Surgical efficacy of locally advanced hypopharyngeal carcinoma after neoadjuvant immunotherapy

Surgical efficacy of locally advanced hypopharyngeal carcinoma after neoadjuvant immunotherapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Surgical efficacy of locally advanced hypopharyngeal carcinoma after neoadjuvant immunotherapy Lifei Feng, Wen Gao, Gaofei Yin, Wei Guo, Qi Zhong, Xiaohong Chen, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6246307/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objectives : This study aimed to explore the clinical efficacy of neoadjuvant immunotherapy in locally advanced hypopharyngeal carcinoma, and to assess the application value of minimally invasive treatment after tumour downstaging. Methods :The clinical data of 73 patients with locally advanced hypopharynx squamous carcinoma were retrospectively analysed.These patients received neoadjuvant immunotherapy at Tongren Hospital, Beijing, China, from January 2022 to September 2024. Statistical analyses were performed to determine the efficacy of the chemotherapy, adverse reactions, the choice of the subsequent therapeutic modalities, and prognosis of the patients. Results : 73 patients were included in this study. They all received 2 cycles of neoadjuvant immunotherapy and were evaluated by imaging after the end of treatment. Response was assessed as complete remission(CR) in 17 patients, partial response(PR) in 40, stable disease(SD) in 14, and progressive disease(PD) in 2. The overall disease control rate (DCR) was 97.3% and objective remission rate (ORR) was 78.1%. 44 patients did not receive surgical treatment, including 11 patients continued chemotherapy and 33 patients treated with radiotherapy after pathological complete remission (pCR). 29 patients received surgical treatment. The laryngeal preservation rate was 88.7%. Minimally invasive and open laryngeal function-preserving surgeries did not show significant differences in progression-free survival (PFS) and overall survival (OS) (P > 0.05). But there were statistically significant differences in the recovery of respiratory function and vocal function (P < 0.05). Conclusions :Neoadjuvant immunotherapy has demonstrated high efficacy and a good safety profile in patients with locally advanced hypopharyngeal squamous cell carcinoma. Transoral minimally invasive therapy provides an effective treatment strategy for patients with locally advanced hypopharyngeal carcinoma who responded well to neoadjuvan chemotherapy. locally advanced hypopharyngeal squamous cell carcinoma Neoadjuvant immunotherapy Minimally Invasive treatment Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Hypopharyngeal carcinoma (HPC) is a rare malignant tumour whichoriginates from the hypopharynx. HPC accounts for 0.15–0.24% of systemic malignant tumours and 2–4% of head and neck malignant tumours [ 1 ]. Squamous cell carcinoma (SCC) is the most common pathological type. Hypopharyngeal squamous cell carcinoma (HPSCC) mostly occurs in the region of the pyriform fossa, followed by the region of the posterior pharyngeal wall, and least in the region of the postcricoid region. Due to its insidious development site and lack of obvious symptoms in early stage, most patients are already in the middle or late stage when they are diagnosed. The prognosis of HPSCC is poor, with a 5-year survival rate of only 40% [ 2 ]. The main risk factors for HPSCC include alcohol, tobacco, betel nut chewing, previous radiation therapy exposure and human papillomavirus (HPV) infection [ 3 – 5 ]. Currently, the treatment of HPSCC is mainly a combination of surgery and radiotherapy. In recent years, neoadjuvant therapy has remarkable efficacy in the therapeutic application of hypopharyngeal cancer. This treatment approach can not only achieve tumour stage reduction, but also improve the feasible laryngeal function preservation rate as much as possible under the premise of guaranteeing complete resection of the tumour, thereby substantially improving patients' quality of life.[ 6 ]. Immunotherapy is a hot spot of clinical research. The programmed death protein-1 (PD-1)/and its ligand (PD-L1) axis is an important component mediating tumour immunosuppression. A study [ 7 ] showed that PD-1 monoclonal antibody combined with chemotherapy prolonged the overall survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Meanwhile, with the continuous progress of minimally invasive technology, the application of transoral minimally invasive surgery in the treatment of head and neck tumours has become more and more widespread. It performs better in terms of laryngeal function recovery, which can significantly improve the quality of life of patients. Therefore, the present study is intended to observe the clinical efficacy and safety of neoadjuvant immunotherapy for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC) and explore the application of minimally invasive surgery for HPSCC after tumour stage reduction, with the aim of providing a more effective, safer, and quality-of-life treatment option for LA HPSCC patients. Materials and methods General information Patients with locally advanced HPC treated with neoadjuvant immunotherapy at the Department of Otorhinolaryngology and Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, from January 2022 to September 2024 were selected. The patients' gender, age, smoking history, drinking history, TNM stage, clinical stage, primary site, degree of differentiation and relevant imaging data were collected and statistically summarised. Clinical staging was performed according to the eighth edition of the American Cancer Consortium (AJCC) staging manual. All patients signed an informed consent form. The study was approved by the Ethics Committee of Beijing Tongren Hospital. Screening Criteria Inclusion Criteria: (1)Patients with stage IIIA-IVB HPSCC definitively diagnosed by histology and/or cytology; (2)Complete receipt of 2 cycles of neoadjuvant therapy (PD-1 monoclonal antibody in combination with paclitaxel liposomal and platinum regimen); (3)Imaging with measurable target lesions prior to neoadjuvant therapy, post-treatment, and post-surgery. Exclusion Criteria: (1)Pathological diagnosis of non-squamous cell carcinoma; (2)Presence of distant metastases; (3)Autoimmune disease or previous immunosuppressive therapy; (4)History of treatment such as surgery, radiotherapy, and targeted therapy. Efficacy Evaluation PD-1 monoclonal antibody (pembrolizumab/tirilizumab) plus paclitaxel liposome and platinum-based chemotherapeutic agents (cisplatin/nedaplatin) were all administered every 3 weeks.Imaging evaluation of the tumour's primary site was carried out before treatment and after 2 cycles chemotherapy. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumours [ 8 ] (RECIST RECIST) 1.1 for efficacy evaluation. Complete response (CR): all lesions completely disappeared after imaging evaluation. Partial response (PR): the sum of the largest diameters of the target lesions was reduced by at least 30% from the previous size. Stable disease (SD): the sum of the largest diameters of the target lesions is reduced from the previous level but does not reach PR, or is increased from the previous level but does not reach progressive disease (PD). The sum of the maximum diameters of the target lesions is more than 20% of the previous one, or there are new lesions. Disease control rate (DCR): the proportion of patients with tumours assessed as CR, PR and SD. Objective response rate (ORR): the proportion of patients whose tumour volume reduction reaches a pre-specified value and can be maintained in the minimum time frame, i.e., the proportion of CR and PR among all patients. Postoperative pathological assessment was based on the residual tumour in the resected specimen. Pathological complete response (pCR) was defined as neoadjuvant therapy-induced tumour regression without residual tumour on pathological grounds. Surgery Patients with LA HPC who were evaluated for pCR or who were physically unable to undergo general anaesthesia for surgery were followed up with radiotherapy and other comprehensive treatments. The remaining patients were selected according to the extent of tumour involvement, depth of infiltration and patient choice after immuno-neoadjuvant chemotherapy. The operative modalities were mainly divided into open surgery with external cervical approach and minimally invasive transoral surgery, the latter including supported laryngoscopy-assisted and curved laryngoscopy-assisted (Fig. 1 ) resections. The decision to perform cervical lymph node dissection depends on the presence or absence of suspicious metastatic signs in lymph nodes assessed by imaging after chemotherapy. Follow-up After neoadjuvant therapy or surgery, patients were followed up by telephone or outpatient clinic every 3 months, and were asked about the recovery of laryngeal function, including (1) Respiratory function: using subjective assessment of respiratory function scale, divided into 5 levels: A: breathing through the nose, living and working freely B: breathing through the nose, daily life activities freely C: breathing through the nose, can be kept in a quiet state D: incomplete respiratory breathing through the nose, without extraction, blocking the tube Calm breathing is normal E: completely unable to breathe through the nose, retaining the respiratory passage of the larynx, but not blocking the tube. (2) Swallowing function: the MDADI Anderson dysphagia questionnaire [ 9 ] was used, and with a swallowing function score of ≥ 80 we considered the swallowing function to be well recovered; (3) Vocal function [ 10 ]: a modified grading scale was used to classify voice quality into 4 levels of levels, as follows: 0: Normal (i.e., subjective normal voice), 1: Mild (i.e., mild dysphonia), 2: Moderate (i.e., moderate articulation distress), 3: Severe (i.e., severe dysphonia or no voice). Adverse reactions to chemotherapy, perioperative complications, postoperative pathological data and survival data were obtained from the patients' inpatient medical record system and outpatient visit records. The follow-up cut-off date was 29 October 2024. The inability to clarify patient status for more than 6 months was defined as loss to follow-up. Overall survival was defined as the time between the patient's definitive hypopharyngeal cancer and death or the end of follow-up. Progression-free survival was defined as the time from when the patient had definite hypopharyngeal cancer to recurrence, death, or the end of follow-up. Data Analysis The study was statistically analysed using SPSS software (IBM SPSS Statistics 29), categorical variables were described as frequencies (percentages), and cross-tests were calculated using Fisher's two-way exact test, with P < 0.05 indicating a statistically significant difference. Results Patient Characteristics Seventy-three cases were studied, 71 males and 2 females, aged 38–73 years, with a median age of 60 years, 56 cases with a clear history of smoking, 59 cases with a history of alcohol consumption, and 12 cases with neither a history of smoking nor alcohol consumption, with a follow-up period of 2–24 months. According to the 2018 AJCC TNM staging, there were 10 cases of T2, 24 cases of T3, and 39 cases of T4; 13 cases of N0, 6 cases of N1, 50 cases of N2, and 4 cases of N3; 9 cases of stage III and 64 cases of stage IV. The tumours originated in the pyriform fossa in 46 cases, the posterior pharyngeal wall in 17 cases, and the postcricoid region in 10 cases. The pathological types were all squamous cell carcinoma, 39 cases were moderately differentiated and 21 cases were poorly differentiated (Table 1 ). Table 1 Patient Demographics Clinical Characteristics case count Clinical Characteristics case count Sex N Stage Male 71 N0 13 Female 2 N1 6 Age N2 50 <60 years old 32 N3 4 ≥60 years old 41 Clinical Stage Smoking History III 9 Yes 56 IV 64 No 17 Primary Site Drinking History Pyriform sinus region 46 Yes 59 Posterior pharyngeal wall region 17 No 14 Postcricoid region 10 T Stage Degree of Differentiation T2 10 Moderately differentiated 39 T3 24 Poorly differentiated 21 T4 39 Assessment of Imaging Efficacy of Neoadjuvant Immunotherapy All of the 73 patients received the full 2 cycles of neoadjuvant immunotherapy, Imaging assessment was performed 3 weeks after the end of the final chemotherapy,and compared with the baseline before treatment. Primary focus efficacy was assessed by imaging in 17 cases of CR, 40 cases of PR, 14 cases of SD, and 2 cases of PD, with an overall DCR of 97.3% (71/73) and an ORR of 78.1% (57/73). The relationship between efficacy and each clinical characteristic is shown in Table 2 . Table 2 Relationship between Efficacy and Clinical Characteristics Primary Tumor Efficacy κ Lymph Node Efficacy κ CR PR SD PD CR PR SD PD Sex Male 16 40 13 2 0.418 2 38 14 7 0.364 Female 1 0 1 0 0 0 1 0 Age < 60 9 16 6 1 0.838 1 13 8 5 0.243 ≥ 60 8 24 8 1 1 25 7 2 Smoking History Yes 3 10 2 0 0.699 1 8 3 1 0.750 No 14 30 12 2 1 30 12 6 Drinking History Yes 3 8 1 0 0.646 1 5 2 1 0.551 No 14 32 13 2 1 33 13 6 Site Pyriform sinus region 13 25 8 0 0.415 2 28 9 3 0.160 Posterior pharyngeal wall region 3 10 3 1 0 8 3 1 Postcricoid region 1 5 3 1 0 2 3 3 TStage 2 2 7 1 0 0.462 0 5 3 2 0.809 3 8 13 3 0 1 11 4 3 4 7 20 10 2 1 22 8 2 N Stage 0 3 6 4 0 0.103 0 0 0 2 < 0.001 1 0 2 4 0 0 1 5 0 2 12 30 6 2 1 34 10 5 3 2 2 0 0 1 3 0 0 CPS < 1 1 0 0 0 0.539 0 0 0 0 0.134 ≥ 1, < 20 8 19 8 1 1 22 5 5 ≥ 20 8 19 4 0 1 14 9 6 Safety of Immune Neoadjuvant Immunotherapy During neoadjuvant chemotherapy 73 patients developed different degrees of myelosuppression, of which 8 patients developed grade III-IV myelosuppression and 48 patients developed grade I-II myelosuppression. 57 patients developed electrolyte disorders, of which 2 developed grade III electrolyte disorders. 9 patients developed abnormal liver function. 6 patients developed grade I gastrointestinal reactions. 6 patients developed fever. Abnormal elevation of blood glucose was observed in 2 patients; abnormalities of thyroid function were observed in 2 patients. Grade II rash was observed in 1 patient. Elevation of cardiac enzymes was observed in 1 patient. And pulmonary infection was observed in 1 patient. All of them got better after symptomatic treatment and completed the treatment (Table 3 ). Table 3 Summary of Adverse Reactions to Neoadjuvant Therapy Adverse effects/severity Grade I Grade II Grade III Grade IV Bone Marrow Suppression 20 28 7 1 Electrolyte Disturbance 27 28 2 Gastrointestinal Reaction 6 Fever 5 1 Abnormal Liver Function 5 4 Elevated Blood Glucose 1 1 Elevated Myocardial Enzymes 1 Abnormal Thyroid Function 2 Skin Rash 1 Lung Infection 1 Post-Neoadjuvant chemotherapy Minimally Invasive Treatment As of October 2024, 44 of the 73 patients underwent non-surgical treatment, including 11 patients who could not undergo surgery under general anaesthesia for medical reasons after neoadjuvant immunotherapy, and 33 patients who underwent radiotherapy after achieving pathological complete remission (pCR); Of the remaining 29 surgical patients, 11 underwent transoral minimally invasive surgery for complete tumour resection, including 3 cases of hypopharyngoscopy (Fig. 2), and 18 underwent open surgery, including 7 patients who underwent total laryngeal surgery. The laryngeal preservation rate was 88.7% (55/62). Prognosis Follow-up after completion of treatment ranged from 2 to 22 months, with a median follow-up time of 10 months. 2 patients died during the follow-up period, 1 of which was accidental. The 73 patients were divided into 5 groups: minimally invasive surgery group (11 patients), partial laryngeal surgery group (11 patients), total laryngeal surgery group (7 patients), radiotherapy after pCR group (33 patients), and continuing chemotherapy group (11 patients). No statistical differences were seen in PFS (P = 0.9730) and OS (P = 0.5316) between the groups (Fig. 3 ,Fig. 4 ). Statistical analyses of the differences in tracheal status and laryngeal function recovery at 2 weeks postoperatively between minimally invasive surgery and open surgery with preservation of laryngeal function after chemotherapy downstaging were performed (Table 4 ), and it was seen that the differences in tracheal status, respiratory function, and vocal function were statistically significant between the two groups (P < 0.05). Table 4 Difference of laryngeal function recovery between groups Laryngeal function recovery minimally invasive surgery open surgery t P Tracheotomy Yes 1 11 −10.000 <0.001 No 10 0 Respiratory function A 7 0 -4.939 <0.001 B 4 4 C 0 3 D 0 3 E 0 1 Swallowing function <80 points 0 8 1.936 0.082 ≥ 80 points 11 3 Vocalization function Grade0 0 0 −6.803 <0.001 Grade1 19 1 Grade2 6 7 Grade3 0 3 Note: (1) The respiratory function status is divided into 5 levels, respectively: A: nasal breathing, life and work freely B: nasal breathing, daily life activities freely C: nasal breathing, can maintain quiet state D: incomplete nasal breathing, not extubation, tube blocked calm breathing normal E: can not breathe through the nose at all, retain the respiratory passage of the throat, but can not block the tube. (2) The swallowing function score ≥ 80 was considered to be a good recovery of swallowing function. (3) The improved scale was used to divide voice quality into four levels: 0: normal (i.e., subjective normal voice), 1: mild (i.e., mild dysphonia), 2: moderate (i.e., moderate dysphonia), and 3: severe (i.e., severe dysphonia or silence). Discussion According to Global Cancer statistics [ 11 ], China is the second most prevalent country for hypopharyngeal cancer. The treatment of HPC is mainly based on surgery, and early hypopharyngeal cancer can be treated with surgical resection or radiotherapy, while intermediate and advanced stages need to be treated with combination therapy of surgery combined with radiotherapy and chemotherapy [ 12 ].In 1983, the PF (cisplatin plus 5-fluorouracil) induction chemotherapy regimen was successfully used in primary head and neck tumours by Wayne State University [ 13 ].Two large randomized controlled studies, the GORTEC 2000-01 study [ 14 ] and the TAX324 study [ 15 ], established the TPF regimen as the new standard induction chemotherapy regimen for locally advanced squamous head and neck cancer. PD-L1 is a key negative regulator of autoreactive T cells. It maintains peripheral immune tolerance and prevents autoimmune reactions. At the same time, it triggers T cell over-exhaustion and abnormal function. Tumor cells use PD-L1 to form an immune barrier and escape immune system surveillance. PD-1/PD-L1 monoclonal antibody restores the function of tumour-specific T cells by blocking the binding of PD-1 to PD-L1 to enhance the antitumor immunity [ 16 ]. With the rise of immunotherapy, a series of clinical studies, such as Keynote 012 [ 17 ], Checkmate 141 [ 18 ], Keynote 040 [ 19 ], and Keynote 048 [ 20 ], have confirmed the value of PD-1 inhibitors in recurrent/metastatic squamous head and neck cancer. But the efficacy of their application as a neoadjuvant approach in the treatment of head and neck squamous carcinoma is unclear. A number of phase II clinical studies have been conducted extensively to explore the efficacy and safety of neoadjuvant therapy with immune checkpoint inhibitors in combination with chemotherapy in patients with locally advanced surgically resectable squamous cell carcinoma of the head and neck. A study explored the efficacy of a PD-1 inhibitor combined with albumin paclitaxel plus cisplatin in the treatment of locally advanced squamous carcinoma of the hypopharynx.Data from 156 patients included showed an overall survival (OS) of 94.1% at one year and 82.5% at two years, a progression-free survival (PFS) of 80.4% at one year and 66.3% at two years. The overall response rate after treatment with TP plus PD-1 inhibitor was 88.5% [ 21]. Another prospective study included 23 patients with locally advanced surgically resectable squamous cell carcinoma of the hypopharynx. A neoadjuvant therapy with pembrolizumab combined with cisplatin and paclitaxel was used: the postoperative pCR rate was 26.1% and the laryngeal surgical retention rate was 87.0% [ 22 ]. This study investigates the clinical efficacy and safety of neoadjuvant treatment of LA HPSCC with PD-1 monoclonal antibody in combination with chemotherapy.It also innovatively explores the feasibility of minimally invasive surgery after downstaging. The inclusion of 73 treated patients in Beijing Tongren Hospital showed that the disease control rate (DCR) was 97.3%, objective remission rate (ORR) was 78.1%, and pathological complete remission (pCR) reached 53.2%, which was significantly better than the traditional chemotherapy regimen. Safety: the incidence of grade III-IV adverse reactions was 13.7%, comparable to that of traditional regimens, confirming that the safety of immunotherapy can be controlled.The current study has the limitations of short treatment time and limited sample size, and the long-term survival benefit needs to be verified by long-term follow-up with enlarged samples. Minimally invasive surgery can usually be used for the treatment of early stage hypopharyngeal cancer, which has the advantages of less trauma, less bleeding and faster recovery. For patients with locally advanced stages, minimally invasive surgery cannot completely remove the tumour and needs to be combined with comprehensive treatment such as radiotherapy and chemotherapy. Among the 29 patients who underwent radical surgery in this study, there were 11 cases of transoral minimally invasive surgery, 11 cases of partial hypopharyngectomy and/or partial laryngectomy surgery, and 7 cases of partial/total hypopharyngectomy and total laryngectomy surgery. Data analysis showed that the overall survival rates of transoral minimally invasive surgery and partial hypopharyngeal resection were comparable in patients with hypopharyngeal cancer in the downstage of neoadjuvant immunotherapy (p > 0.05). However, the transoral minimally invasive group had significant advantages in postoperative laryngeal function recovery, better achieving laryngeal function preservation and quality of life improvement. This study has limitations such as limited sample size and short follow-up period, and the reliability of the conclusion needs to be further verified by prospective clinical trials and case-control studies. The retrospective study confirms that immuno-neoadjuvant therapy combined with chemotherapy regimen has both efficacy and safety in locally advanced hypopharyngeal squamous carcinoma. This study preliminarily validates the value of minimally invasive surgery in descending tumors and provides a new direction for optimizing clinical treatment pathways. The long-term survival benefit and long-term preservation of laryngeal function still need to be evaluated in depth by enlarging the sample size and extending the follow-up period. Declarations Author Contribution L.F. and W.G. wrote the original manuscript. (L.F. and W.G. contributed equally to this manuscript). G.Y. and W. G. design the article. Q.Z., X.C. and J.F. provided typical cases. Z.H. and Y.Z. review the manuscript and approved its publication.All authors critically reviewed and approved the final manuscript. Data Availability Data is provided within the manuscript. References Yan K, Agrawal N, Gooi Z. Head and Neck Masses. Med Clin North Am. 2018 Nov;102(6):1013-1025. doi: 10.1016/j.mcna.2018.06.012. Epub 2018 Sep 20. PMID: 30342605. Subspecialty Group of Head and Neck Surgery, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Head and Neck Surgery, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Expert consensus on surgery and comprehensive treatment of hypopharyngeal carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Jan 7;52(1):16-24. Chinese. doi: 10.3760/cma.j.issn.1673-0860.2017.01.004. PMID: 28104011. Mody MD, Rocco JW, Yom SS, et al. Head and neck cancer [J]. Lancet, 2021, 398(10318): 2289‑2299. DOI: 10.1016/ S0140‑6736(21)01550‑6 Blot WJ, McLaughlin JK, Winn DM, et al.: Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48 (11): 3282-7, 1988. Day GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994. Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. doi: 10.1093/jnci/djp007. Epub 2009 Mar 24. PMID: 19318632. Burtness B, Harrington K J, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study[J]. The Lancet, 2019, 394(10212): 1915-1928. Eisenhauer E A , Therasse P , Bogaerts J ,et al.New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).[J].European journal of cancer: official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR), 2009(2):45. Chen AY, Frankowski R, Bishop-Leone J, Hebert T, Leyk S, Lewin J, Goepfert H. The development and validation of a dysphagia-specific quality-of-life questionnaire for patients with head and neck cancer: the M. D. Anderson dysphagia inventory. Arch Otolaryngol Head Neck Surg. 2001 Jul;127(7):870-6. PMID: 11448365. Yu P, Revis J, Wuyts FL, Zanaret M, Giovanni A. Correlation of instrumental voice evaluation with perceptual voice analysis using a modified visual analog scale. Folia Phoniatr Logop. 2002 Nov-Dec;54(6):271-81. doi: 10.1159/000066150. PMID: 12417797. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751. National Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in Oncology: Head and neck. Version 3.2024 Decker DA, Drelichman A, Jacobs J, et al. Adjuvant chemotherapy with cis-diamminodichloroplatinum Ⅱ and 120-hour infusion 5-fluorouracil in Stage Ⅲ and Ⅳ squamous cell carcinoma of the head and neck[J]. Cancer, 1983, 51(8):1353-1355.DOI:10.1002/1097-0142(19830415)51:83.0.CO;2-I Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation[J]. J Natl Cancer Inst, 2009, 101(7): 498-506. DOI:10.1093/jnci/djp007 Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer[J]. N Engl J Med, 2007, 357(17): 1705-1715. DOI:10.1056/NEJMoa070956 Diskin B, Adam S, Cassini MF, et al. PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Nat Immunol. 2020 Apr;21(4):442-454. doi: 10.1038/s41590-020-0620-x. Epub 2020 Mar 9. PMID: 32152508. Seiert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial[J]. Lancet Oncol, 2016, 17(7): 956-965. DOI:10.1016/S1470-2045(16)30066-3 Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck[J]. N Engl J Med, 2016, 375(19): 1856-1867. DOI:10.1056/NEJMoa1602252 Cohen EEW, Soulières D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study[J]. Lancet, 2019, 393(10167): 156-167. DOI:10.1016/S0140-6736(18)31999-8 Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study[J]. Lancet, 2019, 394(10212): 1915-1928. DOI:10.1016/S0140-6736(19)32591-7 Fang Q, Xu P, Cao F, et al. PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study. Cancer Immunol Immunother. 2023 Dec;72(12):4161-4168. doi: 10.1007/s00262-023-03550-z. Epub 2023 Oct 7. PMID: 37804437; PMCID: PMC10992232. Wang K, Zhang W, Gui L, et al. [The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Apr 7;59(4):343-349. Chinese. doi: 10.3760/cma.j.cn115330-20231015-00147. PMID: 38599640. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6246307","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":432678486,"identity":"2afd4720-3c40-40f9-a8e0-60c5530f0a5b","order_by":0,"name":"Lifei Feng","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lifei","middleName":"","lastName":"Feng","suffix":""},{"id":432678487,"identity":"804c8ca8-e2da-4077-8de6-1672266918eb","order_by":1,"name":"Wen Gao","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"","lastName":"Gao","suffix":""},{"id":432678488,"identity":"5d464e64-2a93-4b85-83a1-d6c30eb4b24a","order_by":2,"name":"Gaofei Yin","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Gaofei","middleName":"","lastName":"Yin","suffix":""},{"id":432678489,"identity":"df600c6f-58b1-4f41-9012-86a4c0c200c8","order_by":3,"name":"Wei Guo","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Guo","suffix":""},{"id":432678490,"identity":"fc905048-f9cb-4517-bc74-0611c4bca045","order_by":4,"name":"Qi Zhong","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Zhong","suffix":""},{"id":432678491,"identity":"2a3f0dd3-c657-47e5-9384-2ef6b2b928db","order_by":5,"name":"Xiaohong Chen","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaohong","middleName":"","lastName":"Chen","suffix":""},{"id":432678492,"identity":"b4cdeb97-1460-4716-9f9d-7f30529d4f6a","order_by":6,"name":"Jugao Fang","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jugao","middleName":"","lastName":"Fang","suffix":""},{"id":432678493,"identity":"d986f1c5-442d-4030-a4e6-eda32e85dfd7","order_by":7,"name":"Zhigang Huang","email":"","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhigang","middleName":"","lastName":"Huang","suffix":""},{"id":432678494,"identity":"94b3be06-7c20-42ee-b0c5-3d13dd645ec0","order_by":8,"name":"Yang Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYDACCWTOBwMbO5K0MDbOKEhLJk1LM8+HQ4wNhHTIz25+9vBrm12evHvv8cc2BgeYGdgPH92ATwvjnGPmxrJtycWGZ84lNucY3OFj4ElLu4FPC7NEgpm0ZBtz4sYZOYZALc+YGSR4zPBqYZNI/wbUUp+4cf4bw2YLg8OMDYS08EjkmEl+bDucOF+Cx7CZgRgtEhI5ZdIM544nbuDJMZzZY5CWzEbIL/Iz0rdJ/iirTpzffsbgw48/Nnb87IeP4dUCAsy8bAwMBgdgviOkHAQYf/wBWtdAjNJRMApGwSgYkQAAlpxK4V33ohwAAAAASUVORK5CYII=","orcid":"","institution":"Beijing Tongren Hospital, Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yang","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-03-17 16:11:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6246307/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6246307/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79101577,"identity":"2e2a9657-35a6-4ab7-8ab4-c38b9b484150","added_by":"auto","created_at":"2025-03-24 12:23:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100764,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCurved laryngoscope to expose the operative field, rigid high-definition endoscope to assist in the visualisation of the lesion, and transoral instruments such as curved grasping forceps and curved electrosurgical knife to manage the lesion\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6246307/v1/fa29637a12fb9e153d7d3bb4.png"},{"id":79101603,"identity":"db698bbf-ecac-489e-acf0-c51dbf2832ad","added_by":"auto","created_at":"2025-03-24 12:23:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":960548,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a) CT before immuno-neoadjuvant therapy (b) CT after immuno-neoadjuvant therapy (c) Before curved laryngoscopy (d) After curved laryngoscopy (e) Laryngoscopy at 1 month postoperatively (f) Laryngoscopy at 6 months postoperatively\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6246307/v1/ccaceae213f0e05e3fd5ef4c.png"},{"id":79101567,"identity":"fcd962a8-c136-40c4-9229-75e197b644ab","added_by":"auto","created_at":"2025-03-24 12:23:14","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":115003,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProgression-free survival in different groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6246307/v1/221feb2c4a3be6a715ad3d6d.png"},{"id":79101606,"identity":"2e1a177a-5667-4ea0-b4ea-d059e56616aa","added_by":"auto","created_at":"2025-03-24 12:23:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":107640,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverall survival in different groups\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6246307/v1/b25303da86c5bcadaf258f92.png"},{"id":82927737,"identity":"9b08aa2e-8674-4289-a27c-49b7038fb5a5","added_by":"auto","created_at":"2025-05-16 20:31:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2240383,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6246307/v1/3fabeebc-8a61-4871-a0f9-e805f395d6c7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Surgical efficacy of locally advanced hypopharyngeal carcinoma after neoadjuvant immunotherapy","fulltext":[{"header":"Background","content":"\u003cp\u003eHypopharyngeal carcinoma (HPC) is a rare malignant tumour whichoriginates from the hypopharynx. HPC accounts for 0.15\u0026ndash;0.24% of systemic malignant tumours and 2\u0026ndash;4% of head and neck malignant tumours [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Squamous cell carcinoma (SCC) is the most common pathological type. Hypopharyngeal squamous cell carcinoma (HPSCC) mostly occurs in the region of the pyriform fossa, followed by the region of the posterior pharyngeal wall, and least in the region of the postcricoid region. Due to its insidious development site and lack of obvious symptoms in early stage, most patients are already in the middle or late stage when they are diagnosed. The prognosis of HPSCC is poor, with a 5-year survival rate of only 40% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The main risk factors for HPSCC include alcohol, tobacco, betel nut chewing, previous radiation therapy exposure and human papillomavirus (HPV) infection [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Currently, the treatment of HPSCC is mainly a combination of surgery and radiotherapy. In recent years, neoadjuvant therapy has remarkable efficacy in the therapeutic application of hypopharyngeal cancer. This treatment approach can not only achieve tumour stage reduction, but also improve the feasible laryngeal function preservation rate as much as possible under the premise of guaranteeing complete resection of the tumour, thereby substantially improving patients' quality of life.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eImmunotherapy is a hot spot of clinical research. The programmed death protein-1 (PD-1)/and its ligand (PD-L1) axis is an important component mediating tumour immunosuppression. A study [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] showed that PD-1 monoclonal antibody combined with chemotherapy prolonged the overall survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Meanwhile, with the continuous progress of minimally invasive technology, the application of transoral minimally invasive surgery in the treatment of head and neck tumours has become more and more widespread. It performs better in terms of laryngeal function recovery, which can significantly improve the quality of life of patients. Therefore, the present study is intended to observe the clinical efficacy and safety of neoadjuvant immunotherapy for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC) and explore the application of minimally invasive surgery for HPSCC after tumour stage reduction, with the aim of providing a more effective, safer, and quality-of-life treatment option for LA HPSCC patients.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eGeneral information\u003c/h2\u003e \u003cp\u003e Patients with locally advanced HPC treated with neoadjuvant immunotherapy at the Department of Otorhinolaryngology and Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, from January 2022 to September 2024 were selected. The patients' gender, age, smoking history, drinking history, TNM stage, clinical stage, primary site, degree of differentiation and relevant imaging data were collected and statistically summarised. Clinical staging was performed according to the eighth edition of the American Cancer Consortium (AJCC) staging manual. All patients signed an informed consent form. The study was approved by the Ethics Committee of Beijing Tongren Hospital.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eScreening Criteria\u003c/h3\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInclusion Criteria:\u003c/h2\u003e \u003cp\u003e(1)Patients with stage IIIA-IVB HPSCC definitively diagnosed by histology and/or cytology;\u003c/p\u003e \u003cp\u003e(2)Complete receipt of 2 cycles of neoadjuvant therapy (PD-1 monoclonal antibody in combination with paclitaxel liposomal and platinum regimen);\u003c/p\u003e\u003cp\u003e(3)Imaging with measurable target lesions prior to neoadjuvant therapy, post-treatment, and post-surgery.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eExclusion Criteria:\u003c/h3\u003e\n \u003cp\u003e(1)Pathological diagnosis of non-squamous cell carcinoma;\u003c/p\u003e\u003cp\u003e(2)Presence of distant metastases;\u003c/p\u003e \u003cp\u003e(3)Autoimmune disease or previous immunosuppressive therapy;\u003c/p\u003e \u003cp\u003e(4)History of treatment such as surgery, radiotherapy, and targeted therapy.\u003c/p\u003e \n\u003ch3\u003eEfficacy Evaluation\u003c/h3\u003e\n\u003cp\u003ePD-1 monoclonal antibody (pembrolizumab/tirilizumab) plus paclitaxel liposome and platinum-based chemotherapeutic agents (cisplatin/nedaplatin) were all administered every 3 weeks.Imaging evaluation of the tumour's primary site was carried out before treatment and after 2 cycles chemotherapy. Efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumours [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] (RECIST RECIST) 1.1 for efficacy evaluation. Complete response (CR): all lesions completely disappeared after imaging evaluation. Partial response (PR): the sum of the largest diameters of the target lesions was reduced by at least 30% from the previous size. Stable disease (SD): the sum of the largest diameters of the target lesions is reduced from the previous level but does not reach PR, or is increased from the previous level but does not reach progressive disease (PD). The sum of the maximum diameters of the target lesions is more than 20% of the previous one, or there are new lesions. Disease control rate (DCR): the proportion of patients with tumours assessed as CR, PR and SD. Objective response rate (ORR): the proportion of patients whose tumour volume reduction reaches a pre-specified value and can be maintained in the minimum time frame, i.e., the proportion of CR and PR among all patients. Postoperative pathological assessment was based on the residual tumour in the resected specimen. Pathological complete response (pCR) was defined as neoadjuvant therapy-induced tumour regression without residual tumour on pathological grounds.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSurgery\u003c/h2\u003e \u003cp\u003ePatients with LA HPC who were evaluated for pCR or who were physically unable to undergo general anaesthesia for surgery were followed up with radiotherapy and other comprehensive treatments. The remaining patients were selected according to the extent of tumour involvement, depth of infiltration and patient choice after immuno-neoadjuvant chemotherapy. The operative modalities were mainly divided into open surgery with external cervical approach and minimally invasive transoral surgery, the latter including supported laryngoscopy-assisted and curved laryngoscopy-assisted (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) resections. The decision to perform cervical lymph node dissection depends on the presence or absence of suspicious metastatic signs in lymph nodes assessed by imaging after chemotherapy.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eFollow-up\u003c/h3\u003e\n\u003cp\u003e After neoadjuvant therapy or surgery, patients were followed up by telephone or outpatient clinic every 3 months, and were asked about the recovery of laryngeal function, including (1) Respiratory function: using subjective assessment of respiratory function scale, divided into 5 levels: A: breathing through the nose, living and working freely B: breathing through the nose, daily life activities freely C: breathing through the nose, can be kept in a quiet state D: incomplete respiratory breathing through the nose, without extraction, blocking the tube Calm breathing is normal E: completely unable to breathe through the nose, retaining the respiratory passage of the larynx, but not blocking the tube. (2) Swallowing function: the MDADI Anderson dysphagia questionnaire [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] was used, and with a swallowing function score of \u0026ge;\u0026thinsp;80 we considered the swallowing function to be well recovered; (3) Vocal function [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]: a modified grading scale was used to classify voice quality into 4 levels of levels, as follows: 0: Normal (i.e., subjective normal voice), 1: Mild (i.e., mild dysphonia), 2: Moderate (i.e., moderate articulation distress), 3: Severe (i.e., severe dysphonia or no voice). Adverse reactions to chemotherapy, perioperative complications, postoperative pathological data and survival data were obtained from the patients' inpatient medical record system and outpatient visit records. The follow-up cut-off date was 29 October 2024. The inability to clarify patient status for more than 6 months was defined as loss to follow-up. Overall survival was defined as the time between the patient's definitive hypopharyngeal cancer and death or the end of follow-up. Progression-free survival was defined as the time from when the patient had definite hypopharyngeal cancer to recurrence, death, or the end of follow-up.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eThe study was statistically analysed using SPSS software (IBM SPSS Statistics 29), categorical variables were described as frequencies (percentages), and cross-tests were calculated using Fisher's two-way exact test, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating a statistically significant difference.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePatient Characteristics\u003c/h2\u003e \u003cp\u003eSeventy-three cases were studied, 71 males and 2 females, aged 38\u0026ndash;73 years, with a median age of 60 years, 56 cases with a clear history of smoking, 59 cases with a history of alcohol consumption, and 12 cases with neither a history of smoking nor alcohol consumption, with a follow-up period of 2\u0026ndash;24 months. According to the 2018 AJCC TNM staging, there were 10 cases of T2, 24 cases of T3, and 39 cases of T4; 13 cases of N0, 6 cases of N1, 50 cases of N2, and 4 cases of N3; 9 cases of stage III and 64 cases of stage IV. The tumours originated in the pyriform fossa in 46 cases, the posterior pharyngeal wall in 17 cases, and the postcricoid region in 10 cases. The pathological types were all squamous cell carcinoma, 39 cases were moderately differentiated and 21 cases were poorly differentiated (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient Demographics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ecase count\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ecase count\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;60 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;60 years old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eClinical Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePrimary Site\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinking History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePyriform sinus region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePosterior pharyngeal wall region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePostcricoid region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDegree of Differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eModerately differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePoorly differentiated\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAssessment of Imaging Efficacy of Neoadjuvant Immunotherapy\u003c/h2\u003e \u003cp\u003eAll of the 73 patients received the full 2 cycles of neoadjuvant immunotherapy, Imaging assessment was performed 3 weeks after the end of the final chemotherapy,and compared with the baseline before treatment. Primary focus efficacy was assessed by imaging in 17 cases of CR, 40 cases of PR, 14 cases of SD, and 2 cases of PD, with an overall DCR of 97.3% (71/73) and an ORR of 78.1% (57/73). The relationship between efficacy and each clinical characteristic is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelationship between Efficacy and Clinical Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003ePrimary Tumor Efficacy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eκ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c11\" namest=\"c8\"\u003e \u003cp\u003eLymph Node Efficacy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eκ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.364\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.838\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSmoking History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.699\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDrinking History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePyriform sinus region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePosterior pharyngeal wall region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePostcricoid region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eTStage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.809\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eN Stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eCPS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.539\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;1, \u0026lt;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eSafety of Immune Neoadjuvant Immunotherapy\u003c/h2\u003e \u003cp\u003eDuring neoadjuvant chemotherapy 73 patients developed different degrees of myelosuppression, of which 8 patients developed grade III-IV myelosuppression and 48 patients developed grade I-II myelosuppression. 57 patients developed electrolyte disorders, of which 2 developed grade III electrolyte disorders. 9 patients developed abnormal liver function. 6 patients developed grade I gastrointestinal reactions. 6 patients developed fever. Abnormal elevation of blood glucose was observed in 2 patients; abnormalities of thyroid function were observed in 2 patients. Grade II rash was observed in 1 patient. Elevation of cardiac enzymes was observed in 1 patient. And pulmonary infection was observed in 1 patient. All of them got better after symptomatic treatment and completed the treatment (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of Adverse Reactions to Neoadjuvant Therapy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse effects/severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGrade I\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGrade II\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGrade III\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGrade IV\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBone Marrow Suppression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElectrolyte Disturbance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal Reaction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal Liver Function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Blood Glucose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eElevated Myocardial Enzymes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbnormal Thyroid Function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin Rash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung Infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003ePost-Neoadjuvant chemotherapy Minimally Invasive Treatment\u003c/h2\u003e \u003cp\u003eAs of October 2024, 44 of the 73 patients underwent non-surgical treatment, including 11 patients who could not undergo surgery under general anaesthesia for medical reasons after neoadjuvant immunotherapy, and 33 patients who underwent radiotherapy after achieving pathological complete remission (pCR);\u003c/p\u003e \u003cp\u003eOf the remaining 29 surgical patients, 11 underwent transoral minimally invasive surgery for complete tumour resection, including 3 cases of hypopharyngoscopy (Fig.\u0026nbsp;2), and 18 underwent open surgery, including 7 patients who underwent total laryngeal surgery. The laryngeal preservation rate was 88.7% (55/62).\u003c/p\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003ePrognosis\u003c/h2\u003e \u003cp\u003eFollow-up after completion of treatment ranged from 2 to 22 months, with a median follow-up time of 10 months. 2 patients died during the follow-up period, 1 of which was accidental. The 73 patients were divided into 5 groups: minimally invasive surgery group (11 patients), partial laryngeal surgery group (11 patients), total laryngeal surgery group (7 patients), radiotherapy after pCR group (33 patients), and continuing chemotherapy group (11 patients). No statistical differences were seen in PFS (P\u0026thinsp;=\u0026thinsp;0.9730) and OS (P\u0026thinsp;=\u0026thinsp;0.5316) between the groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e,Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStatistical analyses of the differences in tracheal status and laryngeal function recovery at 2 weeks postoperatively between minimally invasive surgery and open surgery with preservation of laryngeal function after chemotherapy downstaging were performed (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e), and it was seen that the differences in tracheal status, respiratory function, and vocal function were statistically significant between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDifference of laryngeal function recovery between groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaryngeal function recovery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eminimally invasive surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eopen surgery\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTracheotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026minus;10.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e-4.939\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSwallowing function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;80 points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.936\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.082\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;80 points\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVocalization function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026minus;6.803\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNote: (1) The respiratory function status is divided into 5 levels, respectively: A: nasal breathing, life and work freely B: nasal breathing, daily life activities freely C: nasal breathing, can maintain quiet state D: incomplete nasal breathing, not extubation, tube blocked calm breathing normal E: can not breathe through the nose at all, retain the respiratory passage of the throat, but can not block the tube. (2) The swallowing function score\u0026thinsp;\u0026ge;\u0026thinsp;80 was considered to be a good recovery of swallowing function. (3) The improved scale was used to divide voice quality into four levels: 0: normal (i.e., subjective normal voice), 1: mild (i.e., mild dysphonia), 2: moderate (i.e., moderate dysphonia), and 3: severe (i.e., severe dysphonia or silence).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAccording to Global Cancer statistics [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], China is the second most prevalent country for hypopharyngeal cancer. The treatment of HPC is mainly based on surgery, and early hypopharyngeal cancer can be treated with surgical resection or radiotherapy, while intermediate and advanced stages need to be treated with combination therapy of surgery combined with radiotherapy and chemotherapy [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].In 1983, the PF (cisplatin plus 5-fluorouracil) induction chemotherapy regimen was successfully used in primary head and neck tumours by Wayne State University [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].Two large randomized controlled studies, the GORTEC 2000-01 study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and the TAX324 study [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], established the TPF regimen as the new standard induction chemotherapy regimen for locally advanced squamous head and neck cancer.\u003c/p\u003e \u003cp\u003ePD-L1 is a key negative regulator of autoreactive T cells. It maintains peripheral immune tolerance and prevents autoimmune reactions. At the same time, it triggers T cell over-exhaustion and abnormal function. Tumor cells use PD-L1 to form an immune barrier and escape immune system surveillance. PD-1/PD-L1 monoclonal antibody restores the function of tumour-specific T cells by blocking the binding of PD-1 to PD-L1 to enhance the antitumor immunity [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. With the rise of immunotherapy, a series of clinical studies, such as Keynote 012 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], Checkmate 141 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], Keynote 040 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and Keynote 048 [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], have confirmed the value of PD-1 inhibitors in recurrent/metastatic squamous head and neck cancer. But the efficacy of their application as a neoadjuvant approach in the treatment of head and neck squamous carcinoma is unclear. A number of phase II clinical studies have been conducted extensively to explore the efficacy and safety of neoadjuvant therapy with immune checkpoint inhibitors in combination with chemotherapy in patients with locally advanced surgically resectable squamous cell carcinoma of the head and neck. A study explored the efficacy of a PD-1 inhibitor combined with albumin paclitaxel plus cisplatin in the treatment of locally advanced squamous carcinoma of the hypopharynx.Data from 156 patients included showed an overall survival (OS) of 94.1% at one year and 82.5% at two years, a progression-free survival (PFS) of 80.4% at one year and 66.3% at two years. The overall response rate after treatment with TP plus PD-1 inhibitor was 88.5% [ 21]. Another prospective study included 23 patients with locally advanced surgically resectable squamous cell carcinoma of the hypopharynx. A neoadjuvant therapy with pembrolizumab combined with cisplatin and paclitaxel was used: the postoperative pCR rate was 26.1% and the laryngeal surgical retention rate was 87.0% [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study investigates the clinical efficacy and safety of neoadjuvant treatment of LA HPSCC with PD-1 monoclonal antibody in combination with chemotherapy.It also innovatively explores the feasibility of minimally invasive surgery after downstaging. The inclusion of 73 treated patients in Beijing Tongren Hospital showed that the disease control rate (DCR) was 97.3%, objective remission rate (ORR) was 78.1%, and pathological complete remission (pCR) reached 53.2%, which was significantly better than the traditional chemotherapy regimen. Safety: the incidence of grade III-IV adverse reactions was 13.7%, comparable to that of traditional regimens, confirming that the safety of immunotherapy can be controlled.The current study has the limitations of short treatment time and limited sample size, and the long-term survival benefit needs to be verified by long-term follow-up with enlarged samples.\u003c/p\u003e \u003cp\u003eMinimally invasive surgery can usually be used for the treatment of early stage hypopharyngeal cancer, which has the advantages of less trauma, less bleeding and faster recovery. For patients with locally advanced stages, minimally invasive surgery cannot completely remove the tumour and needs to be combined with comprehensive treatment such as radiotherapy and chemotherapy. Among the 29 patients who underwent radical surgery in this study, there were 11 cases of transoral minimally invasive surgery, 11 cases of partial hypopharyngectomy and/or partial laryngectomy surgery, and 7 cases of partial/total hypopharyngectomy and total laryngectomy surgery. Data analysis showed that the overall survival rates of transoral minimally invasive surgery and partial hypopharyngeal resection were comparable in patients with hypopharyngeal cancer in the downstage of neoadjuvant immunotherapy (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, the transoral minimally invasive group had significant advantages in postoperative laryngeal function recovery, better achieving laryngeal function preservation and quality of life improvement.\u003c/p\u003e \u003cp\u003eThis study has limitations such as limited sample size and short follow-up period, and the reliability of the conclusion needs to be further verified by prospective clinical trials and case-control studies. The retrospective study confirms that immuno-neoadjuvant therapy combined with chemotherapy regimen has both efficacy and safety in locally advanced hypopharyngeal squamous carcinoma. This study preliminarily validates the value of minimally invasive surgery in descending tumors and provides a new direction for optimizing clinical treatment pathways. The long-term survival benefit and long-term preservation of laryngeal function still need to be evaluated in depth by enlarging the sample size and extending the follow-up period.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.F. and W.G. wrote the original manuscript. (L.F. and W.G. contributed equally to this manuscript). G.Y. and W. G. design the article. Q.Z., X.C. and J.F. provided typical cases. Z.H. and Y.Z. review the manuscript and approved its publication.All authors critically reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eData is provided within the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYan K, Agrawal N, Gooi Z. Head and Neck Masses. Med Clin North Am. 2018 Nov;102(6):1013-1025. doi: 10.1016/j.mcna.2018.06.012. Epub 2018 Sep 20. PMID: 30342605.\u003c/li\u003e\n\u003cli\u003eSubspecialty Group of Head and Neck Surgery, Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Subspecialty Group of Head and Neck Surgery, Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association. [Expert consensus on surgery and comprehensive treatment of hypopharyngeal carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2017 Jan 7;52(1):16-24. Chinese. doi: 10.3760/cma.j.issn.1673-0860.2017.01.004. PMID: 28104011.\u003c/li\u003e\n\u003cli\u003eMody MD, Rocco JW, Yom SS, et al. Head and neck cancer [J]. Lancet, 2021, 398(10318): 2289‑2299. DOI: 10.1016/ S0140‑6736(21)01550‑6\u003c/li\u003e\n\u003cli\u003eBlot WJ, McLaughlin JK, Winn DM, et al.: Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res 48 (11): 3282-7, 1988.\u003c/li\u003e\n\u003cli\u003eDay GL, Blot WJ, Shore RE, et al.: Second cancers following oral and pharyngeal cancers: role of tobacco and alcohol. J Natl Cancer Inst 86 (2): 131-7, 1994.\u003c/li\u003e\n\u003cli\u003ePointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. doi: 10.1093/jnci/djp007. Epub 2009 Mar 24. PMID: 19318632.\u003c/li\u003e\n\u003cli\u003eBurtness B, Harrington K J, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study[J]. The Lancet, 2019, 394(10212): 1915-1928.\u003c/li\u003e\n\u003cli\u003eEisenhauer E A , Therasse P , Bogaerts J ,et al.New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).[J].European journal of cancer: official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR), 2009(2):45.\u003c/li\u003e\n\u003cli\u003eChen AY, Frankowski R, Bishop-Leone J, Hebert T, Leyk S, Lewin J, Goepfert H. The development and validation of a dysphagia-specific quality-of-life questionnaire for patients with head and neck cancer: the M. D. Anderson dysphagia inventory. Arch Otolaryngol Head Neck Surg. 2001 Jul;127(7):870-6. PMID: 11448365.\u003c/li\u003e\n\u003cli\u003eYu P, Revis J, Wuyts FL, Zanaret M, Giovanni A. Correlation of instrumental voice evaluation with perceptual voice analysis using a modified visual analog scale. Folia Phoniatr Logop. 2002 Nov-Dec;54(6):271-81. doi: 10.1159/000066150. PMID: 12417797.\u003c/li\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4. PMID: 38572751.\u003c/li\u003e\n\u003cli\u003eNational Comprehensive Cancer Network.NCCN Clinical Practice Guidelines in Oncology: Head and neck. Version 3.2024\u003c/li\u003e\n\u003cli\u003eDecker DA, Drelichman A, Jacobs J, et al. Adjuvant chemotherapy with cis-diamminodichloroplatinum Ⅱ and 120-hour infusion 5-fluorouracil in Stage Ⅲ and Ⅳ squamous cell carcinoma of the head and neck[J]. Cancer, 1983, 51(8):1353-1355.DOI:10.1002/1097-0142(19830415)51:8\u0026lt;1353::AID-CNCR2820510805\u0026gt;3.0.CO;2-I\u003c/li\u003e\n\u003cli\u003ePointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation[J]. J Natl Cancer Inst, 2009, 101(7): 498-506. DOI:10.1093/jnci/djp007\u003c/li\u003e\n\u003cli\u003ePosner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer[J]. N Engl J Med, 2007, 357(17): 1705-1715. DOI:10.1056/NEJMoa070956\u003c/li\u003e\n\u003cli\u003eDiskin B, Adam S, Cassini MF, et al. PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Nat Immunol. 2020 Apr;21(4):442-454. doi: 10.1038/s41590-020-0620-x. Epub 2020 Mar 9. PMID: 32152508.\u003c/li\u003e\n\u003cli\u003eSeiert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial[J]. Lancet Oncol, 2016, 17(7): 956-965. DOI:10.1016/S1470-2045(16)30066-3\u003c/li\u003e\n\u003cli\u003eFerris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck[J]. N Engl J Med, 2016, 375(19): 1856-1867. DOI:10.1056/NEJMoa1602252\u003c/li\u003e\n\u003cli\u003eCohen EEW, Souli\u0026egrave;res D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study[J]. Lancet, 2019, 393(10167): 156-167. DOI:10.1016/S0140-6736(18)31999-8\u003c/li\u003e\n\u003cli\u003eBurtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study[J]. Lancet, 2019, 394(10212): 1915-1928. DOI:10.1016/S0140-6736(19)32591-7\u003c/li\u003e\n\u003cli\u003eFang Q, Xu P, Cao F, et al. PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study. Cancer Immunol Immunother. 2023 Dec;72(12):4161-4168. doi: 10.1007/s00262-023-03550-z. Epub 2023 Oct 7. PMID: 37804437; PMCID: PMC10992232.\u003c/li\u003e\n\u003cli\u003eWang K, Zhang W, Gui L, et al. [The efficacy and safety of immunotherapy combined with chemotherapy neoadjuvant in locally advanced resectable hypopharyngeal squamous cell carcinoma]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Apr 7;59(4):343-349. Chinese. doi: 10.3760/cma.j.cn115330-20231015-00147. PMID: 38599640.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"locally advanced hypopharyngeal, squamous cell carcinoma, Neoadjuvant immunotherapy, Minimally Invasive treatment","lastPublishedDoi":"10.21203/rs.3.rs-6246307/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6246307/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eObjectives\u003c/b\u003e: This study aimed to explore the clinical efficacy of neoadjuvant immunotherapy in locally advanced hypopharyngeal carcinoma, and to assess the application value of minimally invasive treatment after tumour downstaging.\u003c/p\u003e \u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e:The clinical data of 73 patients with locally advanced hypopharynx squamous carcinoma were retrospectively analysed.These patients received neoadjuvant immunotherapy at Tongren Hospital, Beijing, China, from January 2022 to September 2024. Statistical analyses were performed to determine the efficacy of the chemotherapy, adverse reactions, the choice of the subsequent therapeutic modalities, and prognosis of the patients.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e: 73 patients were included in this study. They all received 2 cycles of neoadjuvant immunotherapy and were evaluated by imaging after the end of treatment. Response was assessed as complete remission(CR) in 17 patients, partial response(PR) in 40, stable disease(SD) in 14, and progressive disease(PD) in 2. The overall disease control rate (DCR) was 97.3% and objective remission rate (ORR) was 78.1%. 44 patients did not receive surgical treatment, including 11 patients continued chemotherapy and 33 patients treated with radiotherapy after pathological complete remission (pCR). 29 patients received surgical treatment. The laryngeal preservation rate was 88.7%. Minimally invasive and open laryngeal function-preserving surgeries did not show significant differences in progression-free survival (PFS) and overall survival (OS) (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). But there were statistically significant differences in the recovery of respiratory function and vocal function (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e:Neoadjuvant immunotherapy has demonstrated high efficacy and a good safety profile in patients with locally advanced hypopharyngeal squamous cell carcinoma. Transoral minimally invasive therapy provides an effective treatment strategy for patients with locally advanced hypopharyngeal carcinoma who responded well to neoadjuvan chemotherapy.\u003c/p\u003e","manuscriptTitle":"Surgical efficacy of locally advanced hypopharyngeal carcinoma after neoadjuvant immunotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-24 12:23:09","doi":"10.21203/rs.3.rs-6246307/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"dd62372a-096c-4c32-8cb6-f234cdd07f4e","owner":[],"postedDate":"March 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-16T20:23:13+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-24 12:23:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6246307","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6246307","identity":"rs-6246307","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}