In recent years, the incidence of malignant tumors in children and deaths caused by malignant tumors have been increasing year by year, and malignant tumors are the second leading cause of death in children in developed countries, and the death surveillance report in Shanghai, China in 2005 showed that malignant tumors are the top four causes of death in children [1], therefore, malignant tumors have become one of the major diseases threatening children’s health. Summarizing the experience of diagnosis and treatment of malignant tumors in children in recent years, on the one hand, the incidence is increasing year by year, on the other hand, the treatment is improving and the efficacy is increasing, the overall long-term disease-free survival rate (EFS) has reached 50%-70%, and the EFS of acute lymphoblastic leukemia (ALL) has reached more than 80%-90% [2], early-stage nephroblastoma, hepatoblastoma, retinoblastoma (RB) and other malignant solid tumors also have EFS of more than 85%-93% [3,4]. Therefore, it should be recognized that malignant tumors in children are not incurable. Combined with years of clinical experience, the author believes that the following aspects are crucial to improve clinical outcomes. 1, correct diagnosis and staging Regardless of childhood leukemia or malignant solid tumors, standardized treatment is the prerequisite to obtain good prognosis, and accurate staging is the basis of standardized treatment. For example, in acute childhood leukemia, the international treatment plan design is based on morphology, immunology, cytogenetics and molecular biology typing (MICM typing), and the application of multi-parametric flow cytometry (MP-FCM), high-resolution banding technology, fluorescence in situ hybridization (FISH), multiplex PCR and other technologies provide a guarantee for MICM typing. The design of treatment plans for malignant solid tumors such as non-Hodgkin’s lymphoma (NHL), neuroblastoma (NB), and rhabdomyosarcoma (Rs) are also based on preoperative clinical staging and pathological typing, and are gradually evolving toward molecular typing, such as the inclusion of N-myc gene in the typing of NB. At present, the staging of NHL is widely adopted by the 2008 WHO NHL pathological staging and the St-Jude NHL staging system of the American Children’s Research Center. the staging of NB adopts the International NB Staging System (INSS), the staging of RB adopts the St-Jude staging system, and the staging of Rs adopts the TNM International Cancer Classification System. The prognosis of childhood malignant tumors is generally bipolar. Those with good prognosis can achieve long-term disease-free survival even with very weak treatment regimens, while those with poor prognosis can relapse sooner or later even with stronger treatment, resulting in multidrug resistance and eventual death. In order to avoid unnecessary early death or distant complications in patients with good prognosis who receive overtreatment, and to avoid relapse in patients with really high risk due to insufficient intensity of treatment, in recent years, academics have extensively explored the prognostic factors of childhood malignancies, and now there is a clearer understanding of childhood ALL, and the recognized risk factors at home and abroad are: age at diagnosis, white blood cell count, genetic gene expression, and early treatment response [5,6]. The risk classification of lymphoma is based on the risk stratification system designed by the French Society of Pediatric Oncology (SFOP) and the French, American and British (FAB) Collaborative Group on the basis of the St-Jude staging system.RB risk classification is mostly based on the IRC classification system involving the United States, Canada, France, Sweden and Mexico. It is generally accepted that stage IV NB with >1a and >5-fold N-myc gene amplification is a high-risk patient for NB. Advanced Rs with pathological type of glandular vesicle type, growth in the parietal meninges, bladder, gonads, distant metastases, etc. are high-risk patients. 3. Observation of early treatment response Before formal anti-tumor therapy, a weaker chemotherapy regimen is given to observe the tumor cell reduction to determine the tumor response to treatment as early treatment response. The implementation of early treatment regimen can, on the one hand, avoid the tumor lysis syndrome caused by high-dose chemotherapy, and at the same time, can initially determine the sensitivity of tumor cells to chemotherapy drugs as a way to determine the intensity of subsequent treatment regimen. For example, the early prednisone 7-day treatment response of ALL has been included in the independent prognostic factors. after the diagnosis of B-cell NHL, cyclophosphamide, vincristine and prednisone (COP regimen) were used for 7 days to evaluate the early treatment response, and the subsequent treatment regimen was determined according to the tumor shrinkage after the end of COP regimen. 4 . Optimization of chemotherapy regimen 4.1 Multi-drug combination sequential therapy The chemotherapy regimen for childhood tumors has matured, both for leukemia and malignant solid tumors, emphasizing multi-drug combination sequential therapy, which is the key to reduce the relapse rate and prolong survival. the regimen for ALL is divided into induction of remission (VDLP plus CAT), extramedullary leukemia control (HD-MTX, triple sheath injection), re-induction (VLD plus CAT) and maintenance therapy, with periodic intensification during maintenance therapy in high-risk patients. For lymphoblastoid lymphoma and peripheral T-cell lymphoma, sequential treatment with ALL high-risk group is used, and for B-cell lymphoma, sequential treatment with LMB-89 or BFM-95 with 4-6 drugs in short course and strong regimen for NHL is used. for solid tumors such as NB, RB and Rs, sequential treatment with 2-6 chemotherapeutic drugs is also used. 4.2 Stratified treatment according to different risk levels The goal of modern pediatric oncology treatment is to obtain higher remission rates and long-term disease-free survival while continuously reducing treatment-related mortality and long-term complications, improving the quality of survival, and reducing treatment costs. To this end, in recent years, the design of treatment regimens for childhood malignancies at home and abroad has been based on different risk levels, proposing to stratify treatment according to different risk levels, so that patients with truly high-risk patients receive stronger chemotherapy regimens to achieve remission and long-term disease-free survival, while children without high-risk factors are treated with less intensity to improve survival quality and reduce treatment costs. The most studied area in this regard remains ALL, which is generally classified into three types: standard-risk (SR), intermediate-risk (MR), and high-risk (HR), and is given different intensity chemotherapy regimens. In early stage patients with malignant solid tumors, the tumor is removed directly by surgery, and no or only 1-2 courses of 2-drug combination chemotherapy are used after surgery. For advanced stage III and IV patients, neoadjuvant chemotherapy is used first, and elective surgery is performed after tumor shrinkage, with planned chemotherapy after surgery. Chemotherapy regimens range from 2-drug combinations to 6-drug combinations depending on the risk level. During the course of treatment, the risk level is continuously evaluated, and the intensity of subsequent treatment regimens is adjusted based on the response to each round of chemotherapy, and reclassified. 4.3 Optimization of chemotherapy regimens The chemotherapy regimens are continuously optimized in the process of stratifying treatment according to different risk levels to further improve EFS while reducing treatment-related side effects. For example, in the induction of remission regimen for ALL, the standard-risk group eliminated erythromycin in the COG and Dutch regimens, reducing erythromycin-induced associated death and long-term cardiotoxicity. Due to the ability of dexamethasone to cross the blood-brain barrier into the CNS more often, the Dutch regimen used dexamethasone instead of prednisone in the induction remission regimen, which significantly reduced the bone marrow and CNS relapse rate, but more complications such as infection complications and ischemic necrosis of the femoral head occurred. Currently, most regimens prefer to use prednisone in the induction remission period and use dexamethasone in the re-induction regimen to balance recurrence with complications. L-mentholase (Asp) plays a key role in the long-term disease-free survival of ALL and is an indispensable drug in ALL treatment, but its use in some children is limited by side effects such as allergic reactions and pancreatitis. In recent years, some domestic and international collaborative groups have used pemesterase in first-line chemotherapy regimens, and this drug has a long half-life compared with common menthol, requiring only 1 dose in 2 weeks, and This drug has the advantages of long half-life, only 2 weeks for 1 dose, and very few allergic reactions, and does not require skin testing. Since cerebrospinal radiotherapy not only causes secondary tumors but also affects growth and development, produces endocrine abnormalities, white matter encephalopathy and other side effects, prophylactic cranial radiotherapy has been abolished in recent years in the prevention of central nervous system leukemia (CNSL) in favor of increasing the dose of HD-MTX (HR-ALL has been increased to 5 g/m2… times), increasing the number of IT and applying high-dose cytarabine (HD-AraC) as an alternative to cerebrospinal radiotherapy. Chemotherapy regimens for malignant solid tumors are gradually trending towards shorter courses of high-dose strong regimens [10]. The duration of treatment for both leukemia and malignant solid tumors tends to be shorter, ranging from 2a (female) to 3a (male) for ALL, 18 months for AML, and 6-8 months for B-cell NHL. Other solid tumors such as NB, RB, and Rs have a duration of 0.5a to 1a depending on the stage and risk level. 4.4 Individualized treatment Due to the heterogeneity of tumors, the same tumor treated with Therefore, in recent years, it is proposed to change the intensity of chemotherapy for different individual tumor patients according to their clinical characteristics, molecular biology of tumor cells, early treatment response and pharmacokinetic characteristics under the same overall regimen, i.e. individualization of chemotherapy. For example, the individual response of MTX and 6-MP varies greatly, so the dose and duration of drug administration must be adjusted under the monitoring of blood concentration to implement individualized treatment. 5 .Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation for patients with advanced malignant solid tumors makes high-dose or even mega-dose chemotherapy possible, thus enabling some advanced patients who cannot be completely removed by surgery and have distant metastases to go into remission. For example, in RB, due to the blood-eye barrier, it is difficult for conventional doses of chemotherapeutic drugs to reach the RB lesions, and it is only possible for mega-dose chemotherapeutic drugs to enter the lesions locally, and hematopoietic stem cell transplantation provides a guarantee for mega-dose chemotherapy in RB. Since tumor cells in patients with solid tumors rarely reach the peripheral blood, collecting autologous peripheral blood during chemotherapy, isolating hematopoietic stem cells, freezing and preserving them in vitro, and returning them to the body after mega-dose chemotherapy can not only reduce the death associated with mega-dose chemotherapy, but also do not produce graft-versus-host disease (GVHD) and have a low cost, which has been widely used at home and abroad in recent years [9,10]. The use of immunomagnetic bead stem cell sorting technique during the isolation of bone marrow hematopoietic stem cells can improve the purity of stem cells and further reduce recurrence [9]. The most used domestic application in stem cell transplantation for malignant solid tumors is NB, where autologous peripheral blood hematopoietic stem cell transplantation followed by induction of differentiation therapy after mega-dose chemotherapy has increased the long-term disease-free survival rate of advanced NB from 0 to more than 40% [10]. In the treatment of childhood leukemia, since chemotherapy and hematopoietic stem cell transplantation (HSCT) are equally effective, HSCT has been de-emphasized in modern childhood leukemia treatment protocols and is only considered in the following cases [7, 8]: ?HR-type childhood ALL with persistent positive MRD within six months of CR1. ?AML in children with HR type: AML-M4, AML-M5, AML-M6 and AML-M7;? Cytogenetic t(9;22)/BCR-ABL+ and (-5, -7) AML. 6 , Immune-targeted therapy Immune-targeted therapy has been used clinically and is an effective complement to chemotherapy. For example, rituximab (anti-CD20 monoclonal antibody) has been increasingly used in the treatment of relapsed and refractory B-cell lymphoma and leukemia, and has a tendency to become part of the standard regimen. Jimosumab Ozocin (anti-CD33 monoclonal antibody + spinosporin) has been used as a second-line agent for the treatment of relapsed and refractory AML. 7 , Cell therapy MRD is an important factor in the recurrence of leukemia and malignant solid tumors, and effective treatment of MRD may reduce tumor recurrence. Cytokine-induced killer cells (CIK) are peripheral blood lymphocytes stimulated, cultured and expanded by a variety of cytokines in vitro. Their proliferation ability in vitro and clearance of tumor load in animals is significantly stronger than that of LAK cells. The tumor-killing activity of DC-CIK cells formed by co-culture of dendritic cells and CIK cells is even stronger. At present, CIK cells and DC-CIK cells have been gradually used in the treatment of leukemia and solid tumors [11, 12], especially for advanced patients, the use of CIK or DC-CIK cell therapy after surgery and chemotherapy to reduce the tumor load plays a positive significance in improving the status of the child and clearing residual lesions. 8.Establishing multidisciplinary collaborative treatment model The diagnosis and treatment of pediatric tumors, especially malignant solid tumors, involves many disciplines such as pediatric oncology, radiotherapy, surgery, pathology, imaging, etc. Therefore, the cooperation among multiple disciplines is needed to prospectively develop treatment plans for each patient, so that the patient’s treatment can be well connected and ultimately improve the prognosis effectively. At present, several units in China have formed this multidisciplinary collaborative and comprehensive treatment model, and have shown the superiority of this model. In conclusion, after nearly two or three decades of efforts, some problems in the treatment of childhood malignant tumors have gradually been clearly understood and gradually solved, thus significantly improving the prognosis of childhood malignant tumors.