Long non-coding RNA PVT1 regulates TGF-ß and promotes the proliferation, migration and invasion of hypopharyngeal carcinoma FaDu cells.

Hypopharyngeal carcinoma is one of the malignant tumors of the head and neck with a particularly poor prognosis. Recurrence and metastasis are important reasons for poor prognosis of hypopharyngeal cancer patients, and malignant proliferation, migration, and invasion of tumor cells are important factors for recurrence and metastasis of hypopharyngeal cancer. Therefore, elucidating hypopharyngeal cancer cells' proliferation, migration, and invasion mechanism is essential for improving diagnosis, treatment, and prognosis. Plasmacytoma Variant Translocation 1 (PVT1) is considered a potential diagnostic marker and therapeutic target for tumors. However, it remains unclear whether PVT1 is related to the occurrence and development of hypopharyngeal cancer and its specific mechanism. In this study, the promoting effect of PVT1 on the proliferation, migration, and invasion of hypopharyngeal carcinoma FaDu cells was verified by cell biology experiments and animal studies, and it was found that PVT1 inhibited the expression of TGF-ß, suggesting that PVT1 may regulate the occurrence and development of hypopharyngeal carcinoma FaDu cells through TGF-ß.

The prognostic value of image-identified extranodal extension in laryngeal and hypopharyngeal carcinoma following definitive (chemo-)radiotherapy.

OBJECTIVES: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC. METHODS: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders. RESULTS: A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately. CONCLUSIONS: Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification.

How effective is our current follow-up for patients with hypopharyngeal carcinoma?

BACKGROUND: The study aimed to evaluate the diagnostic efficacy of routine follow-up in detecting recurrent disease in hypopharyngeal carcinoma. METHODS: Data from 76 patients with a total of 620 follow-up visits, 367 radiological studies, and 126 panendoscopies were retrospectively assessed regarding the diagnosis of recurrent disease based on the results of (I) radiological studies, (II) clinical examinations, and (III) clinical symptoms. RESULTS: All locally relapsed patients became symptomatic, and new onset of dysphagia (p < 0.001) was the most frequent complaint. The sensitivity for detecting local recurrences was 100% for both patients' symptom assessments and clinical examinations. The highest overall accuracy was found for clinical examinations (93.4%), followed by symptom assessments (80.5%), and radiological studies (73.8%). The risk of false positive radiological reports and subsequent panendoscopies was 2.2 times higher after previous radiotherapy (32.0% vs. 14.6%; p < 0.001). CONCLUSION: Symptom assessments and clinical examinations are highly efficient for detection of local failures.

Development and validation of a diagnostic model for predicting cervical lymph node metastasis in laryngeal and hypopharyngeal carcinoma.

Objectives: The lymph node status is crucial for guiding the surgical approach for patients with laryngeal and hypopharyngeal carcinoma (LHC). Nonetheless, occult lymph node metastasis presents challenges to assessment and treatment planning. This study seeks to develop and validate a diagnostic model for evaluating cervical lymph node status in LHC patients. Materials and methods: This study retrospectively analyzed a total of 285 LHC patients who were treated at the Department of Otolaryngology Head and Neck Surgery, Daping Hospital, Army Medical University, from January 2015 to December 2020. Univariate and multivariate logistic regression analyses were employed to construct the predictive model. Discrimination and calibration were used to assess the predictive performance of the model. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the model, and validation was conducted using 10-fold cross-validation, Leave-One-Out Cross Validation, and bootstrap methods. Results: This study identified significant predictors of lymph node metastasis in LHC. A diagnostic predictive model was developed and visualized using a nomogram. The model demonstrated excellent discrimination, with a C-index of 0.887 (95% CI: 0.835-0.933). DCA analysis indicated its practical applicability, and multiple validation methods confirmed its fitting and generalization ability. Conclusion: This study successfully established and validated a diagnostic predictive model for cervical lymph node metastasis in LHC. The visualized nomogram provides a convenient tool for personalized prediction of cervical lymph node status in patients, particularly in the context of occult cervical lymph node metastasis, offering valuable guidance for clinical treatment decisions.

The clinical utility of diffusion-weighted imaging in diagnosing and predicting treatment response of laryngeal and hypopharyngeal carcinoma: A systematic review and meta-analysis.

PURPOSE: Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC. METHODS: A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies. RESULTS: A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 103 mm2/s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes. CONCLUSION: DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI's reliability in predicting prognosis and treatment response in patients with LC/HPC.

Clinical Conundrum: Unveiling a Unique Presentation of Hypopharyngeal Carcinoma.

Dysphagia is a common symptom encountered in clinical practice, typically associated with a wide range of etiologies, including structural abnormalities, inflammatory conditions, neoplasms, and neurological disorders. However, the combination of subcutaneous emphysema, vocal cord palsy, enlarged arytenoids, and pooling of saliva in a dysphagic patient represents a rare and intriguing presentation. A 33-year-old female presented at a tertiary care hospital in Western India with hoarseness of voice, difficulty in swallowing, productive cough, and neck pain for two months with an abrupt increase in the severity of all symptoms in two days. A history of chewable tobacco use for six years was disclosed. Clinical evaluation revealed a thin build with platynychia and conjunctival pallor, dental staining, drooling of saliva, the presence of extensive subcutaneous emphysema on palpation of the neck, and absent laryngeal crepitus. Endoscopic evaluation was suggestive of right vocal cord palsy and enlarged, congested arytenoid cartilages, post-cricoid growth with pooling of saliva in bilateral pyriform fossae. A CT scan of the neck showed a 2x3 cm neoplastic growth in the hypopharynx, with subcutaneous emphysema and free air foci in the head and neck region, prompting an immediate tracheostomy and biopsy of the hypopharyngeal growth with Ryle's tube insertion. Squamous cell carcinoma was confirmed on the biopsy report. Due to its rarity, the possible underlying cause of idiopathic subcutaneous emphysema should be sought whenever encountered in clinical practice since these patients are potentially misdiagnosed. A high index of suspicion among clinicians, along with a consideration of the constellation of other symptoms and clinical features of a possible underlying hypopharyngeal cancer whenever encountering such patients is of key importance for prompting further investigations and treatment.

Single-cell transcriptomic landscape and the microenvironment of normal adjacent tissues in hypopharyngeal carcinoma.

BACKGROUND: The cellular origin of hypopharyngeal diseases is crucial for further diagnosis and treatment, and the microenvironment in tissues may also be associated with specific cell types at the same time. Normal adjacent tissues (NATs) of hypopharyngeal carcinoma differ from non-tumor-bearing tissues, and can influenced by the tumor. However, the heterogeneity in kinds of disease samples remains little known, and the transcriptomic profile about biological information associated with disease occurrence and clinical outcome contained in it has yet to be fully evaluated. For these reasons, we should quickly investigate the taxonomic and transcriptomic information of NATs in human hypopharynx. RESULTS: Single-cell suspensions of normal adjacent tissues (NATs) of hypopharyngeal carcinoma were obtained and single-cell RNA sequencing (scRNA-seq) was performed. We present scRNA-seq data from 39,315 high-quality cells in the hypopharyngeal from five human donors, nine clusters of normal adjacent human hypopharyngeal cells were presented, including epithelial cells, endothelial cells (ECs), mononuclear phagocyte system cells (MPs), fibroblasts, T cells, plasma cells, B cells, mural cells and mast cells. Nonimmune components in the microenvironment, including epithelial cells, endothelial cells, fibroblasts and the subpopulations of them were performed. CONCLUSIONS: Our data provide a solid basis for the study of single-cell landscape in human normal adjacent hypopharyngeal tissues biology and related diseases.

Early-stage hypopharyngeal squamous cell carcinoma treated with radical radiotherapy at a uniform dose of 70 Gy in 35 fractions: a single-center study.

INTRODUCTION: Hypopharyngeal squamous cell carcinoma (HSCC) is often undetected until advanced stages, which contributes to poor survival rates. Recent advances in diagnostic techniques have enhanced the feasibility of early detection, and this study evaluated the efficacy and safety of radical radiotherapy that specifically targets early stage HSCC. METHODS: This retrospective cohort study consecutively analyzed patients with clinical stage I or II HSCC between December 2008 and February 2023. These patients underwent radical radiotherapy with a uniform dose of 70 Gy delivered in 35 fractions to the primary site, followed by elective nodal irradiation. We assessed clinical outcomes, including overall survival (OS), disease-free survival (DFS), and 5-year locoregional control (LRC). Multivariate analyses were performed to identify the independent prognostic factors for OS. RESULTS: The 5-year OS rate of the entire cohort was 80.7% (95% confidence interval [CI] = 66.5-89.4%), with no significant difference between patients with clinical stage I and II HSCC. Stratified by subsite, the 5-year OS for pyriform sinus, posterior pharyngeal wall, and postcricoid region were 81.6, 68.2, and 100%, respectively. The ECOG-Performance status (PS) was identified as an independent risk factor for OS (hazard ratio [HR] = 8.457; 95% CI 1.325-53.970; p = 0.024). DFS at 5 years was 66.4%, with local recurrence being the most frequent, and LRC rate at 5 years was 79.3%. Acute and late-phase toxicities were predominantly mild to moderate, with no grade 3 or higher toxicities reported. CONCLUSION: This study supports radical radiotherapy as an effective approach for optimal tumor control in patients with early stage HSCC. Despite the limitations of this study, including its retrospective design and single-center confinement, our results revealed the effectiveness and feasibility of radical radiotherapy in the management of early stage HSCC.

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

OBJECTIVES: To explore the predictive significance of baseline absolute peripheral lymphocyte counts (ALC) in the effectiveness of radiation in hypopharyngeal squamous cell carcinoma (HPSCC) patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of pathologically confirmed HPSCC patients who had definitive radiation between 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). MAIN OUTCOME MEASURES AND RESULTS: 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. CONCLUSION: 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.

PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating epithelial-mesenchymal transition: an experimental research.

BACKGROUND: Patients with hypopharyngeal carcinoma (HPC) have a poor prognosis mainly because of lymphatic metastasis. This research aimed to determine the PKM2 role in lymphatic metastasis in HPC and the underlying molecular mechanism contributing to this phenomenon. METHODS: PKM2 in HPC was studied for its expression and its likelihood of overall survival using TCGA dataset. Western blotting, qRT-PCR, and IHC were employed to confirm PKM2 expression. Methods including gain- and loss-of-function were used to examine the PKM2 role in HPC metastasis in vitro and in vivo. In vitro and in vivo studies also confirmed lymphatic metastasis's mechanism. RESULTS: Prominent PKM2 overexpression was seen in patients with lymphatic metastasis of HPC, and there was an inherent relationship between a high PKM2 level and poor prognosis. In vitro research showed that knocking down PKM2 decreased tumor cell invasion, migration, and proliferation while promoting apoptosis and inhibiting epithelial-mesenchymal transition, but overexpressing PKM2 had the reverse effect. Animal studies suggested that PKM2 may facilitate tumor development and lymphatic metastasis. CONCLUSIONS: Our findings suggest that PKM2 may be a tumor's promoter gene of lymphatic metastasis, which may promote lymphatic metastasis of HPC by regulating epithelial-mesenchymal transition. PKM2 may be a biomarker of metastatic potential, ultimately providing a basis for exploring new therapeutic targets.

Cutaneous metastasis in hypopharyngeal carcinoma: a case report.

Background: 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. Case presentation: 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. Conclusion: 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.

Anlotinib suppressed tumor cell proliferation and migration in hypopharyngeal carcinoma.

OBJECTIVE: The purpose of this study is to study the in-vitro effects of multitarget inhibitor anlotinib on hypopharyngeal cancer cell proliferation and cell migration, and the underlying mechanism, which will provide new drug choices for hypopharyngeal cancer treatment. METHODS: The Hypopharyngeal cancer Fadu cells were treated with anlotinib at a concentration of 0, 5, and 10 µmoL/L, respectively. Cell counting kit-8 and the colony-forming assay were used to detect the inhibition of cell proliferation. Wound-healing assay and transwell assay were used to detect the migration and invasion ability of cells. Flow cytometry was used to detect the effects of anlotinib on cell cycle and apoptosis. RT-qPCR and Western blot were used to measure gene expression levels. RESULTS: CCK-8 and colony-forming assay showed that anlotinib could significantly inhibit cell proliferative activity. Wound-healing assay and transwell assay showed that anlotinib could inhibit cell migration and scratch. These results showed that anlotinib has obvious antitumor activity. Flow cell cycle experiment showed that anlotinib could promote Fadu cell apoptosis and block the G2/M phase for inhibiting cell proliferation. In addition, anlotinib decreased the expression of HIF-1α. CONCLUSIONS: Anlotinib has an excellent suppressing effect on the proliferation, migration, and invasion of hypopharyngeal cancer Fadu cells in-vitro. Moreover, it can play an anti-tumor role through blocking cell cycle G2/M and promoting apoptosis, which may be related to the decrease of HIF-1a expression. Our study would provide a potential treatment method for patients with hypopharyngeal cancer. LEVEL OF EVIDENCE: Level 3.

Anlotinib suppressed tumor cell proliferation and migration in hypopharyngeal carcinoma

Abstract Objective The purpose of this study is to study the in-vitro effects of multitarget inhibitor anlotinib on hypopharyngeal cancer cell proliferation and cell migration, and the underlying mechanism, which will provide new drug choices for hypopharyngeal cancer treatment. Methods The Hypopharyngeal cancer Fadu cells were treated with anlotinib at a concentration of 0, 5, and 10 μmoL/L, respectively. Cell counting kit-8 and the colony-forming assay were used to detect the inhibition of cell proliferation. Wound-healing assay and transwell assay were used to detect the migration and invasion ability of cells. Flow cytometry was used to detect the effects of anlotinib on cell cycle and apoptosis. RT-qPCR and Western blot were used to measure gene expression levels. Results CCK-8 and colony-forming assay showed that anlotinib could significantly inhibit cell proliferative activity. Wound-healing assay and transwell assay showed that anlotinib could inhibit cell migration and scratch. These results showed that anlotinib has obvious antitumor activity. Flow cell cycle experiment showed that anlotinib could promote Fadu cell apoptosis and block the G2/M phase for inhibiting cell proliferation. In addition, anlotinib decreased the expression of HIF-1α. Conclusions Anlotinib has an excellent suppressing effect on the proliferation, migration, and invasion of hypopharyngeal cancer Fadu cells in-vitro. Moreover, it can play an anti-tumor role through blocking cell cycle G2/M and promoting apoptosis, which may be related to the decrease of HIF-1a expression. Our study would provide a potential treatment method for patients with hypopharyngeal cancer. Level of evidence: Level 3.

ESCO2 promotes hypopharyngeal carcinoma progression in a STAT1-dependent manner.

BACKGROUND: The establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized. METHODS: This study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners. RESULTS: We found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration. CONCLUSIONS: These findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.

Prevalence and risk factors for retropharyngeal and retro-styloid lymph node metastasis in hypopharyngeal carcinoma.

BACKGROUND: We evaluated the prevalence and identified the risk factors for retropharyngeal and retro-styloid lymph node metastasis (LNM) in patients with hypopharyngeal carcinoma (HPC). This was achieved using a combination of magnetic resonance (MR) and [18 F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) images. METHODS: Two board-certified radiation oncologists retrospectively reviewed pretreatment FDG-PET/CT images and contrast-enhanced thin-slice CT and MR images of 155 patients with HPC who underwent radiotherapy. Fisher's exact tests and logistic regression analyses were performed to assess the risk factors for LNM. RESULTS: Retropharyngeal LNM (RPLNM) was confirmed in 20 (13%) patients. Posterior wall (PW) tumors (odds ratio [OR]: 4.128, 95% confidence interval [CI]: 1.339-12.727; p = 0.014) and bilateral or contralateral cervical LNM (OR: 11.577, 95% CI: 2.135-62.789; p = 0.005) were significantly correlated with RPLNM. The RPLNM was found in 9 (32%) of the 28 patients with PW tumors. Of these 9 patients, 2 (7%) had ipsilateral RPLNM, 3 (11%) had contralateral RPLNM, and 4 (14%) had bilateral RPLNM. The PW tumors were significantly associated with contralateral RPLNM (p < 0.001). Retro-styloid LNM (RSLNM) was confirmed in two (1%) patients, both of whom had ipsilateral RSLNM with lymph nodes (LNs) of ≥ 15 mm in the upper limit of ipsilateral level II. A significant association was found between LNs of ≥ 15 mm in the upper limit of ipsilateral level II and ipsilateral RSLNM (p = 0.001). CONCLUSIONS: The RPLNM was identified in 13% of patients with HPC. The PW tumors and bilateral or contralateral cervical LNM were risk factors for RPLNM; particularly, PW tumors were a specific risk factor for contralateral RPLNM. Although the RSLNM was rare, LNs of ≥ 15 mm in the upper limit of ipsilateral level II were a risk factor for ipsilateral RSLNM.

Chemical modification of curcumin increases its potency against hypopharyngeal carcinoma.

Hypopharyngeal carcinoma is notorious for its poor prognosis among all head and neck cancers, posing a persistent challenge in clinical settings. The continuous hyperactivation of the NFκB signalling pathway has been noted in various cancer types, including hypopharyngeal carcinoma. In our quest to develop a novel drug that targets hypopharyngeal cancer via the NFκB pathway, we employed curcumin, a well-known lead compound, and performed chemical modifications to create a mono-carbonyl analogue called L42H17. This compound exhibited exceptional stability and displayed an enhanced binding affinity to myeloid differentiation protein 2 (MD2). Consistent with expectations, L42H17 demonstrated the ability to inhibit TNF-α-induced phosphorylation of inhibitor of κB (IκB) kinase (IKK), prevent IκB degradation, and subsequently impede NFκB-p65 nuclear translocation in hypopharyngeal cancer cells. Additionally, L42H17 exhibited a remarkable capacity to induce cell cycle arrest at the G2-M phase by inactivating the cdc2-cyclin B1 complex. Moreover, it facilitated cell apoptosis by reducing Bcl-2 levels and augmenting the expression of cle-PARP and cle-caspase3. Importantly, we observed a significant enhancement in the anti-cancer efficacy of L42H17 in a patient-derived tumour xenograft (PDTX) model of hypopharyngeal carcinoma. In conclusion, our findings strongly suggest that L42H17 holds promise as a potential candidate drug for the treatment of hypopharyngeal carcinoma in the future.

[Comparison of different laryngeal preservation strategies based on chemoradiotherapy in locally advanced hypopharyngeal carcinoma].

Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response（more than 80% tumor regression）, patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS（overall survival）, progression free survival（PFS）, locoregional recurrence-free survival（LRRFS） and LDFS. Results:In IC-directed group, 75.0%（57/76） patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%（109/155） patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%（HR 0.67; 95%CI 0.43-1.05; P=0.07） and 27.8% versus 39.8%（HR 0.68; 95%CI 0.46-0.99; P=0.04） between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.

A Randomized Study to Evaluate Efficacy and Toxicity Profile of Paclitaxel-carboplatin as Neo-adjuvant Chemotherapy in Locally Advanced Supraglottic and Hypopharyngeal Primaries.

This study was conducted in locally advanced supraglottic and hypopharyngeal squamous cell carcinoma patients to ascertain the efficacy and toxicity profile of a two drug combination neo adjuvant chemotherapy (NACT) schedule containing Taxane and Platinum; prior to definitive concurrent chemo-radiotherapy (Def CCRT); sixty patients with stage III, IVA and IVB locally advanced squamous cell cancers of larynx and hypopharynx were randomised to two arms. Thirty patients in study group were treated with NACT with Paclitaxel (175 mg/m2) and Carboplatin (AUC 5-7) for 3, 3 weekly cycles; followed by CCRT in the patients who showed at-least a partial response (PR). These patients were compared with the 30 patients of control group who received upfront CCRT. More patients in Study arm developed grade 3 dysphagia (p = 0.001) and mucositis (p = 0.003). Renal, hematogenous and skin toxicities were identical in two arms. At 3 months post treatment complete response (CR) at primary site was 83.3% and 66.6% (p = 0.245) in study and control arms respectively. At 6 months post treatment; 20 patients (66.6%) in the study group and 17 patients (56.6%) in the control group continued to be in clinic-radiological CR (p = 0.20). NACT with Paclitaxel and Carboplatin is tolerated with manageable toxicities in patients with LAHNSCC (Locally advanced head and neck squamous cell carcinoma), with increased Grade 3 dysphagia and mucositis as compared to patients getting upfront CCRT. A longer follow-up period with a larger sample size is required to further evaluate any statistically significant benefit of adding NACT prior to CCRT.

LncRNA LINC01569 promotes M2 macrophage polarization to accelerate hypopharyngeal carcinoma progression through the miR-193a-5p/FADS1 signaling axis.

Background: Long non-coding RNA (lncRNA) LINC01569 plays an important role in regulating the tumor microenvironment (TME) and macrophage polarization. However, whether it participates in the progression of hypopharyngeal carcinoma by regulating the TME remains unclear. Methods: An online database was used to analyze clinical data. Macrophage polarization was detected using qRT-PCR and flow cytometry. In vivo experiments were performed using tumor-bearing nude mice. A co-culture system of hypopharyngeal carcinoma cells and macrophages was used to explore the interactions between the two cell types. Results: LINC01569 enhancement was observed in hypopharyngeal carcinoma tumor-associated macrophages (TAMs). In IL4-induced M2 macrophages, the expression of LINC01569 increased, while LINC01569 expression declined significantly in LPS-induced M1 macrophages. SiRNA-mediated downregulation of LINC01569 inhibits IL4-induced M2 macrophage polarization. Using online databases and a dual-luciferase reporter, miR-193a-5p was confirmed as a potential downstream sponge of LINC01569. MiR-193a-5p expression decreased in IL4-mediated M2 macrophages, which was restored by LINC01569 downregulation. Additionally, LINC01569 inhibition-mediated blocking of M2 macrophage polarization was moderately abolished by transfection with the miR-193a-5p inhibitor. Fatty acid desaturase 1 (FADS1) was verified as a downstream target of miR-193a-5p, and LINC01569 downregulation-mediated inhibition of FADS1 was blocked by miR-193a-5p mimics. Importantly, LINC01569 downregulation-mediated decline in M2 macrophage polarization was abolished by miR-193a-5p mimics, which was further reversed by FADS1 knockdown. Implantation of a mixture of FaDu cells and IL4-induced macrophages promoted tumor growth and proliferation, which were abrogated by the knockdown of LINC01569 in macrophages. Using an in co-culture system of FaDu cells and macrophages in vitro, M2 macrophage-regulated cell growth and apoptosis of FaDu cells were found to be mediated by the LINC01569/miR-193a-5p signaling axis. Conclusion: LINC01569 is highly expressed in the TAMs of hypopharyngeal carcinoma. LINC01569 downregulation restrains macrophages from polarizing toward M2 through the miR-193a-5p/FADS1 signaling axis, thereby helping tumor cells escape inherent immune surveillance and promoting the occurrence and development of hypopharyngeal carcinoma.

Salvage transoral videolaryngoscopic surgery for post-irradiation recurrence of hypopharyngeal carcinoma.

Background: Transoral salvage surgery has the potential to preserve a patient's quality of life. Therefore, we investigated the outcomes, safety, and risk factors for postoperative complications of salvage transoral videolaryngoscopic surgery (TOVS) for recurrent hypopharyngeal carcinoma after radiotherapy (RT) or chemoradiotherapy (CRT). Methods: This retrospective analysis enrolled patients with hypopharyngeal cancer who had a history of RT or CRT and underwent TOVS from January 2008 to June 2021. The factors related to postoperative complications, postoperative swallowing functions and survival rates were analyzed. Results: Seven patients (36.8%) of the 19 patients developed complications. Severe dysphagia was the primary complication, and post-cricoid resection was a complication risk factor. The FOSS score was significantly lower in the salvage treatment group. The survival rates were: 3-year overall survival: 94.4%; disease-specific survival: 94.4%; 5-year overall survival: 62.3%; and disease-specific survival: 86.6%. Conclusions: Salvage TOVS for hypopharyngeal cancer was feasible, and oncologically and functionally reasonable. Level of Evidence: 2b.