Diagnosis and treatment of nasopharyngeal cancer
Nasopharyngeal cancer refers to epithelial-derived malignant tumors occurring in the nasopharynx, which is one of the highly prevalent tumors in China, accounting for 12,4~27,9% of systemic malignant tumors and 60% of otolaryngological malignant tumors according to domestic statistics. The age of onset is between 30~50 years old, and there are more men than women (about 2-3 times). It is more common in Guangdong, Guangxi, Hunan, Fujian and other provinces, also known as “Guangdong cancer”. Squamous cell carcinoma is the most common.
The etiology of nasopharyngeal carcinoma is multifactorial, and is mainly thought to be related to genetic factors, environmental factors and EBV infection, etc.
This suggests that nasopharyngeal carcinoma may be a hereditary disease. Studies have also found that certain genetic factors determining human leukocyte antigen HLA are closely related to the development of nasopharyngeal carcinoma.
Environment and diet: Environmental factors are also causes of nasopharyngeal carcinoma. It has also been reported that consumption of salted fish and pickled food is a high risk factor for nasopharyngeal carcinoma in southern China, and it is related to the age of eating salted fish, the duration of consumption, the amount and the cooking method.
③ EBV infection: Old et al. first detected EBV antibodies from the serum of patients with nasopharyngeal carcinoma in 1966, and in recent years, the application of molecular hybridization and multiplex chain reaction (PCR) technology has confirmed the expression of EBV DNA-specific viral mRNA or gene products in nasopharyngeal carcinoma biopsy tissues, which further confirmed the important role of EBV in the development of nasopharyngeal carcinoma.
Clinical manifestations.
Nasopharyngeal carcinoma mostly occurs in the posterior wall of nasopharyngeal apex and pharyngeal crypt, which is difficult to examine because of its deep and hidden location. The disease lacks characteristics in the early stage and is overlooked or misdiagnosed because of general symptoms. Common symptoms are
1, bleeding
There can be bleeding symptoms in the early stage, manifested as blood in the sputum after nasal aspiration or blood in the snot when blowing the nose. In the early stage, there is only a small amount of blood in the sputum or in the snot, which is sometimes absent. More bleeding in the late stage, and nosebleeds may be present.
2.Tinnitus, hearing loss, feeling of occlusion in the ear
When nasopharyngeal cancer occurs in the lateral wall of nasopharynx, lateral fossa or the upper lip of the opening of the eustachian tube, unilateral tinnitus or hearing loss may occur when the tumor compresses the eustachian tube, and kataric middle ear infection may also occur. Unilateral tinnitus or hearing loss and the feeling of occlusion in the ear are one of the symptoms of early stage nasopharyngeal carcinoma.
3.Headache
It is a common symptom, accounting for 68.6%. It may be the first symptom or the only symptom. In the early stage, the headache site is not fixed and intermittent. In late stage, it is persistent migraine with a fixed location. In the early stage, it may be caused by neurovascular reflex or stimulation of the first peripheral nerve of trigeminal nerve. In advanced stage, it is often caused by the tumor destroying the skull base and spreading intracranially to involve the cranial nerves.
4. Diplopia
Due to tumor invasion of the abducens nerve, it often causes double vision outward. The invasion of nerve of carriage often causes inward strabismus and diplopia. Diplopia accounts for 6.2% to 19%. It is often damaged together with trigeminal nerve.
5.Facial numbness
It refers to the numbness of facial skin. Clinical examination shows that the sensation of pain and touch is reduced or disappeared. Tumor invading the cavernous sinus often causes damage to the 1st or 2nd branch of trigeminal nerve; tumor invading the foramen ovale, pre-steminal area and the 3rd branch of trigeminal nerve often causes numbness or abnormal sensation in the skin of anterior auricle, temporal area, cheek, lower lip and chin. Facial skin numbness accounts for 10% to 27,9%.
6.Nasal congestion
Nasal congestion can occur when the tumor blocks the posterior nostril. When the tumor is small, the nasal congestion is lighter, and as the tumor grows, the nasal congestion will increase, mostly unilateral nasal congestion.
7. Symptoms of lymph node metastasis in the neck
Nasopharyngeal cancer is prone to cervical lymph node metastasis, about 60.3% to 86.1%, half of which are bilateral metastasis. Cervical lymph node metastasis is often the first symptom of nasopharyngeal carcinoma (23.9%~75%). In a few patients, the nasopharyngeal examination cannot detect the primary lesion, and lymph node metastasis in the neck is the only clinical manifestation. This may be related to the fact that the primary lesion of nasopharyngeal cancer is small and expands into the submucosal tissue.
8.Tongue muscle atrophy and tongue extension deviation
Direct invasion of nasopharyngeal carcinoma or lymph node metastasis to the posterior region of the caudate or the sublingual nerve canal, resulting in invasion of the sublingual nerve, causing tongue extension deviation to the diseased side, accompanied by tongue muscle atrophy on the diseased side
9.Eye risk ptosis and eye fixation
associated with damage to the motoneural nerve. Loss or disappearance of visual acuity associated with optic nerve damage or orbital cone invasion.
10.Distant metastasis
The rate of distant metastasis of nasopharyngeal carcinoma ranges from about 4,8% to 27%. Distant metastasis is one of the main reasons for treatment failure of nasopharyngeal carcinoma. Common metastatic sites are bone, lung, liver, etc. Simultaneous metastasis of multiple organs is common.
11.Concomitant dermatomyositis
Dermatomyositis can also accompany with nasopharyngeal cancer, so patients with dermatomyositis should be carefully examined in the nasopharynx regardless of whether they have symptoms of nasopharyngeal cancer.
12.Menopause
It is rare as the first symptom of nasopharyngeal carcinoma, and is related to the invasion of nasopharyngeal carcinoma into the butterfly sinus and pituitary.
Examination
(a) Nasopharyngoscopy: Indirect nasopharyngoscopy, if necessary, can detect the primary site of cancer, which can be nodular, cauliflower-like or ulcerated, showing mucosal congestion, rough erosion and bulging of the lateral wall of nasopharynx, etc.
(b) Exfoliative cytological examination: the nasopharynx can be scraped or the secretions can be attracted by negative pressure and smears can be examined for cancer cells, and the positive rate can reach 70-90%.
(c) Biopsy: take biopsy from nasopharynx for pathological examination; if the biopsy is negative and clinically suspicious, multiple biopsies should be performed. If the primary focus is unknown and there are suspicious enlarged lymph nodes in the neck, lymph node puncture or biopsy is feasible.
(iv) X-ray radiography or CT, MRI scan: thickening of soft tissue shadow or bone destruction in the nasopharynx is seen.
(e) Serological examination: increased titer of EBV antibody in serum or EBV immunofluorescence antibody assay has a positive rate of 84% in the diagnosis of nasopharyngeal carcinoma.
(f) Nasopharyngeal fluorescein staining examination: staining with acridine orange and observation under fluorescent microscope.
Diagnosis
Early diagnosis of nasopharyngeal cancer is extremely important. Any unexplained headache, neck mass, nasal discharge with blood, paralysis of one abductor muscle and fluid accumulation in one tympanic chamber should be examined in the nasopharynx to avoid delaying the diagnosis. Submucosal infiltrating type of cancer is not easy to detect, so special attention should be paid and various examinations should be performed repeatedly.
Nasopharyngeal cancer with cervical lymph node metastasis should be differentiated from cervical lymphatic tuberculosis, Hodgkin’s disease and mixed tumor of parotid gland.
Treatment
(a) Treatment principle: comprehensive treatment based on radiation therapy, including chemotherapy, surgery, Chinese medicine treatment, immunotherapy, etc.
(II) Treatment methods.
1.Radiotherapy
Radiotherapy is the first choice of treatment for nasopharyngeal carcinoma. The reason is that most nasopharyngeal carcinomas are hypofractionated carcinomas with high sensitivity to radiation, and the primary focus and the lymphatic drainage area of the neck are easily included in the irradiation field. Since the 1940s, deep x-ray radiotherapy for nasopharyngeal cancer has been carried out in China, and 60Co external radiation radiotherapy has been carried out since the 1950s and 1960s. At present, the most effective and sure method is to use 60Co teletherapy machine.
(1) Indications and contraindications of radiation therapy for nasopharyngeal cancer
a. Indications for radical radiotherapy: ① those with moderate or above general condition; ② those without obvious bone destruction at the skull base; ③ those with no or only mild to moderate infiltration in the nasopharynx on CT or MRI film; ④ those with maximum diameter of cervical lymph nodes less than 8cm, active and not yet reaching the supraclavicular fossa; ⑤ those without distant organ metastasis.
b. Indications for palliative radiotherapy: ① KS grading of 60 or more; ② severe headache, nasopharynx with more than medium amount of bleeding; ③ single distant metastasis or cervical lymph node metastasis of more than 10 cm.
c. Contraindications to radiation therapy: ① below 60 KS grade; ② extensive distant metastases; ③ combined with acute infectious disease; ④ radioactive cerebrospinal cord injury.
d. Principles of re-radiation therapy after radiation therapy: those with the following conditions should not be re-radiated: ① the same target area (including nasopharyngeal and cervical targets) after radiation therapy for less than one year; ② the emergence of radiation encephalopathy or radiation myelopathy after radiation therapy; ③ the total course of nasopharyngeal targets should not exceed three courses, and cervical targets should not exceed two courses.
(2) Radiation selection and irradiation range
a. Design of irradiation field: The principle of designing irradiation field is “small but not leaky”. All parts involved in the tumor should be included in the irradiation field, but the normal tissues in the irradiation field, especially those sensitive to radiotherapy, should be protected. If the nasopharynx and paranasal space are involved, the anterior nasal field can be irradiated, and if the orbit is involved, the superior or inferior orbital field can be irradiated, and attention should be paid to protect the eye with lead sheet to avoid radioactive cataract. The scope of irradiation of the neck depends on the lesion of the lymph nodes, and the radiation dose of the lymph nodes can be increased by adding a lead film to protect the eyes and prevent the occurrence of radioactive cataract.
(3) Radiation dose and time
a.Continuous radiation therapy: 200 cGY each time 5 times a week, total TD6000~7000 cGY/6~7 weeks.
b, segmental radiation therapy: generally divide the radiation therapy into two segments, 5 times a week, 200cGY each time, each segment about 3, 5 weeks, four weeks rest between the two segments, the total dose TD6500~7000cGY.
(4) Post-mounted intracavitary radiation therapy
a. Indications.
①Limited small nasopharyngeal lesions (tumor thickness less than 0, 5 cm), located in the parietal, anterior or lateral wall.
② Those whose residual lesions after external irradiation or surgical resection of nasopharyngeal cancer meet item ①.
b. Treatment method: usually external irradiation plus intracavitary irradiation is combined with external irradiation amount of 4500~6000cGY external irradiation for 1~2 weeks and then add intracavitary radiation for 1~2 times, each time with an interval of 7~10 days, each time with the dose point of 0,25cm under the mucosa, giving 1000~2000cGY/time.
(5) Radiation reaction and regression and its treatment
a. Complications of radiotherapy
(1) Systemic reactions: including weakness, dizziness, loss of appetite, nausea, vomiting, tastelessness or change of taste in the mouth, insomnia or drowsiness, etc. Individual patients may experience blood picture changes, especially leukopenia. Although the degree varies, it can generally be overcome with symptomatic treatment to complete radiation therapy. If necessary, vitamins B1, B6, C, and gastrofacial can be taken. (a) Radiotherapy should be suspended if the white blood cell count drops below 3*109/L.
②Local reactions: including skin, mucous membrane, salivary gland reactions. The skin reaction is dry dermatitis or even wet dermatitis, local anti-inflammatory ointment with a base of 0 or 1% ice chips and talc or lanolin can be used. Mucosal reactions are characterized by congestion, edema, exudation and accumulation of secretions in the nasopharynx and oropharynx mucosa. In a few patients, swelling of the parotid gland can occur after 2Gy of parotid irradiation, and the swelling gradually decreases in 2-3 days. When 40Gy is irradiated, salivary secretion is obviously reduced, while oral mucosal secretion increases, mucosal congestion, redness and swelling, and patients have dry mouth and difficulty in eating dry food.
b.Radiotherapy regression: mainly temporomandibular joint dysfunction and soft tissue atrophy fibrosis, radioactive dental caries and radioactive jaw spur osteomyelitis and radioactive encephalomyelopathy. There is no proper solution for reversal, symptomatic treatment and support methods can help. The over-irradiation of important tissues and organs should be strictly avoided.
2.Chemotherapy
(1) Indications of chemotherapy for nasopharyngeal carcinoma
aStage IV patients and those with obvious lymphatic metastases in stage IV.
b Any patient who is suspected of having distant metastasis
c huge mass metastasis of regional lymph nodes in the neck for pre-radiotherapy induction chemotherapy.
d as chemotherapy with a sensitizing effect prior to radiotherapy.
e as adjuvant chemotherapy after radiotherapy or surgical treatment.
(2) Commonly used combination chemotherapy regimens
A. CBF regimen: cyclophosphamide 600-1000mg/time, intravenous injection, applied on the 1st and 4th day. 5-Fluorouracil 500mg, intravenous injection, applied on the 2nd and 5th day, with a rest period of 1 week after the course of treatment, and a total of 4 courses of treatment. The effectiveness rate was 60, 8%.
B. PFA regimen: cis-chloroplatinum 20mg and 5-fluorouracil 500mg, intravenously for 5 days; adriamycin 40mg, intravenously on the first day of the course. repeat after 3-4 weeks, with significant tumor shrinking effect.
C. PF regimen: cis-chloroplatinum 20mg/m2 and 5-fluorouracil 500mg/m2, intravenously for 5 days and then rest for 2 weeks, available for 2~3 courses. This regimen can be used to shrink the tumor before radiotherapy, or for cases of chemotherapy alone, with an efficiency of 93,7%.
(3) Regional intra-arterial cannula perfusion chemotherapy
Arterial cannulation chemotherapy can be used for nasopharyngeal carcinoma with episodic and local recurrence after radiotherapy. Retrograde cannulation of superficial temporal artery or facial artery can be chosen. Combination or sequential treatment of several chemotherapeutic drugs with high potency and short duration of action is often chosen. Before administration, 2 ml of 2% procaine is injected to prevent arterial spasm, and then anti-cancer drugs are injected, followed by filling the lumen with 2 or 5% sodium citrate solution and closing the end of the tube. If continuous medication is needed, 5% glucose saline with 100ml of heparin solution and anti-cancer drug can be used to inject 1500mg continuously for 24 hours.
3.Surgical treatment
(1) Excision of primary foci of nasopharyngeal cancer
a Indications.
①Highly differentiated nasopharyngeal carcinoma, such as adenocarcinoma, squamous carcinoma grade I and II, early cases of malignant mixed tumor.
② local recurrence of nasopharynx after radiation therapy, lesions limited to the posterior parietal wall or anterior parietal wall, or involving only the edge of the pharyngeal crypt without infiltration of other parts, no difficulty in opening the mouth and still in good physical condition.
(iii) If the radical dose of radiotherapy has been given, and the primary nasopharyngeal lesion has not disappeared, or if anti-radiation phenomenon appears, surgical excision is feasible after a rest period of one month.
b Contraindications.
① those who have skull base bone destruction or paranasal infiltration, cranial nerve damage or distant metastasis.
②Patients with poor liver and kidney function and poor general condition.
c Surgical method: first tracheotomy intubation, surgery under general anesthesia. A horseshoe-shaped incision is made along the root of the palate at 0.5 cm from the alveolus, and the mucosa of the hard crotch bone is incised. The mucosa of the nasal floor was transected at the junction of the hard and soft palate to expose the parietal wall of the nasopharyngeal cavity, the anterior division of the two walls and the tumor. The nasopharyngeal mucosa is incised at the posterior edge of the nasal septum and the upper edge of the posterior nostril to reach the bony surface, and blunt or sharp separation is made, and the mucosa is incised along the junction of the nasopharyngeal apex and lateral nasopharynx.
(2) Cervical lymph node dissection
a Indications: If the primary nasopharyngeal cancer lesion has been controlled after radiotherapy or chemotherapy, and the general condition is good, only residual or recurrent foci in the neck remain, and the scope is limited and active, cervical lymph node dissection can be considered.
b Contraindications.
① residual foci or recurrent foci in the neck with deep tissue adhesions and fixation in the neck.
(ii) Those with distant metastases or extensive skin infiltration.
③ those who are old and frail, with cardiopulmonary, hepatic and renal insufficiency and fail to correct.
(3) Simple removal of lymph nodes in the neck
Simple excision is feasible for single lymph nodes in the neck that are insensitive to radiotherapy or for those with isolated lymph node recurrence in the neck after radiotherapy. After local infiltration anesthesia, the skin and subcutaneous tissues on the surface of the metastases are incised, and the metastases are completely removed together with some surrounding normal tissues. The wound can be dressed with slight pressure after the operation.
4.Chinese medicine treatment
5.Immunotherapy
Outlook.
The natural course of nasopharyngeal carcinoma varies greatly from patient to patient. The natural course of disease from the first symptoms to death ranges from 3 months to 113 months. Nasopharyngeal cancer is mainly treated with radiation therapy. With the update of radiation therapy equipment and improvement of radiation therapy technology, the 5-year survival rate after radiation therapy for nasopharyngeal cancer has been increasing. Local recurrence and distant metastasis after radiotherapy for nasopharyngeal carcinoma are the main causes of patient death. Therefore, in addition to improving radiotherapy techniques and radiotherapy effects, research should be conducted on the biological characteristics of nasopharyngeal carcinoma, the factors of nasopharyngeal carcinoma patients’ organism and the interaction between tumor and patient organism. According to the biological characteristics of nasopharyngeal carcinoma in patient’s organism, we should select and formulate suitable treatment plan by considering radiotherapy, chemotherapy, surgery, traditional Chinese medicine, immunotherapy and other treatment methods, so as to improve the efficacy of treatment.