Đánh giá điều trị ung thư biểu mô vảy hạ họng giai đoạn III, IV (m0) bằng cisplatin taxane và 5 FU trước phẫu thuật và hoặc xạ trị tt tieng anh

MINISTRY OF EDUCATION & TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY PHUNG THI HOA EVALUATING THE OUTCOME OF TREATMENT STAGE III AND IV HYPOPHARYNGEAL CARCINOMA WITH CISPLATIN - TAXANE AND FU BEFORE SURGERY AND / OR RADIOTHERAPY Major Code : Otorhinolaryngology : 62720155 SUMMARY OF DOCTORAL THESIS IN MEDICINE HA NOI – 2020 THESIS COMPLETED AT: HA NOI MEDICAL UNIVERSITY Supervisor: Prof PhD Tong Xuan Thang, MD Reviewer 1: Reviewer 2: Reviewer 3: Thesis will be defended at The Commission for PhD thesis assessment of Ha Noi Medical University At , date Thesis can be consulted at: - National Library of Vietnam - Library of Hanoi Medical University LIST OF RESEARCH WORKS OF THE AUTHOR PUBLISHED RELATED TO THE THESIS Phung Thi Hoa, Tong Xuan Thang, Phan Duc Chinh Vu Truong Phong Le Minh Ky (2017) Evaluating the results of treatment of squamous cell carcinoma of the Hypopharynx of Stage III – IV (M0) with the pre – operation cisplatin – Taxane – 5FU protocol Vietnam Medical Journal, November - Issue 2- In 2017, Vol 460, 82-90 Phung Thi Hoa, Tong Xuan Thang (2019) Evaluation of the response in treatmenting hypopharynx squamous cell carcinoma of stage III-IV (M0) with Cisplatin-Taxane-5 FU prior to surgery and / or radiation therapy Vietnam Journal of Medicine, August- Issue - in 2019, Vol 481, 137-142 Phung Thi Hoa, Tong Xuan Thang (2019) Describe of clinical symptoms and evaluating the treatment response of hypopharynx squamous cell carcinoma of stage III-IV (M0) with Cisplatin-Taxane-5 FU regimen before surgery and / or radiotherapy Vietnam Medical Journal, December - Issue + – in 2019, Vol 485, 239-244 Phung Thi Hoa, Tong Xuan Thang (2019) Results of the response in treating hypopharynx squamous cell carcinoma of stage III – IV (M0) with cisplatin – Taxane – Fu prior to surgery and/ or radiothary Journal of VietNam medical association, June 2019, volume INTRODUCTION Hypopharyngeal Cancer belongs to the upper Aero-Digestive tract In Vietnam, according to Nguyen Tuan Hung, Hypopharyngeal Cancer accounts for the second rank in head and neck cancer, after nasopharyngeal cancer The incidence in men is 2,8/100 000/ year Currently there has been great advance in imaging, histopathology, immunohistochemistry, treatment (surgical, radiotherapy, chemotherapy, target treatment, and prognosis assessment such as P53, HPV, EGFR , A multi-modal treatment strategy has been researched and applied to conserving treatment of organs of anatomical structures and physiological funtions of the hypopharynx-laryngeal region Some chemicals applied to treating hypopharynx and head and neck cancer such as (1970) Leucovorine, Methotrexate, Mitomycin C Bleomycin, (1980) Cisplatin, 5-FU, (1990) Taxane, (2000) Nimotuzunab In which the regimen has Taxane with Cisplatin and 5-FU (TCF- TPFDCF-PCF) gave high-response rates; and about toxicity, undesirable effects are also at the acceptable level In Vietnam, there are only a few studies on Induction ChemoTherapy (ICT) (or adjuvant chemotherapy), followed by radiotherapy, and there has been no research on ICT but the surgery to treat late stage to follow is not available, locally advanced hypopharyngeal cancer Therefore, we conducted the project: "Evaluating the outcome of treatment stage III and IV hypopharyngeal carcinoma with Cisplatin - Taxane and FU before surgery and / or radiotherapy" with the twofollowing goals: Description of clinical and subclinical characteristics, stage III and IV hypopharyngeal carcinoma (M0) Evaluating the response and some toxicity of TCF adjuvant regimen to patients at stage III, IV hypopharyngeal carcinoma (M0) before surgery and/or radiotherapy NEW CONTRIBUTIONS OF THE THESIS 1.This dissertation is the first research into the ENT specialized approach using multi-modal treatment (neoadjuvant regimen (NACT) or induction chemotherapy (ICT) + surgery and / or radiotherapy) Research results have been obtained in terms of clinical and subclinical characteristics data: - The overall response (OR) rate was 73,2% (complete response (CR) 12,2%; partial response (PR) 61,3%) - No response was 26,8% (stable disease 12,2%; progressive disease 7,3%; second primary cancer 7,3%) - The rate of hypopharyngo-laryngeal preservation was 65,9% - Changes in surgical designation after ICT: there were 27/41 patients from no chance of surgery transferred to laryngeal conservative treatment (65,9 %), in which patients had T0 (already undergoing radiation therapy), 21 are transferred to conservative surgery - In reality, 20 patients have had surgery, in which 15 tumor removal combined with lymph node dredging Among 15 said patients, there were being conservatively operated, under Laser surgery and 11 going through radical surgery Among the 11 patients there were patients under flap great breast muscle, another patients have been treated with gastrostomy The rest patients were applied dredging neck lymph nodes - Apart from the above 20 patients, another 21 patients were asked for radiation therapy alone after adjuvant chemotherapy Toxicity and unwanted effects: The toxicity is at a low rate, at level 1, The toxicit includes decreased hemoglobin 61%, platelets 12,2%; digestive disorders 9,8%; leukocyte 4,9%; mild acute renal failure 2,4% Research results in survival time are: - Average life of extra time: 26,655 + 2,911 months, - The survival of the surgical group (with postoperative radiotherapy) is 35months - The radiotherapy group is only 15 months According to Multivariate regression analysis the coefficient obtained is R2 = 0,629: The prognosis is accurate to 62,9% based on the prior ICT response and radical treatment after the previous neoadjuvant The patients who have a certain response rate is 7,202 times as compared with the patients without response rate Chapter OVERVIEW 1.1 History of Studies and Conservative Treatment in Hypopharyngeal Carcinoma 1.1.1 History of the Studies in the World Theodor Billroth, 1873 cuts off the entire larynx Hautant and Aubry, 1940 cut the larynx and throat sections for tumors of immobilized cartilage Section cutting on the glottis Huet (1938), Alonso (1947), Leroux Robert (1955), Ogura (1958) Partial laryngeal resection of the ring to treat Hypopharyngeal Carcinoma (Andre, Pinel, Laccourreye (1962), and Piquet (1974) In 1930 teletherapy radium, radioisotope was used in the UK But the low energy X-ray generator (Kilovolt - KV) and Cobalt - 60 transmitters Gamma rays was invented in the world in the 1960s Computer tomography was invented in 1973 by Godfrey M Hounsfild (British) and Allan Mc Lead Carmack (American) They were awarded Nobel Prize in Biomedical, in 1979 Archer (1984 ) classified radiologic cancer in hypopharyngeal cancer After 1990, the rate of laryngeal preservation increased to 60% thanks to conservative and Laser surgery, modulated radiotherapy and concurent radiotherapy 1.1.2 History of the Studies in Vietnam In 1956 Tran Huu Tuoc, was the first to perform hypopharyngolaryngeal cancer and transferred surgical techniques to his students His famous scientific work is to make use of the good side of the sinus mucosa to reconstruct the hypopharynx after total and partial hypopharyngolaryngeal operation In 1978, 1990, 1993, Tran Huu Tuan reported his surgery for voice restoration In 2002 Nguyen Tien Quang, doctor at K-Hospital summarized 46 patients were treated with external radiation therapy In 2002, Pham Tuan Canh studied the surgery of more than 222 patients of hypopharyngo-laryngyl cancer In 2005, Ngo Thanh Tung reported his two ways of treatments, one with radiation therapy alone and the other with combination chemotherapy for late-stage Hypopharyngeal Cancer In the field of clinical and surgical study, it includes: Nguyen Dinh Phuc, Tong Xuan Thang, Nguyen Quang Trung, Pham Van Huu, Nguyen Quoc Dung, Trinh Xuan Ku, Nguyen Thi Mong Binh, Tran Anh Bich and Tran Minh Truong, Nguyen Nhu Ước In the field of chemical and radiation treatment, it includes: Tu Thi Thanh Huong , Nguyen Thi Thai Hoa, Le Van Quang , Ngo Thanh Tung, Tran Bao Ngoc,, Dam Trong Nghia 1.2 Anatomy and the Spread of Hypopharyngeal Cancer Lymphatic vessels are very rich It drains into the Kuttne, deep neck lymph nodes, viscera, fore- trachea (group VI) The cancer lymph nodes are greater than cm Some indications and surgical methods are different in hypopharyngeal positions, due to differences in anatomy and regional involvement, pathology and treatment: + The notations for Hypopharynx are C12 and C13 The Piriform sinus, is noted as C12.9 Its damage to the thyroid cartilage would spread to the front of the neck, the mouth and throat, the sides of the throat, down to the mouth of the esophagus, then to the cartilaginous ring cartilage, to the upper and lower pharynx It is possible to entirely or partially remove it + The pharyngo oesophageal junction (or postcrico-arytenoid) is noted as C 13.0 The lesion spreads the cartilaginous ring cartilage which forms the anterior wall of the hypopharynx, then it spreads to the esophagus, When cutting-off the pharyngo oesophageal junction, the rectum (or stomach) must be removed to be replace + Posterior pharyngeal wall is noted as C13.2 The cancer of C13.2 spreads to the front of the cervical spine The injury spreads to the oral tongue, oral pharynx, lower cartilage margin, down to the esophagus The surgery requires orthopedic skin flap or free covering of the front of the cervical spine (From: UICC, TNM Classification Malignant Tumors, Eighth Edition - 2018.) 1.3 Epidemiology: characteristics, causes and risk factors 1.3.1 Epidemiology - In 2018, there were 80600 new patients that include 67500 male (83,6%), female 13100 (16,4%), and 35000 deaths (43,4%) In the USA, there were 29400 male (91,8%) and 5600 female (9,2%) -In Vietnam: Hypopharyngeal Cancer ranks second in head and neck cancers and its incidence in male is 2,8 /100 000 /year, female is 0,3 /100 000/year The average age of the cancer is 53 years old, in which male accounted for 91,2%; female 8,8% In the research conducted by Pham Tuan Canh et al over 222 patients with throat cancer there were 31,1% hypopharyngeal cancer among them 95,45% were men Compared with European-American authors, in Vietnam, throat cancer is lower in age, but the incidence in men is higher 1.3.2 Causes and risk factors The causes and risk factors found in the patients are as following: - Alcohole-tobacco: 85% throat-related cancers were related to alcohol-tobacco - Occupation: According to Tran Huu Tuan's research in the field of occupation, farming occupies 64,6% and handicrafts, with 15%, in the rural areas which is times as many as in the city - HPV virus: not highly positive in hypopharyngeal cancer, but in HPV-positive patients has a better survival prognosis 1.4 Pathological characteristics of hypopharyngeal cancer 1.4.1 Clinical characteristics - Functional symptoms: Dysphagia (is from 61,3% to 66,6%) , swallowing pain (30 - 40%), disorders of voice (25% to 50%), cough expectorant with bloody mucus, bad breath, weight loss (78,3%) - Physical symptoms: Early cervical lymph nodes in the primary tumor range from 10-20% - The precancerous entity transformation over production, red property, leukoplakia, hyperplasia (mildly thick mucous mucosa), whitish (easily bleed), endoscopic examination and biopsy (carcinoma inssitu), papillpma (HPV) must be treated early and thoroughly - Morphological lesions of hypopharyngeal: vegetative (warts), ulcers, infiltrates, necrosis and coordination The wart can be found above 85% The location of the lesion originating from throat cancer is more than 75% The lesions are widespread to: the larynx, up the throat, destroy the cartilage cartilage, and in front of the larynx, spread behind the funnel area, down the mouth of the esophagus, , esophagus cervical spine, lymph nodes: (60 - 75%) 1.4.2 Subclinical characteristics 1.4.2.1 Histopathology is rge gold standard and definite diagnosis Hypopharyngeal cancer is squamous cell carcinoma, accounting for 95% The degree of differentiation is divided by degrees of malignancy (Grade) In practice is three levels of differentiation for clinical prognosis, which include high, moderate and less differentiated Histopathologycal examination are the cell aspiration, the needle biopsy (under ultrasound), the test markers of cancer anđ HPV, and diagnosis of metastatic neck lymph nodes and the second cancer 1.4.2.2 About imaging diagnosis: CT or MRI scan It must the 0,6mm multi-sectional area FDG - PET/ CT: is the early detection of malignant tumors, and distant metastatic tumors, and accurate location of primary tumors and regional lymph nodes Ultrasound is the detection of regional metastatic lymph nodes 1.4.2.3 Basic tests: There are the blood formula, blood biochemistry, blood group, liver and kidney function, the bilan before treatment and after treatment 1.4.3 Diagnosis of Hypopharyngeal cancer 1.4.3.1 Definitive diagnosis: It is based on clinical (indirect examination, , optic hard and soft endosscopy, panendoscopy); and on biopsy and on histopathological diagnosis, and on cytology aspiration, and on imaging diagnosis (CT, ultrasound, or MRI, or PET / CT) 1.4.3.2 Diagnosis pTNM is according to AJCC 2010: Stage (S) SIII: T3N0M0 or T1-3N1M0; SIVa: T4a (N0-N2) M0 or (T1-T3) N2M0; SIVb: T4b (any N) M0 or (Anything) N3M0; SIVc: (Any T) (Any N) M1 1.4.4 Treatment 1.4.4.1 Surgical treatment Indications for surgery (according to NCCN Guideline Head and Neck Cancer Version 1.2018): -T1, T2 (N0): Surgery for conserving the throat and larynx (sugar open or laparoscopic) and one or two-sided lymph node dredge, ( It is include the partial thyrotomy and lymph nodes near the trachea one or both sides -T2, T3 (any N), T1 (N +): Hypopharyngolaryngectomy partial or total (with cervical lymph node dredge, thyroidectomy and tracheotomy) -T4a (Regardless of N): Total hypopharyngolaryngectomy, partial or total thyroidectomy, and dredging lymph nodes next to the trachea.Or It is include neoadjuvant chemotherapy before surgery -T4b: Inoperable (Chemical - Radiotherapy) -M1: Inoperable (Chemical-Radiotherapy) Surgical methods: + conservative operation - Partial hypopharyngectomy - Supracricoid Hemihypopharyngolaryngectomy (Endoscopic CO2 laser resection) -Transoral Robotic Surgery (T1, T2) + Radical operation - Total hypopharyngolaryngectomy - Hypopharyngolaryngoesophagectomy (indication: the tumor is spreads to the esophagus T4a) - Surgery to restore the hypopharygolarynx: (the skin flap, large chest muscle, the jejunum (stomach) to replace the esophagus and throat tube) - Cervical lymph node dredge: (selective, functional, and radical dredge of either or both) 1.4.4.2 Radiotherapy (IMRT or 3D) (NCCN Guidrline Head and Nrck Cancer Version 1.2018) +Simultaneous radiation therapy: High dose 70 Gy daily 2.0 Gy (Low dose 44-50 Gy Routine radiotherapy: High dose of 60 Gy daily 2.2 or 2.0 Gy The average dose of 44-50 Gy) +Postoperative radiotherapy: Routine or simultaneous radiotherapy: (Height of 60 Gy daily 2.2 or 2.0 Gy The average dose of 44-50 Gy) 1.4.4.3 EGFR imprint and target treatment: Epidermal growth factor (EGFR in the treatment of lung and breast cancer Nimotuzumab is used in the treatment of head cancer 1.5.Treatment of neoadjuvant chemotherapy (NACT) or Induction chemotherapy in hypopharyngeal carcinoma 1.5.1 Chemotherapy is a method of treatment using chemical drugs that cause cytotoxic to kill malignant cells Chemotherapy is one of the methods to combine with radiation, surgery, and immunology 1.5.2 Definition “Neoadjuvant or Induction chemotherapy is a method of chemotherapy used before the initial treatment This makes treatment easier and increases the chance of cure The adjuvant chemotherapy will transmit from two to three waves of chemicals, in order to reduce the volume of primary tumors and metastatic lymph nodes The next radical treatments are surgery or radiotherapy which/ includes concurrent chemoradiotherapy, adjuvant chemotherapy,sequencial chemoradiothera py, alternating chemoradiotherap 1.5.3 Some adjuvant - Induction chemotherapy regimens in advance 1.5.3.1 Some adjuvant - Induction chemotherapy regimens in advance are used clinically: (1) TCF regimen with Docetaxel; (2) TCF regimen with Palitaxel; (3) PFL regimen; (4) TC regimen with Palitaxel; (5) PF regimen; (6) Docetaxel regimen; (7) Methotrexate regimen; (8) Palitaxel regimen 1.5.3.2 The main chemicals in the adjuvant chemical include: Cisplatin, Docetaxel, 5FU 1.5.4 A number of studies on neoadjuvant chemotherapy before advanced throat cancer 1.5.4.1 The Studies on adjuvant chemotherapy in the World In 1989 as a report from Lefebvre JL et al over 2418 patients were diagnosed with AD and radiotherapy between the period of 1976 1980 The repor yields the survival rate after one year of treatment is 2/3, three years 1/3; five years 1/4; eight years 1/7 (numbers ò patien) Laryngeal tumors have a better prognosis than lower throat In 1997,Alan Y.C Cheung, et al at Taxes - USA, has studied the ICT and radiotherapy for patients with hypopharyngolaryngeal cancer at the stage III – IV The result yields the overal response 84%, complete response 42 % In 2009, Yaonn Pointreau, has conducted a research a neoadjuvant chemotherapy with TPF for 213 patients, of hypopharyngolaryngeal cancer at the stages III and IV The repor yields the overal response 80% (complete response 41.8%, partial response 38.2%) With the above advantages WHO has allowed the use of neoadjuvant chemotherapy in all T and N stages, locally advanced tumors T3, T4 to N3 or had metastases 1.5.4.1 The Studies on adjuvant chemotherapy in Vietnam In 2006, Tu Thi Thanh Huong has studied the ICT (Cisplatin and 5Fluorouracil) for 51 patients with pharyngeal, hypopharyngeal, laryngeal cancer at the stage III- IV (M0) at K hospital, between the period of 2002-2006 The repor yields The overall response to the tumor was 80,4%; complete response 25,5%; stability 19,0%; complete response to the lymph nodes 37,3%; partial response to the lymph nodes 47,1%; stability to the lymph nodes 17,6% In 2012, Le Van Quang has conducted a research on treatement of ICT for 117 patients with tongue cancer at the stage III, IV (M0), the CF-PF regimen, before and / or radiotherapy The result yields the complete response of 12%, partial response of 50,4%; stability 30,8%; progression 6,8%; Especially, the are 52,1% of patients Which is changed from inoperable to surgery, the overall survival rate after one year of treatment is 75,2%, and two year 57,5%; three years 45,2%; four year39,2%; five years 22,4% A very well-established study has provided a demonstration of the good effects of adjuvant chemicals In 2016, Le Minh Ky has the study on ICT, over 25 patients at the stage advanced hypopharyngeal cancer (T3-4, N1-2-3, M0) The reported yields, complete reponse 28%, partial reponse 60 %, stability 8%, progression 4% In 2018, Dam Trong Nghia has conducted a research the ICT for 41 hypopharyngolaryngeal cancer stage III, IV (M0), with the PF regimen The result yields the overall response 78% (complete reponse 2,4% , partial response 75,6% In Vietnam, there is no research on neoadjuvant or induction chemotherapy in hypopharyngeal carcinoma before surgery So that, I made this thesis Y U F M D S IN A -P J B O E H T r2 te p a h C 2.1 Research Target Patients The research covers 41 Hypopharyngeal squamous cell carcinoma.at stage T3-4 (M0) All of them fully receive three cycles of neoadjuvant chemotherapy (NACT) or induction chemotherapy (ICT), (cisplatin, docetaxel, 5FU symbolised as (TCF) regimen Following this is surgery and postoperative radiotherapy, or single radiotherapy The research was implemented at National Otolaryngology Hospital from December 2015 to August 2019 and regulary examined This process goes on until 2/2020 to define the survival rate 10 the anatomical planes (9) Cervical lymph nodes lesions on ultrasound: Metastatic lymph nodes of the neck, abdomen: location size reduced or increased, central necrosis, ganglion, fibrosis (10) At upper gastrointestinal tract: Detecting and eliminating 2nd cancer (11) Metastases far from whole body: Di radiomas, liver, kidney, spleen, and abdominal conditions (12) Histopathological diagnosis: squamous cell carcinoma, Grade 1-4, cell degeneration rate Lymph nodes metastasize, rupture, central necrosis, microvascular - nerve invasion (13) Systemic bilan: Leukemia ≥ G / L Hemoglobin ≥ 125g / l, Platelets ≥ 150G / LAST / ALT ≤ 40 UI / l, Creatinin ≤ 100 mmol / l- Blood glucose, electrolytes - ECG, respiratory function (14) Panendoscopy or flexible tube examination of the throat - lower throat - esophagus, bronchial gas C- Diagnosis of pTNMS: (15) pT3, T4; (16) pN (1,2,3); (17) pS (III, IV) - AJCC 2010 Tools and methods for data collection for objective 1: Clinical examination, Endoscopy, CT, Ultrasound, histopathological diagnosis of biopsy, Panendoscopy or soft-tube endoscopy 2.2.3.2 Content of objective research B1- Response evaluation: The response according to RECIDS * Perform neoadjuvant chemotherapy: Docetaxel (dose 50mg / m2 of skin area, mixed in 250ml of 5% sugar, infused in hour), followed by Cisplatin (dose of 75mg / m2 of skin area, mixed with 200 ml of solution 0.9% saline serous fluid, slow intravenous infusion of 40 drops / minute on day 1); 5-Fluorouracil (dose 750mg / m2 body area, intravenous injection on 2-5) A cycle of 21 days, infusion cycles * Clinical examination, tests to assess the response of tumors and lymph nodes (RECIST): (18) Evaluation of overall response: Complete / partial / partial / unchanged - stable / progressive response - secondary cancer (19) Response to functional symptoms: (20) Response to physical symptoms (21) Response to pTNMS diagnosis, (22) Response to Grade histopathology B3 Evaluation of indicative changes and surgical methods (23) Indications for surgery before the CID; (24) Changes in surgical design after CAB; (25) Surgical methods used; (26) Surgical complications; (27) Treatment results B2- Assessment of toxicity and undesirable effects after neoadjuvant chemotherapy + Toxicity and unwanted effects after adjuvant chemicals on hematopoietic system (28); Outside the hematopoietic system (29); Toxicity and undesirable effects of adjuvant chemicals with TCF-3 cycle regimen (30) B4 Live more after treatment (31) Overall living standard, extra living according to Kaplan-Meier analysis,: (32) Relevance of extra living according to response; (33) under surgery; radiotherapy; (34) by pTNMS diagnosis; (35) Multivariate 11 regression analysis of the response of CBCI, surgery and radiation treatments with additional survival time 2.2.4 Steps to conduct research Step 1: Clinical diagnosis Diagnostic Imaging Diagnostic Anatomy pathology Step 2: Perform diagnostic procedures: Hanging biopsy, Panendoscopy (or soft tube examination) Step Complete the profile + medical record and explain the procedure for the patient Step 4: Post abortion with full control of TCF and Evaluation according to RECIST1 and some clinical features Indications for treatment according to response (Choice of surgical / radiotherapy patients) Step 5: Assessment of toxicity and undesirable effects WHO 2000 Step 6: Surgical treatment after HCBTT Postoperative care, radiotherapy Periodical monitoring Evaluate the results Step 7: Evaluate the outcome of survival, treat MCM with surgery and radiation Chemicals: Cisplatin: EBWE Arzneimittel Ges.m.b.H, Austria.Docetaxel: Sanofi - Aventis Deutschland - Germary5FU: EBWE Arzneimittel Ges.m.b.H, Austria 2.2.5 Tools and methods for data collection: Statistical algorithms: (mean, standard deviation, max, min) Comparative test: (For qualitative variables using comparative test χ2 , statistically significant comparisons with p ≤ 0,05; T - Student for mean comparison (p ≤ 0,05); Kaplan-Meier analysis Chapter RESULTS 3.1 Describe the clinical, subclinical characteristics of stage III IV(M0) Hypopharyngeal squamous cell carcinoma 3.1.1 Clinical characteristics + The lowest age is 35, the highest age is 65 The common age group is 51-60 (53,7%) Average age 52,3 ± 7,3; 100% of men + Time of disease progression: 95,3% of examination and treatment patients in the first months (from 3-6 months, only patient has a fast enlargement of neck lymph nodes) After months 9,8% Reasons for admission to the hospital with swallowing disorders: 100% with disorders of the larynx coughing and spitting blood 48,8%; hoarseness 22%, difficulty breathing 14,6%; lymph nodes to enlarge 14,6% Tumors of sinus periforme 85,4%; posterior pharyngeal wall and back of funnel rings have 7,3%), (p 0,05) From 28 patients with T3 and 13 patients with T4, after cycles after the previous adjuvant, patients in T3 and patients in T4 were reduced Before after the adjuvant, there were no T2, T1, T0, after the previous adjuvant, there were 27 patients, only with T2, there were 16 patients with CI(95% going from 24,6% ÷ 53,4% + Evaluation of response according to pN diagnosis: Before treatment there were 16 patients with N (0) classification (39,1%), after treatment increased to 23 N0 (56,1%), N1 from patients increased to 14 patients and N2 from 16 decreased to patients, N3 was no longer The lymph node response rate was 39,1% But there were patients (7,3%) with N (+) from N0 + Evaluation of response according to pS: SIII diagnosis reached 82,3% (CI(95% = 62,7% ÷ 100%); SIVa reached 65,2% (CI(95% = 44,6% ÷ 85,8%) Before after the auxiliary chemical, there was no SI-SII, after the 14 previous auxiliary chemical, there were 17 patients with S0, SI and SII And only patients in SIV (compared with before HC had 24 patients), (p