Nghiên cứu vai trò của xạ hình xương và đánh giá kết quả điều trị sarcom xương tt tiếng anh

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE VIETNAM MILITARY MEDICAL UNIVERSITY TRINH VAN THONG STUDY THE ROLE OF BONE SCINTIGRAPHY AND EVALUATE THE RESULTS OF TREATMENT OF OSTEOSARCOMA Specialty: Surgery Code: 9720104 PH.D THESIS SUMMARY HANOI - 2019 THE RESEARCH WAS FINISHED AT VIETNAM MILITARY MEDICAL UNIVERSITY Supervisors: Assoc.Prof Ph.D Tran Dinh Chien Assoc.Prof Ph.D Nguyen Dai Binh Judge 1: Assoc.Prof Ph.D Tran Trung Dung Judge 2: Assoc.Prof Ph.D Le Ngoc Ha Judge 3: Assoc.Prof Ph.D Nguyen Manh Khanh The thesis will be defended before the Thesis Assessment Council at Institute level At: Vietnam military medical university Date month year The thesis can be found at: - National library - Vietnam military medical university library INTRODUCTION Regarding the current situation, necessity, scientific and practical significance of the dissertation topic Osteosarcoma is the most common primary bone cancer and accounts for about 35% of all primary bone cancers In the years before 1980, the only treatment was amputation and even with early surgery, the overall survival rate after years was not more than 20% and the main cause of death is due to lung metastasis From the 1980s onwards, the combination of chemotherapy and then surgery has significantly improved the survival rate for patients When chemotherapy is combined, the problem is how to assess the level of histomorphological response to the drug Evaluation measures through tissue necrosis have many limitations due to surgical intervention and depending on method of taking samples, reading test results… Bone scintigraphy allows assessment of preoperative chemotherapy respond through TBR index changes in the tumor, allows detection of recurrence of local lesions and more complete distant metastasis than other diagnostic imaging methods such as conventional X-rays, CT scans and MRI Whereby, chemotherapy is indicated, especially supplementation of treatment when relapsing and metastasis is performed timely and effectively The dissertation topic: “Study the role of bone scintigraphy and evaluate the results of treatment of osteosarcoma” with following research objectives: (1) Studying the role of bone scintigraphy in stage diagnosis and the process of monitoring osteosarcoma treatment (2) Evaluating the effects of osteosarcoma treatment at K hospital in Ha Noi 2.New contributions The dissertation is the result of bone scintigraphy research at times, assessing the role of bone scintigraphy in the stage diagnosis through the early detection of micrometastases The appropriateness between changing AR index before and after chemotherapy in 57 patients with biopsy results assessing the degree of tumors necrosis has shown that bone scintigraphy can be used to evaluation the tumor response to chemotherapy in osteosarcoma patients instead of tumor conventional biopsy methods applied previously The results also showed that bone scintigraphy is very valuable in monitoring early detection of relapse and distant metastasis The thesis shows results of treatment, survival rate, survival rate, disease-free survival rate, function of preserved limbs, and factors affecting survival rate This is a valuable reference for osteosarcoma treatment The dissertation structure The dissertation consists of 129 pages, including: Introduction (2 pages), Overview (33 pages), Subjects and method (18 pages), Results (29 pages), Discussions (47 pages), Conclusions (2 pages) References have 118 documents including 14 Vietnamese documents, 104 English documents The number of documents published from 2009 onwards has 47/118 accounting for 39,8% (4 Vietnamese and 43 English) CHAPTER 1: OVERVIEW 1.1 Bone scintigraphy in diagnosis of osteosarcoma Bone scintigraphy has a very high sensitivity, giving a general picture of the whole bone system, helping to detect bone lesion if any The presence of one or more regions increasing uptake of radionuclide called "hot zones" Such lesions may include osteomyelitis, a recent fracture, benign bone tumors or malignant lesions For differential diagnosis of benign or malignant bone lesions, Otto Sneppen conducted simultaneously anatomical investigation and bone scintigraphy in patients with different lesions With bone scintigraphy, the author measured count values at the lesion area compared to the opposite bone area in the body (TBR) After comparing the result, the author found high TBR index in patients with malignant lesions and lower in benign lesions According to the author, the threshold of TBR index: 1.5 is considered as the threshold that distinguishes benign and malignant lesions on bone scintigraphy The presence of secondary lesion (metastasis) of bone changes the stage of the tumor to stage III (Enniking) from any stage and therefore, the treatment strategy also changes In osteosarcoma, micrometastasis is present in about 20% of patients before starting treatment This explains why prior to the development of chemotherapy, although the decision of amputations was extensive for cases of osteosarcoma, the rate of early relapse after treatment was also high Bone scintigraphy, in addition to the role of primary tumor monitoring through stages in which the patient is at risk of developing bone metastases, is also used to detect possible tumor mass after chemotherapy The change in radiation uptake (reduction or disappearance) after treatment shows tumor cell necrosis The changes TBR index before and after treatment shows the grade of respond to treatment 1.2 Histopathological Diagnosis The histopathological results are the criteria in diagnosing osteosarcoma Biopsy play an important role to accurately diagnose of tumor malignancy before treatment In osteosarcoma, the Hematocylin Eosine (HE) stain results mainly determine whether the tumor composition can have three forms: osteoblast cells, osteoclast cells and fibrous-forming cells In most cases, just relying on histopathology examination helps to make the diagnosis be accurate However, some cases of histopathology have not been clearly distinguished Immunohistochemistry is used to distinguish the primary bone cancer Immunohistochemistry analysis proves tissue origin and is an absolute reliable method 1.3 Diagnose the osteosarcoma stage Enneking stage system with bone sarcoma Primary tumor (T) Metastasis Stage Malignancy (G) IA Low malignancy (G1) Inside cavity (T1) M0 IB Low malignancy (G1) Outside cavity (T2) M0 IIA High malignancy (G2) Inside cavity (T1) M0 IIB High malignancy (G2) Outside cavity (T2) M0 III Gx Tx M1 (M) CHAPTER 2: SUBJECTS AND METHODS 2.1 Subjects Research is performed on 70 patients with osteosarcoma who are treated in Hanoi K Hospital from January 2008 to June 2014 2.1.1 Patient’s selection criteria The patient selected must meet the following criteria: - Histopathological diagnosis are osteosarcoma - Get bone scintigraphy according to the process: Before and after the patient has cycles of preoperative chemotherapy, after discharge and after leaving hospital for 3-6 months - The tumors were located in the upper and lower limbs - Surgical treatment combined chemotherapy with EOI regimen - Patients agreed to participate in research 2.1.2 Exclusion criteria - The patient had pulmonary metastases before treatment - Patients with accompanying kidney and heart diseases - Patients only treat surgery or chemicals alone - Treatment combined with other regimens from the beginning - Do not follow the full course of treatment 2.2 Methods Non-control prospective clinical study, cross-sectional description with follow-up monitoring 2.2.1 Histopathological diagnosis Locate tumor on the limbs based on clinical symptoms, radiograph images, CT scans Biopsy samples taken in areas of the tumor not have necrosis or bleeding The minimum size of biopsy sample is 1cm Biopsy will be stained by HE and the results will be read by a doctor in Department of Cellular Disease Surgery at K Hospital under microscope with magnification 400 The diagnosis results of histopathological osteosarcoma based on criterion: - Cellular component of osteosarcoma: polymorphic, diverse, multi-size cells with abnormal cell division (multiple nuclei), dark alkaline-colored nucleus - Substrates with bone, cartilage, and fiber substances, in which bone subtances always exists Osteosarcoma classification is made according to the classification table of WHO, 2002 Before surgery, remove the tumor or amputate, perform a biopsy at least twice: + The first time was implemented immediately after the patient was admitted to the hospital for a definitive diagnosis of histopathology as osteosarcoma + The second time: after the patient has cycles of preoperative chemotherapy to evaluate the histplogical effect of treatment according to Huvos’s grades Grade IV: 100% necrosis (Complete response) Grade III: 90 - 100% necrosis (Good response) Grade II: 50-89% necrosis (Partial response) Grade I: < 50% necrosis(No response) 2.2.2 Bone scintigraphy Whole body bone scintigraphy is performed on SPECT (Single Photon Emission Computed Tomography) 740 MBq 99m Tc-MDP was administered intravenously, and scintigraphic images were obtained after hours Each patient with osteosarcoma was taken bone scintigraphy at the following times: First time: Immediately after diagnosis of osteosarcoma 2nd time: after the end of preoperative chemotherapy according to EOI regimen with the aim of comparing with pretreatment bone scintigraphy, to detect new bone metastatic lesions, cell necrosis and evaluate the Grade of respond to chemotherapy, make comparision of the suitability of two methods to assess preoperative chemotherapy response - Based on the grade of tumor cell necrosis through the biopsy tissue - Based on AR (Alteration Ratio) value through bone scintigraphy Evaluate the change in radiation uptake expressed by the TBR of bone scintigraphy before and after treatment The TBR is determined as folows: TBR = (T-BG) /BG, in which: T is the count of radioactivity at the tumor and BG is the count at the position which is opposite to the tumor on the body (Background) Compared pretreatment TBR (TBR1) with post-treatment TBR (TBR2), and the change was defined as Alteration Ratio (AR) AR(%) = (TBR1TBR2) /TBR1 The results of the alteration ratio were divided into the following levels: good scintigraphic respond as AR ≥ 60%; partially respond AR 20 – 60% and not respond AR < 20% Comparing the results of assessing the treatment respond on bone scintigraphy with the assessment effects of treatment respond by assessing tumor cell necrosis through biopsy tissue samples according to Huvos - Result: 10 + Normal bone scintigraphy: Distribution of radioactive pharmaceutical density according to physiological characteristics, not detected abnormally on bone scintigraphy According to Otto Sneppen, TBR > 1,5 which is diagnostic threshold of malignant lesion Images on bone scintigraphy may be encountered: + "Hot zone" is the area of increased radiation uptake + "Cold zone" is the area that reduces or loses radiation uptake + Mixture: Have defects in central area, also increasing radioactivity in edging area + Micrometastases are small lesions that increase radiation uptake with TBR > 1,5 2.2.3 Surgical treatment - Indication to amputation surgery + No response to preoperative chemotherapy: AR index