Nasopharyngeal cancer has a different biological behavior from other squamous cancers of the head and neck in that it grows locally in an extensive invasive manner. Nasopharynx is adjacent to skull base, brainstem, spinal cord, eyes, parotid gland and other important organs. Lymph node metastasis is the most common clinical manifestation of nasopharyngeal cancer, and about more than 60% of patients present with neck masses. The entire cervical lymphatic drainage area including the retropharyngeal lymphatic drainage area is the subclinical area of nasopharyngeal cancer. Therefore, the clinical target area of nasopharyngeal carcinoma is large, including the area from above the base of the skull to the lower edge of the clavicle. The most common sequelae after radiation therapy for nasopharyngeal cancer are such as dry mouth and radiological caries due to damage to parotid gland function; difficulty in opening the mouth due to damage to masticatory muscles and temporomandibular joints; and difficulty in swallowing due to radiation damage to swallowing structures such as epiglottis, larynx and esophagus. The decrease or loss of function of these organs and tissues will seriously affect the quality of survival of patients. With the improvement of radiotherapy technology and the continuous understanding of biological behavior of nasopharyngeal cancer and the accumulation of clinical treatment experience, the 5-year survival rate of radiotherapy for nasopharyngeal cancer has been greatly improved, from 34%-59% in the 20th century to about 64.44%-87% at present. Therefore, the quality of survival after radiotherapy for nasopharyngeal carcinoma patients is increasingly important, and it is extremely important to understand and prevent the long-term toxic side effects after radiotherapy for nasopharyngeal carcinoma.
I. Radioactive brain and spinal cord injury
1.Radiation brain injury
Acute reactions are rarely seen in conventional brain radiotherapy, and the symptoms are often reversible. Late reactions are localized radiation necrosis, diffuse white matter encephalopathy, neuropsychological reactions, cerebrovascular reactions. Clinical manifestations include amnesia, personality changes, dullness, non-response, transient pauses in thinking or loss of consciousness, temporal lobe epilepsy, etc. Some patients are associated with increased intracranial pressure. Pontine brain injury mainly manifests cranial nerve palsy plus hemiparesis in the corresponding brainstem segments. Treatment.
(1) Treatment of cerebral edema: high-dose steroid corticosteroid therapy can be applied.
(2) Treatment to improve cerebral circulation: dihydroergot alkaloids, calcium antagonists, nicotinic acid preparations, and traditional Chinese medicine can be applied.
(3) Cerebral metabolic resuscitators: such as: pyrrolidone drugs (brain rejuvenation), Ducoxib, cytidylcholine, etc.
(4) Brain protective drugs: Quantitative analysis of clinical normal tissue effects (QUANTEC) showed that the maximum dose of 59 Gy for small volume (1-10 ml) of brainstem irradiation with a fractionated dose of ≤ 2 Gy; however, the risk increases significantly when the dose is > 64 Gy. For fractionated doses of 2Gy the predicted probability of brain necrosis at irradiation doses of 72Gy and 90Gy is 5% and 10%, respectively.
2.Radiation spinal cord injury
Radiation-induced changes in the spinal cord are relatively common in relatively early complications, Lhermitte’s sign, which is usually reversible. Demyelination can occur a few months after the end of treatment and last from a few months to more than a year. The advanced types of myelopathy include 2 major complications. The first occurs 6 to 18 months after radiotherapy and is mainly demyelination and white matter necrosis; the second occurs 1 to 4 years later and is mainly vasculopathy. The main manifestations of spinal cord injury are low head touch sensation limb numbness, feeling cold and hot, weakness, abnormal urination and defecation, hemiparesis, etc.; paraplegia is less common, but the consequences are serious because it is irreversible. Treatment: The main management of radiation myelitis is the use of corticosteroids, but the efficacy is limited. Transient improvement of symptoms can be seen in some cases and may be related to the reduction of spinal cord edema. In recent years, some progress has been made in the treatment of traumatic spinal cord lesions with vasoactive drugs, but they have less effect on slowly progressive radiation myelitis.
II. Radioactive swallowing impairment
Swallowing difficulty is one of the main late complications after radiotherapy for nasopharyngeal cancer, and the literature reports that the incidence of swallowing difficulty after radiotherapy for nasopharyngeal cancer reaches 70-80%, which will continue to increase with time. Aspiration pneumonia is one of the major causes of death after radiotherapy. What structures are affected by radiation damage that can cause dysphagia and choking? This involves 30 pairs of muscles and 6 pairs of cranial nerves. When these muscles are abnormal, they often manifest as stiffness of the lateral pharyngeal wall and tongue root and abnormal activity of the epiglottis and vocal cords, which cause swallowing dysfunction. In addition, damage to the hypoglossal nerve causes impaired tongue movement; damage to the vagus nerve causes paralysis of the vocal cords, which, together with direct damage to the laryngeal epiglottis, results in restricted epiglottal movement during swallowing and also causes some degree of dysphagia and choking. Dysphagia and choking are irreversible and there is no effective treatment. A “gastrostomy” can be a solution for feeding and avoiding aspiration pneumonia. Intensity-modulated radiation therapy can play a preventive role to some extent.
Third, radiological hearing damage
Despite the continuous improvement of radiotherapy methods and radiation field design, the auriculotemporal region and brainstem cannot be isolated from the radiation field. deafness. The most commonly encountered clinical findings and more frequently reported in the literature are ear closure, tinnitus and conductive hearing loss due to reactive swelling of the radiopharyngeal canal and secretory otitis media in some patients at an early stage, while sensorineural damage is less often considered. In recent years, there have been some reports in foreign literature about the occurrence and extent of hearing damage after radiotherapy. A significant proportion of hearing loss after radiation therapy for nasopharyngeal carcinoma is sensorineural hearing loss, with an incidence of 30%-50% and a latency period of 0.5-1 year, which is more serious than the conductive hearing loss due to radiation otitis media. Sensorineural hearing loss is related to age, basic hearing and the dose to the inner ear, and the severity and incidence of sensorineural hearing loss are closely related to the dose.
Radioactive salivary gland function damage
Xerostomia is one of the serious long-term toxic side effects after conventional radiotherapy for nasopharyngeal carcinoma patients, which is caused by the destruction of major salivary glands due to radiation therapy. The saliva secreted by parotid, submandibular and sublingual glands in the oral cavity accounts for 90% of the total saliva, while the other 10% is secreted by microscopic glands. Loss of salivary gland function may occur when the major salivary glands are within the radiation field. When the radiation dose reaches 20-30Gy in the second to third week of radiotherapy, the basal salivary secretion drops to the lowest point; when the salivary gland receives a radiation dose of 42Gy, the salivary gland secretion function is completely lost. The destruction of the salivary glands caused by radiation therapy is permanent. After radiotherapy, the quality and quantity of salivary gland secretion are obviously changed, which leads to the reduction of its antibacterial effect and the loss of oral self-cleaning function, and the formation of an extremely sticky gelatinous film on teeth, which provides extremely favorable conditions for oral bacteria to adhere and grow on teeth, making oral tissues easily damaged and diseased, such as soreness and weakness of teeth when chewing and radiation caries.
Post-radiotherapy dry mouth syndrome will be relieved to different degrees with the prolongation of time after the end of radiotherapy and the change of patient’s habit. Most of the patients have remission of dry mouth within 1 to 2 years after the end of radiotherapy, and those who have no remission of dry mouth within 2 years have little chance of remission in the future. Since the destruction of salivary glands caused by radiotherapy is permanent, why does the dryness improve after radiotherapy with the extension of time after the end of radiotherapy? The reason for this may be that some of the microscopic glands in the oral cavity are not irradiated and can continue to secrete saliva. The treatment methods for post-radiotherapy dry mouth include salivary gland replacement method, hard sugar method, antibacterial rinse method, fluoride and trichothecene medication, but the efficacy is not satisfactory. Methods to prevent dry mouth after radiotherapy. There are drug method (amifostine) and intensity-modulated radiotherapy (IMRT).
V. Radiation visual impairment
1.Radiological optic nerve and optic cross injury
The damage to the optic path includes the damage to the optic nerve, optic cross and optic beam. Depending on the extent of local invasion of nasopharyngeal carcinoma, the optic pathway of some patients is within the target area. The initial manifestation of radiation optic neuropathy is visual field loss, painless sudden loss of vision in one eye, or transient blurred vision, combined with periorbital and retro-orbital pain, and the final result is optic nerve atrophy. The latency period of optic pathway injury is 2 to 3 years, and visual evoked potentials improve after treatment with hormones and blood-stasis activating drugs.
2.Radioactive crystal and retinal injury
The latency period of radioactive crystal injury induced cataract is 0.5-32 years. Radiation retinopathy is caused by occluded microangiopathy, with clinical manifestations such as cotton dots, retinal hemorrhage, macular edema, exudation, and vitreous hemorrhage. Quantitative analysis of clinical normal tissue effects (QUANTEC) showed that all these injuries are related to the radiation dose and to the area of the retina receiving high doses; splitting the total irradiation dose below 500 cGy does not produce significant visible crystal clouding.
Sixth, radiation nasopharyngeal necrosis
Post-radiotherapy nasopharyngeal necrosis is one of the important complications after radical radiotherapy for nasopharyngeal cancer. At present, it is mostly believed that radiation, trauma and infection are the three elements in the pathogenesis of radiation nasopharyngeal necrosis. The low blood supply, low oxygen supply and impaired microcirculation of local tissues caused by radiotherapy affect the regeneration of collagen and cells, leading to local necrosis, which causes soft tissue necrosis or formation of dead bone, mucosal necrosis and detachment or bone exposure. The occurrence of radiation nasopharyngeal necrosis is closely related to the radiation dose and the course of treatment. The results of many studies have shown that radiation dose is one of the main factors for the occurrence of post-radiation osteonecrosis. The incidence of nasopharyngeal necrosis increases in patients with higher nasopharyngeal mucosal exposure after local residual post-radiation and nasopharyngeal cancer local recurrence re-course radiotherapy. The key to prevention of nasopharyngeal necrosis after radiotherapy is prevention. After radiotherapy, local cleanliness of nasopharynx should be maintained: daily nasopharyngeal irrigation to remove accumulated pus and dry crusts; endoscopic cleaning if necessary to reduce infection damage of nasopharyngeal mucosa, with local anti-inflammatory, nasal drops with oxyfloxacin ear drops are recommended. When nasopharyngeal necrosis occurs, nasopharyngeal necrosis removal under nasopharyngoscopy and with systemic or local anti-inflammatory treatment can achieve more satisfactory results.
VII. Radioactive temporomandibular joint injury
Radiation therapy for nasopharyngeal cancer can cause soft tissue atrophy and fibrosis leading to dysfunction and difficulty in opening mouth. In conventional radiotherapy for nasopharyngeal cancer, the dose to the two temporomandibular joints is often higher than the nasopharyngeal dose, which often leads to soft tissue atrophy and mouth opening difficulties. Therefore, the radiation field should be used as three-field irradiation or intensity-modulated conformal radiotherapy to reduce the dose to the temporomandibular joint, which is useful for protecting soft tissues and temporomandibular joint function. In addition, patients should do more mouth opening exercises and massage the temporomandibular joint during radiotherapy. The incidence of difficult mouth opening after radiotherapy for patients with nasopharyngeal carcinoma is high, and the dose to the temporomandibular joint, mouth opening exercises and patient’s age are the main influencing factors.