I. Current status of treatment
Nasopharyngeal carcinoma (NPC) refers to malignant tumors occurring in the top and side walls of nasopharyngeal cavity. It is one of the most prevalent malignant tumors in China, and the incidence rate is the first among the malignant tumors of head and neck. The incidence of NPC is more common in Guangdong, Fujian and other places, and the incidence rate has been on the rise in recent years. At present, the treatment of nasopharyngeal carcinoma is still a comprehensive treatment mainly based on radiation therapy, including early radiotherapy alone, mid- and late-stage radiotherapy combined with chemotherapy or targeted therapy.
1.Modulated Radiation Therapy gradually becomes the core radiotherapy technique for nasopharyngeal cancer
Modulated Radiation Therap (IMRT) is a product of the combination of radiation technology, radiation physics, medical imaging and computer technology. The dose can be increased safely. It is possible to improve the local control rate of tumor and the quality of patient’s survival from radiotherapy technology. At the same time, concurrent chemotherapy has also attracted more and more attention. For example, weekly or three-weekly chemotherapy with docetaxel and DDP can achieve better recent efficacy, and the toxic side effects and adverse reactions are relatively mild and tolerated by most patients.
2.Chemotherapy for nasopharyngeal cancer
The intensity-modulated radiotherapy technology has greatly improved the survival rate without local recurrence after radiotherapy, and 83% of tumor recurrence occurs within the target area of high irradiation dose, indicating that the recurrence of nasopharyngeal cancer is closely related to the tumor cells’ own radiosensitivity in addition to the T stage of the tumor. On the other hand, the increase of local control rate makes distant metastasis a major factor affecting the survival of nasopharyngeal carcinoma. Therefore, how to reduce the distant metastasis rate of nasopharyngeal cancer and improve the local control rate and survival rate has become a hot spot of research at home and abroad. And induction chemotherapy, concurrent radiotherapy and chronotherapy are the main concentrated aspects of chemotherapy for nasopharyngeal carcinoma in recent years.
Neoadjuvant chemotherapy is now gradually accepted by scholars, and its advantages are.
(i) there is no fibrosis caused by radiation and the tumor blood supply is good, which is conducive to the distribution and effect of chemotherapeutic drugs in the primary foci of nasopharyngeal tumor and lymph node metastases; (ii) the general condition of patients before radiotherapy is good and they have good tolerance to chemotherapy, which can improve the tumor local control rate and survival rate of advanced nasopharyngeal cancer.
(3) Induction chemotherapy can reduce the tumor load and alleviate various symptoms caused by tumor in a short period of time.
④Some chemotherapeutic drugs also have radiotherapy sensitizing effect to increase the recent efficacy of radiotherapy.
⑤ Combination chemotherapy may kill distant metastases or subclinical foci, thus improving the survival rate of patients.
The shortcomings are that it may cause delay in radiotherapy, decrease in nutritional status, partially reduce the tolerance of radiotherapy, aggravate the side effects of radiotherapy, and increase the treatment cost accordingly. At present, neoadjuvant chemotherapy mostly adopts DDP-based combination chemotherapy regimens, such as PF and TPF. Some scholars also suggest that the following points should be noted when neoadjuvant chemotherapy is used.
① Minimize the interval between chemotherapy and the time to start radiotherapy after chemotherapy as long as it can be tolerated.
(ii) Chemotherapy should not narrow the radiotherapy target area and reduce the radiation dose even if complete remission is achieved.
③ Different chemotherapy regimens and courses of treatment should be selected according to the actual situation of patients and different treatment purposes to minimize chemotherapy-related deaths.
Concurrent radiotherapy is currently regarded as the standard treatment for nasopharyngeal carcinoma, with the advantage of no delay in the start of radiotherapy and the disadvantage of forced interruption of radiotherapy due to the accumulation of toxic side effects caused by nonspecific sensitization, which may affect the therapeutic gain. Some studies have shown that concurrent radiotherapy can reduce local tumor recurrence and distant metastases and improve overall survival and progression-free survival, but other studies have shown that concurrent radiotherapy can only reduce distant metastases and does not improve overall survival. Another study reported that concurrent chemotherapy with high-dose DDP can improve overall survival and progression-free survival, while weekly administration of moderate dose DDP can reduce distant metastasis in T advanced nasopharyngeal carcinoma.
3.Targeted therapy for nasopharyngeal carcinoma
Targeted therapy for nasopharyngeal carcinoma is richly researched. It is reported that the targeted drugs applied to nasopharyngeal carcinoma mainly include: cetuximab, nitrozumab, erlotinib, gefitinib, bevacizumab and Endo.
Their advantages: avoiding the large toxic side effects of traditional chemotherapy and radiotherapy due to the lack of specificity, creating a new milestone in medical oncology treatment, and bringing encouraging efficacy to patients with nasopharyngeal cancer.
II. Treatment confusion
At present, the 5-year survival rate of nasopharyngeal cancer has reached 80% or more with conventional treatment, but with the prolongation of survival of nasopharyngeal cancer, more and more patients have nasopharyngeal recurrence with radioactive brain injury after radiotherapy, recurrence after second or multiple courses of radiotherapy and multiple distant metastases that failed by second-line treatment, and some patients have recurrent nasopharyngeal cancer that failed by standard treatment. These conditions are complicated to treat, have high risk and poor prognosis, and become difficult to treat at present.
The definition of refractory nasopharyngeal carcinoma has been proposed as patients with local recurrence who cannot tolerate surgery or re-course irradiation and chemotherapy after adequate radiotherapy, which can be extended to the following four types.
① nasopharyngeal recurrence after radiotherapy for nasopharyngeal carcinoma with radiation brain injury.
②Recurrence after second-course radiotherapy or multi-course radiotherapy.
(iii) continued systemic multiple distant metastatic nasopharyngeal carcinoma that has failed second-line therapy.
④Recurrent nasopharyngeal carcinoma that has failed standard treatment.
For refractory nasopharyngeal carcinoma, there is no good treatment method yet, such as giving nedaplatin + 5-Fu, 5-Fu single agent continuous pumping therapy, molecular targeted therapy and other programs can achieve certain efficacy. A clinical trial of chemotherapy combined with Endo continuous pumping for refractory nasopharyngeal carcinoma conducted by Prof. Yunfei Xia at Sun Yat-sen University Cancer Hospital is expected and believed to have good results.