How is neuroblastoma treated?

Currently, the program treatment for neuroblastoma is carried out in accordance with the risk group. Independent risk factors include the age of the patient older than one year and the presence of amplification of the N-MUC gene. Many research groups introduce various additional risk factors.

The effectiveness of treatment is assessed by the criteria for responding to treatment:

• complete remission (CR) - the tumor is not detected;
• very good partial remission (VGPR) - reduction of tumor volume by 90-99%;
• partial remission (PR) - reduction of tumor volume by more than 50%;
• mixed remission (MR) - no new foci, a decrease in old foci by more than 50%, an increase in some foci by no more than 25%;
• there is no remission (NR) - a decrease in foci by less than 50%, an increase in some foci by no more than 25%;
• Progression (PROG) - new foci or an increase of more than 25% in the old one, or de novo bone marrow involvement .

Treatment of neuroblastoma should be complex. Surgical removal of the tumor is based on the principle of possibly more complete excision within healthy tissues. An obstacle to observing this principle can be the location of the tumor in hard-to-reach areas. The results of most studies show that complete removal of the primary tumor improves survival.

The tactics of treatment depend on the stage of the process and the risk group.

During the I-II stage, a "surveillance" group is identified, for which chemotherapy is not provided. This group includes patients younger than a year without amplification of the N MUS gene and without life-threatening symptoms (severe general condition, severe respiratory, renal failure, etc.). Some researchers also include children older than one year with neuroblastoma of stage 1-IIa without amplification of the N MYC gene and without life-threatening symptoms.

The cure rate of low-risk patients exceeds 90%. Most of the investigators refer to this group as the I-II stage of the disease in the absence of amplification of N-MNC and stage IVS in the presence of favorable biological factors (favorable histological type, hyperploidy and lack of amplification of the N-MUC gene ). In the first stage, treatment is limited to surgical excision of the tumor and observation. If the residual tumor is preserved, chemotherapy is performed. The presence of severe life-threatening complications is an indication for chemotherapy. The most widely used carboplatin, cyclophosphamide, doxorubicin and etoposide. If there is no effect, radiotherapy is possible. Management IVS stage in a number of cases (the absence of serious complications and the profession of the tumor) is limited only by observation. In a study that included 80 children with IVS neuroblastoma. The survival rate when using this tactic was 100%; With the development of symptoms, low-dose chemotherapy enabled survival in 81% of cases. According to a number of studies, resection of the tumor in these cases does not lead to an increase in survival.

The average risk group includes patients younger than the year with neuroblastoma III-IV stage and the absence of NMyC amplification, as well as patients older than the year with neuroblastoma of stage III, the absence of N MUC amplification and favorable histological variant of the tumor. Curing patients in the middle risk group is possible in 70% of cases. At the same time, the highest rates of cure are observed in children under the age of one year. Chemotherapy includes the same drugs as for the low-risk group, but its duration and cumulative doses of cytostatics increase.

The most difficult task is to treat patients at high risk, which include cases with NM -amplification and / or an unfavorable histological variant of the tumor and stage IV in children older than one year. Survival in this group is low and amounts to 10-40%. Even with aggressive treatment tactics, relapse is often observed.

The standard approach is the use of high-dose regimens of chemotherapy with inclusion of cyclophosphamide, ifosfamide, cisplatin, carboplatin, vincristine, doxorubicin, dacarbazine and etoposide. The location of the primary tumor is subject to subsequent irradiation. 

A certain role in improving the results of treatment is played by autologous transplantation of hematopoietic stem cells. In a large randomized study, in a group of children who received high-dose chemotherapy with an autologous transplant of purified hematopoietic stem cells, a 3-year event-free survival was 34% (only 18% in the group receiving only consolidative chemotherapy). The same study showed the advantage of using isotretinoin (13-cis-retinoic acid) for 6 months after the end of chemotherapy. The event-free survival for 3 years with differentiating therapy with this drug was significantly higher.

At present, new therapeutic approaches to the treatment of high-risk neuroblastoma are being explored. Certain successes have been achieved with the use of monoclonal antibodies to antigens of neuroblastoma cells. The experience of using chimeric immunoglobulins to ganglioside 2, expressed on neuroblastoma cells, is accumulated. After binding of the antibody to the tumor cell, as a result of the activation of complement or antibody-dependent cytotoxicity, its lysis occurs. The method is used in patients of high-risk group as an adjuvant therapy in the presence of a tumor of a minimum volume. Directed radiotherapy with dewengung (I ¹³¹ ) was successful in a number of patients with residual tumor. At the stage of clinical trials are new methods of transplantation of hematopoietic stem cells (myeloablative regimens with dengue-1 ¹³¹, tandem transplantation, etc.).

Radiation therapy

The results of the conducted studies did not show any advantages with respect to the survival of patients with neuroblastoma receiving radiotherapy. At present, irradiation is used in the presence of a residual tumor after chemotherapy or with a palliative purpose. The dose of irradiation is 36-40 Gy. Young children should carefully calculate the maximum allowable radiation load on various organs and tissues and possible negative effects on the growing organism.

Neuroblastoma is one of the most unique human tumors, capable of both regression and rapid growth. The prognosis for this disease depends on the age of the patient and a number of biological signs. The following problems are currently most relevant for neuroblastoma:

• expediency of mass screening;
• definition of a group of children who do not need therapy (observation group);
• treatment of relapses and refractory forms of the tumor;
• search for targeted drugs for neuroblastoma cells;
• the possibility of antitumor vaccination.

Solving these issues can radically change the prognosis of one of the most frequent malignant diseases in children.

[1], [2], [3], [4], [5], [6]