Assessment of chemotherapy effects

  Section IV Assessment of chemotherapy effectiveness Before the introduction of neoadjuvant chemotherapy into the comprehensive treatment of malignant bone tumors, the exact efficacy of chemotherapy on malignant bone tumors lacked scientific evaluation criteria, and most of the efficacy was confirmed by the results of clinical practice. It is not certain which drug is more effective in postoperative combination chemotherapy. Chemotherapy regimens can only be designed based on previous estimates. The introduction of neoadjuvant chemotherapy provides a basis for scientific assessment of drug sensitivity to tumors. It can be specifically assessed by clinical, imaging and laboratory examinations as well as histological grading of postoperative tumor cell necrosis. Tang Shun, Department of Bone Oncology, Peking University People’s Hospital Clinical assessment is based on whether the patient’s subjective symptoms are reduced by chemotherapy, especially pain relief and improvement of general condition. Clinical examination is based on whether the tumor volume is reduced, whether the boundary with normal tissue is clear, whether the edema reaction zone around the tumor is reduced, and whether the mobility of adjacent joints is improved. If Ewing sarcoma has a history of increased blood sedimentation and fever, it should also be included as a clinical index for observing the efficacy of treatment.  On imaging, whether the calcification and ossification of tumor increase, whether the boundary of soft tissue mass shadow is clear, whether the size of the mass is reduced and whether the boundary between the mass and normal bone is clear in comparison with X-ray plain film before and after chemotherapy (Figure 4-1). Enhanced CT and angiography examination to show whether tumor neovascularization is reduced or disappeared are objective indicators to observe the efficacy. MRI examination can show whether the soft tissue of the tumor is reduced, the boundary with the surrounding tissue and necrosis (Figure 4-2). In the laboratory examination of osteosarcoma, whether alkaline phosphatase and lactate dehydrogenase decrease is also one of the indicators to observe the efficacy. Comparison of the results of isotope bone scans before and after chemotherapy showed that the degree and extent of radionuclide concentration was also an important indicator for observing the efficacy of chemotherapy. Among them, the isotope thallium 201 (Ti) is currently considered to be the most effective.      The patient was a 30-year-old female with right pelvic osteosarcoma, showing osteolytic and osteogenic destruction of the right iliac bone with a huge soft tissue mass before chemotherapy; Figure C D shows that after 2 courses of preoperative chemotherapy, the effect of chemotherapy was obvious, and the X-ray plain showed increased tumor ossification, and the CT soft tissue window showed a significantly reduced soft tissue mass of the tumor, in which there was increased ossification with clear borders. Figure E Pathological section before chemotherapy, (100×) Osteosarcoma osteoblast predominant type; Figure F (100×) Post-chemotherapy changes of osteosarcoma, remnant tumor cell anisotropy is obvious, scattered deeply stained strange cells as well as necrotic irregular bone trabeculae images are seen.    The patient is a 20-year-old male with a malignant nerve sheath tumor of the right pelvis. Figure B shows that after 2 courses of chemotherapy with the MAID regimen, the tumor shrank slightly, with liquefied cystic lesions in some areas, and the T2 image became high signal; it shows that after 4 courses of chemotherapy, the tumor shrank significantly and most of it liquefied.  The most important, sensitive and objective assessment criterion for the efficacy of preoperative chemotherapy is the histological response of the tumor to chemotherapeutic drugs. Proper assessment is essential for the development of postoperative chemotherapy regimens. This assessment requires the active participation of pathologists and the completion of a significant amount of work. They have to take specimen photographs of the resected tumor specimens and then take them according to the lattice graphic method developed by the Sloan-Kettering Cancer Center to determine the individual tissue sections for microscopic assessment of the efficacy of neoadjuvant chemotherapy. The number of lattices and sections depended on the size of the tumor, the assessment criteria according to the histological grading of tumor response to chemotherapy developed by Huvos et al. Grade I: almost no tumor cell necrosis; Grade II: mildly effective chemotherapy with reduced number of tumor cells, necrosis rate > 60%, and some areas with surviving tumor cells; Grade III: effective chemotherapy with tumor cell necrosis rate > 90% and very few surviving tumor cells; Grade IV: total tumor cell necrosis and no surviving tumor cells. According to the neoadjuvant chemotherapy data from Sloan-Kettering Cancer Center, 20% of the patients were grade IV, 21% were grade III, 29% were grade II, and 20% were grade I chemotherapy response. According to this assessment, for chemotherapy response grade III or IV, the preoperative chemotherapy regimen can be followed after surgery; for grade I and II, the chemotherapy regimen should be changed after surgery by shortening the chemotherapy interval and using more potent drugs. It has been shown that whether the lesion is located in the distal femur, proximal tibia, or proximal humerus-the three most common sites for osteosarcoma-there is no significant difference in their response to chemotherapy.