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Objectives: Clinical extranodal extension (cENE) is a cN modifier in TNM-8 for laryngo-hypopharygeal carcinoma (LHC). We hypothesize that image-detected ENE (iENE) can provide additional prognostic value over cENE in LHC., Methods: Baseline CTs/MRIs of cN+ LHC patients treated with definitive (chemo-)radiotherapy between 2010-2019 were re-reviewed by a neuroradiologist using internationally accepted criteria for iENE-positive/negative (iENE+/iENE-). Overall survival (OS) was compared by iENE status. Multivariable analysis (MVA) was performed to confirm the prognostic value of iENE, adjusted for known potential confounders., Results: A total of 232 LHC patients were identified, including 154 iENE-/cENE-, 60 iENE+/cENE-, and 18 iENE+/cENE+. A higher proportion of iENE+ (vs iENE-) patients had lymph node (LN) size > 3 cm [53 (67 %) vs 4 (3 %)], >=5 LNs [51 (65 %) vs 33 (21 %)], and retropharyngeal LN [12 (15 %) vs 6 (4 %)] (all p < 0.01). Median follow-up was 4.8 years. iENE+/cENE- and iENE+/cENE+patients had similarly low 5-year OS [28 % (18-44) and 29 % (13-63)] vs iENE-/cENE- [53 % (45-62)] (p < 0.001). On MVA, mortality risk was higher with iENE+vs iENE- [hazard ratio (HR) 2.22 (95 % CI 1.47-3.36)]. The prognostic value of iENE remained with MVA in larynx (n = 124) (HR 2.51 [1.35-4.68], p = 0.004] or hypopharynx (n = 108) (HR 1.87 [1.02-3.43], p = 0.04) patients, separately., Conclusions: Our study confirms the independent prognostic importance of iENE for LHC following definitive (chemo-)radiotherapy beyond TNM-8 cN status that already contains the cENE parameter. Further research is needed to explore whether iENE could replace cENE for future cN classification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma., Methods: This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate., Results: This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control., Conclusion: This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database., Methods: All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses., Results: Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively)., Conclusions: Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT., (© 2024. Society of Surgical Oncology.)

Immune system biomarkers in cancer pathogenesis offer new therapeutic avenues, as seen in cytokine (CK) profiles of laryngeal and hypopharyngeal tumors. A retrospective analysis was conducted on 58 patients with laryngeal and hypopharyngeal tumors and 27 patients with benign vocal cord lesions to explore the role of serum CKs in these diseases' characteristics and immunotherapy. The differences in the levels of 12 cytokines were measured. Additionally, the study examined the correlation between T helper cells (Th)1/Th2 cytokine levels and the clinical characteristics and immunotherapy efficacy of laryngeal and hypopharyngeal cancers. The results show that the balance of Th1/Th2 is biased towards Th2 in patients with laryngeal and hypopharyngeal tumors. Among these, interleukin (IL)-6 (P = 0.021) was highly expressed in laryngeal tumors, and the expression levels of IL-1β (P = 0.008), IL-6 (P = 0.005), and IL-8 (P = 0.05) were higher in patients with poorly differentiated laryngeal tumors. The level of IL-4 (P = 0.0048) was significantly correlated with tumor location. The expression levels of IL-2 (P = 0.010), IL-4 (P = 0.028), IL-10 (P = 0.011), IL-12p70 (P = 0.034), IL-17 (P = 0.024), tumor necrosis factor (TNF)-α (P = 0.003), and interferon (IFN)-γ (P = 0.007) were related to lymph node metastasis. The level of IFN-γ (P = 0.016) was correlated with the efficacy of neoadjuvant therapy, while the level of IFN-α (P = 0.013) was significantly correlated with programmed death ligand 1 (PD-L1) expression. The Principal Component Analysis (PCA) results showed that patients with tumors, poor differentiation, and lymph node metastasis had higher levels of Th1 and Th2 cytokine separation. In conclusion, the shift in the balance of Th1 and Th2 cytokine expression indicates higher tumor invasiveness, and IFN has potential as a circulating molecular marker for immunotherapy of head and neck squamous cell carcinoma.

Part II of the S3 guideline report deals with the surgical treatment of hypopharyngeal carcinoma, neck dissection for oropharyngeal and hypopharyngeal carcinomas and adjuvant therapy options. Primary surgical therapy ± adjuvant radio- or radiochemotherapy and primary radio- or radiochemotherapy are established as primary therapies for local-regional hypopharyngeal carcinomas. Direct randomized comparisons of both basic therapeutic procedures were never conducted. Available registry data show a worse prognosis of hypopharyngeal carcinoma compared to oropharyngeal carcinomas in all locoregional tumor stages, regardless of the treatment method. For T1N0-T2N0 squamous cell carcinoma of the hypopharynx, there are no relevant differences in overall survival and locoregional relapse rate between primary surgical and primary non-surgical treatment. Primary surgical therapy ± adjuvant radiotherapy or radiochemotherapy and primary radiotherapy or radiochemotherapy are established as primary therapies for advanced but locoregionally limited hypopharyngeal carcinomas. Neck dissection is an integral part of the primary surgical treatment of oropharyngeal and hypopharyngeal cancer. There are only a few randomized studies on non-surgical organ preservation for advanced hypopharyngeal cancer as an alternative to pharyngolaryngectomy, but these have led to the recommendation of alternative concepts in the new guideline. The indication and implementation of postoperative adjuvant radiotherapy and radiochemotherapy for hypopharyngeal carcinoma do not differ from those for HPV/p16-negative and -positive oropharyngeal carcinoma., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: This study investigated the impacts of the number of positive lymph nodes (NPLN) and lymph node ratio (LN ratio) for patients with hypopharyngeal squamous cell carcinoma (HPSCC) based on SEER database, which were validated in the real-world data of China., Methods: A total of 520 patients from SEER database were analyzed. Then 195 patients with pathologically stage III or IV HPSCC in our center were retrospectively studied., Results: In the SEER database, NPLN ≥ 3 was found in 36.9% of patients. Multivariate analysis revealed that LN ratio ≥ 0.138 was significant with poorer overall survival (OS) (hazard ratio [HR] = 1.525, p = 0.001) and cancer-specific survival (CSS) (HR = 1.697, p < 0.001), so was the NPLN ≥ 3 (HR = 1.388, p = 0.013; HR = 1.479, p = 0.008). Patients with NPLN ≥ 3 were found in 103 (52.8%) in our center. Multivariate analysis confirmed a significant association regarding OS (p = 0.005) or CSS (p = 0.003) between patients with LN ratio ≥ 0.138 or not. In addition, disease recurrence rate differed significantly between the patients with NPLN ≥ 3 (27.2%) and NPLN < 3 (14.1%, p = 0.026). Moreover, postoperative chemoradiotherapy (CCRT) was significantly associated with better prognosis in patients with NPLN ≥ 3., Conclusion: In the SEER database, NPLN ≥ 3 and LN ratio ≥ 0.138 were independent poor prognostic factors for patients with HPSCC. Whereas identifying worldwide cut-off values for LN ratio is difficult and surgeon-dependent. In our cohort, adjuvant CCRT was beneficial for OS in patients with NPLN ≥ 3., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Despite advances in treatment, residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal squamous cell carcinoma (SCC) remain a challenge in clinical management and require accurate and timely detection for optimal salvage therapy. This study aimed to compare the diagnostic value of Fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC., Methods: A prospective study was conducted on 30 patients who presented with new symptoms after definitive (chemo) radiotherapy for laryngeal (n = 21) and hypopharyngeal (n = 9) carcinoma. Both 18 F-FDG PET/CT and DW-MRI were performed and histopathologic analysis served as the standard of reference., Results: Histopathology showed 20 patients as positive and 10 as negative for tumors. 18 F-FDG PET/CT detected all tumors correctly but was falsely positive in one case. DW-MRI detected tumors in 18 out of 20 positive patients and correctly excluded tumors in all negative patients. The sensitivity and specificity of 18 F-FDG PET/CT were 100% and 90%, respectively, while the values for DW-MRI were 90% and 100%, respectively., Conclusions: The study concludes that 18 F-FDG PET/CT is slightly superior to DW-MRI in detecting residual or recurrent tumors after definitive (chemo) radiotherapy for laryngeal and hypopharyngeal SCC. The combined use of 18 F-FDG PET/CT and DW-MRI can potentially improve specificity in therapy response evaluation., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objectives: To retrospectively investigate the pathological response rate, laryngeal preservation surgery (LPS) rate and progression free survival (PFS) of neoadjuvant chemoimmunotherapy in the treatment of locally advanced hypopharyngeal cancer (LAHPC)., Materials and Methods: In this study, LAHPC patients, who were first diagnosed and underwent surgery at the First Affiliated Hospital of Naval Medical University between January 2021 and January 2024, preoperatively administered PD-1 inhibitor and TP induction regimen (albumin-bound paclitaxel 260 mg/m 2 and cisplatin 80 mg/m 2 ). The primary endpoint was major pathological response (MPR), with ORR rate, LPS rate and PFS as the secondary endpoints. Then, the correlation between MPR and overall response rate (ORR) was further validated., Results: A total of 46 patients satisfied the inclusion criteria, with the median follow-up period of 10.5 months. After neoadjuvant chemoimmunotherapy, the ORR was observed to be 71.9 %, and the LPS rate reached 80.4 % (76.5 % in stage IV patients). The pathological response indicated a favorable response, with the MPR ratio at 52.2 % and pathological complete response (pCR) ratio at 32.6 %. The imaging score highly correlated with pathological response (Kappa = 0.058, P<0.001), while the MPR and ORR shared a strong positive linear relationship (r = 0.753, P<0.001). The 1-year and 2-year PFS rates were 97.1 % and 93.8 % for all patients, with stage IV patients having a 1-year PFS of 92.2 %. Patients who achieved MPR demonstrated a significant prognostic advantage (P=0.008), with no recurrence instances or mortality reported. Grade 3 adverse events were observed in 8.7 % of the cohort. The most common Grade 1-2 adverse events were alopecia, reactive telangiosis and loss of appetite, and no delayed surgery occurred., Conclusion: Neoadjuvant therapy of PD-1 inhibitor combined with TP effectively improved the MPR and LPS rates of LAHPC patients, especially in those at clinical stage IV., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Hypopharyngeal squamous cell carcinoma (HPSCC) has the poorest prognosis among head and neck cancers. Its treatment may significantly affect breathing, speaking, and swallowing. Induction chemotherapy (ICT) followed by transoral laser microsurgery (TLM) could reduce these adverse effects and achieve good outcomes., Methods: This was a retrospective study of 11 patients with advanced HPSCC. All patients underwent ICT and TLM alongside tailor-made adjuvant therapy based on the pathological features., Results: Adjuvant therapy was done in seven of 11 patients (64%). The 3-year disease-free survival and laryngeal preservation rates were 78% and 91%, respectively. At the last follow-up, 10 of 11 patients (91%) had no tracheostomy or feeding tube., Conclusion: ICT followed by TLM is an appropriate treatment for good tumor control in select patients with advanced HPSCC while preserving laryngeal function., Competing Interests: Conflicts of interest: Dr. Muh-Hwa Yang, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Purpose: Laryngeal and Hypopharyngeal Carcinomas (LC/HPC) constitute about 24 % of head and neck cancers, causing more than 90,000 annual deaths worldwide. Diffusion-Weighted Imaging (DWI), is currently widely studied in oncologic imaging and can aid in distinguishing cellular tumors from other tissues. Our objective was to review the effectiveness of DWI in three areas: diagnosing, predicting prognosis, and predicting treatment response in patients with LC/HPC., Methods: A systematic search was conducted in PubMed, Web of Science, and Embase. A meta-analysis by calculating Standardized Mean Difference (SMD) and 95 % Confidence Interval (CI) was conducted on diagnostic studies., Results: A total of 16 studies were included. All diagnostic studies (n = 9) were able to differentiate between the LC/HPC and other benign laryngeal/hypopharyngeal lesions. These studies found that LC/HPC had lower Apparent Diffusion Coefficient (ADC) values than non-cancerous lesions. Our meta-analysis of 7 diagnostic studies, that provided ADC values of malignant and non-malignant tissues, demonstrated significantly lower ADC values in LC/HPC compared to non-malignant lesions (SMD = -1.71, 95 %CI: [-2.00, -1.42], ADC cut-off = 1.2 × 10 3  mm 2 /s). Furthermore, among the studies predicting prognosis, 67 % (4/6) accurately predicted outcomes based on pretreatment ADC values. Similarly, among studies predicting treatment response, 50 % (2/4) successfully predicted outcomes based on pretreatment ADC values. Overall, the studies that looked at prognosis or treatment response in LC/HPC found a positive correlation between pretreatment ADC values in larynx/hypopharynx and favorable outcomes., Conclusion: DWI aids significantly in the LC/HPC diagnosis. However, further research is needed to establish DWI's reliability in predicting prognosis and treatment response in patients with LC/HPC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cutaneous metastases from squamous cell carcinomas of the head and neck region are uncommon, and their location at the nasal tip is exceptionally rare. A patient, previously treated with surgery and chemoradiation for a hypopharyngeal squamous cell carcinoma, developed several red nodular skin lesions at the nasal tip. Biopsy revealed cutaneous metastasis from the primary tumor. This manifestation was previously described as a "clown nose," given their appearance and location. Skin lesions should raise suspicion of malignancy, despite their location at uncommon places, particularly in patients with previous diagnosed cancer. Clinicians must be aware that metastases from head and neck cancer can present as a "clown nose.", Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024 Wiley Periodicals LLC.)

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.

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.

Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2 ) and cisplatin (60 mg/m 2 ) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI : 74.0% to 94.8%) and 50.3% (95% CI : 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI : 88.9% to 100.0%) and 58.2% (95% CI : 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI : 74.2% to 94.9%) and 53.5% (95% CI : 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

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/m 2 d1, cisplatin 25 mg/m 2 d1-3, and capecitabine 800 mg/m 2 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., (© 2024. The Author(s).)

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.

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© 2024. The Author(s) under exclusive licence to Japan Human Cell Society.)

Importance: The management of hypopharyngeal squamous cell carcinoma (HPSCC) continues to be one of the most formidable challenges in the realm of head and neck oncology., Objectives: The aim of this meta-analysis was to evaluate the disparity in survival outcomes between upfront surgery and upfront concurrent chemoradiotherapy as the primary treatment modality in patients with HPSCC., Design: Systemic review with meta-analysis., Setting: The meta-analysis was conducted in strict accordance with the PRISMA guideline. A literature search through PubMed, EMBASE, and the Cochrane Library were conducted until January 2023. The adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled., Participants: Studies that incorporated HPSCC patients without receiving induction chemotherapy., Interventions: Upfront surgery versus upfront concurrent chemoradiotherapy., Main Outcome Measures: Overall survival (OS) and disease-free survival (DFS)., Results: Eight studies published between 2015 and 2023, with a pooled patient population of 1619, were included in this meta-analysis. The outcomes reveal that upfront surgery was notably linked with improved OS (aHR 0.66, 95% CI 0.57-0.78) and DFS (aHR 0.75, 95% CI 0.63-0.90). Subgroup analyses were conducted to investigate the impact of the overall stage of the tumor and the extent of surgery on OS. In patients with advanced HPSCC (stages III and IV), upfront surgery remained associated with better OS (aHR 0.65, 95% CI 0.56-0.77). Concerning the extent of surgery, both subgroups exhibited a superior OS outcome associated with upfront surgery (exclusive total laryngopharyngectomy group: aHR 0.54, 95% CI 0.39-0.75; total/partial laryngopharyngectomy group: aHR 0.71, 95% CI 0.59-0.84)., Conclusions and Relevance: The results demonstrated that upfront surgery showed better OS and DFS than concurrent chemoradiation and remind the clinicians of the potential reduction in survival outcomes when choosing concurrent chemoradiotherapy as primary treatment., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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.

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., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

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 (χ 2 =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 (χ 2 =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.

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.

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., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

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., (© 2023. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (© 2022 John Wiley & Sons Australia, Ltd.)

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.

Several studies have reported the value of neutrophil-to-lymphocyte ratio (NLR) for the prognosis of hypopharyngeal cancer. However, contradictory findings have also been published. We aimed to clarify the effect of NLR on the prognosis of hypopharyngeal cancer through meta-analysis. Systematic search of PubMed and other database with study selection and data extraction. The combined hazard ratio (HR) and 95% confidence intervals (CI) were calculated using STATA, applying either a fixed-effects or random-effects model. Meta-regression, subgroup analysis, and sensitivity analysis were used to analyze sources of heterogeneity. Publication bias were also assessed. This meta-analysis included 2232 patients with hypopharyngeal cancer from seven studies. The combined HR (OS, HR = 1.80, 95CI%, 1.14-2.82; PFS, HR = 1.88, 95CI%, 1.26-2.79) suggested that high NLR was associated with poor overall survival (OS) and progression-free survival (PFS). Pretreatment NLR can be used as an effective serological indicator to assess the prognosis of patients with hypopharyngeal cancer., (© 2022 Wiley Periodicals LLC.)

Background: The role of the Human Papillomavirus (HPV) status in patients with hypopharyngeal squamous cell carcinoma (HSCC) remains controversial., Objective: Our aim was to determine the prognostic and predictive effects of HPV status in patients with locally advanced HSCC (stage III-IVB) receiving primary radiotherapy., Methods: Patients diagnosed with stage III-IVB HSCC between 2010 and 2016 were identified. HPV status, demographics, clinicopathological characteristics, treatment, and survival data were captured. Kaplan-Meier analysis, multivariable Cox regression analysis, and propensity score matching analysis were performed., Results: We identified 531 patients in this study and 142 (26.7%) patients with HPV-positive diseases. No significant differences were observed between those with HPV-negative and HPV-positive diseases with regard to demographics, clinicopathological characteristics, and chemotherapy use. HPV-positive HSCC had better head and neck cancer-specific survival (HNCSS; P=.001) and overall survival (OS; P<.001) compared to those with HPV-negative tumors. Similar results were found using the multivariable Cox regression analysis. Sensitivity analyses showed that the receipt of chemotherapy was associated with significantly improving HNCSS (P<.001) and OS (P<.001) compared to not receiving chemotherapy in HPV-negative HSCC, whereas comparable HNCSS (P=.59) and OS (P=.12) were found between both treatment arms in HPV-positive HSCC. Similar results were found after propensity score matching., Conclusions: Approximately one-quarter of HSCC may be HPV-related, and HPV-positive HSCC is associated with improved survival outcomes. Furthermore, additional chemotherapy appears to be not related to a survival benefit in patients with HPV-positive tumors who received primary radiotherapy., (©Shi-Ping Yang, Xiang-Ying Lin, Min Hu, Cheng-Fu Cai. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 16.12.2022.)

Purpose: This study aimed to identify whether the platelet-to-lymphocyte ratio (PLR) correlated with the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) undergoing radiotherapy combined with chemotherapy., Methods: This study enrolled 103 patients diagnosed with LA-HPSCC and treated with radiotherapy combined with chemotherapy between 2008 and 2021. The optimal PLR cut-off value was chosen from the receiver operating characteristic (ROC) curve analysis. According to the cut-off value of PLR, patients were divided into two groups: a low PLR group (< 133.06) and a high PLR group (≥ 133.06). Propensity score matching (PSM) was used to balance the confounding factors between the two PLR groups. Univariate and multivariate Cox proportional hazard regression models, the Kaplan-Meier curve by the log-rank test, and univariate and multivariate Fine-Gray competing risk models were all used for assessment., Results: After PSM, 27 pairs were left, and the high PLR group correlated with higher local failure (sHR 6.91, 95% CI 2.14-22.35, p = 0.001) in the multivariate Fine-Gray competing risk model. Moreover, the low PLR group had a significantly longer 3-year progression-free survival (43.7% vs. 29.2%, p = 0.038) and overall survival (55.1% vs. 32.1%, p = 0.034) than the high PLR group had. Multivariate Cox analysis showed that a low PLR was an independent protective factor for PFS (HR 0.43, 95% CI 0.21-0.92, p = 0.019) and OS (HR 0.46, 95% CI 0.22-0.96, p = 0.039) in patients with LA-HPSCC., Conclusion: Pretherapy PLR might be a factor in predicting the risk of local failure and survival in LA-HPSCC patients undergoing radiotherapy combined with chemotherapy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Concurrent 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 Materials: Patients (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., Results: Ultimately, 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)., Conclusions: Adding 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 Registration: ClinicalTrials.gov , number NCT03558035. Date of first registration, 15/06/2018., (© 2022. The Author(s).)

Laryngeal preserving concurrent chemoradiation has been advocated for hypopharyngeal cancers. The use of radiotherapy (RT) in the larynx could lead to increased rates of radionecrosis. In this study, we investigated a rare but disastrous complication, carotid blow-out syndrome (CBS), related with the persistent radionecrosis. Retrospective cohort study. This retrospective study enrolled hypopharyngeal cancer patients with biopsy-proven pharyngeal and laryngeal chondronecrosis (PLCRN), which was rated by the Chandler Grading System. From 2002 to 2018, a total of 346 hypopharygeal cancer patients received upfront radiation therapy, 13 PLCRN patients were identified in a rate of 3.8%. All PLRN patients received RT with a mean radiation dose of 70.81 ± 0.85 Gy. All patients had Chandler Grade IV at the time of presentation, which was a mean of 15.08 months (range: 5-109 months) from the time of cancer diagnosis to PLCRN diagnosis. In 5 of the 13 PLCRN patients developed CBS. Three of the CBS originated from superior thyroid artery, one from lingual artery and one from the carotid artery. Three (60%) of the 5 CBS patients expired due to loss of airway and hemodynamic instability. Two (40%) were rescued by emergent airway secure and emergent angiographic embolization. Persistent PLCRN could lead to disastrous vascular complications. CBSs were demonstrated to be more frequently originated from the branches of carotid artery rather than carotid artery per se. Clinical alert with early airway protection could strive for time to do interventions and prevent mortalities., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Surgery is the recommended treatment for resectable T 4 a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients., Method: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T 4 a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes., Results: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment., Conclusion: Surgery is the preferred treatment for T 4 a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC., Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score)., Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<-0.16) was associated with improved PFS ( p < 0.05)., Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

Nivolumab administration to patients with organ transplantation history requires careful management. Herein, we report the case of a living-donor liver-transplant recipient, a 52-year-old man, with recurrent and metastatic hypopharyngeal cancer treated with nivolumab. He was diagnosed with T2N2bM0 stage IVA hypopharyngeal squamous cell carcinoma. While using oral immunosuppressants (cyclosporine and mycophenolate mofetil), the patient underwent right neck dissection followed by radiotherapy as an initial treatment. Three months after radiotherapy, positron emission tomography scans revealed multiple bone metastases. We administered two courses of the EXTREME regimen, comprising cisplatin, 5-fluorouracil, and cetuximab, as the first-line treatment for distal metastasis, but the patient presented with progressive disease. The patient was administered nivolumab as the second-line treatment. The programmed death-ligand 1 (PD-L1) expression level in a biopsy specimen of the primary hypopharyngeal tumor and resected specimen of the cervical lymph node metastasis was 40% and 10%, respectively. PD-L1 expression was not detected in hepatocytes of the liver biopsy sample obtained before nivolumab introduction. The patient received four courses of nivolumab 240 mg. Although liver dysfunction was alleviated by adjusting the dose of the hepatoprotective agent and cyclosporine, the progressive disease status persisted after completing nivolumab courses. The patient died of hypopharyngeal cancer progression., Competing Interests: Declaration of Competing Interest K. Tsukahara has received grant support from Ono Pharmaceutical Co., Ltd. Other Authors have no potential conflicts of interest or financial relationships to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy., Methods: All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis., Results: A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes., Conclusion: In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Patients with locally advanced laryngeal and hypopharyngeal cancer (LHC) are often treated with chemo-radiotherapy to avoid total laryngectomy, although voice problems may occur even if not markedly manifest. We sought to evaluate the impact of chemoradiation on voice and quality of life., Methods: We studied 21 patients with locally advanced LHC with tumour control at least two years after chemo-radiotherapy. None manifested clinical symptoms related to the treatment and maintained an activity considered as within normal limits. All patients had a voice handicap index (VHI) of less than 15. Voice function was evaluated by perceptual vocal analysis (CAPE-V) and aerodynamic and acoustic study. Quality of life was assessed with the EORTC-H&N35 (voice items 46, 53 and 54)., Results: Voice changes were frequent, with alterations in all CAPE-V attributes, and predominantly type II and III spectrograms in acoustic analysis (78%). The EORTC-H&N35 scale showed a reduction in scores in 10-40% of items related to voice., Conclusions: Subclinical voice disorders are common after chemo-radiotherapy. Although patients consider vocal impairment to be very minor and to not interfere with their daily life, it may contribute to a reduced quality of life., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: There is increasing evidence that locoregional treatment (LRT, surgery or/and radiotherapy) for the primary tumor can improve survival in some cancers with systemic dissemination. This study aimed to investigate the survival benefit of LRT and prognostic factors in patients with hypopharyngeal cancer with distant metastasis., Methods: A retrospective population-based analysis was performed using the Surveillance, Epidemiology, and End Results database. Cox regression analysis was used to account for the imbalance of baseline covariates. The Kaplan-Meier method, log-rank test, and competing risk analysis were used to compare survival outcomes between treatment patterns., Results: Four hundred and sixty-three eligible patients were included in the analysis with a median overall survival of 7 months. LRT plus systemic therapy was the most common treatment modality (47%) and was associated with the most prolonged survival compared with other treatment methods (log-rank test, P<0.001). In multivariate analysis, bone metastasis, liver metastasis, and treatment were identified as independent prognostic factors for survival. Patients receiving LRT and systemic therapy had a 35% reduced risk of death compared with patients receiving systemic therapy (HR =0.65, 95% CI: 0.39-0.92, P=0.028). Further subgroup analysis and competing risk analysis also confirmed this survival trend favoring LRT and systemic therapy. Interestingly, interaction analysis revealed that only age variable affected the treatment effect and younger patients (<65 years) were more likely to benefit from LRT plus systemic therapy., Conclusions: Our results suggest that bone metastasis, liver metastasis, and treatment were prognostic factors for the survival of patients with metastatic hypopharyngeal cancer. Patients with distant metastasis are often treated with systemic therapy for a palliative intention. In our work, LRT plus systemic therapy was associated with improved survival compared with systemic therapy alone in selected patients. Particularly, patients younger than 65 years may be the potential subpopulation that can benefit from LRT with improved survival.

Purpose: This study aimed to identify the clinical characteristics of hypopharyngeal squamous cell carcinoma (HPSCC) patients with multiple primary cancers (MPCs) and to compare differences between patients with metachronous and synchronous MPCs., Material and Methods: This study included 219 patients with HPSCC treated at our center between 2008 and 2020; the clinical characteristics and prognosis of 66 patients with MPCs were analyzed. Propensity score matching (PSM) was used to balance the factors between patients with synchronous and metachronous MPCs., Results: Sixty-six patients with HPSCC (66/219, 30.1%) experienced MPCs, of which 29 were synchronous and 37 were metachronous. The esophagus (n = 39, 59.1%), lung (n = 10, 15.2%), and oropharynx (n = 4, 6.1%) were the three most common sites of MPCs in both the synchronous and metachronous groups. More patients with synchronous MPCs were stage T1-2 (82.8% vs. 59.5%, P = 0.041) compared to those with metachronous MPCs. Among the 24 pairs of patients after PSM, patients with metachronous MPCs had higher 3-year progression-free survival (PFS) (52.5% vs. 16.3%, P < 0.001) and overall survival (OS) (58.5% vs. 22.1%, P = 0.001) than those with synchronous cancers. Multivariate Cox analysis showed that patients with synchronous MPCs had shorter PFS (HR 4.45, 95% CI 1.819-10.885, P = 0.001) and OS (HR 3.918, 95% CI 1.591-9.645, P = 0.003)., Conclusion: MPCs are common among patients with HPSCC, and patients with metachronous MPCs had better survival than those with synchronous MPCs. Clinicians should be aware of the possibility of MPCs in patients with HPSCC and optimize treatment to improve outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Importance: Laryngeal preservation strategies for resectable locally advanced hypopharyngeal carcinoma (LAHPC) have been explored. However, the optimal strategy remains unclear., Objective: To evaluate a response-adapted strategy based on an early response to radiotherapy (RT) in patients with resectable LAHPC., Design, Setting, and Participants: This cohort study was conducted from May 2009 to October 2019 with a median (IQR) follow-up period of 66.5 (44.7-97.0) months. The study was conducted at a tertiary academic medical center and included 423 patients pathologically confirmed stage III and IVB LAHPC. A total of 250 patients with previous cancer history, synchronous primary cancer, stage I or II, or with unresectable hypopharyngeal carcinoma were excluded., Exposures: Patients who reached 80% or greater tumor regression when evaluated endoscopically and by imaging methods at 50 Gy received definitive RT or concurrent chemoradiotherapy, and those with less than 80% regression underwent surgery 4 to 6 weeks after RT., Main Outcomes and Measures: Five-year overall survival and survival with a functional larynx., Results: Overall, 423 patients were included in the study (median [IQR] age, 55 [50-63] years; 408 [96.5%] men and 15 [3.5%] women). The response-adapted and primary surgery groups had significantly better survival than the primary RT group (52.7% and 54.4% vs 27.7%, respectively; P < .001). The response-adapted and primary surgery groups had similar 5-year overall survival of 52.7% vs 54.4%, respectively (hazard ratio [HR], 1.02; 95% CI, 0.75 to 1.39; P = .89). The response-adapted group had better 5-year survival with functional larynx than the primary surgery group (40.6% vs 33.9%; HR, 0.64; 95% CI, 0.49 to 0.84, P = .001). Surgery complications did not significantly differ between the 2 groups. Among patients in the response-adapted group who required total laryngectomy (n = 186) as indicated by pretreatment evaluation, the 5-year cumulative Kaplan-Meier survival with functional larynx was 39.8%., Conclusions and Relevance: In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, maximum tumor control, and higher laryngeal preservation compared with primary surgery and primary RT strategies. This approach could provide a feasible laryngeal preservation strategy in patients with LAHPC.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy for hypopharynx. Intensity-modulated radiotherapy is the gold standard treatment for hypopharynx cancers. Early T1 and T2 tumors could be treated by exclusive radiotherapy or surgery followed by postoperative radiotherapy in case of high recurrence risk. For locally advanced tumours requiring total pharyngolaryngectomy (T2 or T3) or with significant lymph nodes involvement, induction chemotherapy followed by exclusive radiotherapy or concurrent chemoradiotherapy were possible. For T4 tumour, surgery must be proposed. The treatment of lymph nodes is based on initial primary tumour treatment. In non-surgical procedure, for 35 fractions, curative dose is 70Gy (2Gy per fraction) and prophylactic dose are 50 to 56Gy (2Gy per fraction in case of sequential radiotherapy or 1.6Gy in case of integrated simultaneous boost) radiotherapy; for 33 fractions, curative dose is 69.96Gy (2.12Gy per fraction) and prophylactic dose is 52.8Gy (1.6Gy per fraction in integrated simultaneous boost radiotherapy or 54Gy in 1.64Gy per fraction); for 30 fractions, curative dose is 66Gy (2.2Gy per fraction) and prophylactic dose is 54Gy (1.8Gy per fraction in integrated simultaneous boost radiotherapy). Doses over 2Gy per fraction could be done when chemotherapy is not used regarding potential larynx toxicity. Postoperatively, radiotherapy is used in locally advanced cancer with dose levels based on pathologic criteria, 60 to 66Gy for R1 resection and 54 to 60Gy for complete resection in bed tumour; 50 to 66Gy in lymph nodes areas regarding extracapsular spread. Volume delineation were based on guidelines cited in this article., (Copyright © 2021. Published by Elsevier Masson SAS.)