1.What are the indications for chemotherapy? What are the contraindications of chemotherapy? Indications: (1) preoperative and postoperative adjuvant chemotherapy; (2) malignant bone tumors sensitive to chemotherapy, such as osteosarcoma, Ewing sarcoma, malignant lymphoma, etc.; (3) malignant tumors that are inoperable or difficult to operate due to advanced tumor or anatomical site, but have some sensitivity to chemotherapy; (4) bone metastases. Contraindications: (1) low total number of white blood cells or platelets; (2) abnormal liver and kidney function; (3) heart disease, heart dysfunction, not to choose cardiotoxic Adriamycin and other drugs; (4) poor general condition, can not tolerate chemotherapy; (5) with infection. 2.What are the commonly used chemotherapy drugs for bone tumor? Different tumors should choose different chemotherapy. The selection is mainly based on the biological characteristics of the tumor and the sensitivity of anti-tumor drugs. For example, high-dose methotrexate, cisplatin, adriamycin and isocyclophosphamide are the main chemotherapy for osteosarcoma. In contrast, Ewing sarcoma is a combination chemotherapy based on vincristine, adriamycin, cyclophosphamide and Vp-16 (Etoposide 鬼臼乙叉甙). 3.Is the dose of chemotherapy as high as possible? Chemotherapy not only kills tumor cells, but also inevitably damages normal cells, especially proliferating hematopoietic stem cells and mucosal epithelium. The common complications of chemotherapy include: gastrointestinal reaction, bone marrow suppression and serious infection, liver and kidney function impairment and cardiotoxicity, etc. The chemotherapy regimen used nowadays is determined by strict clinical trials, which can optimize the effect of chemotherapy and reduce the adverse effects. 4.Is there any requirement of chemotherapy cycle for bone tumor? What can be done to ensure the successful completion of the chemotherapy cycle? There are requirements for chemotherapy cycles for malignant bone tumors, such as osteosarcoma, which generally requires 4 courses of chemotherapy before surgery and 12-18 courses of chemotherapy after surgery, with an interval of about 10 days between chemotherapy before surgery and 14 days after surgery. The number of chemotherapy sessions may need to be increased on top of the surgery. To ensure the successful completion of the chemotherapy cycle, patients need to overcome the adverse effects of chemotherapy, such as loss of appetite due to nausea and vomiting, and actively fight against the disease. The doctor will check the blood image and liver function before the next chemotherapy, and liver-protective therapy and leukocyte-raising therapy may be needed to ensure the successful implementation of chemotherapy. 5.What is adjuvant chemotherapy? A portion of tumor patients have micro metastases when their disease is detected or at the time of getting the diagnosis. These metastases cannot be detected by the current available diagnostic techniques because of their small size. Because of this, the prognosis of these patients is affected by the existence of micro-metastases even if the local treatment for them is done thoroughly. Therefore, malignant tumor can be considered as a systemic disease by nature, which cannot be cured by single local treatment, but should be complemented by systemic treatment to control or eliminate micro-metastases. Adjuvant chemotherapy refers to chemotherapy as a component of comprehensive therapy for malignant bone tumors, which is helpful to improve the efficacy of surgery or radiotherapy. Postoperative chemotherapy can kill the tumor cells that may remain and metastasize in order to reduce local recurrence and metastasis and improve long-term survival rate. Postoperative chemotherapy should be applied early, adequate and standardized. 6.What is neoadjuvant chemotherapy? Neoadjuvant chemotherapy refers to chemotherapy before surgery. Its functions are: (1) to make tumor shrink and boundary become clear, which is conducive to surgical resection, and even make some tumors which were difficult to be removed by local surgery can be more completely removed after chemotherapy; (2) to kill potential micro-metastases and tumor cells in blood, and reduce the chance of metastasis; (3) to make tumor cells less vigorous and less likely to spread metastasis during surgery; (4 ) to detect the sensitivity of chemotherapy by postoperative tumor specimens. Preoperative chemotherapy can be administered intravenously and intra-arterially. With the development of pre- and post-operative chemotherapy and the continuous improvement of tumor removal technology, the five-year survival rate of osteosarcoma has increased from 20% in the past to more than 60% at present with simple surgical treatment. 7.How to evaluate the effect of chemotherapy? Clinical evaluation is mainly based on clinical manifestations, imaging examinations and postoperative pathology. Clinical manifestations include: (1) pain relief; (2) tumor volume reduction; (3) edema subsidence; (4) increased movement of adjacent joints. The imaging manifestations are: (1) X-ray plain film shows tumor shrinkage, increased osteogenesis and clear boundary; (2) CT and MRI show clear boundary, increased ossification, disappearance of edema and increased necrosis; (3) ECT shows decreased tumor uptake. Laboratory tests showed decreased alkaline phosphatase and lactate dehydrogenase. The tumor histological necrosis rate is the most effective index to respond to the sensitivity of osteosarcoma to chemotherapy. A tumor necrosis rate of 90% or more indicates a good response to chemotherapy. Preoperative chemotherapy should be administered for at least two courses of regular treatment so that the tumor necrosis rate can be properly assessed. The tumor histological necrosis rate of preoperative chemotherapy is also the most important predictor of prognosis in osteosarcoma. The higher the necrosis rate, the better the prognosis. 8.Does the mass not disappear because the chemotherapy is not effective? After preoperative chemotherapy patients may have partial or most of the pain relief after a few hours or days. However, it is difficult to reduce the size of osteosarcoma itself rapidly, and it is more difficult to absorb the tumor completely. Pathological histology proves that the volume reduction of osteosarcoma is mainly due to the disappearance of edema, inflammatory reaction and neovascularization in the tumor, not the disappearance of the tumor cells themselves. In other words, as long as the tumor volume is no longer bigger but smaller, and the pain is relieved, it means that the effect of chemotherapy has been received, and it is not necessary for the mass to disappear completely. 9.What is targeted therapy for tumor? In the treatment of malignant tumors, most chemotherapeutic drugs produce serious toxic side effects in the whole body while killing cancer cells, and most chemotherapeutic drugs have obvious dose-effect dependence. The emergence of targeted therapy has opened up a new field and a broad prospect for the treatment of tumors. Targeted therapy is a method to improve therapeutic efficacy and reduce toxic side effects by selectively delivering drugs or other active substances that kill tumor cells to tumor sites using carriers with certain specificity, and limiting the therapeutic effect or drug effect to specific target cells, tissues or organs as much as possible without affecting the function of normal cells, tissues or organs. Targeted therapy is a major direction of tumor treatment in the future, and some drugs have been used in clinical practice. 10.What should be done if chemotherapy is not effective? The studies of some scholars have proved that the modification of postoperative chemotherapy regimen for those with poor histological response to preoperative chemotherapy cannot improve their prognosis, and it is difficult to determine the histological response of patients to chemotherapy before surgery. Therefore, to increase the overall efficiency, more potent preoperative chemotherapy should be administered to all patients, and the most effective drugs and best regimens should be applied preoperatively and should not be left for the postoperative period to improve the chemotherapeutic effect of the tumor. Tumor necrosis rate plays a guiding role in the formulation of postoperative chemotherapy. When the tumor necrosis rate is grade three or four, that is, when the necrosis rate is large 90%, the preoperative chemotherapy program can continue to be applied. If the tumor necrosis rate is grade one or two, that is, when the necrosis rate is less than 90%, it is necessary to change the chemotherapy program and add new drugs or increase the dose of drugs. 11.Can chemotherapy work well without surgery? Is it okay to operate directly without chemotherapy before surgery? Surgery is still the main part of bone tumor treatment, the purpose of which is to remove the tumor to reduce or eliminate its harmful effects in local evolution and development, while chemotherapy increases the possibility and safety of limb preservation surgery. It can be seen that the purpose of chemotherapy is to control the tumor locally and eliminate the micro-metastases to improve the long-term survival rate of patients. Therefore, surgery and chemotherapy are both important components of bone tumor treatment, and they play important roles from different perspectives. 12.What are the main effects and toxic side effects of methotrexate? Methotrexate (MTX) is an antimetabolic antitumor drug. Tumor tissues are metabolically active tissues, so they need a lot of nutrients as raw materials for their biosynthesis. MTX has a chemical mechanism much like these metabolic substances, which can be taken up by cells and then hinder the normal metabolism of cells, inhibit tumor growth and promote its death. A series of toxic effects such as bone marrow suppression and liver and kidney dysfunction can be produced after applying large doses of MTX. MTX can also cause serious mucosal reactions such as stomatitis, ulcerative gastritis, hemorrhagic enteritis, etc. In order to release these toxic effects, calcium methyl tetrahydrofolate is used after applying large doses of MTX for relief to stop the toxic reactions and protect normal cells. 13.What are the main effects and toxic side effects of isocyclophosphamide? Isocyclophosphamide (IFO) belongs to the alkylating agent class of antitumor drugs, which can combine with proteins and nucleic acids in tumor cells, thus affecting the energy metabolism and respiration of cells and leading to cell death. It is suitable for various soft tissue sarcomas and bone sarcomas, bone metastases. toxic side effects of IFO include bone marrow suppression, urinary tract and nephrotoxicity, central nervous system toxicity, gastrointestinal reactions, hair loss, etc. The most prominent one is hemorrhagic cystitis, so the uroprotective agent methotrexate must be given at the same time to prevent the occurrence of hemorrhagic cystitis. 14.What are the main effects and toxic side effects of Adriamycin? The main action of Adriamycin (ADM) is to embed in the DNA double helix and bind to DNA, causing changes in the DNA template, thus hindering the synthesis of DNA and RNA and leading to cell death.ADM has a broad anti-tumor spectrum and significant efficacy. The main toxic side effects are: bone marrow suppression, cardiotoxicity, etc. The cardiotoxicity of ADM has a cumulative dose phenomenon, generally the cumulative dose of <400mg/m2 has a low incidence of cardiotoxicity of 1%, so the application of ADM will generally control the total dose, if necessary, will add new drugs in combination with chemotherapy to reduce the cumulative dose of ADM. The maximum dose of Adriamycin is 550 mg/m2. 15.What are the main toxic effects and side effects of cisplatin? Cis-chloroplatinum (CDP), also known as cisplatin, is a complex of metallic platinum, which can interact with DNA strands to prevent DNA templates from being replicated normally, thus hindering DNA and RNA synthesis and inhibiting the division of cancer cells. However, toxic side effects are also obvious, such as gastrointestinal reactions, nephrotoxicity, bone marrow transplantation, allergic reactions, and neurotoxicity and ototoxicity. Therefore, high-dose CDP chemotherapy should be used to reduce nephrotoxicity by hydration and diuresis, and the changes of serum electrolytes and liver and kidney functions should be monitored closely. 16.What are the characteristics of Kaplan? Kaplan is a new type of liposomal adriamycin, liposomal adriamycin is a kind of polyethylene glycol liposome-encapsulated adriamycin, which can evade the human immune system, cloak adriamycin and prolong the circulation time in the body, the drug is encapsulated in liposomes, the molecules of the drug are released from the liposomes, through the tumor neovascularization and enter the tumor cells to produce the effect of targeting and killing the tumor, liposomal adriamycin can reduce the anti-tumor The active ingredient is non-specifically distributed to normal tissues and reduces the peak plasma level of free drug, thus reducing toxic reactions. It has the property of long circulation time and easy to pass through tumor neovascularization, so its antitumor activity is increased, while the incidence of cardiotoxicity and bone marrow suppression is relatively low. The biggest advantage of Kaplanai compared with common adriamycin is its safety to the heart.