potential therapeutic target in HNSCC metastasis management.

Assessment of endpoint definitions in recurrent and metastatic mucosal head and neck squamous cell carcinoma trials: Head and Neck Cancer International Group consensus recommendations.

Transparent and precise endpoint definitions are a crucial aspect of clinical trial conduct and reporting, and are used to communicate the benefit of an intervention. Previous studies have identified inconsistencies in endpoint definitions across oncological clinical trials. Here, the Head and Neck Cancer International Group assessed endpoint definitions from phase 3 trials or trials considered practice-changing for patients with recurrent or metastatic mucosal head and neck squamous cell carcinoma, published between 2008 and 2021. We identify considerable and global heterogeneity in endpoint definitions, which undermines the interpretation of results and development of future studies. We show how fundamental components of even incontrovertible endpoints such as overall survival vary widely, highlighting an urgent need for increased rigour in reporting and harmonisation of endpoints.

Lymph node metastasis burden identifies head and neck squamous cell carcinoma patients benefiting from adjuvant chemoradiation: A propensity score-matching.

INTRODUCTION: To examine the influence of adjuvant chemoradiation therapy (CRT) on survival, stratified by varying numbers and level involved of metastatic lymph nodes in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Patients who underwent surgery for metastatic, negative margin HNSCC without extranodal extension were retrospectively enrolled and divided into two groups based on adjuvant therapy received: radiotherapy (RT) and CRT. The impact of RT versus CRT, stratified by the number of positive lymph nodes and the level involved, on Disease-Free Survival (DFS) and Overall Survival (OS) was analyzed. RESULTS: Following propensity score matching, a total of 580 patients were included. The burden and level of lymph node metastasis were independent predictors of poorer survival. Among patients with no more than two positive lymph nodes or involvement of levels I-III, the addition of chemotherapy to RT did not demonstrate a significant improvement in prognosis. However, in patients with three or more positive lymph nodes, CRT showed improved DFS and OS compared to RT. In patients with involvement of levels IV-V, the addition of chemotherapy to RT resulted in a significant 24 % reduction in the risk of recurrence and a 20 % decrease in the risk of death. CONCLUSION: Incorporation of adjuvant chemoradiation can lead to a favorable prognosis in patients with metastatic HNSCC. This impact was notable in cases where there were three or more positive lymph nodes or involvement of levels IV-V.

The role of non-oropharyngeal biopsies in head and neck squamous cell carcinoma of unknown primary: A systematic review.

INTRODUCTION: This systematic review aims to evaluate the role of biopsies in non-oropharyngeal subsites in patients with cervical metastasis from head and neck squamous cell carcinoma of unknown primary (HNSCCUP). METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles that encompassed non-oropharyngeal biopsies in HNSCCUP as part of the diagnostic work-up were selected and analysed. RESULTS: A comprehensive search strategy was used to search relevant literature in PubMed from inception to October 2021. Eleven articles out of 860 were included, comprising 990 patients. There are no randomised control trials comparing the outcomes of survival and or locoregional control between patients who have or have not undergone non-targeted biopsies of non-oropharyngeal sub-sites for HNSCCUP. Several retrospective studies which showed an extremely low yield from random biopsies (range of yield, 0%-9%) of non-oropharyngeal subsites. Even targeted biopsies showed a low yield (range of yield, 0.6%-16.6%) from non-oropharyngeal subsites. The primary site identified for Epstein-Barr virus (EBV) positive cervical lymph nodes with an unknown primary is mainly the nasopharynx (51.7%). Narrow band imaging (NBI) (sensitivity range, 64%-91%) helps in the detection of primaries to target biopsies in non-oropharyngeal subsites. CONCLUSIONS: On the basis of this systematic review, it is not appropriate to offer biopsies of clinically and radiologically normal upper aerodigestive tract mucosa at non-oropharyngeal sites. Offer nasopharyngeal biopsies when the cervical node sampling reveals EBV-positive metastasis. Where available, NBI should be used to help detect and target biopsies in non-oropharyngeal subsites.

De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Comparative safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis.

BACKGROUND: To indirectly compare the safety of immune checkpoint inhibitors (ICIs) in the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) by network meta-analysis (NMA). METHODS: Through August 1, 2023, we searched PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov for randomized clinical trials (RCTs) of ICI-based treatment for R/M HNSCC. Outcomes of interest included overall and organ-specific immune-related adverse events (irAEs). Addis 16.5 software was used to perform NMA. Confidence in Network Meta-Analysis (CINeMA) was used to assess confidence in the evidence. RESULTS: Nine RCTs were included in this NMA, involving a total of 4016 patients. The general safety of ICI-based treatments in descending order was as follows: Durvalumab + Tremelimumab, Camrelizumab + Chemotherapy, Durvalumab, Toripalimab + Chemotherapy, Pembrolizumab, Pembrolizumab + Chemotherapy, Nivolumab, Tremelimumab. There were differences in the toxicity profile among Toripalimab + Chemotherapy (dermatologic irAEs), Camrelizumab + Chemotherapy (hypothyroidism), Nivolumab + Ipilimumab (hyperthyroidism, pneumonitis), Pembrolizumab (nephrotoxicity), Pembrolizumab + Chemotherapy (colitis). ICI-based treatment increased the incidence of endocrine irAEs (hyperthyroidism and hypothyroidism) and pneumonitis compared to conventional therapy. Besides, the combination of dual ICIs resulted in a greater occurrence of irAEs compared to the use of a single ICI. CONCLUSIONS: The safety ranking of treatments based on ICIs is significantly influenced by specific irAEs. These irAEs, which vary in type and severity, play a crucial role in determining the overall safety profile of each ICI regimen. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460267.

Quality of Life of Oligometastatic and Polymetastatic Head and Neck Squamous Cell Carcinoma Patients.

OBJECTIVE: Evidence suggests that distant metastasis in head and neck squamous cell carcinoma is a spectrum of disease. Previous studies show that oligometastasis has favorable survival compared with polymetastasis. The quality of life of patients with oligometastasis remains unknown. To further solidify the position of oligometastasis as a separate entity, we hypothesized that oligometastatic patients experience better quality of life than polymetastatic patients. METHODS: Patients with distant metastasis were stratified into three groups: oligometastasis (≤3 metastatic foci in ≤2 anatomic sites), explosive metastasis (≥4 metastatic foci at one anatomic site), and explosive-disseminating metastasis (spread to ≥3 anatomic sites). Quality of life was assessed every 2 months post distant metastasis diagnosis. RESULTS: Between January 1, 2016, and December 31, 2021, a total of 161 patients with distant metastasis were identified, with a total of 397 measurements. In this group, 57 (35.4%) patients had oligometastasis, 35 (21.7%) patients had explosive metastasis, and 69 (42.9%) patients had explosive-disseminating metastasis. Their median post-distant metastasis survivals were 8.5 months, 3.2 months, and 3.2 months respectively (p < 0.001). A significantly better overall quality of life was observed in the oligometastasis group compared with the polymetastatic groups (+0.75 out of 7, p < 0.05). Furthermore, oligometastatic patients performed better in the subdomains of "physical functioning," "fatigue," and "pain." CONCLUSION: Results from this study underscore that subgroups exist regarding quality of life and survival within distant metastasis, with polymetastatic patients performing worse than oligometastatic patients. This highlights the significance of tailored interventions that consider the unique challenges faced by each metastatic group of patients. LEVEL OF EVIDENCE: 3, retrospective cohort study Laryngoscope, 134:3170-3176, 2024.

Results of surgical treatment of lymph node metastases in patients with cutaneous squamous cell carcinoma of the head and neck.

INTRODUCTION: Out of all cutaneous squamous cell carcinomas originating in the head and neck (HNCSCC), 2-4% are associated with parotid or cervical lymph node metastasis. The aim of this study is to analyse the prognostic factors of patients with HNCSCC with lymph node involvement treated surgically. Additionally, we aim to compare the prognostic capacity of the classification of these patients according to the 8th edition of the TNM, and an alternative classification proposed by O'Brien et al. PATIENTS AND METHODS: Retrospective review of 65 patients with HNCSCC with lymph node metastasis treated surgically during the period 2000-2020. RESULTS: During the study period we carried out 13 neck dissections and 52 parotidectomies + neck dissection in patients with lymph node metastases from a HNCSCC. The great majority of patients (89.2%) received post-operative radiotherapy. The 5 year disease-specific survival was 69.9%, and the overall survival it was 42.8%. The classification proposed by O'Brien et al., based on the parotid or cervical location of the lymph node metastases, and the size and number of the metastatic lymph nodes, had a better prognostic capacity than the TNM classification. CONCLUSIONS: The surgical treatment of lymph node metastases in patients with HNCSCC achieved a high disease control. The classification based on the location, size and number of lymph node metastases proposed by O'Brien et al had better prognostic capacity than the TNM classification.

The impact of LncRNA-SOX2-OT/let-7c-3p/SKP2 Axis on head and neck squamous cell carcinoma progression: Insights from bioinformatics analysis and experimental validation.

BACKGROUND: LncRNA SRY-box transcription factor 2 overlapping transcript (SOX2-OT) is linked to multiple cancers, but its specific role and mechanism in head and neck squamous cell carcinoma (HNSCC) remain poorly understood. METHODS: We harnessed clinical data and HNSCC transcriptome profiles from UCSC Xena, TCGA, and GEO databases. Employing various algorithms, we assessed the correlation between SOX2-OT expression and the HNSCC immune microenvironment. Differential expression analysis identified immune-enriched miRNAs (DEmiRNAs) and mRNAs (DEmRNAs). Utilizing miRanda, miRWalk, and Cytoscape, we constructed a ceRNA network encompassing SOX2-OT, DEmiRNAs, and DEmRNAs. A Sankey diagram visualized pivotal SOX2-OT-miRNA-mRNA-pathways. Functional assays validated SOX2-OT silencing effects in HNSCC cells. Luciferase reporter assays verified SOX2-OT/let-7c-3p/SKP2 relationships. Additionally, a xenograft mouse model revealed SOX2-OT's impact on xenograft growth and lung metastasis. RESULTS: SOX2-OT expression demonstrated a predominantly positive correlation with B lineage and VTCN1, while manifesting a negative correlation with Neutrophil and CD47 in HNSCC tissues. We discerned a ceRNA network comprising 65 DEmiRNAs and 116 DEmRNAs, while a protein-protein interaction (PPI) network revealed 97 protein nodes among DEmRNAs. Notably, the Sankey diagram spotlighted six key DEmRNAs intricately linked to the SOX2-OT-regulated DEmiRNAs immune-related pathway. Experimental assays established that SOX2-OT silencing exerted inhibitory effects on cell proliferation, migration, tumor growth, and lung metastasis within HNSCC cells, both in vitro and in vivo. We identified let-7c-3p as a target miRNA of SOX2-OT and SKP2 as a target mRNA of let-7c-3p. CONCLUSIONS: Our study establishes the critical SOX2-OT/let-7c-3p/SKP2 axis as a pivotal regulator of HNSCC tumorigenesis and metastasis.

Distant metastasis at the time of presentation of head and neck squamous cell carcinoma: a retrospective chart review from a tertiary cancer care centre.

OBJECTIVE: To evaluate the rates and patterns of distant metastasis in head and neck SCC at the time of presentation and to study the association between distant metastasis with pre-treatment, clinical, and pathological predictors of outcomes. METHOD: This is a retrospective study conducted in a tertiary care hospital. All patients with primary head and neck squamous cell carcinoma that had been evaluated at our institute between October 2018 and December 2020 were included in the study. Various clinical data were analysed and pattern of metastasis was studied. RESULT: Ten per cent (50 cases) of 501 studied patients had distant metastasis. The most common site of distant metastasis was lung. The rate of distant metastasis was high in patients with poorly differentiated cancers. By Kaplan-Meier analysis, the median survival duration after diagnosis of metastasis was four months. CONCLUSION: The rate of distant metastasis was 10 per cent in the study. Patients with poorly differentiated tumours, locally advanced primary lesions, higher nodal stage, particularly with extra nodal extension, and hypopharyngeal primary, tend to exhibit increased risk for distant metastasis at the time of presentation.

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: This study evaluated the efficacy of nivolumab and pembrolizumab in treating platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas (R/M-HNSCC). PATIENTS AND METHODS: Platinum-sensitive patients with R/M-HNSCC were selected at Tokyo Medical University Hospital from May 1, 2017, to June 30, 2022. Patients with a history of treatment with nivolumab or pembrolizumab were included. Nivolumab was used in 21 cases and pembrolizumab in 15 cases. RESULTS: The median overall survival (OS) was 16.9 months in the nivolumab group and 19.2 months in the pembrolizumab group and no significant differences were observed between the two groups. The median progression-free survival (PFS) was 4.8 months in the nivolumab group and 9.3 months in the pembrolizumab group. No significant differences were observed between the two groups. The objective response rates (ORR) were 38% and 47% in the nivolumab and pembrolizumab groups, respectively. CONCLUSION: Nivolumab as well as pembrolizumab were found to be effective in platinum-sensitive patients with R/M-HNSCC. Nivolumab can be considered a potential treatment option for platinum-sensitive R/M-HNSCC in the future.

Diagnostic Value of MRI Combined with CXCR4 Expression Level in Lymph Node Metastasis Head and Neck Squamous Cell Carcinoma.

Objective: To explore the diagnostic value of magnetic resonance imaging (MRI) combined with CXCR4 expression levels in lymph node metastasis of the head and neck squamous cell carcinoma (HNSCC). Methods: 289 patients with HNSCC were divided into lymph node metastasis group (LNM group, n = 171) and non-LNM group (n = 118) according to the pathological examination results. MRI was used to scan the patient's lesions and cervical lymph nodes, and ADC was measured by MRI diffusion weighting imaging. The expression of CXCR4 in tumor tissues was detected by qRT-PCR. Logistic regression was used to analyze the risk factors of HNSCC lymph node metastasis. ROC curve was used to analyze the diagnostic effects of MRI, CXCR4, and MRI combined with CXCR4 on HNSCC lymph node metastasis. Results: Compared with the non-LNM group, patients in the LNM group had a lower degree of pathological differentiation, and the positive rate of TNM staging and vascular invasion was higher. The signal intensity of T1WI and T2WI were low intensity and high intensity, respectively, and the ADC value was significantly reduced. At the same time, the expression level of CXCR4 in the tumor tissues of the LNM group was also significantly increased. In addition, compared with MRI and CXCR4 used alone, MRI combined with CXCR4 has a higher predictive value. Conclusion: MRI has a good effect in demonstrating lymph node metastasis. CXCR4 is significantly upregulated in lymph node metastasis tumor tissue. The combination of the two can be used for clinical diagnosis of HNSCC lymph node metastasis.

Single-center prospective study on the efficacy of nivolumab against platinum-sensitive recurrent or metastatic head and neck squamous cell carcinoma.

Nivolumab, an immune checkpoint inhibitor, is beneficial to patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC). However, platinum-sensitive R/M-HNSCC has not yet been studied. Hence, in this prospective study, we evaluated the efficacy and safety of nivolumab in patients with platinum-sensitive R/M-HNSCC. This prospective single-arm study was conducted in a single institution in Japan. Patients with platinum-sensitive R/M-HNSCC (defined as head and neck cancer that recurred or metastasized at least 6 months after platinum-based chemotherapy or chemoradiotherapy) were enrolled. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), overall response rate (ORR), immune-related adverse events (irAEs), and quality of life (QOL). This study was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031324). Twenty-two patients with platinum-sensitive R/M-HNSCC were enrolled. The median OS was 17.4 months, and the 1-year OS rate was 73%. The median PFS was 9.6 months, 1-year PFS rate was 48%, and ORR was 36%. Sixteen irAEs were recorded in 12 patients; however, no grade 4 or 5 irAEs were observed. The QOL assessments revealed that nivolumab did not decrease the QOL of patients. Nivolumab is effective against platinum-sensitive R/M-HNSCC with acceptable safety.

G-Protein-Coupled Receptor Kinase-Interacting Protein 1 (GIT1) Promotes Head and Neck Squamous Cell Carcinoma Metastases via Activating the PI3K/AKT/mTOR Signal Pathway.

OBJECTIVE: GIT1 is identified as a novel tumor oncogene in breast cancer. In this article, we aimed to explore the role of GIT1 in the progression of head and neck squamous cell carcinoma (HNSCC). METHODS: GIT1 expression in HNSCC was detected by RT-qPCR, immunohistochemistry assay, and Western blot. HNSCC cell proliferation, migration, and invasion were examined by CCK-8 assay, Wound healing assay, and Transwell assay, respectively. Cell apoptosis was detected by flow cytometric analysis. RESULTS: In our study, GIT1 was notably upregulated in HNSCC tissues and cells. Moreover, GIT1 expression level had positive corelation with pathological grade and nodal status of HNSCC. Functional experiments showed that knockdown of GIT1 restrained HNSCC proliferation, invasion, migration, and EMT and facilitated cell apoptosis. Furthermore, GIT1 knockdown was found to restrain HNSCC tumor growth and lung metastasis. Additionally, PI3K/AKT/mTOR signal pathway inhibitors suppressed the effect of GIT1 on HNSCC cell progression. CONCLUSION: GIT1 was upregulated in HNSCC and facilitated HNSCC cell progression by inducing PI3K/AKT/mTOR signal pathway. Therefore, we suggested that GIT1 might be a potential target for HNSCC treatment.