Hypopharyngeal Squamous Cell Carcinoma Patients 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.

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.

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.

Fusobacterium nucleatum facilitates proliferation and autophagy by activating miR-361-3p/NUDT1 axis through oxidative stress in hypopharyngeal squamous cell carcinoma

BackgroundTo investigate how Fusobacterium nucleatum (Fn) promotes oxidative stress and mediates proliferation and autophagy in hypopharyngeal squamous cell carcinoma (HPSCC).MethodsThe prognosis for 82 HPSCC cases was retrospectively analyzed. HPSCC cell line FaDu was co-cultured with Fn. Knockdown of NUDT1 (shNUDT1 group) was done after observing DNA damage response. CCK8 and tumorigenesis assays for proliferation observation, mitochondria ROS (MitoROS) measurement to examine intracellular oxidative stress, and ELISA to analyze concentration of 8-oxo-2’-deoxyguanosine (8-oxo-dG) in cells. Dual-luciferase reporter assays clarified miR-361-3p connection with NUDT1. Autophagy flow was observed using electron microscopy and related proteins.ResultsFn was highly associated with NUDT1. The shNUDT1 group experienced lower proliferation compared with normal FaDu (NC group) in vivo and in vitro. The shNUDT1 group showed 8-oxo-dG and γH2AX to be elevated. Intracellular ROS decreased in shNUDT1Fn group when compared to Fn group. Upregulating miR-361-3p could suppress NUDT1 expression and downstream proliferation and autophagy. Fn modulated miR-361-3p via OH−, which could be proven by H2O2 assay and N-acetylcysteine.ConclusionsHigher Fn in HPSCC patients suggests poorer prognosis. NUDT1 might affect cell proliferation and autophagy and modulate DNA damage response. The oxidative stress induced miR-361-3p/NUDT1 axis is first introduced in microbiome-carcinoma research.

CPT1A mediates chemoresistance in human hypopharyngeal squamous cell carcinoma via ATG16L1-dependent cellular autophagy

Hypopharyngeal squamous cell carcinoma (HSCC) is a highly aggressive malignancy that constitutes approximately 95% of all hypopharyngeal carcinomas, and it carries a poor prognosis. The primary factor influencing the efficacy of anti-cancer drugs for this type of carcinoma is chemoresistance. Carnitine palmitoyltransferase 1A (CPT1A) has been associated with tumor progression in various cancers, including breast, gastric, lung, and prostate cancer. The inhibition or depletion of CPT1A can lead to apoptosis, curbing cancer cell proliferation and chemoresistance. However, the role of CPT1A in HSCC is not yet fully understood. In this study, we discovered that CPT1A is highly expressed in HSCC and is associated with an advanced T-stage and a poor 5-year survival rate among patients. Furthermore, the overexpression of CPT1A contributes to HSCC chemoresistance. Mechanistically, CPT1A can interact with the autophagy-related protein ATG16L1 and stimulate the succinylation of ATG16L1, which in turn drives autophagosome formation and autophagy. We also found that treatment with 3-methyladenine (3-MA) can reduce cisplatin resistance in HSCC cells that overexpress CPT1A. Our findings also showed that a CPT1A inhibitor significantly enhances cisplatin sensitivity both in vitro and in vivo. This study is the first to suggest that CPT1A has a regulatory role in autophagy and is linked to poor prognosis in HSCC patients. It presents novel insights into the roles of CPT1A in tumorigenesis and proposes that CPT1A could be a potential therapeutic target for HSCC treatment.

A retrospective analysis: follow-up with FDG-PET/CT in oro- and hypopharyngeal squamous cell carcinoma patients.

Abstract Objective This study evaluated the significance of positron emission tomography/computed tomography (PET/CT) in detecting recurrences or other primary malignancies in patients treated for oro- and hypopharyngeal squamous cell carcinoma. Method A retrospective analysis of the follow up of 132 patients was performed and 370 PET/CT scans were assessed for their accuracy. Results All asymptomatic clinical occult recurrences were detected by PET/CT and accounted for 28 per cent of recurrences. Asymptomatic patients with metastases detected by PET/CT had a significant survival benefit compared to patients diagnosed in a symptomatic stage. For locoregional recurrence, no significant difference in overall survival could be demonstrated. In total, 33 primary malignancies were discovered, of which 48 per cent were first detected by PET/CT. The specificity and negative predictive value of the PET/CT scans had ranges of 85–100 and 83–100 per cent, respectively. Conclusion The role of PET/CT scans in detecting primary malignancies, clinical occult recurrences and especially asymptomatic metastases was observed.

[Analysis of efficacy and prognosis of neoadjuvant chemotherapy and （or） surgery plus radiotherapy for hypopharyngeal squamous cell carcinoma].

Objective:To analyze the risk factors that affect the prognosis of patients with hypopharyngeal squamous cell carcinoma（HPSCC） and to compare the efficacy of surgical resection followed by adjuvant radiotherapy（SR） with that of neoadjuvant therapy consisting of platinum-based chemotherapy and fluorouracil combined with either cetuximab or nimotuzumab, followed by SR. The study also aimed to evaluate the overall survival（OS） of patients, their postoperative eating function, tracheostomy decannulation rate, and tumor response to the two neoadjuvant chemotherapies. Methods:A retrospective analysis was performed on the medical records of HPSCC patients who received SR or neoadjuvant therapy followed by SR treatment at the Shanghai General Hospital from 2012 to 2019 and had not undergone any prior treatment. The prognostic factors were analyzed, and the survival analysis of patients who underwent SR treatment with two neoadjuvant chemotherapy regimens was performed. Results:A total of 108 patients were included in the study. The results of the univariate analysis showed that gender（P=0.850） had no significant correlation with the survival rate of HPSCC patients who underwent SR. However, age, smoking history, alcohol consumption history, platelet-to-lymphocyte ratio（PLR）, neutrophil-to-lymphocyte ratio（NLR）, T stage, N stage, neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil, and histological grade were significantly associated with prognosis（P<0.05）. The multivariate analysis revealed that smoking history, histological grade, and neoadjuvant therapy with either cetuximab or nimotuzumab combined with platinum-based chemotherapy and fluorouracil were independent risk factors affecting the prognosis of HPSCC（P<0.05）. Patients who received neoadjuvant therapy had longer OS than those who underwent SR only（P<0.001）. There was no significant difference in tumor response to the two neoadjuvant therapies and in OS（P>0.05）, and there was no significant difference in the rate of oral feeding and tracheostomy decannulation among the three treatment groups（P>0.05）. Conclusion:Univariate analysis showed that age at tumor onset, smoking history, alcohol consumption history, NLR, PLR, T stage, N stage, whether receiving neoadjuvant chemotherapy, and pathological grade were associated with the prognosis of HPSCC patients receiving SR treatment. Multivariate analysis showed that smoking history, pathological grade, and neoadjuvant chemotherapy were independent risk factors affecting the prognosis. Neoadjuvant chemotherapy with cetuximab or nimotuzumab can prolong the OS of patients, providing a certain basis and reference for the treatment of HPSCC.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Comparison of Survival Outcomes Between Larynx-Preserving Open Partial Pharyngectomy and Radiotherapy or Chemoradiotherapy in Patients with Hypopharyngeal Squamous Cell Carcinoma: A Single-Center Retrospective Analysis with Inverse Probability of Treatment Weighting Adjustments.

There is a group of hypopharyngeal squamous cell carcinoma (HPSCC) patients for whom larynx-preserving open partial pharyngectomy (PP) and radiotherapy/chemoradiotherapy (RT/CRT) are indicated. We aimed to retrospectively evaluate the survival difference as there is no evidence directly comparing the two therapies. This study evaluated HPSCC patients who were initially treated by PP or RT/CRT at our institution between January 2007 and October 2019. Overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival (LFS), and local relapse-free survival (LRFS) were evaluated. The main analyses were performed with inverse probability of treatment weighting (IPTW) adjustments. Sensitivity analyses compared hazard ratios (HRs) obtained with three models: unadjusted, multivariate Cox regression, and propensity score-adjusted. Overall, 198 patients were enrolled; 63 and 135 underwent PP and RT/CRT, respectively. IPTW-adjusted 5-year OS, DSS, LFS, and LRFS rates in the PP and RT/CRT groups were 84.3% and 61.9% (p = 0.019), 84.9% and 75.8% (p = 0.168), 94.8% and 90.0% (p = 0.010), and 75.9% and 74.1% (p = 0.789), respectively. In the IPTW-adjusted regression analysis, PP was associated with a significant benefit regarding OS (HR 0.48, 95% confidence interval [CI] 0.26-0.90) and LFS (HR 0.17, 95% CI 0.04-0.77). The results obtained with the three models in the sensitivity analyses were qualitatively similar to those of the IPTW-adjusted models. Despite the risk of bias related to unadjusted factors, our results suggest that PP is associated with significantly better OS and LFS compared with RT/CRT for HPSCC.

DACH1 regulates macrophage activation and tumour progression in hypopharyngeal squamous cell carcinoma.

Dachshund family transcription factor 1 (DACH1) has been shown to exhibit a tumour-suppressive role in a number of human cancers. However, the role of DACH1 in hypopharyngeal squamous cell carcinoma (HPSCC) and its function in the tumour microenvironment (TME) are still not clear. Crosstalk between cancer cells and tumour-associated macrophages (TAMs) mediates tumour progression in HPSCC. The expression of DACH1, CD86 and CD163 was detected in 71 matched HPSCC-non-cancerous tissue pairs using quantitative real-time polymerase chain reaction and IHC analysis. Cell proliferation, migration and invasion were monitored by colony formation, Transwell and EdU incorporation assays. ChIP-qPCR and dual-luciferase reporter assays were applied to verify the targeting relationships between DACH1 and IGF-1. Stably transfected HPSCC cells were co-cultured with MΦ macrophages to assess macrophage polarization and secretory signals. DACH1 was decreased in HPSCC tissues and was indicative of a poor prognosis for HPSCC patients. Decreased DACH1 expression in HPSCC was associated with fewer CD86+ TAMs and more CD163+ TAMs. Knockdown of DACH1 inhibited the proliferation, migration and invasion of FaDu cells via Akt/NF-κB/MMP2/9 signalling. Additionally, DACH1 was found to directly bind to the promoter region of IGF-1 to downregulate the secretion of IGF-1, which inhibited TAMs polarization through the IGF-1R/JAK1/STAT3 axis. Furthermore, in nude mice, the effects of DACH1 inhibition on tumour progression and M2-like TAMs polarization were confirmed. These findings suggest that IGF-1 is a critical downstream effector of DACH1 that suppresses cell migration and invasion and inhibits TAMs polarization. DACH1 could be a therapeutic target and prognostic marker for HPSCC.

The diagnostic combination of serum circulating miR-488 and lncRNA AC018761 as biomarkers for hypopharyngeal squamous cell carcinoma (HPSCC)

ObjectiveThe search for rapid and effective early diagnostic markers of hypotharyngeal carcinoma becomes particularly critical and important. Therefore, we explored the value of circulating expression of non-coding RNAs for the diagnosis of early hypotharyngeal cancer. MethodsAfter screening HPSCC-related research data in the NCBI-GEO database, the practical report extraction language (Perl) was used to give genes different biotype attributes. The R language limma package was utilized to analyze the differential expression of lncRNAs and mRNAs, respectively.The quantitative RT-PCR (Reverse transcription-polymerase chain reaction) analysis were performed to determine the plasma expression levels of non-coding RNAs ResultsCompared with the control groups, the differential expression of 137 lncRNAs and 297 mRNAs in the plasma of HPSCC patients was statistically significant. There were 32 differentially expressed lncRNAs, 19 differentially expressed mRNAs. The score of LncRNA AC018761 + miR-488 was AUC = 0.846, the best cut-off value was ≥ 40 points, the sensitivity was 74.58%, and the specificity was 79.88%. ConclusionOur results indicated that the over-expression of lncRNA-AC018761 and miR-488 were significantly up-regulated in serum of patients with HPSCC. Therefore, lncRNA-AC018761 and miR-488 maybe the non-invasive independent predictor for early HPSCC with high sensitivity and specificity.

Evaluating the prognostic significance of p53 and TP53 mutations in HPV-negative hypopharyngeal carcinoma patients: a 5-year follow-up retrospective study

PurposeTo evaluate prognostic significance of human papillomavirus (HPV) in hypopharyngeal squamous cell carcinoma patients, and to investigate the effect of p53 and TP53 mutations on the prognosis of patients.MethodsA total of 111 patients were enrolled in our retrospective study. HPV infection status was detected in formalin-fixed paraffin-embedded tissue by real-time multiplex PCR test. p53 expression was evaluate by immunohistochemical staining. TP53 exon mutations were analyzed by PCR amplification and Sanger sequencing. HPV infection status, p53 expression and TP53 mutation were compared with clinical outcome including overall survival and recurrence-free survival by Kaplan-Meier method and Log-rank test.ResultsOf the 111 investigated patients, 18 (16.22%) were positive for HPV infection. HPV(-) patients have a worse clinical outcome than HPV(+) patients. TP53 mutations have similar mutation rates in patients with and without HPV (55.56% vs. 41.94%). p53 and TP53 mutation were not associated with prognosis of patients in HPV(-) patients. TP53 disruptive mutations were found both in patients with or without HPV infection. Furthermore, TP53 non-disruptive mutation had a significantly better clinical outcome than those with disruptive mutation in HPV(-) patients.ConclusionOur results showed that HPV infection status is a strong prognostic indicator of survival. p53 and TP53 mutations do not appear to significantly impact survival in HPV(-) patients. TP53 disruptive mutation is associated with reduced survival in HPV(-)/TP53 mutation patients.

Updated racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous carcinoma in the United States.

This study was to determine the racial disparities in incidence, clinicopathological features and prognosis of hypopharyngeal squamous cell carcinoma (HPSCC) in the US. The National Program of Cancer Registries and Surveillance, Epidemiology, and End Results (SEER) database was used to determine racial disparity in age adjusted incidence rate (AAIR) of HPSCC and its temporal trend during 2004-2019. Using the separate SEER 17 database, we further evaluated racial disparity in clinicopathological features, and in prognosis using Kaplan-Meier curves and Cox proportional hazard models. HPSCC accounted for 95.8% of all hypopharyngeal cancers and occurred much more frequently in males. Its incidence decreased in both male and females, in male non-Hispanic white (NHW), non-Hispanic black (NHB) and Hispanic as well as female NHW and NHB during the study period. NHB had the highest, whereas non-Hispanic Asian or Pacific Islanders (API) had comparable and the lowest incidence in both males and females. Among 6,172 HPSCC patients obtained from SEER 17 database, 80.6% were males and 83.9% were at the advanced stages III/IV. Five-year cancer specific and overall survival rates were 41.2% and 28.9%, respectively. NHB patients were more likely to be younger, unmarried, from the Southern region, larger sized tumor, and at the stage IV, but less likely to receive surgery. They also had higher proportions of dying from HPSCC and all causes. Multivariate analyses revealed that NHB with HPSCC at the locally advanced stage had both significantly worse cancer specific and overall survival compared with NHW, but not at early stage (I/II) or distant metastatic stage. Hispanic patients had significantly better prognosis than NHW at locally advanced and metastatic stages. NHW and API had comparable prognoses. HPSCC displays continuously decreased incidence and racial disparity. The majority of the disease is diagnosed at the advanced stage. NHB have the highest burden of HPSCC and a worse prognosis. More studies are needed to curtail racial disparity and improve early detection.

A Survival Nomogram Containing Lymph Node Ratio for Hypopharyngeal Carcinoma Patients After Neck Dissection.

The purpose of our study is to establish a survival nomogram based on lymph node ratio (LNR) in hypopharyngeal carcinoma. Retrospective cohort study. Hypopharyngeal squamous cell carcinoma (HPSCC) is prone to regional metastasis. Emerging evidence has shown that LNR is a promising prognostic factor in HPSCC. From January 2004 to January 2018, 411 HPSCC patients who underwent neck dissection at our institution were retrospectively studied. The enrolled patients were divided into training and validation cohorts at a ratio of 7:3. A survival nomogram was finally built based on factors screened from multivariate analysis using the bidirectional stepwise method. LNR was superior to other nodal classifications for survival prediction and was used to establish the R classification. A nomogram was developed using R classification (p < .001), pT classification (p < .001), tumor invasive depth (p < .001), and internal jugular vein adhesion (p = .001). The C-indexes were 0.712 and 0.703 in the training and validation dataset. The 36- and 60-month AUCs were 0.767 and 0.766 in the training dataset and 0.713 and 0.757 in the validation dataset, respectively. The calibration curves showed relatively good agreement between the predicted and actual probability. Based on the LNR, we developed a survival nomogram for HPSCC after neck dissection, which will be a practical tool to discriminate patients with different survival risks.

Long Non-coding RNA Linc01224 Regulates Hypopharyngeal Squamous Cell Carcinoma Growth Through Interactions with miR-485-5p and IGF2BP3.

Increasing evidence illustrates that long non-coding RNAs (lncRNAs) play significant oncogenic roles, including hypopharyngeal squamous cell carcinoma (HSCC). The function and mechanism of long non-coding RNAs (lncRNAs) in hypopharyngeal squamous cell carcinoma (HSCC) have not been fully elucidated. Therefore, this study aimed to investigate the role of a specific lncRNA, linc01224, in regulating the miR-485-5p/IGF2BP3 axis in HSCC. We confirmed the lncRNA expression profiles in 5 pairs of HSCC and normal tissues by lncRNA sequencing. Another 28 HSCC tissues were further validated by quantitative real-time PCR (qRT-PCR). qRT-PCR was also used to detect the expression levels of linc01224, miR-485-5p and IGF2BP3 in HSCC cell lines. Next, functional experiments in vitro and in vivo were applied to determine the effects of linc01224 silencing on tumor proliferation, migration, apoptosis and progression in HSCC. Linc01224 expression was significantly higher in HSCC tissues than in adjacent normal tissues. In addition, HSCC patients with low IGF2BP3 expression had good survival. In vitro assays were mechanistically performed to explore whether linc01224 positively regulates IGF2BP3 expression via its competitive inhibition of miR-485-5p. An in vivo animal model also confirmed that linc01224 could promote the occurrence and development of HSCC. Our study first identified that linc01224 plays an oncogenic role in HSCC. It suggests that linc01224 may act as a prognostic biomarker and potential therapeutic target for HSCC.

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 (175mg/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 3months post treatment complete response (CR) at primary site was 83.3% and 66.6% (p = 0.245) in study and control arms respectively. At 6months 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.

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment

BackgroundTo cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies.Patients and MethodsFrom 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared.ResultsOne hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT.ConclusionsFor patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

Prognostic Nomogram for Postoperative Hypopharyngeal Squamous Cell Carcinoma to Assist Decision Making for Adjuvant Chemotherapy.

We aimed to investigate the effect of lymph node parameters on postoperative hypopharyngeal squamous cell carcinoma (HSCC) and to establish a nomogram to predict its prognosis and assist in adjuvant chemotherapy decisions. A retrospective analysis of postoperative HSCC in the Surveillance, Epidemiology, and End Results database (2004–2019) was performed. Cutoff points for continuous variables were determined by X-tile software. Univariate and multivariate analyses were performed to identify prognostic factors on overall survival (OS), and these variables were used to construct a nomogram. The nomogram’s accuracy was internally validated using concordance index, area under the curve, calibration plot, and decision curve analyses. Furthermore, the value of chemotherapy in each risk subgroup was assessed separately based on individualized scores from the nomogram. In total, 404 patients were eligible for analysis, and the median OS was 39 months. Age, origin, primary site, T stage, number of lymph nodes examined, lymph node ratio, and radiotherapy were identified as prognostic factors for OS and incorporated into the nomogram. In both the training and validation cohorts, favorable performance was exhibited compared with the other stage systems, and patients could be classified into low-, intermediate-, and high-risk subgroups. Chemotherapy significantly improved the OS in the high-risk subgroup, whereas chemotherapy did not confer a survival benefit in the low- or intermediate-risk groups. The lymph node parameter-based nomogram model can better stratify the prognosis of HSCC patients and screen out patients who would benefit from chemotherapy, suggesting that the model could be used as a reference for clinical decision making and to avoid overtreatment.