Advanced Hypopharyngeal Carcinoma Research Articles

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

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

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

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

Coiled tube of femoral anterolateral flap for repair of circumferential defect after operation of advanced hypopharyngeal carcinoma

Objective: To investigate the clinical application value of coiled tube of femoral anterolateral flap in the repair of circumferential defect after resection of advanced hypopharyngeal carcinoma. Methods: Clinical data of 42 patients with advanced hypopharyngeal cancer admitted to the Second Affiliated Hospital of Fujian Medical University from January 2016 to April 2022 were retrospectively analyzed, including 41 males and 1 female, aged from 33 to 82 years old. All patients received surgical treatment, including total laryngectomy plus total laryngopharyngectomy in 20 cases, total laryngectomy, total laryngopharyngectomy and resection of partial tongue base in 8 cases, total laryngectomy, total laryngopharyngectomy and resection of cervical esophagus in 9 cases, total laryngectomy, total laryngopharyngectomy, and resection of partial tongue base and cervical esophagus in 5 cases. The postoperative circumferential defects were repaired with the coil tube of anterolateral femoral skin flap in phase Ⅰ, and the healing status of the flap, wound healing and swallowing function were observed. All cases were followed up. Results: The lengths of the hypopharyngeal defects were 7-18 cm and the sizes of the harvested flaps were 6 cm×9.5 cm-10 cm×20 cm. Flaps survived in 41 cases, flap necrosis occurred in one case, and the survival rate of flaps was 97.6%. One artery and one vein were anastomosed in 40 cases, and one artery and two veins were anastomosed in 2 cases. Postoperative cervical wound infection occurred in 5 cases, and pharyngeal fistula occurred in 2 cases. Three months of follow-up after surgery, 31 cases had normal diet, 9 cases presented with semi-liquid diet and 2 cases with liquid diet. Following up for 6-65 months, recurrence and metastasis occurred in 14 patients (33.3%), including primary site recurrence in 4 cases (9.5%), cervical lymph node recurrence in 6 cases (14.3%), and distant metastasis in 4 cases (9.5%). The 1-year and 3-year overall survival rates were respectively 79.4% and 60.5%. Conclusion: Coiled tube of femoral anterolateral flap is an ideal skin flap for repair of circumferential defects after resection of advanced hypopharyngeal carcinoma.

Matched-pair analysis of the impact of low-dose postoperative radiotherapy on prognosis in patients with advanced hypopharyngeal squamous cell carcinoma without positive surgical margins and extracapsular extension.

We conducted a comparative analysis between low and high-dose postoperative radiotherapy in patients with hypopharyngeal squamous cell carcinoma (HPSCC) in stage III or IV without positive surgical margins and extracapsular extension (ECE). Propensity score matching (PSM) was used to eliminate confounding factors and reduce bias. The matched-pair analysis included 156 patients divided into two groups: the low-dose radiotherapy group (LD-RT 50 Gy, 78 cases) and the high-dose radiotherapy group (HD-RT 60 Gy, 78 cases). Both cohorts were statistically comparable in terms of age, gender, subsite, and TNM classification. The median follow-up time was 49 months (ranging from 5 to 100 months). The overall survival (OS) rate, progression-free survival (PFS) rate, locoregional control rate (87% vs. 85.7%; p = 0.754), distant metastases-free survival (79.2% vs. 76.6%; p = 0.506), and the occurrence of second primary tumors (96.1% vs. 93.5%; p = 0.347) showed no significant differences between the LD-RT group and the HD-RT group. The 3-year OS was 64.9% and 61% in the low-dose and high-dose group, respectively, and 63% in the entire group (p = 0.547). The 3-year PFS was 63.6% and 54.5% (p = 0.250), respectively, and the 3-year PFS of the entire group was 59.1%. Multivariate analyses revealed that pathological T and N classification, and pathological differentiation were associated with 3-year OS, PFS, and LRFS and were independent prognostic factors (p < 0.05). LD-RT was not associated with an increased risk of death and disease progression compared to HD-RT. The results of postoperative low-dose radiotherapy did not show inferiority to those of high-dose radiation for patients with advanced hypopharyngeal cancer without positive surgical margins and ECE in terms of OS, PFS, locoregional control, and metastases-free survival.

Significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma

Objective:To evaluate the clinical significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma. Methods:Patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were eligible. All received 2 cycles of pembrolizumab combined with docetaxel and platinum neoadjuvant induction therapy. After two cycles, the efficacy was evaluated, followed by radical chemoradiotherapy or surgery and adjuvant chemoradiotherapy according to the efficacy. The primary endpoints were objective response rate（ORR） ，larynx-preservation（LP） rate at 3 months post-treatment and the adverse reactions during neoadjuvant therapy. Results:From December 2021 to December 2022, 10 patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were enrolled. After 2 cycles of the neoadjuvant therapy, 2 patients achieved complete response（CR）, 7 patients achieved partial response（PR）, 1 patient was stable disease（SD）, objective response rate（ORR） was 90%, and disease control rate（DCR） was 100%. 5 patients received radical chemoradiotherapy, 5 patients received surgery and adjuvant chemoradiotherapy, four of them received partial laryngectomy and partial hypopharyngeal resection surgery, and one of them received total laryngectomy and partial hypopharyngeal resection surgery. All patients were able to withstand adverse reactions of neoadjuvant therapy and successfully completed the whole treatment of HPSCC without grade 3-4 treatment-related adverse reactions. There was no recurrence or metastasis during 3-18 months of follow-up. 1 patient died of severe pneumonia 3 months after the completion of radical chemoradiotherapy. At 3 months after treatment, the larynx-preservation rate was 80%. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy has good short-term efficacy and the adverse reactions were tolerable. It can improve the larynx-preservation rate of patients with locally advanced HPSCC, thus improving the prognosis and quality of life of patients.

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.

Tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery in locally advanced hypopharyngeal squamous cell carcinoma: A single-arm, phase II trial.

6087 Background: Induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) is the standard of care for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC). We aimed to assess whether add immunotherapy to ICT further improving patient outcomes. Methods: In this phase II, single-arm study, eligible pts aged 18-70 yrs diagnosed with stage III-IVB (AJCC 8th) HPSCC received induction therapy with tislelizumab (200 mg), cisplatin (75 mg/m2) and nab-paclitaxel (260 mg/m2) Q3W for 3 cycles. After assessment by multidisciplinary team, pts received surgery or CRT. The primary endpoint was objective response rate (ORR). Secondary endpoints include major pathologic response (MPR) in surgery group, disease control rate (DCR), 2-yr PFS rate in CRT group and 2-yr DFS rate. Results: 29 pts were enrolled (median age, 61 y; 97% male; stage III/IVA/IVB, 7%/90%/3%) from May to Nov 2022. Median follow-up was 7.3 months, no disease progression occurred in all patients. For all pts, the post-induction ORR and DCR were 82% and 100%. In surgery group (n = 10), all pts achieved R0 resection, and 5 (50%) pts reached pathological complete response (pCR). A patient with stable disease underwent a total laryngectomy achieved pCR by postoperative pathologic evaluation. Grade 3 and 4 treatment-related adverse event (TRAE) reached 82.8%, and mainly come from chemotherapy-related neutropenia. There was no TRAE leading to treatment discontinuation. Conclusions: These early data suggested that tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery was safe and had the potential to provide clinical benefits for patients in LA HPSCC. The inconsistency between radiographic and pathological evaluation needs further exploration. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200060094 .

Induction therapy of toripalimab combined with docetaxel and cisplatin in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC): A single-arm, phase II clinical trial.

6070 Background: PD-1 (programmed cell death protein-1) inhibitors combination with chemotherapy has a significant efficacy and approved indications in the first-line treatment of head and neck squamous cell carcinoma (HNSCC), but the efficacy of these combination therapies in locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) remains unexplored. We conducted a single-arm, phase II trial to assess the efficacy and safety of toripalimab (a novel PD-1 inhibitor) combined with chemotherapy as induction treatment in locally advanced HPSCC. Methods: Patients with locally advanced HPSCC (cT1N+M0 or T2-4NanyM0, AJCC 8.0) were eligible. All patients received 2 cycles of intravenous docetaxel (75mg/m2), cisplatin (75mg/m2) and toripalimab (240mg) on day 1 every 21 days, followed by radical surgery or concurrent chemoradiotherapy (CCRT) with cisplatin (100mg/m2, q21d). The primary endpoint was objective response rate (ORR) assessed by investigators per RECIST v1.1. Secondary endpoints were major pathologic response (MPR), 2 year disease-free survival (DFS) rate in patients received surgery, 2 year progression-free survival (PFS) rate in patients received CCRT and 2 year overall survival (OS) rate in all patients. Results: From July 2020 to January 2023, 34 patients (median age: 59, range: 46-72, male: 100%, stag IV: 100%) were enrolled. Patients with stage IVA an IVB disease were 19 (19/34, 55.9%) and 15 (15/34, 44.1%), respectively. 33 patients completed 2 cycles induction treatment and efficacy evaluation (1 patient dropped out). The evaluated ORR was 54.5%, including 3 pts achieving complete response and 15 achieving partial response. PD-L1 status (combined positive score, CPS) were known in 8 patients, ORR were 80% (4/5) and 66.7% (4/6) in patients with CPS≥20 and CPS≥1, respectively, 2 patients with CPS＜1 had stable disease. Treatment-related grade 3-4 adverse events occurred in 45.5% (15/33) of patients, leukopenia (42.4%) and neutropenia (3.1%). Immune-related AEs were acceptable, 1 patient (1/33, 3.0%) experienced grade 2 interstitial pneumonia and 2 patients (2/33, 6.1%) experienced grade 1 rash. In the following treatment, 27 patients (27/33, 81.8%) performed CCRT. 4 patients (4/33, 12.1%) underwent surgery followed by CCRT and 2 patients (2/33, 6.1%) refused further treatment. Among these 17 patients finished CCRT and radiological assessment, 9 patients (9/17, 52.9%) had complete response, 7 patients (7/17, 41.2%) had partial response and 1 patient (1/17, 5.9%) had progressive disease. Survival data are not mature by cut-off date. Conclusions: Induction therapy of toripalimab combined with docetaxel and cisplatin was well tolerated and highly efficient for locally advanced HPSCC. Clinical trial information: NCT04296747 .

Efficacy and safety of nab-paclitaxel+cisplatin/nedaplatin + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer.

e18050 Background: Targeted therapy and immunotherapy are efficacious treatment options for advanced head and neck cancer. However, the treatment of locally advanced hypopharyngeal carcinoma still consists of surgery, radiotherapy, and chemotherapy. Combining docetaxel, cisplatin (DDP), and 5-fluorouracil as standard induction chemotherapy provided opportunities for further surgical larynx preservation in some patients. This study retrospectively analyzed the short-term efficacy and adverse events of nab-paclitaxel + DDP/nedaplatin (NDP) + S-1 as an induction chemotherapy regimen for locally advanced hypopharyngeal cancer. Methods: The study included 22 patients with locally advanced hypopharyngeal cancer treated via induction chemotherapy at the Affiliated Hospital of Guilin Medical University from December 2020 to July 2022. Among these patients, 11 received nab-paclitaxel (125mg/m2, days 1 and 8) + DDP (35- 40mg/m2, days 1-2) or NDP (65-75mg/m2, day 1) + S-1 (30-40 mg/m2 bid, days 1-14) every 21 days for a total of three cycles. A baseline enhanced magnetic resonance imaging (MRI) of the head and neck was performed for all patients to confirm the presence of suspicious lesions. Another MRI was performed before the third cycle of induction chemotherapy to confirm the efficacy of the treatment regimen. Patients, who were responsive to the induction therapy, were allowed to choose their respective sequential therapy regimen. The response was assessed using RECIST v1.1. Adverse reactions were evaluated according to CTCAE5.0. Results: The response to treatment of the 11 patients was assessed by the investigators. There was one patient with a complete response (9.1%), eight patients with a partial response (72.7%), and two patients with stable disease (18.2%). The objective response rate was 81.8% (9/11), and the disease control rate was 100%. Five of the nine patients with a partial or complete response opted for surgery after three cycles of induction chemotherapy. The pathological complete response rate was 100% (5/5). The most common grade 3 treatment-emergent adverse events (TEAE) were leukopenia (45.5%), neurotoxicity (36.3%), and anemia (18.2%). Grade 4/5 TEAEs were not observed. Conclusions: Based on the results of this retrospective study, the nab-paclitaxel + DDP/ NDP + S-1 was a safe and viable induction chemotherapy regimen for locally advanced hypopharyngeal cancer. It allowed more options for subsequent treatment. Further research is warranted to validate the findings of this study. [Table: see text]

Developing a predictive nomogram and web-based survival calculator for locally advanced hypopharyngeal cancer: A propensity score-adjusted, population-based study.

Understanding the clinical features and accurately predicting the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) is important for patient centered decision-making. This study aimed to create a multi-factor nomogram predictive model and a web-based calculator to predict post-therapy survival for patients with LA-HPSCC. A retrospective cohort study analyzing Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for patients diagnosed with LA-HPSCC was conducted and randomly divided into a training and a validation group (7:3 ratio). The external validation cohort included 276 patients from Sichuan Cancer Hospital, China. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was used to identify independent factors associated with overall survival (OS) and cancer-specific survival (CSS), and nomogram models and web-based survival calculators were constructed. Propensity score matching (PSM) was used to compare survival with different treatment options. A total of 2526 patients were included in the prognostic model. The median OS and CSS for the entire cohort were 20 (18.6-21.3) months and 24 (21.7-26.2) months, respectively. Nomogram models integrating the seven factors demonstrated high predictive accuracy for 3-year and 5-year survival. PSM found that patients who received surgery-based curative therapy had better OS and CSS than those who received radiotherapy-based treatment (median survival times: 33 months vs 18 months and 40 months vs 22 months, respectively). The nomogram model accurately predicted patient survival from LA-HPSCC. Surgery with adjuvant therapy yielded significantly better survival than definitive radiotherapy. and should be prioritized over definitive radiotherapy.

Comprehensive prognostic modeling of locoregional recurrence after radiotherapy for patients with locoregionally advanced hypopharyngeal squamous cell carcinoma.

To propose and evaluate a comprehensive modeling approach combing radiomics, dosiomics and clinical components, for more accurate prediction of locoregional recurrence risk after radiotherapy for patients with locoregionally advanced HPSCC. Clinical data of 77 HPSCC patients were retrospectively investigated, whose median follow-up duration was 23.27 (4.83-81.40) months. From the planning CT and dose distribution, 1321 radiomics and dosiomics features were extracted respectively from planning gross tumor volume (PGTV) region each patient. After stability test, feature dimension was further reduced by Principal Component Analysis (PCA), yielding Radiomic and Dosiomic Principal Components (RPCs and DPCs) respectively. Multiple Cox regression models were constructed using various combinations of RPC, DPC and clinical variables as the predictors. Akaike information criterion (AIC) and C-index were used to evaluate the performance of Cox regression models. PCA was performed on 338 radiomic and 873 dosiomic features that were tested as stable (ICC1 > 0.7 and ICC2 > 0.95), yielding 5 RPCs and DPCs respectively. Three comprehensive features (RPC0, P<0.01, DPC0, P<0.01 and DPC3, P<0.05) were found to be significant in the individual Radiomic or Dosiomic Cox regression models. The model combining the above features and clinical variable (total stage IVB) provided best risk stratification of locoregional recurrence (C-index, 0.815; 95%CI, 0.770-0.859) and prevailing balance between predictive accuracy and complexity (AIC, 143.65) than any other investigated models using either single factors or two combined components. This study provided quantitative tools and additional evidence for the personalized treatment selection and protocol optimization for HPSCC, a relatively rare cancer. By combining complementary information from radiomics, dosiomics, and clinical variables, the proposed comprehensive model provided more accurate prediction of locoregional recurrence risk after radiotherapy.

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.

Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells.

Most of advanced hypopharyngeal squamous cell carcinoma (HSCC) are resistant to chemotherapy, and there is still lack of effective treatment for HSCC now. The present study aimed to investigate whether downregulation of RNA-binding motif protein 17 (RBM17) could enhance cisplatin sensitivity and inhibit cell invasion in HSCC and the underlying mechanism. We observed that RBM17 was upregulated in tumor tissues and associated with poor progression. Treatment of FaDu cells with cisplatin increased RBM17 expression in mRNA levels. Downregulation of RBM17 enhanced cisplatin-mediated inhibition of FaDu cells. In addition, downregulation of RBM17 effectively suppressed tumor cell migration and invasion through the reversion of epithelial-mesenchymal transition. Moreover, downregulation of RBM17 could significantly slow tumor growth in FaDu xenograft tumor model. Liquid chromatography-mass spectrometry/mass spectrometry detection and independent PRM analysis showed that 21 differentially expressed proteins were associated with the downregulation of RBM17. Taken together, our study implied that downregulation of RBM17 could serve as a novel approach to enhance cisplatin sensitivity in HSCC.

Retracted: Nursing Observation on the Clinical Efficacy and Toxicity of Lobaplatin Compared with Cisplatin in the Treatment of Locally Advanced Hypopharyngeal Carcinoma Based on Intelligent CT Imaging.

[This retracts the article DOI: 10.1155/2021/9982888.].

Dual-energy CT iodine map in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma: a preliminary study

Neoadjuvant chemotherapy has become one of the important means for advanced hypopharyngeal carcinoma. So far, there is no effective index to predict the curative effect. To investigate the value of iodine map of dual-energy computed tomography (CT) in predicting the efficacy of neoadjuvant chemotherapy for hypopharyngeal carcinoma. A total of 54 hypopharyngeal carcinomapatients who underwent two courses of TPF neoadjuvant chemotherapy were recruited in this study. Three cases had a complete response (CR), thirty-six cases had a partial response (PR), eleven cases had stable disease (SD), and four cases had a progressive disease (PD) after the chemotherapy. All patients underwent a dual-source CT scan before chemotherapy and rescanned after chemotherapy. The normalized iodine-related attenuation (NIRA) of the mean of maximum slice and most enhanced region of lesion at arterial and parenchymal phase were measured: NIRAmean-A, NIRAmax-A, NIRAmean-P, and NIRAmax-P, respectively. Correlation analysis was conducted between different metrics of NIRA and the diameter change rate of lesions, and the curative effect was evaluated based on the receiver operating characteristic (ROC) curve. There were a significant correlation between NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P and the change rate of lesion's maximum diameter (ΔD%) (all P < 0.01). The NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between CR, PR, SD, PD groups, but NIRAmean-A did not reach a significant difference. All NIRAmean-A, NIRAmax-A, NIRAmean-P, NIRAmax-P had significant differences between effective (CR + PR) and ineffective (SD + PD) groups. The ROC analysis revealed that NIRAmean-P had the largest AUC and prediction efficacy (AUC = 0.809). Dual-energy CT iodine map could predict the efficacy of neoadjuvant chemotherapy and provides imaging evidence to assist in treatment decisions for hypopharyngeal carcinoma patients.

Induction TPF followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locally advanced hypopharyngeal cancer: a preliminary analysis of a randomized phase 2 trial

PurposeConcurrent chemoradiotherapy (CCRT) is a standard treatment choice for locally advanced hypopharyngeal carcinoma. The aim of this study was to investigate whether induction chemotherapy (IC) followed by CCRT is superior to CCRT alone to treat locally advanced hypopharyngeal carcinoma.Methods and materialsPatients (n = 142) were randomized to receive two cycles of paclitaxel/cisplatin/5-fluorouracil (TPF) IC followed by CCRT or CCRT alone. The primary end point was overall survival (OS). The secondary end points included the larynx-preservation rate, progression-free survival (PFS), distant metastasis-free survival (DMFS), and toxicities.ResultsUltimately, 113 of the 142 patients were analyzed. With a median follow-up of 45.6 months (interquartile range 26.8–57.8 months), the 3-year OS was 53.1% in the IC + CCRT group compared with 54.8% in the CCRT group (hazard ratio, 1.004; 95% confidence interval, 0.573–1.761; P = 0.988). There were no statistically significant differences in PFS, DMFS, and the larynx-preservation rate between the two groups. The incidence of grade 3–4 hematological toxicity was much higher in the IC+ CCRT group than in the CCRT group (54.7% vs. 10%, P < 0.001).ConclusionsAdding induction TPF to CCRT did not improve survival and the larynx-preservation rate in locally advanced hypopharyngeal cancer, but caused a higher incidence of acute hematological toxicities.Trial registrationClinicalTrials.gov, number NCT03558035. Date of first registration, 15/06/2018.

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 impact of the number of metastatic lymph nodes after surgery in locally advanced hypopharyngeal cancer

BackgroundPostoperative chemoradiotherapy (CRT) is a standard therapy for patients with high-risk factors for head and neck squamous cell carcinoma, including positive margin and extra-nodal extension (ENE). However, the prognostic impact of the number of pathological metastatic lymph nodes (pLNs) in hypopharyngeal carcinoma (HPC) is unclear. Thus, this study aimed to investigate postoperative prognostic factors for locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) with a focus on the number of pLNs.MethodsWe retrospectively analyzed medical records of 99 consecutive patients with LA-HPSCC who underwent total pharyngo-laryngo-esophagectomy (TPLE) and bilateral neck dissection (ND) between December 2002 and May 2019.ResultsThe median follow-up time for all censored patients was 63.2 months. The median overall survival (OS) was 101.0 months (95% confidence interval [CI] 48.1–134.9). patients had pLNs ≥ 3. Forty-six (45.5%) patients were diagnosed with ENE. Twenty (20.2%) patients received postoperative CRT. The multivariate analysis revealed that pLNs ≥ 3 (median OS: 163.2 vs. 31.8 months, hazard ratio [HR] 2.39, 95% CI 1.16–4.94, p < 0.01) and ENE (median OS: 161.0 vs. 26.3 months, HR 4.60, 95% CI 2.26–9.36, p < 0.01) were significantly associated with poor prognosis and that postoperative CRT (HR 0.34, 95% CI 0.16–0.72, p < 0.01) was significantly associated with better prognosis. The cumulative incidence of distant metastasis was higher in patients with pLNs ≥ 3 than in those with pLNs < 3 (p < 0.01).ConclusionpLNs ≥ 3 and ENE were significant poor prognostic factors for patients with LA-HPSCC who underwent TPLE and bilateral ND.

Downregulation of S100A9 Reverses Cisplatin-Resistance and Inhibits Proliferation and Migration in Hypopharyngeal Carcinoma.

Purpose Patients with hypopharyngeal carcinoma (HPC) often progress to an advanced clinical stage at diagnosis. Cisplatin has been widely used in first-line chemotherapy for advanced HPC. However, acquired chemotherapeutic resistance leads to recurrence, metastasis, and a poor survival rate. Therefore, identifying new drug targets to improve treatment effects is still in need. Methods To screen the differential expression genes (DEGs) and proteins (DEPs), we conducted transcriptomic and proteomic analysis on cisplatin-sensitive cell lines (FaDu) and cisplatin-resistant cell lines (FaDu/DDP) of hypopharyngeal carcinoma. DEGs and DEPs, possibly the most associated with cisplatin-resistance, were verified by real-time polymerase chain reaction (RT-PCR) and western blot (WB), respectively, and the biological function of the screened S100A9 was further tested by CCK8, wound healing, and transwell assays. Results We identified S100A9 as a target for resensitizing the response to cisplatin in an acquired resistance model. S100A9 overexpression was significantly related to cisplatin resistance. Functional studies in vitro models demonstrated that downregulation of S100A9 overcame cisplatin-resistance and inhibited proliferation and migration. Later, we verified that downregulation of S100A9 suppressed the interleukin-6 (IL6) expression and epithelial-mesenchymal transition (EMT) pathway. Conclusion In all, S100A9 plays a crucial role in cisplatin-resistance, proliferation, and migration of HPC. Targeting S100A9 may become a novel strategy for the treatment of HPC.