1 INTRODUCTION Soft tisue sarcoma is a rare malignancy that arises from connective tissue outside the bone and peripheral nervous system It can locate anywhere on the body, but are common in the lower limbs especially Soft tissue sarcoma is a rare disease that accounts for about 1% of all malignant lesions in adults and about 21% of malignant lesions in children Diseases diversified in location, diverse in histopathological type According to the World Health Organization (WHO) classification, the subgroup of soft tissue sarcoma includes more than 50 different histologic categories, based on the origin of the tissue The most common clinical manifestations are tumor appearance, the tumor gets bigger in size, the initial tumor is usually less painful, when the large tumor compresses nearby tissue causing pain symptoms, the tumor may be located superficial that easy to detect, or may be located deep within the muscle bundles that when tumor bigger in size that can be detectted Enlarged tumors can break the skin, ulcers, bleed Among the diagnostic methods, MRI scan plays an important role in diagnosing tumor size, its association with muscle, nerve and blood vessels Tumor biopsy by open biopsy or needle biopsy of histopathological diagnosis is a method with definite diagnostic value Aims of limb sparing treatment of soft tissue sarcoma are to increase the survival rate, avoid local complications, maintain maximum function of the limb The principle of surgery is wide local resection, achieving negative microscopic margin However, the major challenge in surgery is that large tumors located close to the vascular, nerve, or bone bundles are difficult to perform wide local resection For these, it is possible to resect marginal, however, it must be ensured that the microscopic section does not have cancer cells, then combined with radiation therapy to reduce local recurrence Adjuvant radiotherapy plays a role in reducing local recurrence, but does not improve the survival rate, the average radiation dose (50-60Gy) can effectively eliminate microscopic lesions around the tumor, achieved when compared to amputation In the 1970s, more than half of patients with extremity soft tissue sarcoma had amputation With the advancement of surgical methods, especially plastic surgery, microsurgery combined with adjuvant radiotherapy, the rate of amputation is reduced to about 1% without changing the survival rate Role of chemotherapy, immunotherapy and targeted treatment are still limited Currently in Vietnam, there is no meticulous research on multi-modal coordination in limb sparing treatment Therefore, I perform research “research the results of limb sparing treatment of extremity soft tissue sarcoma with stage T2N0M0” with two objectives Assessing some clinical and paraclinical characteristics of extremity soft tissue sarcoma T2N0M0 Evaluation of limb sparing surgery results and adjuvant radiotherapy 2 NEW CONTRIBUTION OF THESIS This is the first study in Vietnam with a sample size large enough to reach the most complete results on the effectiveness of limb sparing surgery combined with adjuvant radiotherapy in extremity soft tissue sarcoma The results from the study show that: The most common tumor location in the thigh is 59,2% The surperficial tumors accounted for 27,5%, deep lesions were 72,5% 84.5% of tumors had heterogeneous signal intensity on MRI 71,1% tumors had irregular border Undifferentiated pleomorphic sarcoma were 21,2% Grade was highest with 52,1% Tumor resection was 85,2% Wide tumor resection with margin over 1cm was 52,8% The incidence of lymphoedema following adjuvant radiotherapy was 23,2% Acute radiation skin toxicities were mostly mild (grade 1) accounted for 59,2% Late radiation skin toxicities were 45,1% with mostly grade 37,4% Joint stiffness were rare by 7,8% Extremity edema met 18,1% Five year overall survival rates were 63,2% Five-year disease free survival rates were 54,5% Five-year recurrent rates were 28,8% Factors affecting five year overall survival rates were tumor size, tumor depth and histologic grade Tumor size, tumor depth, histologic grade and surgical procedures that affect the five-year recurrent rates STRUCTURE OF THESIS The thesis includes136 pages and consist of: Introduction (2 pages), Chapter 1: Overview (35 pages), Chapter 2: Subjectsand methods (18 pages), Chapter 3: Results (34 pages), Chapter 4: Discussion (42pages), Conclusion (2 pages), Recommendation(1 page) In this thesis, there are 41 tables, 14 graphs and figure References contain 136 documents (13 in Vietnamese and 223 in English) The appendix includes patient list, illustration pictures, study parameters and standards, case report form, questionaire, letters and informed consent of patients CHAPTER 1: OVERVIEW 1.1 Epidemiology and pathogenesis 1.2 Diagnotic - Tumor: usually a little pain, gradually enlarged Tumor that suspect malignancy when: size > 5cm, pain, increasing in size, deeply tumor and recurrence after surgery - MRI scan: valuable diagnostic and stage evaluation, accurate assessment of anatomical location, related to nerves, blood vessels, invasion of the tumor into one or more muscle bundles Suspected malignancy when larger than 5cm, heterogeneous and irregular boder - Tumor biopsy for histopathological diagnosis may involve needle biopsy or open biopsy Histopathological classification according to WHO 2013 and histologic classification according to the French Federation of Cancer Prevention (FNCLCC) 1.3 Treatment - Limb sparing surgery: tumor resection (wide local resection without cutting into the tumor cutting the healthy tissue surrounding the tumor, preserving nerve structure, blood vessels, bones) is the most important step in treatment of extremity soft tissue sarcoma The purpose of surgery is to resect the tumor wide with a negative microscopic margin Nerves, large blood vessels are often preserved during surgery if the tumor is carefully dissected, peeled of the sheath of nerves because the tumor rarely invades the nerves or blood vessels If microscopic margin is positive (except for bone, neural, and large blood vessels) resection should be performed to obtain a microscopic section without cancer cells Large tumors located close to the vascular bundles, nerves can be resectted marginal in order to achieve negative microscopic margin but still preserve these important structures - Radiotherapy: radiotherapy reduce local recurrence The average radiation dose (5060Gy) can effectively remove microscopic lesions around the tumor, providing good results when comparing amputation with radical surgery Reports of local control rates of 85-90% for extremity soft tissue sarcoma and 95-100% for low-grade extremity soft tisue sarcoma depending on tumor size Radiotherapy techniques such as 3D-CRT (three-dimensional conformal radiotherapy), intensity-modulated radiotherapy (IMRT), proton beam therapy provide high efficiency Currently at K hospital, most of them apply 3D-CRT, the radiation field covers an average distance of 5-20cm from the outside of the tumor Field diameter depend on tumor size and tumor conservation surgery surgical area of limb sparing operation Filed of radiation will be narrowed to 1-2cm in length Dose of 1.8 - Gy / day x days / week Duration of 5- weeks - Other treatment procedures The role of chemotherapy for soft tissue sarcoma is still controversial Valuable evidence from meta-analyzes and randomized clinical trials suggests that postoperative epirubicin and ifosfamide chemicals improve nonrecurrent survival (RFS) in patients with extremity soft tisue sarcoma However, the data related to overall survival is controversial Targeted therapy has shown promise in some advanced or metastatic soft tissue sarcoma CHAPTER PARTICIPANT AND STUDY METHOD 2.1 Study participant This study included 142 extremity soft tissue sarcoma patients treated with limb sparing surgery and adjuvant radiotherapy Vietnam National Cancer Hospital from January 1st 2013 to November 31st 2018 * The eligibility criteria included: - Extremity soft tissue sarcoma (upper and lower limb) Stage T2N0M0 according to AJCC 2010 classification - Tumors have not invaded nerves, large blood vessels, and have not lost limb function - Pathology is soft tissue sarcoma Histopathology grade classification according to FNCLCC Patients were done Immunohistochemistry - Patients were performed limb sparing surgery and treated adjuvant radiotherapy - Patients and families voluntarily participated in the study - There is information about the post-treatment condition through follow-up examination and / or information from the reply sent to the patient and family or phone * Exclusion criteria - Non-extremity soft tissue sarcoma 4 - Histopathology is not soft tissue sarcoma - The tumor is not in the pT2N0M0 stage - Tumors invaded nerve, large blood vessels, causing loss of limb function - Amputation of disarticulation - Abandoning treatment, not completed treatment course - Patients had other serious illnesses that at risk of death 2.2 Study methods 2.2.1 Study design: this was a retrospectively and prospectivelydescriptive study with longitudinal follow-up 2.2.2 Sample size of study The formula to calculate the sample size: p (1-p) n= Z21-/2 2 n: is the sample size of the study p: 5-year survival rate of the domestic study is 0.6 (1-p = 0.4) : absolute tolerance allowed The error estimate is 10% (absolute tolerance allowed The error estimate is 10% (=0,1) Z21-/2: 5% confidence limit coefficient, look up tables (= 1.96) Applying the above formula, sample size is 92 In this study, we included 142 patients 2.2.3 Study process - Enroll eligiblepatients Information was collected based on a consensus medical record sample All patients participating in this study were treated with limb sparing surgery with negative microscopic margin and adjuvant radiotherapy Data were collected at the following moments: starting point of treatment, during treatment,ending of treatment and ending of follow-up (time of death or whenfinal information was collected or whenfollow-up was ended (November 31st 2018)) - Assessment of several characteristics of study patients: age, gender, tumor clinical symptoms, tumor location, tumor size, tumor depth (superficial, deep tumor), tumor characteristics on MRI (tumor margin, signal intensity), histopathology and grade - Evaluation of treatment results including evaluation of surgical characteristics, surgical methods, early postoperative complications Features of adjuvant radiation therapy, lymphatic edema complications, acute skin complications due to radiation, radiation-induced wound complications, late skin complications, stiffness, radiation edema Overall 5-year survival, disease-free year survival, year recurrent rate - Evaluate several factors affecting overall 5-year survival, year recurrent rate: age, gender, tumor location, tumor size, depth of tumor, histology, methods of surgery, radiation dose Factors related to multivariate analysis 2.3 Data analysis Information was collected based on designed case report forms Data collection methods: clinical examination, laboratory test, follow-up examination, prescription, call or write letter to the patients to record treatment efficacy Data were processed and analyzed on SPSS 16.0 software with statistical algorithms Survival was pn = Z21 - /2 p (1 - p) n  Z (21   / ) 2 p  p estimated by the Kaplan- Meier method The univariate analysis: use log-rank test when comparing survival curves among groups The multivariate analysis: use Cox proportional hazards models with 95% confidence interval (p=0.05) CHAPTER 3.RESULTS 3.1 CHARACTERISTICS OF PATIENTS Table 3.1 Characteristicsof patients Characteristics N % Characteristics Male 76 53,5 arm Gender Forearm and Female 66 46,5 hand location 50.4 Mean age thig ±16.7