I. Neuroblastoma
The treatment of neuroblastoma depends on the clinical stage, whether the tumor can be completely resected and the histopathological staging. Low-risk groups with limited complete resection of the tumor usually require only surgical treatment. The low-risk Ivs stage is closely followed up after surgery. Intermediate and high-risk groups require a combination of surgical chemotherapy and radiation therapy. Intensive radiotherapy followed by surgery is required for large tumors invading adjacent organs and large blood vessels. The intermediate-risk group with pathological FH type receives a shorter course of chemotherapy than the high-risk group. The high-risk group needs to have their own bone marrow transplantation.
II. Surgical treatment
Surgical treatment is one of the main treatments for childhood neuroblastoma. Surgery is important in diagnostic staging and histobiological studies. Surgical resection of the primary tumor and adjacent lymph nodes can be curative for stage I and II.
In children with abdominal neuroblastoma, a transverse incision is often used to fully expose the relationship between the tumor and the surrounding tissues. stage I tumors have an intact envelope and no infiltration or adhesions with the surrounding tissues. stage II and III tumors often have adhesions with the paraspinal tissues, which need to be carefully peeled off. if it is difficult to remove the adhesions between the tumor and the important organs, some of the tumor can be left after postoperative chemotherapy and then a second surgery can be performed. Most of the mediastinal neuroblastomas are adherent to the paraspinal sulcus, intercostal space and vascular tissues, and most of them are less malignant and can be removed completely. If the tumor can be resected together, if it is difficult to be resected, then chemotherapy should be given, and when the neurological symptoms are relieved and the tumor outside the spinal canal is shrunken, the second stage surgery should be performed.
Chemotherapy
1.Postoperative chemotherapy
Post-surgical chemotherapy for neuroblastoma is now generally recognized. The modern concept is that while neuroblastoma occurs, tumor cells are continuously shed and enter the blood circulation, most of which are killed by the host’s immune defense mechanism, but a small number of tumor cells will become the source of postoperative recurrence and metastasis. Therefore, it is emphasized that there may still be microscopic lesions lurking after neuroblastoma surgery, which are often not easily detected by ultrasound, CT and other imaging studies, and surgical resection alone cannot achieve true cure. Seventy-five percent of children with advanced neuroblastoma have metastases to bone marrow, blood, and distant lymph nodes, and are treated with chemotherapy for 1 to 1.5 years after surgery for stage II and III tumors.
2.Pre-operative chemotherapy
The application of preoperative chemotherapy in neuroblastoma is fully affirmed. Preoperative chemotherapy shrinks the primary tumor, thickens the envelope, reduces surgical bleeding, creates conditions for complete resection of the tumor, and reduces intraoperative dissemination of tumor cells. The length of preoperative chemotherapy for neuroblastoma depends on the efficacy of chemotherapy, the extent of tumor volume reduction, and the control of distant metastases such as bone marrow. Premature surgery often results in difficulties in surgical resection because the efficacy of chemotherapy has not yet been fully reflected, poor control of metastases, and insignificant tumor volume reduction, and too long chemotherapy results in increased toxic side effects of chemotherapy drugs and higher medical costs. Therefore, it is better to delay the timing of surgery clinically for 4-6 courses of treatment.
In chemotherapy for neuroblastoma, dose adjustment can be made according to clinical efficacy, or several regimens can be used alternately, but attention needs to be paid to toxic side effects, application of mestat to prevent hemorrhagic cystitis, attention to hydration when cisplatin is used, and monitoring of nephrotoxic effects when carboplatin is used.
Intensive chemotherapy supplemented with bone marrow or stem cell transplantation Intensive induction chemotherapy supplemented with autologous or allogeneic bone marrow transplantation and stem cell transplantation carried out in recent years have positive significance for tumor cell killing, prevention of fatal chemotherapy complications such as bone marrow suppression and secondary infection in advanced neuroblastoma. Generally, autologous or allogeneic bone marrow or stem cells are prepared before chemotherapy, and high-dose cisplatin, VM-26, VP-6, melphalan supplemented with CTX/ADM/DTIC are applied for intensive chemotherapy, followed by bone marrow or stem cell transplantation, which can achieve desirable results. In recent years, autologous stem cell transplantation is mostly used as an adjuvant therapy after intensive chemotherapy for neuroblastoma instead of bone marrow transplantation, mainly applied after complete clinical remission of stage III and IV neuroblastoma and after partial clinical remission of children with refractory drug-resistant neuroblastoma. Most children with advanced neuroblastoma are treated with preoperative chemotherapy, deferred or secondary surgery for complete or near-complete removal of the tumor, and after 6 courses of postoperative chemotherapy After 6 courses of postoperative chemotherapy, stem cell transplantation can be started if the bone marrow is free of metastasis and the blood routine and liver and kidney function are normal as confirmed by bone marrow aspiration.
IV. Radiation therapy
The application of radiation therapy for neuroblastoma depends entirely on the sensitivity of radiation therapy for the tumor and the estimation of the damage to the growth and development of the child treated with radiation therapy. Generally, it is mainly used for those with incomplete resection and unsatisfactory chemotherapy effect, and for palliative treatment of advanced neuroblastoma to relieve pain and reduce compression. However, because neuroblastoma is generally sensitive to chemotherapy and radiotherapy has serious radiation damage effects on bones and gonads, it should be applied with caution. Children with stage III and IV neuroblastoma, especially those with incomplete resection, are often given local radiotherapy at a dose of 25-35Gy, while children with bone and liver metastases who are given palliative radiotherapy are often given radiotherapy at a dose of 6.5-8.5Gy.
V. Other treatments
1.Guided therapy
Guided therapy is to kill tumors by using highly specific pro-tumor substances as carriers and radionuclides, chemotherapy drugs and toxins as warheads to focus on tumors. At present, it is more certain to apply MIBG method to treat neuroblastoma, that is, 123I or 131I is used as a carrier, whose chemical structure is similar to that of norepinephrine, which can be taken up by neuroblastoma, so as to attack the tumor cells and treat the tumor.
2. Induction of differentiation therapy
In vitro culture, each drug can be used to differentiate neuroblastoma into mature cells or promote apoptosis of tumor cells. However, not all neuroblastoma can undergo induction of differentiation in clinical practice, and only certain cases can be selectively applied at present. The commonly used differentiation-inducing factors are 13 cis-retinoic acid, nerve growth factor and cyclic adenosine monophosphate.
3.Immunotherapy
Immunotherapy for childhood neuroblastoma is to mobilize the immune mechanism of the child’s body to achieve the stability of the internal environment, stimulate hematopoietic function, promote bone marrow recovery, enhance tolerance to chemotherapy and radiotherapy, and also strengthen the sensitivity of the tumor to anti-tumor drugs, resulting in tumor necrosis and direct killing of tumor cells. The commonly used cytokines include IL-2, IL-12, IFN-γ, etc.
4.Gene therapy
Gene therapy is the introduction of exogenous genes into the corresponding target cells at the DNA or RNA level to obtain expression and produce specific biological effects to achieve therapeutic purposes. For example, cytokine gene is introduced into tumor cells, recombinant retroviral vector of MHCII molecule gene is introduced into neuroblastoma or a sensitivity gene is transferred into tumor cells to make the cells specifically sensitive to a non-toxic/low toxic drug, resulting in the death of tumor cells.
VI. Prognosis
In recent years, although comprehensive treatment measures such as surgery, chemotherapy and radiotherapy have been used to make some progress in the efficacy of neuroblastoma, the overall survival rate has been improved by a small margin of 30-40%.
The prognosis depends on the age of the patient and the stage of the disease, and the following factors should be taken into consideration.
1. Age: less than 1 year old has a better prognosis.
2, disease stage.
The prognosis is better in stage I. The prognosis is also better in stage IV-S patients because of the combination of low serum ferritin and usually lack of N-myc oncogene amplification.
3. Urinary 3-methoxy-4hydroxy-picotinic acid to homovanillic acid ratio is greater than 1:5, so the prognosis is better.
4.Serum ferritin >=150mg/l, poor prognosis.
5.N-myc copy number>=10, poor prognosis.
6. Regional lymph node invasion at the time of diagnosis, poor prognosis.
In conclusion, according to the biological characteristics of neuroblastoma, the best prognosis is considered to be in infant patients whose tumor DNA content is super 2-fold and lack of N-myc gene amplification.