Hypopharyngeal Squamous Cell Carcinoma Research Articles

Peripheral lymphocyte count as an indicator of radiotherapy effectiveness in hypopharyngeal squamous cell carcinoma.

To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. A retrospective study of pathologically confirmed HPSCC patients who had definitive radiationbetween January 2020 and January 2022 at Fudan University Eye and ENT Hospital. The routine blood results of patients were obtained to determine if the baseline ALC was connected with the response to radiation. The receiver operator characteristic (ROC) curve and LASSO-based Cox regression were employed to assess the predictive value of ALC for the efficacy of radiotherapy (RT). RT induced a considerable drop in ALC and the level of ALC did not revert to the baseline values 1 year after radiation. The baseline level of ALC was higher in patients who met complete response after RT. The baseline ALC and monocyte counts demonstrated the predictive value of radiation effectiveness and ALC was an independent predictor. In HPSCC, lymphocytes were sensitive to radiation and reduced significantly during RT. The baseline ALC might be regarded as a predictive indicator of the effectiveness of RT.

[The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma].

Objective: To explore the efficacy and safety of immunoneoadjuvant therapy with pembrolizumab combined with chemotherapy in locally advanced resectable hypopharyngeal squamous cell carcinoma patients. Methods: This study was a prospective, single arm, single center clinical study that was opened for enrollment in April 2021. Patients who met the inclusion criteria at the Cancer Hospital of the Chinese Academy of Medical Sciences were treated with neoadjuvant therapy of pembrolizumab combined with cisplatin and paclitaxel, and after treatments, received surgery and postoperative adjuvant therapy. The main endpoint of this study was postoperative pathological complete response (pCR), and other observations included adverse reactions and long-term prognoses of patients after neoadjuvant therapy. Results: By September 2023, a total of 23 patients who underwent neoadjuvant therapy and surgery were enrolled in the study and all patients were males aged 49-74 years. All patients were locally advanced stage, including 3 patients in stage Ⅲ and 20 patients in stage Ⅳ. There were 12 cases of primary lesions with posterior ring involvement accompanied by fixation of one vocal cord and 20 cases of regional lymph node metastases classified as N2. Eighteen cases received a two cycle regimen and 5 cases received a three cycle regimen for neoadjuvant therapy. The postoperative pCR rate was 26.1% (6/23), with no surgical delay caused by adverse drug reactions. The laryngeal preservation rate was 87.0% (20/23). Pharyngeal fistula was the main surgical complication, with an incidence of 21.7% (5/23). The median follow-up time was 15 months, and 3 patients experienced local recurrence. Conclusions: The immunoneoadjuvant therapy of pembrolizumab combined with chemotherapy has a high pCR rate in locally advanced resectable hypopharyngeal squamous cell carcinoma, with increased laryngeal preservation rate and no significant impact on surgical safety.

[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase Ⅱ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Patterns of head and neck lesions among HIV/AIDS patients on highly active antiretroviral therapy at Dodoma Regional Referral Hospital in Tanzania

Introduction: Head and neck lesions associated with Human Immunodeficiency Virus are considered to occur in over 50% of HIV- positive patients and occur in nearly 80% of all patients with acquired immunodeficiency syndrome. The introduction of highly active antiretroviral therapy has led to a remarkable reduction in the global burden of such lesions. Suppose such lesions are undiagnosed or untreated on a prompt basis. In that case, they may cause morbidity and mortality since some lesions, for example, head and neck cancers may interfere with vital functions of life such as respiration, deglutition, and speech. This study determined head and neck lesions among HIV/AIDS patients in Tanzania. Methods: This was a hospital-based descriptive cross-sectional study that recruited 222 HIV/AIDS patients at a care and treatment clinic at Dodoma Regional Referral Hospital.  Physical examination and laboratory investigations (histopathology, viral load and CD4 counts) were collected and data was analyzed using Statistical Package for Social Sciences (SPSS) version 23. P-value&lt;0.05 was statistically significant. Results: Of all the 222 patients recruited in this study, 26 (11.7%) had head and neck lesions. Most patients with head and neck lesions were females (57.6%). Half of the patients (50.0%) were between 40 and 59 years old. About 21 (80.8%) patients were diagnosed with HIV/AIDS within two years, and 22 (84.6%) were initially diagnosed with CD4 counts less than 200 cells/μL. The most common head and neck lesion was oral candidiasis (46.2%) and others were cervicofacial lymphadenitis (15.4%), head and neck squamous cell carcinoma (laryngeal and hypopharyngeal) (11.5%), sinonasal Kaposi’s sarcoma (7.7%), odontogenic abscess (7.7%) and aphthous ulcers (7.7%) and the least encountered head and neck lesion was a ranula in 3.8% of patients. Similarly, a significant association was found between the occurrence of head and neck lesions with viral load, CD4 counts, duration since a patient was diagnosed with HIV/AIDS, presence of comorbid illness, alcohol consumption and cigarette smoking. Conclusions: The prevalence of head and neck lesions among HIV/AIDS patients on HAART was low. Females outnumbered males in terms of being affected by head and neck lesions. Oral candidiasis was the most common head and neck lesion. Head and neck (laryngeal and hypopharyngeal) squamous cell carcinoma was the predominant subtype of malignant lesions in HIV/AIDS patients on HAART.

A meta-analysis evaluating the role of calcium channel alpha-2 delta-1 subunit in carcinogenesis

There is hardly found any study accumulating all the experiments reported with the expression of alpha-2 delta-1 (α2δ-1) in cancer cells. This meta-analysis aimed to advance our knowledge about the role of calcium channel alpha2 delta-1 subunit in carcinogenesis in the present time. PubMed searches for peer-reviewed articles were conducted using the keywords “α2δ-1 protein in oncogenesis”, “α2δ-1 protein expression in cancer cells”, and “α2δ-1 protein as cancer cell marker”. The databases were developed in accordance with PRISMA guidelines. Seventeen studies out of 80 citations met the inclusion criteria pertaining to α2δ-1 expression in different cancer cells. The cancer patterns were hepatocellular carcinoma in 41%, non-small cell lung carcinoma in 12% and laryngeal squamous cell carcinoma in 12%. The remaining studies included small-cell lung cancer (6%), gastric cancer (6%), pancreatic cancer (6%), hypopharyngeal squamous cell carcinoma (6%), breast cancer (6%) and glioblastoma multiforme (6%). α2δ-1+ cells had a higher sphere-forming and tumorigenic efficiency in 76.5% of experiments. 58.8% experiments explored mechanistically in self-renewal efficiency and tumorigenesis of α2δ-1+ cancer cells. The cancer cells expressing α2δ-1 have the potential to serve as cell surface markers for tumour-initiating cells and cancer stem cells. These intriguing findings open up a promising avenue for future research, focusing on the targeting of α2δ-1 as a potential therapeutic strategy for cancer treatment.

Abstract 3233: EP102: Pharmacological Inhibition of METTL3 causes tumor growth inhibition and prolongs survival in preclinical models of NSCLC, ovarian and squamous cell carcinoma

Abstract METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-6-methyladenosine (m6A), the most abundant epigenetic modification to mRNA. The prevalence of m6A and the activity and expression of METTL3 have been linked to the appearance and progression of numerous hematological and solid tumor cancers. EPICS has discovered and optimized small molecule inhibitors of METTL3 (“M3i”). The aim of the current study is to evaluate the efficacy of M3i in various CDX mouse tumor models. M3i compound potency was evaluated in vitro by measuring enzymatic inhibition of METTL3/14 by scintillation proximity assay (IC50 = 2 nM). The anti-proliferative effects of M3i were measured in cell viability assays following a 72h treatment of A549 (NSCLC, IC50 = 190 nM), SKOV3 (ovarian, IC50 = 9 nM) and FaDu (hypopharyngeal squamous cell carcinoma, IC50 = 24 nM) cells. Complementary data in all three cell lines demonstrates a clear concentration-response for a target engagement biomarker (m6A; IC50 = 2-8 nM, across cell lines) as well as M3i-induced changes in biomarkers of oncogenic drivers. M3i (30 mg/kg, IP, QD) was tested in vivo in mouse models using FaDu (subcutaneous implant) in addition to A549 and SKOV3 (both orthotopic implants); all animal models were performed by LabCorp (MI, USA). Daily M3i treatment significantly prolonged survival in all three disease models consistent with efficacy on tumor growth inhibition as measured by imaging (A549, SKOV3) or direct measurement of tumor volume in the case of subcutaneous implant (FaDu). M3i has previously been shown to be effective in mouse CDX and PDX models of AML. The current results extend the application of METTL3 inhibitors to include the treatment of various types of solid tumors. The efficacy of M3i as a single-agent on tumor growth inhibition and survival advances the validation of METTL3 as a cancer target and provides additional evidence for the applicability of mRNA epigenetic mechanisms to the treatment of solid tumors. Citation Format: Graeme Fraser, Catherine Sorlet, Nicolas Parmentier, Elodie Brunel, Christian Coremans, Sarah Rorive, Anne-France Hartiel, Killian Oukoloff, Guillaume Dutheuil. EP102: Pharmacological Inhibition of METTL3 causes tumor growth inhibition and prolongs survival in preclinical models of NSCLC, ovarian and squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3233.

TMEM16A inhibits autophagy and promotes the invasion of hypopharyngeal squamous cell carcinoma through mTOR pathway.

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell, and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy, and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared to normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion, and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.

PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma.

It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p < 0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p = 0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p ≤ 0.04). Positive correlations (R ∈ [0.43, 0.71], p < 0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R ∈ [0.35, 0.47], p < 0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.

Prognostic effects of different treatment modalities for hypopharyngeal squamous cell carcinoma: Experience of two tertiary hospitals in Southwestern China

BackgroundThe prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. MethodsHPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan–Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). ResultsA total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). ConclusionsSurgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma

BackgroundHypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25–30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC.MethodsA retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates.ResultsOf the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event.ConclusionThe Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

Polygenic Risk Score in Predicting Esophageal, Oropharyngeal, and Hypopharynx Cancer Risk among Taiwanese Population.

Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.

The value of dual-layer spectral detector CT in preoperative T staging of laryngeal and hypopharyngeal squamous cell carcinoma

PurposeTo explore the optimal kiloelectron voltage (keV) of virtual monochromatic images (VMIs) of dual-layer spectral detector computed tomography (DLSCT) to display laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) and its diagnostic performance for preoperative T staging of LHSCC. MethodsA total of 67 LHSCC patients were included, and the contrast between the tumor and sternocleidomastoid muscle (SM), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image noise of 40–100 keV VMIs and conventional polyenergetic images (CIs) were evaluated. The image quality of the CI and 40–100 keV VMI was evaluated by a five-point method. The VMI with the best image quality was screened out, and the accuracy of the optimal keV VMI and CI for T staging was assessed using clinical T staging as the reference standard. ResultsThe contrast between the tumor and SM, SNR, CNR and subjective image quality scores of LHSCC on 40–50 keV VMIs were higher than those on CIs (P < 0.05); the image noises of 40–100 keV VMIs were lower than those of CIs (P < 0.05). The 40 keV VMI had the highest SNR, CNR and subjective score of image quality. The accuracy rates of the 40 keV VMI and CI for T staging of LHSCC were 0.86 and 0.63 (P < 0.001), respectively. ConclusionThe image quality of 40–50 keV VMI is higher than that of CI, and the diagnostic accuracy of 40 keV VMI is better than that of CI, which is most suitable for preoperative T staging of LHSCC.

Cutaneous metastasis in hypopharyngeal carcinoma: a case report.

Occurrence of cutaneous metastasis in hypopharyngeal carcinoma is an extremely rare event reported in the literature, with an incidence of only 0.8%-1.3%. Early diagnosis of cutaneous metastasis would have a positive impact on treatment response and disease prognosis with diagnosis mainly dependent on physical examination and radiological imaging (ultrasonography, computed tomography scan or PET-CT). Palliative care is, however, the mainstay of treatment for cutaneous metastasis. We report a middle-aged female patient, with known case of hypopharyngeal squamous cell carcinoma, who initially showed partial response to chemoradiotherapy but developed cutaneous nodules in the region of the right axilla and bilateral lateral chest wall posterior to the posterior axillary fold. Excision biopsy of one of these nodules showed metastatic squamous cell carcinoma. The patient was again referred to the Oncology Department of INMOL Hospital and her chemotherapy was planned for cutaneous metastasis. Being uncommon, the occurrence of cutaneous lesions in a patient with hypopharyngeal carcinoma should prompt detailed evaluation to rule out metastasis. Early detection will help in improving disease prognosis and median survival.

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer

BackgroundPre-clinical studies suggest AZD1775, a WEE1 kinase inhibitor, potentiates the activity of various chemotherapeutic agents.MethodsWISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. Eligible patients had histologically confirmed oral, laryngeal, or hypopharyngeal squamous cell carcinoma, ECOG performance status 0/1, and aged ≥18-to-≤70 years. Primary outcomes were adverse events and defining recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative (Group A), or with cisplatin/radiotherapy in post-operative (Group B) patients. Dose determination was guided by a modified time-to-event continual reassessment method (mTITE-CRM).ResultsBetween 30-Oct-2017 and 15-Jul-2019, nine patients were registered: Three into Group A and six into Group B. WISTERIA was closed early due to poor recruitment. Five dose-limiting toxicities (DLTs) were reported in four Group B patients. Seven serious adverse events were reported in four patients: One in Group A, and three in Group B. Three were related to treatment. No treatment-related deaths were reported.ConclusionsWISTERIA did not complete its primary objectives due to poor recruitment and toxicities reported in Group B. However, use of the novel mTITE-CRM improved flexibility in reducing accrual suspension periods and should be considered for future trials in complex patient populations.Clinical Trial RegistrationISRCTN76291951

Establishment and characterization of a novel hypopharyngeal squamous cell carcinoma cell line CZH1 with genetic abnormalities.

Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among head and neck squamous cell carcinomas. The lack of available tumor cell lines poses a significant obstacle to the development of efficient treatments for HPSCC. In this study, we successfully established a novel cell line, named CZH1, from the postcricoid region of a Chinese male patient with a T3N0M0 HPSCC. Short tandem repeat analysis confirmed the uniqueness of CZH1. The cell line was characterized by its phenotypes, biomarkers, and genetics. Importantly, CZH1 cells retained the typical features of epithelial malignancy, similar to the primary tumor tissue. Furthermore, CZH1 demonstrated a greater capacity for invasion and increased susceptibility to irradiation in comparison to FaDu, which is the most commonly used HPSCC cell line. Whole-exome sequencing analysis revealed that CZH1 cells had typical genomic features of HNSCC, including mutations of TP53 and amplifications of multiple transcripts. Therefore, our newly developed CZH1 cell line could serve as an efficient tool for the in vitro investigation of the etiology, pathogenesis, and preclinical treatment of HPSCC.

Combined average standard uptake value and rate constant can predict expression of EGFR in hypopharyngeal squamous cell carcinoma: A pilot study with integrated PET/MRI

PurposeTo investigate whether the quantitative multiparameters of 18F-FDG PET/MRI can predict expression of epidermal growth factor receptor (EGFR) of hypopharyngeal squamous cell carcinoma (HSCC). MethodsTwenty-one patients with HSCC confirmed by biopsy underwent neck integrated 18F-FDG PET/MRI and EGFR expression detection. Quantitative parameters derived from 18F-FDG PET, difusion-weighted imaging (DWI), and dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) were measured. The efficacies of quantitative multiparameters derived from 18F-FDG PET/MRI for predicting the expression of EGFR of HSCC were evaluated. ResultsThe patients were divided into positive expression group (PEG, n = 14) and negative expression group (NEG, n = 7). Mann-Whitney U nonparametric test showed that SUVmean and Kep had statistical difference between PEG and NPG, while other parameters had no statistical difference. Using 14.50 and 2.10 min−1 as the threshold values, areas under the curve (AUCs) for SUVmean and Kep were 0.786 with specificity of 92.9 % and sensitivity of 57.1 %. The combined use of SUVmean and Kep had better efficacy to evaluate the expression of EGFR with AUC of 0.980, sensitivity of 92.9 %, and specificity of 100.0 %. ConclusionCombined use of SUVmean and Kep showed good performance in predicting the expression of EGFR in HSCC. Integrated 18F-FDG PET/MRI enables simultaneous acquisition of SUVmean and Kep, so it represents as a powerful tool to noninvasively and repeatably evaluate the expression of EGFR during the management of HSCC.

Machine learning model to preoperatively predict T2/T3 staging of laryngeal and hypopharyngeal cancer based on the CT radiomic signature.

To develop and assess a radiomics-based prediction model for distinguishing T2/T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) METHODS: A total of 118 patients with pathologically proven LHSCC were enrolled in this retrospective study. We performed feature processing based on 851 radiomic features derived from contrast-enhanced CT images and established multiple radiomic models by combining three feature selection methods and seven machine learning classifiers. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the models. The radiomic signature obtained from the optimal model and statistically significant morphological image characteristics were incorporated into the predictive nomogram. The performance of the nomogram was assessed by calibration curve and decision curve analysis. Using analysis of variance (ANOVA) feature selection and logistic regression (LR) classifier produced the best model. The AUCs of the training, validation, and test sets were 0.919, 0.857, and 0.817, respectively. A nomogram based on the model integrating the radiomic signature and a morphological imaging characteristic (suspicious thyroid cartilage invasion) exhibited C-indexes of 0.899 (95% confidence interval (CI) 0.843-0.955), fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram. The nomogram based on the radiomics model derived from contrast-enhanced CT images had good diagnostic performance for distinguishing T2/T3 staging of LHSCC. Accurate T2/T3 staging assessment of LHSCC aids in determining whether laryngectomy or laryngeal preservation therapy should be performed. The nomogram based on the radiomics model derived from contrast-enhanced CT images has the potential to predict the T2/T3 staging of LHSCC, which can provide a non-invasive and robust approach for guiding the optimization of clinical decision-making. • Combining analysis of variance with logistic regression yielded the optimal radiomic model. • A nomogram based on the CT-radiomic signature has good performance for differentiating T2 from T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma. • It provides a non-invasive and robust approach for guiding the optimization of clinical decision-making.

2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein.

Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 μM) and in nude mouse xenograft models (50 μmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.

Long-Term Treatment Outcomes of Hypopharyngeal Cancer Using Different Surgical Modalities

Background and Objectives In the present study, we evaluated the treatment results of hypopharyngeal squamous cell carcinoma (HPSCC) patients and analyzed the occurrence of secondary primary malignancies. Treatments were based on two different surgical modalities (conventional pharyngo-laryngectomy vs. transoral surgery). In addition, prognostic factors of the patients were evaluated.Subjects and Method We analyzed medical data of 232 patients diagnosed with HPSCC and underwent surgery at our hospital from January 2006 to December 2019.Results The 5-year recurrence-free survival was 67.2% for the stage I-II group and 64.9% for the stage III-IV group. The 5-year disease-specific survival was 78.2% for the stage I-II group and 54.5% for the stage III-IV group. N classification was significantly correlated with disease relapse and patient mortality. Patient age, sex, perineural invasion, extranodal extension, initial tumor stage, and early recurrence (within 6 months) were significantly associated with successful salvage treatment. The two surgical modalities did not yield different oncological outcomes. Secondary primary malignancies occurred most frequently in the esophagus, with no observed inferior survival rate in patients with second malignancies.Conclusion The 5-year survival rate for HPSCC patients who received surgical treatment was 78% for stage I-II and 54% for stage III-IV. While no difference in oncological outcome was observed based on surgical modality, the transoral surgery group showed better functional outcomes.