[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

[Analysis of tumor regression after concurrent radiochemotherapy for locally advanced hypopharyngeal carcinoma].

Objective: To investigate the pathological characteristics of tumor regression and the expression level of chemoradiotherapy resistance-related molecular markers after preoperative concurrent radiochemotherapy in patients with locally advanced hypopharyngeal carcinoma. Methods: The clinical data of 44 patients with locally advanced hypopharyngeal carcinoma who underwent preoperative concurrent radiochemotherapy in the Department of Head and Neck Surgery of Shandong Otolaryngology Hospital from August 2016 to August 2020 were retrospectively analyzed. All patients received preoperative concurrent chemotherapy and radiotherapy. After radiochemotherapy, electronic laryngoscopy and imaging examination were performed to assess the tumor regression status. After 4 weeks, surgical resection was performed, and the specimens of the primary focus were processed as continuous pathological sections. After operation, HE staining and TdT-mediated dUTP nick-end labeling (TUNEL) method were used to detect the distribution characteristics and apoptosis of the remaining cancer focus, and immunohistochemistry was performed to determine the proliferation of the remaining cancer focus and the expression of radiation resistance-related molecular markers [signal transducer and activator of transcription 3 (STAT3), hypoxia-inducible factor-1alpha (HIF-1α), sex determining region Y-box 2 (SOX2), and P53]. Results: A total of 44 patients were included, all of whom were male, with a mean age of (58.3±3.5) years. There were 40 cases of pyriform sinus carcinoma and 4 cases of posterior pharyngeal wall carcinoma. Twenty-nine cases were in stage T3 and 15 cases were in stage T4. There were 6 stage Ⅲ cases and 38 stage Ⅳ cases. According to the response evaluation criteria in solid tumors (RECIST), 13 patients achieved complete response (CR), 22 patients had partial response (PR), and 9 patients achieved stable disease (SD) after concurrent radiochemotherapy. The primary lesion resection methods included 19 cases of hypopharyngeal circumferential resection and 2 cases of total laryngectomy and partial hypopharyngeal resection. Twenty-three cases underwent supracricoid cartilage subtotal laryngectomy cricoid tongue fixation (CHP). Among 22 patients with PR, 10 had large PR (remission rate ≥70%) and 12 had small PR (remission rate <70%). The residual tumor was found in 30 patients (68.2%) after resection of all primary lesions by HE staining of pathological sections, of which 3 patients (3/13) with CR had residual cancer, all of which were focal residues. In large PR patients, residual cancer was detected in 6 cases (6/10), scattered in 4 cases, and focal residual in 2 cases, respectively. Large residual tumors were detected in small PR and SD patients. TUNEL method did not show any sign of apoptosis in 30 specimens with residual cancer focus, and the positive expression rate of Ki-67 was less than 10%. The expression of STAT3 (3.40±2.49 vs 5.23±3.02, t=-2.932, P=0.007) in 19 cases (63.3%) and HIF-1α (3.73±2.66 vs 6.97±3.05, t=-4.45, P<0.001) in 22 cases (73.3%) of residual cancer were significantly higher than those before radiochemotherapy. Other molecular markers showed no significant changes. All patients were followed up for 3 years. The 2-year survival rate was 59.3%, and the 3-year survival rate was 54.1%. Conclusions: Preoperative radiochemotherapy can make some patients with locally advanced hypopharyngeal carcinoma achieve complete or significant remission in clinical evaluation, but pathological detection still shows some residual cancer lesions with enhanced anti-apoptosis ability and decreased proliferation activity.

Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial.

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

Laryngectomy plus postoperative radio(system)therapy versus primary radio(system) therapy for the treatment of locally advanced laryngeal and hypopharyngeal cancer - results from the University Clinical Cancer Registry Regensburg.

BACKGROUND: There are few adequate randomized clinical trials directly comparing the therapeutic options of primary laryngectomy (pLE) vs. primary radio(system)therapy (pR(S)T) in patients with locally advanced laryngeal and hypopharyngeal carcinoma and thus little clear scientific evidence to decide which patients will benefit most from which procedure. AIMS/OBJECTIVES: Aim was to compare survival between the therapeutic options and to learn from the limitations of this study, especially in the context of improved clinical assessment. MATERIAL AND METHODS: The clinical data of patients treated between January 2010 and February 2022 were obtained from the electronic database of the University Hospital Regensburg. Overall survival (OS) and progression-free survival (PFS) were compared between the treatment groups. RESULTS: The study included 193 patients (pLE n = 68, pR(S)T, n = 125). Median OS was 31.2 months and median PFS was 24.7 months with no significant difference between the treatment groups (p > .050). Patients who did not receive complete treatment as recommended by the tumor conference (n = 47, 24.4%) had a higher risk of death (p = .024). CONCLUSIONS AND SIGNIFICANCE: The results of our study are consistent with the survival data reported in the literature. More detailed systematic data in clinical routine (e.g. relevant comorbidities) are required to ensure guideline-based recommended therapy.

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

BACKGROUND: Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. METHODS: We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. RESULTS: 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). CONCLUSIONS: 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.

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.

Radiomics analysis for the prediction of locoregional recurrence of locally advanced oropharyngeal cancer and hypopharyngeal cancer.

PURPOSE: By radiomic analysis of the postcontrast CT images, this study aimed to predict locoregional recurrence (LR) of locally advanced oropharyngeal cancer (OPC) and hypopharyngeal cancer (HPC). METHODS: A total of 192 patients with stage III-IV OPC or HPC from two independent cohort were randomly split into a training cohort with 153 cases and a testing cohort with 39 cases. Only primary tumor mass was manually segmented. Radiomic features were extracted using PyRadiomics, and then the support vector machine was used to build the radiomic model with fivefold cross-validation process in the training data set. For each case, a radiomics score was generated to indicate the probability of LR. RESULTS: There were 94 patients with LR assigned in the progression group and 98 patients without LR assigned in the stable group. There was no significant difference of TNM staging, treatment strategies and common risk factors between these two groups. For the training data set, the radiomics model to predict LR showed 83.7% accuracy and 0.832 (95% CI 0.72, 0.87) area under the ROC curve (AUC). For the test data set, the accuracy and AUC slightly declined to 79.5% and 0.770 (95% CI 0.64, 0.80), respectively. The sensitivity/specificity of training and test data set for LR prediction were 77.6%/89.6%, and 66.7%/90.5%, respectively. CONCLUSIONS: The image-based radiomic approach could provide a reliable LR prediction model in locally advanced OPC and HPC. Early identification of those prone to post-treatment recurrence would be helpful for appropriate adjustments to treatment strategies and post-treatment surveillance.

[A Case of Hypopharyngeal Cancer Discovered after Recurrent Aspiration Pneumonia].

CASE: A 69-year-old man reported globus sensations since November X and was diagnosed with bilateral pneumonia in December at a local clinic. The patient was subsequently admitted to our hospital for a diagnosis and treatment. His pneumonia improved with antibiotics, but pneumonia recurred. However, pneumonia recurred in February X+1, and antibiotic treatment once again provided relief. However, globus sensations persisted even after the remission of pneumonia. Endoscopic observations revealed a tumor in the hypopharynx, which caused saliva aspiration into the insufficiently closed vocal cords. The hypopharyngeal cancer was treated with chemoradiotherapy, and thereafter, the frequency of aspiration pneumonia decreased. CONCLUSION: The present case illustrated that sometimes aspiration pneumonia may be caused by laryngeal and hypopharyngeal cancer.

Socioeconomic disparities in treatment and survival in patients with hypopharyngeal malignancy.

BACKGROUND: This retrospective study utilizes The Surveillance, Epidemiology, and End Results database to investigate socioeconomic factors leading to treatment disparities in hypopharyngeal malignancy. METHODS: Treatment was compared to National Cancer Care Network guidelines. Novel analyses, including logistic modeling, allowed survival analysis and identification of socioeconomic variables not previously considered in staging and management guidelines. RESULTS: Black and older patients, and residence in low-income areas predict lower likelihood of standard therapy (p < 0.05). Early-stage disease and standard therapy correlate with improved survival (p < 0.001). Medicaid, advanced age, advanced disease, and treatment outside of consensus guidelines correlated with lower survival (p < 0.0001). CONCLUSIONS: There are clear socioeconomic factors impacting treatment and survival in hypopharyngeal malignancies. Standard therapy affords superior survival rate. Black, low socioeconomic status, and older patients are less likely to receive standard therapy. Education and language isolation do not predict treatment or survival. Understanding these discrepancies is paramount to palliating disparities in healthcare.

[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.

[Efficacy of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion].

Objective: To analyze the treatment effects and side effects of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma invading cervical esophagus. Methods: A retrospective analysis was performed on sixty-six patients with locally advanced hypopharyngeal carcinoma invade the esophagus. These patients were treated in the Department of Otolaryngology, Head and Neck Surgery of Chinese People's Liberation Army General Hospital between January 2011 and May 2022, including sixty-five males and one female, aged 43-71 years. Treatment regimen consisted of induction chemotherapy and concurrent chemoradiothrapy and epidermal growth factor receptor (EGFR)-targeted therapy, three of these cases were treated with programmed cell death 1 (PD-1) immunotherapy. The Kaplan-Meier method was used for survival analysis. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 5.0 criteria. The factors affecting prognosis were analyzed by Cox multivariate regression analysis. Results: Sixty-four (97.0%, 64/66) patients completed the radiotherapy and chemotherapy plan. The most common grade three side effects were radioactive oropharyngeal mucositis (89.1%, 57/64) and leukopenia (23.4%, 15/64). Five (7.8%, 5/64) patients showed grade three hoarseness; two patients (3.1%, 2/64) suffered from grade three swallowing dysfunction and required feeding tube and intravenous nutrition; the remaining patients(89.1%) retained good vocal and swallowing functions. The overall survival (OS) of all patients was 81.5% after one year, 54.0% after three years, and 39.9% after five years; the progression-free survival (PFS) was 78.3% after one year, 54.9% after three years, and 42.6% after five years; local control rate (LCR) was 80.9% after one year, 62.5% after three years, and 52.0% after five years. T4a patients showed better OS, PFS and LCR than T4b patients, with statistically significant differences (χ2=8.10, 8.27, and 6.64, respectively, all P<0.05). Cox multivariate regression analysis showed that lymph node metastasis was an independent factor affecting prognosis (χ2=10.21, P<0.05). Conclusion: Non-surgical comprehensive treatment can provide with another option of radical treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion, offering the patients higher rate of larynx and esophageal preservation with tolerable side effects.

Bioengineering of a tumour-stroma 3D-tumouroid co-culture model of hypopharyngeal cancer.

Head and neck cancer (HNC) differs at anatomical sites and hypopharyngeal cancer (HPC) is a type of HNC. The non-surgical treatment option for advanced cases of HPC is radiotherapy (RT) with or without chemotherapy but survival is poor. Thus, new treatment approaches in combination with RT are essential. Yet, obtaining post-RT treated tumour specimens and lack of animal models with identical anatomical sites are the major translational research barriers. To overcome these barriers, for the first time, we have developed a tumour-stroma based in vitro three-dimensional (3D)-tumouroid co-culture model of HPC by growing FaDu and HS-5 cells together to mimic the complex tumour-microenvironment in a Petri dish. Before growing the cells together, imaging flow cytometry revealed distinct epithelial and non-epithelial characteristics of the cells. Growth rate of the 3D-tumouroid co-culture was significantly higher compared to the tumouroid monoculture of FaDu. Histology and morphometric analysis were done for the characterisation as well as the development of hypoxia was measured by CAIX immunostaining in this 3D-tumouroid co-culture. Taken together, this innovative in vitro 3D model of HPC resembles many features of the original tumour. The wider application of this pre-clinical research tool is in understanding newer combination (e.g. immunotherapy) treatment approaches with RT in HPC and beyond.

Integrated transcriptome study of the tumor microenvironment for treatment response prediction in male predominant hypopharyngeal carcinoma.

The efficacy of the first-line treatment for hypopharyngeal carcinoma (HPC), a predominantly male cancer, at advanced stage is only about 50% without reliable molecular indicators for its prognosis. In this study, HPC biopsy samples collected before and after the first-line treatment are classified into different groups according to treatment responses. We analyze the changes of HPC tumor microenvironment (TME) at the single-cell level in response to the treatment and identify three gene modules associated with advanced HPC prognosis. We estimate cell constitutions based on bulk RNA-seq of our HPC samples and build a binary classifier model based on non-malignant cell subtype abundance in TME, which can be used to accurately identify treatment-resistant advanced HPC patients in time and enlarge the possibility to preserve their laryngeal function. In summary, we provide a useful approach to identify gene modules and a classifier model as reliable indicators to predict treatment responses in HPC.

The Patients' Characteristics And Non-Surgical Treatment Results For Hypopharyngeal Cancer In Southeast Of Iran: A 13-Year Study.

BACKGROUND: Various modalities have been used to treat hypopharyngeal cancer. Non- surgical modalities include radiotherapy alone, sequential chemoradiation and concomitant chemoradiation or bio radiation. This study was conducted to evaluate the primary non-surgical treatment. METHODS: A total number of 67 patients treated from March 2009 to January 2022 were enrolled in this study. The 2-year and 5-year survival rates were estimated using the Kaplan-Meier method. Log-rank test was used to compare the survival outcomes according to various factors. To define independent prognostic factors, we used Cox regression analysis. RESULTS: The mean age of the patients was 56.2 years, and 55.2% of them were male. These patients were treated by radiation alone (9 patients) or induction chemotherapy followed by either radiation (4 patients), chemoradiation (33 patients), or bio-radiation (21 patients). The mean follow-up time was 18.12 months. The 2-year and 5-year overall survival rates were estimated to be 43% and 18%, respectively. Multivariate analysis showed that T stage, N stage, and treatment modality had a statically significant relationship with overall survival. CONCLUSIONS: The results of non-surgical treatment for hypopharyngeal cancer are not satisfactory. More studies are needed to investigate the role of salvage surgery.

Clinical Management of Early-Stage Hypopharyngeal Squamous Cell Carcinoma: A Single-Institution Clinical Analysis.

OBJECTIVE: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs. METHODS: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed. RESULTS: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively. CONCLUSIONS: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended.

Efficacy evaluation of different measurement methods for target lesions after neoadjuvant chemotherapy and radical radiotherapy in locally advanced hypopharyngeal carcinoma.

AIM: To assess the diagnostic efficacy in response evaluation of hypopharyngeal carcinoma (HPC) using different CT measurement methods. METHODS AND MATERIALS: One hundred and three patients with locally advanced HPC receiving neoadjuvant chemotherapy (NACT) and radical radiotherapy (RT) were retrospectively enrolled. The long diameter, short diameter and largest axial area of the tumors and the largest metastatic cervical lymph node (LN) were measured before and after NACT, at the end of RT and 1 month after RT. Tumor regression ratios of the sum of the tumor's long diameter and LN's short diameter (LDTSDL), the sum of tumor and LN's short diameter (TTSDL), the sum of tumor and LN's largest axial area (AATML) were calculated. Analysis was conducted for overall survival (OS), metastasis-free survival, regional recurrence-free survival (RRFS), and local recurrence-free survival (LRFS). RESULTS: Note that 35, 28, 23, and 16 patients suffered death, local recurrence, regional recurrence and distant metastasis, respectively. TTSDL-defined effective group demonstrated better LRFS (p = .039) and RRFS (p = .047) after NACT and better OS since the end of RT (p = .037); AATML-defined effective groups demonstrated better OS, LRFS, and RRFS since the end of RT (p = .015, .008, and .005). While LDTSDL-defined groups showed differences in OS and LRFS until 1 month after RT (p = .013 and .014). CONCLUSIONS: The regression rate of TTSDL and AATML can distinguish prognosis at an earlier time and demonstrated better reliability compared with LDTSDL. They were recommended for response evaluation in HPC.

Single-cell discovery of the scene and potential immunotherapeutic target in hypopharyngeal tumor environment.

Hypopharyngeal carcinoma is a cancer with the worst prognosis. We constructed the first single-cell transcriptome map for hypopharyngeal carcinoma and explored its underlying mechanisms. We systematically studied single-cell transcriptome data of 17,599 cells from hypopharyngeal carcinoma and paracancerous tissues. We identified categories of cells by dimensionality reduction and performed further subgroup analysis. Focusing on the potential mechanism in the cellular communication of hypopharyngeal carcinoma, we predicted ligand-receptor interactions and verified them via immunohistochemical and cellular experiments. In total, seven cell types were identified, including epithelial and myeloid cells. Subsequently, subgroup analysis showed significant tumor heterogeneity. Based on the pathological type of squamous cell carcinoma, we focused on intercellular communication between epithelial cells and various cells. We predicted the crosstalk and inferred the regulatory effect of cellular active ligands on the surface receptor of epithelial cells. From the top potential pairs, we focused on the BMPR2 receptor for further research, as it showed significantly higher expression in epithelial cancer tissue than in adjacent tissue. Further bioinformatics analysis, immunohistochemical staining, and cell experiments also confirmed its cancer-promoting effects. Overall, the single-cell perspective revealed complex crosstalk in hypopharyngeal cancer, in which BMPR2 promotes its proliferation and migration, providing a rationale for further study and treatment of this carcinoma.

Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment.

PURPOSE: Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. METHODS: We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. RESULTS: The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. CONCLUSIONS: The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.