1. Overview
Laryngeal carcinoma is a common malignant tumor of the head and neck, 96%-98% of which are squamous cell carcinoma, while other pathological types are rare. The incidence of laryngeal carcinoma has increased significantly in recent years, and the age of onset is 40-60 years old most often.
There are racial and regional differences in the incidence of laryngeal cancer. Although there is a lack of large-scale epidemiological survey data in China, scholars recognize that the incidence rate in northern and northeastern China is much higher than that in southern provinces. Some data show that the global incidence rate of laryngeal cancer in 2008 was less than 6.0/100,000 people, which is lower than that reported in previous textbooks (7.0~16.2)/100,000 people. The etiology of laryngeal cancer is still not clear, but epidemiological data confirm that it is related to smoking and alcohol consumption, viral infections, environmental and occupational factors, radiation, micronutrient deficiencies, and disorders of sex hormone metabolism, and is often the result of the synergistic effect of multiple carcinogenic factors.
According to the site and area of tumor, laryngeal cancer is clinically divided into three types, including supraglottic, glottic and subglottic types, which are characterized by local infiltration and metastasis. The clinical treatment mainly adopts the multidisciplinary comprehensive treatment mainly based on surgery. To completely eradicate the tumor lesion while preserving and reconstructing the function of larynx as much as possible, and to improve the survival quality of patients while curing the tumor is the recognized treatment principle and ideal goal of scholars in recent years.
1.1 Pre-surgical evaluation of laryngeal cancer
A comprehensive assessment of the patient and tumor before laryngeal cancer surgery is essential for choosing the correct and effective treatment plan.
It mainly includes two aspects: patient condition and lung tumor condition assessment.
1.2 Patient assessment
Assessment of systemic condition: The assessment of patient’s systemic condition should be combined with medical history, physical examination, laboratory examination, assessment of vital organ function and special examination related to the disease. Understand the relationship between the systemic condition and the nature of the disease, pay attention to the changes in the systemic condition caused by the disease, and clarify the impact of the current systemic condition on the disease itself and the anticipated surgery. Pay attention to the correction of anemia, dehydration and other adverse factors that can be corrected in a relatively short period of time Among the systemic conditions, common problems of the cardiovascular system are heart disease, arrhythmia, heart failure, hypertension, etc., which must be controlled to a reasonable degree and level.
Pulmonary function is assessed to understand the patient’s compensatory reserve function and to predict the likelihood of postoperative complications. The presence of renal impairment in the patient should be noted. The main assessment of the digestive system is liver function, and severe liver impairment can significantly reduce the patient’s tolerance for surgery. Endocrine system assessment is mainly for hyperglycemia, and blood glucose level must be controlled before surgery can be performed.
Assessment of other conditions: Depending on the tumor site, size, scope and stage, the treatment of laryngeal cancer will have different degrees of damage and impact on the structure and function of the larynx. Therefore, in addition to tumor factors, the patient’s occupation, living habits, education level, religion, family status and financial ability may have an impact on the choice of treatment modality, which needs to be treated, considered and evaluated seriously.
Meanwhile, patients’ spiritual and psychological status, patients’ and family members’ understanding of the disease itself and treatment, as well as their choice of treatment modality, willingness to retain laryngeal function and expectations of treatment outcome are all important elements that need to be carefully understood, communicated and included in the assessment, which determine patients’ compliance and understanding of the treatment plan and are part of the reference basis for the choice of treatment modality.
1, 3 Oncologic assessment
1, 3, 1 Specialized evaluation: It occupies an important position in preoperative diagnosis and comprehensive review of tumor and is an important means to obtain basic information about tumor.
History, symptom and sign collection: Careful questioning of the chief complaint and related medical problems, personal history (especially the duration and amount of smoking and alcohol consumption and family history of malignancy) should be performed to determine the lesion By careful history taking and symptom and sign collection as well as complete systematic review, it is often possible to initially determine the lesion site and the extent of invasion.
Physical examination: The larynx is examined using indirect laryngoscopy for initial observation of the tumor, but further endoscopic adjuncts are often required due to the patient’s sensitive pharyngeal reflex and structural changes in the morphology of the epiglottis that prevent observation of the anterior commissure. Palpation of all supraclavicular areas is performed to look for cervical metastases or extra-laryngeal spread.
Specialized adjuvant examinations: The most important endoscopic adjuvant examinations are to observe the site of the lesion, the general presentation and growth pattern of the tumor, and to assess the involvement of the lingual root, epiglottis, epiglottic valley, aryepiglottic folds, aryepiglottic cartilage, pseudo-vocal cords in the interaryepiglottic region, laryngeal chambers, true vocal cords, subglottis, and some anatomic subregions of the hypopharynx. Electronic (fiber) laryngoscopy can be used in combination with dynamic laryngoscopy to also directly observe the laryngeal structures, mucosal changes, and vocal fold activity, and to make a pathologic diagnosis by biopsy.
1,3,2 Other auxiliary examinations: mainly include pathological examination and imaging examination, which can provide further detailed information for determining the nature, extent and expansion of the tumor.
Pathological examination: Although squamous cell carcinoma of the larynx accounts for the majority of laryngeal neoplasms, biopsy pathology is still needed to obtain the most reliable diagnostic basis before finalizing the treatment plan. If there is high clinical suspicion of malignancy, repeated biopsies are required.
Imaging examinations: mainly include ultrasonography, CT, MRI and PET examination. For tumor staging, imaging can provide valuable anatomical information and also help to make preliminary determination of resectability of the primary tumor for surgical planning. ‘
Combining the advantages of CT to show anatomical details and PET to show subtle changes in metabolism, it can detect contemporaneous or metastatic lesions and target biopsies of metabolically active areas [5] to finally clarify the nature of the tumor.
Ultrasonography: It has the advantages of easy operation, non-invasive, real-time dynamic, and low price, etc. The high-frequency probe has low near-field interference and high image resolution, which can determine the origin of neck tumors and the nature of lesions, and can reflect the size (resolution can reach more than 2 mm), shape and extent of cervical lymph nodes more accurately, and can also observe the relationship between tumors and blood vessels from horizontal, vertical or oblique directions.
CT examination: It is one of the main evaluation methods for preoperative diagnosis and clinical staging of laryngeal cancer, which can directly show the structural morphological changes of the soft tissues in the larynx and the parapharyngeal space, the anterior epiglottis space, the subglottis area, and the external neck of the larynx, and determine whether the cartilage is destroyed, which is very helpful for preoperative staging of tumors and the accuracy of diagnosing cervical lymph node metastasis [1-3]. CT enhancement scan is especially important in the evaluation of laryngeal cancer.
MRI: CT or MRI from the base of the skull down to the clavicle can be the initial choice for imaging. t2-weighted MRI can sensitively detect submucosal invasion of the anterior epiglottis and paraventricular space. ct is more specific and less sensitive than MRI for the diagnosis of thyroid cartilage involvement [2, 4]. Although MRI imaging can be helpful in determining the involvement of blood vessels and soft tissue structures, it is not used as a routine preoperative examination.
PET-CT examination: In patients with distant metastasis and recurrence of tumor, PET-CT examination is feasible when available. Since PET_CT combines CT to show anatomical details and PET to show subtle changes of metabolism, it can detect simultaneous or metastatic lesions and biopsy the metabolically active area in a targeted manner to finally clarify the nature of tumor.
2. Laser surgery for laryngeal cancer microsurgery
Laser (lightamplificationbystimulatedemissionofradiation, Laser) is a new science and technology that has developed exceptionally rapidly since the 1960s. The laser beam produced by using high power or high energy lasers can produce strong thermal effects on biological tissues after focusing, thus achieving the cutting, vaporization and coagulation of biological tissues. Laser laryngeal surgery applies laser technology to laryngeal microsurgery, so that the superiority of both is superimposed on each other. It has the following advantages over conventional (i) surgery.
(i) Less injury and no need for neck incision and tracheotomy.
(ii) Good functional preservation.
(iii) It has the advantages of short operation time and less patient pain. However, transoral supported laryngoscopic surgery has certain limitations in both exposure and resection, and should be used rationally [6].
2, 1 Equipment conditions for surgery
①Laser machine: CO2 laser machine is mostly used in clinical practice.
② Support laryngoscope and laryngeal microsurgical instruments.
(iii) Microscope: The focal length of the required microscope should be above 350 mm.
(B) Indications for surgery
Patients should be able to tolerate general anesthesia and supported laryngoscopic operation mainly for the treatment of early-stage acoustic and supraglottic laryngeal cancer. The lesions suitable for laser surgery should be fully exposable under the supported laryngoscope, all lung tumor circles should be in the field of view, and the tumor should be completely resected in the area reachable by the laser beam [7-8].
1, Τ1-Τ2 stage vocal fold type laryngeal cancer: T1a stage lesions of vocal fold carcinoma in situ are preferred, as well as Tlb and T2 vocal fold carcinomas that can be fully exposed.
2, stage T1-Τ2 supraglottic laryngeal carcinoma.
3.Limited carcinoma of the aryepiglottic folds.
2.2 Tumor resection and cervical lymph node management
Tumor resection should follow the principles of surgical oncology, and resection should be performed at the periphery of the tumor. A safe boundary of more than 3 mm should be preserved during surgical resection of acoustic laryngeal carcinoma, and more than 5 mm of supraglottic laryngeal carcinoma should be preserved for pathological examination of the cut edge during surgery to ensure the safety of the cut edge [9].
Whether transoral laser surgery or open surgery for laryngeal cancer, the principles of treatment for the neck are the same. The treatment of lymphatic tissues in the neck should be performed simultaneously with laser surgery to remove the local lesion according to the extent of the lesion and the neck examination. For patients who are unwilling to undergo open surgery, postoperative neck radiotherapy is feasible to control lymphatic metastasis. If the local lesion is very limited and no lymph node enlargement is found in the neck examination, observation and follow-up may also be chosen [10-11].
3. Open partial laryngectomy for laryngeal cancer
The theoretical basis of partial laryngectomy to preserve laryngeal function is that from the perspective of embryogenesis, the left and right sides of the larynx and the upper and lower parts of the vocal cords are fused separately; from the perspective of anatomy, the lymphatic drainage of the left and right sides of the larynx and the upper and lower parts of the vocal cords are each formed into a system, and there are clear boundaries between the various regions of the larynx; from the perspective of pathology, serial sections of laryngeal cancer specimens have confirmed the development and spread of laryngeal cancer in each anatomical region. It is proved that it is feasible to preserve the normal part of the larynx under the principle of complete resection of the tumor and restore all or part of the functions of the larynx through repair, and the tumor resection effect is not inferior to total laryngectomy [12-15].
3.1 Selection of surgical methods for preserving laryngeal function in supraglottic laryngeal cancer
1.For stage T1 supraglottic laryngeal carcinoma with poor laryngoscopic exposure, horizontal partial laryngectomy can be chosen [11].
2. For stage T1_T3 lesions limited to the epiglottis, laryngeal vestibule or aryepiglottic folds, without involving the aryepiglottic cartilage, laryngeal ventricular floor and anterior commissure, horizontal partial laryngectomy can be chosen [16].
Τ3 stage supraglottic laryngeal carcinoma involving one side of the arytenoid cartilage with fixed vocal folds on that side and good vocal fold movement on the opposite side can be selected for expanded laryngeal horizontal
partial resection or laryngeal horizontal plus vertical (3/4) partial resection [16]. The cricoid cartilage supraglottic partial laryngectomy ring – hyoid fixation (SCPL-CHP) can also be chosen.
4, Stage T4 supraglottic laryngeal carcinoma involving the epiglottis valley or tongue root, not exceeding the contour papillae in the forward direction, preoperative pulmonary function assessment estimating that the patient can tolerate misaspiration during swallowing training, and bilateral vocal fold live, an enlarged horizontal partial laryngectomy with myofascial flap extension of the strap muscle to repair the tongue root can be chosen [16].
3, 2 Choice of surgical approach for preserving laryngeal function in vocal fold type laryngeal cancer
1. For T1a or T2 stage vocal hilar laryngeal carcinoma with poor laryngoscopic exposure, vertical partial laryngectomy can be chosen [17].
2. For T1b stage vocal hilar laryngeal cancer, vertical partial laryngectomy can be chosen [18].
3.For stage T2 hilar laryngeal cancer with forward involvement of the anterior commissure, horizontal partial laryngectomy can be chosen [19].
4.For stage T3 hilar laryngeal carcinoma with tumor involving the hemilarynx and fixed vocal cords, vertical partial laryngectomy can be chosen [19].
5.For stage T3 hilar laryngeal carcinoma, the tumor involves one half of the larynx and the front of the anterior connecting and most vocal folds, one side of the vocal folds is fixed, and the opposite side of the vocal folds has normal activity, so subtotal laryngectomy can be chosen [20-21]. The cricoid cartilage supraglottic partial laryngectomy ring – glottis – epiglottis fixation (SCPL-CHEP) can also be chosen.
6. Stage T4 acoustic laryngeal cancer with tumor located in the anterior coalition, total resection. SCPL-CHEP or SCPL-CHP can also be chosen.
(vii) In addition, SCPL-CHEP or SCPL-CHP can also be chosen for Tla stage vocal fold laryngeal carcinoma with anterior commissure involvement, Tib stage vocal fold laryngeal carcinoma with or without anterior commissure involvement, unilateral or bilateral T2 stage vocal fold laryngeal carcinoma with or without fixation of one vocal cord, and partial T3 stage vocal fold laryngeal carcinoma with good arytenoid cartilage activity on at least one side [12, 22-23].
3, 3 Choice of surgical approach for preserving laryngeal function in subglottic laryngeal carcinoma
3, 3, 1 Tumors that originate in the subglottic region on one side and involve the vocal folds, laryngeal chambers, and ventricular bands upward, with normal contralateral laryngeal cavity and good vocal fold activity, can be selected for vertical partial laryngectomy [24].
3,3,2 Tumors originating in the anterior conjoined subglottic region, involving the anterior part of the vocal cords and ventricular bands bilaterally, with no involvement of the epiglottis and no involvement of the conformal cartilage bilaterally, can be selected for enlarged vertical partial laryngectomy.
3,4 Others
For the defects after partial laryngectomy, the anterior cervical band muscle myofascial flap (such as single-tipped or double-tipped sternocleidomastoid muscle myofascial flap, double-tipped relay muscle thyroid cartilage flap), broad cervical muscle flap, sternocleidomastoid muscle clavicular periosteal flap and inferior displacement of the epiglottis can be used alone or in combination for repair according to the actual need to reconstruct the laryngeal function. For patients with locally advanced laryngeal cancer and recurrent laryngeal cancer after surgery and radiotherapy who are not suitable for the above-mentioned surgery to preserve laryngeal function, comprehensive and adjuvant treatment such as total laryngectomy or radiotherapy is needed.
4. Cervical lymphatic dissection for laryngeal cancer
Lymph node metastasis in the neck of laryngeal cancer has a certain regularity, and metastatic cancer metastasizes from near to distant lymph nodes along the direction of lymphatic drainage. Among patients with no clinically enlarged lymph nodes out (cN0), i.e., those diagnosed and found to have enlarged nodes by various imaging, supraglottic laryngeal cancer has the characteristic of being prone to cervical lymph node metastasis, and the possibility of potential or occult metastasis is higher [25]. Cervical lymphatic metastases are rare in the early stage of the acoustic hilar type [26]. Usually, cervical lymph node metastasis in laryngeal cancer frequently occurs in zones II-IV, and metastasis in zone V is uncommon [27], and elective cervical lymphadenectomy refers to the clearance of 2 or fewer zones, which in laryngeal cancer mainly refers to zones IIa and III [28-29]. Depending on the metastatic status of the cervical lymph nodes and the T-stage of the primary laryngeal cancer, different cervical clearance strategies are adopted.
The following principles should be taken into account in the implementation of neck clearance.
(1) Whether to use bilateral neck clearance for early stage (T1-T2) supraglottic laryngeal cancer depends on whether the primary lesion crosses the midline or not If the lesion is only on one side, unilateral clearance is recommended [30-31].
(2) The decision to preserve the paramedian nerve, sternocleidomastoid muscle and internal jugular vein should be based on whether the tumor invades.
(3) subglottic invasion or subglottic lesion of laryngeal cancer requires surgery including ipsilateral tracheoesophageal lymph (VI area); (4) if postoperative pathology has multiple lymph node metastases, additional postoperative radiotherapy is recommended, and if extra-peripheral lymph node invasion occurs, simultaneous postoperative radiotherapy is recommended.
5. Surgery to save recurrence of laryngeal cancer after treatment
5.1 Classification of recurrence of laryngeal cancer after treatment
Regardless of the initial treatment method, recurrence of laryngeal cancer after treatment can be classified into the following types.
(1) In situ recurrence: recurrent tumor is more confined to the site of primary tumor of larynx.
(2) Local recurrence: tumor directly spreads and breaks through outside the larynx, and adjacent organs outside the larynx are invaded, such as invasion of tongue root, hypopharynx, cervical esophagus, skin and thyroid gland.
(3) regional recurrence: combined or alone manifesting as metastatic recurrence of cervical lymph nodes.
(4) Tracheostomy recurrence. Sometimes multiple recurrence modalities can coexist.
5.2 Selection of indications for salvage surgery
Due to the invasive growth of recurrent tumor, wide infiltration, poor physical condition of patients who have received radiotherapy and surgery, disorder of anatomical structure at the surgical site, and destruction of vascular bed leading to weakened tissue repair ability, re-operation is challenging, and postoperative repair and reconstruction is more difficult. According to the different types of tumor recurrence, different methods are adopted for salvage surgery treatment after determining the indications.
(i) In situ recurrence: Salvage surgery is the most effective treatment for early recurrent laryngeal cancer. For cases of simple recurrence in situ, total laryngectomy or partial laryngectomy should be considered. Conditions permitting, patients (but not all patients) with early vocal and supraglottic laryngeal cancer and in situ recurrence after initial radiation therapy are suitable to choose partial laryngectomy for salvage, and organ surgery for in situ recurrence can choose secondary laser surgery or partial laryngectomy for salvage [32].
(ii) Local recurrence: for those who underwent partial laryngectomy for the first surgery, total laryngeal excision or expanded excision of the recurrent foci is generally preferred in local recurrence, and laryngeal function-preserving surgery can also be considered in some cases limited to recurrence with intra-laryngeal. In cases with invasion of the vocal fold area but not beyond the laryngeal cavity (T1, T2, and some T3 stages), supra-cricoid partial resection, including crico-hypophyseal-epiglottic fixation (CHP/CHEP), can be considered in those who can preserve at least one side of the arytenoid cartilage and can be followed by a satisfactory safety border after complete resection of the disease.
Some studies have shown [33-34] that CHP or CHEP performed in selected cases of recurrent laryngeal carcinoma provides better control of the local lesion with functional preservation. If the invasion of the tumor is extensive, total laryngectomy is inevitable, especially when the tumor extends beyond the larynx and involves the hypopharynx, cervical esophagus, cervical trachea and tongue root, or even breaks through the thyroid cartilage plate to involve the thyroid gland and neck skin, the huge defect formed after surgical resection of the tumor needs to be repaired with a tissue flap.
(iii) Regional recurrence: For those who have not performed cervical lymphatic dissection in the past, because the anatomical markings of the neck are not destroyed, the fascial gap exists, and there are relative boundaries to separate the vascular neck, the salvage surgery is difficult but can still be performed according to the standard neck dissection. If transcervical clearance or expanded neck clearance has been performed previously. Recurrent tumors in the neck are often closely related to the carotid artery, so it is very important to dissect and protect the carotid artery.
Since surgery and radiotherapy have been performed, anatomic landmarks are unclear, scar adhesions are present, and surgical risks are high, so separation and dissection of the carotid artery should be performed carefully, dissecting out the distal and proximal ends of the carotid segment first and then the middle segment, which can be ligated in time to stop bleeding in case of accidental rupture of the artery [35]. For recurrent carcinoma of the neck that cannot be separated from the carotid artery, the treatment can be performed by cervical arteriotomy with one-stage vascular grafting when available, otherwise palliative treatment should be used.
(iv) Tracheostomy recurrence [36]: Recurrent tumor is located around the stoma, and the enlarged tumor and/or necrotic bleeding can block the airway and lead to asphyxia, which directly threatens the life of patients, especially for patients with low tracheotomy, because the lesion is close to the upper mediastinum and closer to the great vessels. Stoma recurrent cancer is considered to be a more serious type of recurrence after total laryngectomy, with a poor prognosis and more difficult treatment. Stoma recurrent cancer is considered to be a serious type of recurrence after total laryngectomy with poor prognosis and more difficult to treat. Stoma recurrent cancer is insensitive to radiotherapy, and surgery is risky with serious and complicated postoperative complications. However, surgery can only effectively relieve the patient’s airway obstruction and is the most important treatment method to prolong the patient’s life. Removal of recurrent cancer sometimes requires upper longitudinal and transverse exposure and tissue flap repair, and sometimes requires stoma of the tracheal dissection on the anterior cervical metastatic flap or cleft sternum low tracheostomy on the chest.
5.3 Management of Complications
There are relatively many complications after laryngeal recurrent cancer retrieval surgery, with an incidence of 27.0%-38.5% [37], among which the most important complications are wound infection and other consequences caused by it, such as pharyngeal fistula and infection and rupture of large blood vessels in the neck. The higher incidence of pharyngeal fistula is associated with poor local circulation after radiological and/or surgical treatment of the patient. Large vessel rupture is the most dangerous complication of salvage surgical treatment, leading to patient death. Therefore, when performing salvage surgery for recurrence of laryngeal cancer after treatment, we should have adequate mental and technical preparation to deal with and manage all possible complications.
6. Principles of comprehensive treatment for laryngeal cancer
6.1 Principles of comprehensive treatment
(1) Carcinoma in situ: generally choose endoscopic resection or radiotherapy without other adjuvant treatment.
(2) T1-2 stage laryngeal cancer: if radical radiotherapy is chosen, no other adjuvant treatment is needed after radiotherapy, and salvage surgery is feasible for recurrence.
(3) T1-3N0-3M0 stage laryngeal cancer: if surgery is chosen, postoperative comprehensive treatment should be considered according to the presence or absence of lymph node metastasis and risk factors [38]; if NO0 or no risk factors exist, observation is generally chosen and no other adjuvant treatment is required, if there is a positive lymph node but no risk factors, postoperative radiotherapy can be chosen; if there are risk factors (such as extraperitoneal invasion) or N2-3, postoperative radiotherapy can be chosen. ) or N2-3, radiotherapy or radiochemotherapy should be chosen according to the specific situation [39-40]. In addition, if simultaneous chemotherapy or radiotherapy alone is preferred, the treatment should be followed up only if the lesion is in complete remission [41], or salvage surgery should be considered if there is residual tumor in the national primary site, or cervical lymph node dissection if there is residual lymph node in the neck [39-42].
(4) T4N0-3M0 laryngeal cancer: T4aN0-3M0 surgery is preferred, followed by radiotherapy and radiotherapy for those with risk factors [39-43]. If patients refuse surgery, simultaneous radiotherapy or induction chemotherapy can be chosen. After induction chemotherapy, the next step of treatment should be decided according to the patient’s response: radical radiotherapy or concurrent radiotherapy if the primary site is in complete or partial remission; surgery if the primary site is not in remission or remains after treatment [39, 41, 44]; cervical lymph node metastases according to the results of treatment; T4Bn0- 3M0 or unresectable lymph node lesions and those who are not suitable for surgery, generally choose non-surgical options such as simultaneous radiotherapy and radical radiotherapy or combined with targeted drug therapy [45-47]
(5) Recurrent or persistent laryngeal cancer: for focal recurrence (including local recurrence and regional recurrence), surgery is chosen as much as possible, and if patients still have in risk factors, postoperative radiotherapy or chemotherapy is added, or chemotherapy alone [45, 48]. If resection is not possible, radiotherapy or re-radiotherapy, or chemotherapy alone [45, 48]
(6) Laryngeal cancer with distant metastases: single agent chemotherapy or combination chemotherapy or platinum + fluorouracil (5-Fu) + cetuximab [39, 49]
(7) Risk factors: including extra-peripheral lymph node invasion, positive margins, T4 stage lesions in cases, positive lymph node metastasis pathology, ≥2 cervical lymph node metastases [39]
6, 2 Chemotherapy regimen
(1) Induction chemotherapy: platinum-based agents are recommended, either platinum alone (e.g., cisplatin) or or cisplatin + docetaxel + 5-Fu regimens, or in combination with targeted agents (e.g., the EGFR monoclonal antibody cetuximab) [39, 41, 42, 45-46].
(2) Simultaneous radiotherapy: the following chemotherapeutic agents are available [38-40, 42, -45-46], still based on platinum drugs, including.
1, cisplatin monotherapy (class I recommendation).
2. cetuximab (class I recommendation, targeted therapy)
3, carboplatin / 5-Fu (class I recommendation)
4. cisplatin / paclitaxel.
5, cisplatin / 5-Fu.
(3) Palliative chemotherapy: palliative chemotherapy can be used in combination or in a but-for manner for recurrent and metastatic lesions that cannot be cured. Combination chemotherapy is recommended for cisplatin or carboplatin +5-Fu+- cetuximab, cisplatin or carboplatin + docetaxel or paclitaxel, cisplatin + cetuximab. Single-agent chemotherapy can be used with cisplatin, carboplatin, 5-Fu, cetuximab, docetaxel, paclitaxel, bleomycin, methotrexate, and isocyclophosphamide as needed [39, 40, 49, 50-51].
6, 3 Radiotherapy regimens
(a) radical radiotherapy: based on the different clinical staging of patients, the total amount of radiation given to the primary foci and early lesions of invaded lymph nodes should be ≥ 63 Gy, and ≥ 70 Gy (2 Gy / times) for intermediate and late lesions [39, 41, 4546, 48]
(ii) Radiotherapy before and after surgery: total radiation of 40-50 Gy (2 Gy/time) is given preoperatively, and surgery is performed 2-3 weeks later; radiotherapy (2 Gy/time) is given within 4-6 weeks after surgery, with 60-66 Gy given to the primary lesion, 60-66 Gy to the invaded region of the neck, and 44-64 Gy to the non-invaded region [39, 41, 45-6, 48].