MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES DANG TRUNG DUNG OUTCOMES OF SURGICAL TREAMENT FOR RADIOACTIVE IODINE REFRACTORY DIF[.]
MINISTRY OF EDUCATION MINISTRY OF DEFENCE AND TRAINING 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES DANG TRUNG DUNG OUTCOMES OF SURGICAL TREAMENT FOR RADIOACTIVE IODINE-REFRACTORY DIFFERENTIATED THYROID CANCER Major: Surgical Medicine/Thoracic Surgery Number code: 9720104 SUMMARY OF MEDICAL DOCTORAL THESIS HA NOI - 2023 WORK COMPLETED AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES SCIENTIFIC SUPERVISOR: Associate Professor Le Ngoc Ha, MD, PhD Associate Professor Tran Trong Kiem, MD, PhD Counter-argument 1: Counter-argument 2: Counter-argument 3: The thesis will be defended before the School-level Thesis Judging Committee at: date month The thesis can be found at: National Library 108 Institute of Clinical Medical and Pharmaceutical Sciences Library year NEW CONTRIBUTIONS OF THE THESIS Review of clinical and subclinical characteristics of radioactiveiodine refractory The topic clearly analyzed surgical techniques in surgery, analyzed the factors affecting the patient's prognosis; which can be applied in the assessment, prognosis and indication of adjuvant treatment methods for patients after surgery This is the first work published in Vietnam on surgery for radioactive-iodine refractory differentiated thyroid cancer (98 patients), which is the basis for prognosis and treatment of this group of patients LAYOUT OF THESIS The thesis consists of 128 pages (excluding appendices and references) Introduction pages, literature overview 34 pages, object and methods 27 pages, results 27 pages, discussion 36 pages, conclusion pages, recommendations page Includes 158 references in English and Vietnamese INTRODUCTION Differentiated thyroid cancer is a cancer originating from the epithelial cells of the thyroid gland, the disease usually progresses slowly, mainly with local recurrence and metastasis to the cervical lymph nodes Treatment of differentiated thyroid cancer is multidisciplinary treatment, including combined surgery, 131 I radiation therapy, hormone therapy However, the recurrence rate is from 10 to 30% About 1/3 1/2 of the recurrent and metastatic lesions will gradually reduce or not absorb 131 I and are radioactive iodine-refractory differentiated thyroid cancer, with a worse prognosis Currently, the guidelines for the treatment of radioactive iodine-refractory differentiated thyroid cancer of the American Thyroid Association, the National Comprehensive Cancer Network and the European Thyroid Society are also gradually improving on the treatment process for this disease However, surgery is still the first choice for surgically resectable localized lesions In Vietnam, there have been a number of studies on radioactive iodinerefractory differentiated thyroid cancer Therefore, we conducted a study on the topic "Outcomes of surgical treatment for radioactive iodine-refractory differentiated thyroid cancer" to improve the treatment results of this group of patients, with the following objectives: Remark on clinical and paraclinical characteristics in patients with radioactive iodine-refractory differentiated thyroid cancer having surgical indications Evaluate surgical results and related factors to surgical outcomes in patients with radioactive iodine-refractory differentiated thyroid cancer at 108 Military Central Hospital CHAPTER LITERATURE REVIEW 1.1 Overview of radioactive-iodine refractory differentiated thyroid cancer 1.1.1 Concept, mechanism of radioactive-iodine refractory differentiated thyroid cancer 1.1.2.1 Definition and classification of radioactive-iodine refractory differentiated thyroid cancer According to the 2015 ATA, cervical cancer that can differentiate against 131I includes the following groups: - Group I: cancer tissue does not absorb 131I in the first time - Group II: Tumor organization gradually lost the ability to absorb 131 I - Group III: 131 I only absorb some lesions but there are some other lesions that not absorb 131I - Group IV: lesions still progress despite 131I absorb In clinical practice, there are some other indicators in assessing resistance to 131 I such as cumulative 131 I treatment dose > 600 mCi but no complete response, increased serum Tg after 131 I treatment, FDG absorb lesions on PET/CT 1.1.2.2 Mechanism of radioactive-iodine refractory differentiated thyroid cancer Decreased and absent iodine uptake in thyroid cancer cells is associated with abnormal function of NIS (sodium iodide symporter), decreased expression of other components involved in iodine metabolism, including Tg (thyroglobulin), TPO (thyroperoxidase) and Thyroid Stimulating Hormone Receptor (TSHR) Furthermore, decreased iodine concentration of differentiated thyroid cancer cells was due to decreased NIS expression There are two main signaling pathways leading to gene changes that reduce differentiation in thyroid cancer: MAPK (mitogen-activated protein kinase) and PI3K/AKT (phosphoinositide 3-kinase) pathways In addition, several other signaling pathways also play a role in the reduction and loss of iodine absorption 1.1.3 Clinical symptoms of radioactive-iodine refractory differentiated thyroid cancer - Functional symptoms: The functional symptoms of radioactiveiodine refractory differentiated thyroid cancer are often poor - Physical symptoms: recurrent lymph nodes in the neck can be central or lateral cervical lymph nodes, supraclavicular Nodes are usually less movable, dense, and painless Some enlarged lymph nodes or soft tissue lesions under the skin can cause pain 1.1.4 Subclinical symptoms of radioactive-iodine refractory differentiated thyroid cancer 1.1.4.1 Serum thyroglobulin and anti-Thyroglobulin tests Thyroglobulin (Tg) is a protein produced by thyroid follicular epithelial cells The existence of Tg indicates the functional activity of thyroid tissue For patients who have undergone total thyroidectomy and thyroidectomy with 131 I, the presence of Tg is considered one of the hallmarks of recurrent or metastatic disease Anti-thyroglobulin (anti-Tg) is an anti-Tg antibody 1.1.4.2 Ultrasound Central and lateral cervical ultrasonography is recommended in the diagnosis of cervical lymph node metastasis 1.1.4.3 Computed tomography and magnetic resonance imaging Computed tomography (CT) or Magnetic Resonance Imaging (MRI) imaging of the neck and chest can complement the limitations of ultrasound, providing a complete image of invasive lesions Multifocal extension or metastasis to guide appropriate treatment 1.1.4.4 Scanning in the diagnosis of metastatic lesions radioactiveiodine refractory differentiated thyroid cancer Whole-body bone scan using 99mTc-MDP gamma camera is a classic nuclear medicine technique that provides information on the extent and extent of bone metastases 1.1.4.5 18F-FDG PET/CT in radioactive-iodine refractory differentiated thyroid cancer For many years, the clinical application of 18F-FDG PET in thyroid cancer has been to locate recurrence and metastasis in patients with high Tg test (≥ 10ng/ml) and 131 I scan results negative body Studies have shown that the sensitivity and specificity of 18FFDG PET in diagnosing the location of recurrence and metastasis of thyroid cancer ranges from 82-95% and 83-95%, respectively 1.1.4.6 Fine needle aspiration cytology test Fine Needle Aspiration (FNA) and ultrasound-guided FNA are effective modalities for the diagnosis of lymph node metastasis This method can achieve a diagnostic sensitivity of 75% to 85% with a false negative rate of 6% to 8% 1.1.5 Treatment of radioactive-iodine refractory differentiated thyroid cancer 1.1.5.1 Active follow-up In most cases, tumors smaller than 1-2cm in size can be actively monitored without any other treatment 1.1.5.2 Local treatment Local treatment is indicated when recurrent lesions cause symptoms and/or pose a risk of damage to vital structures Local treatments include surgery, External Beam Radiation Therapy (EBRT), radio frequency (RF), cryoablation, laser ablation, and chemo-embolization 1.1.5.3 Whole body treatment Using small molecule anti-tyrosin kinase drugs (Tyrosine Kinase Inhibitor: TKI) in the treatment of patients with radioactiveiodine refractory differentiated thyroid cancer In 2013, Sorafenib was the first drug to be approved, indicated for patients with recurrent, metastatic differentiated thyroid cancer that no longer responds to radioactive iodine therapy In 2015, the FDA also approved lenvatinib for the treatment of patients with differentiated, metastatic, and lost to respond to 131I 1.2 Surgery for radioactive-iodine refractory differentiated thyroid cancer 1.2.2 Indications for surgery for radioactive-iodine refractory differentiated thyroid cancer - Lesions in the central cavity ≥ 8mm; lateral cervical lymph node involvement ≥ 10 mm - Progressive local lesions - High-risk lesions cause tracheoesophageal compression or nerve compression - Isolated distant metastatic lesions - Injury at the site of pain 1.2.3 Surgery for radioactive-iodine refractory differentiated thyroid cancer 1.2.3.1 Resection of recurrent thyroid cancer lesions and central lymph node dissection There are three approaches to exposing the recurrent nerve in this case: - Access by side road - Access from below - Approach from above - Invasion of the recurrent nerve - Invasion of the trachea: Tangential resection of the tracheal wall Removal of a small portion of the tracheal wall In cases of extensive tracheal invasion, tracheal resection and tracheal anastomosis are necessary - Esophageal invasion: Removal of part of the esophagus or the whole wall of the esophagus 1.2.3.2 Lateral cervical lymphadenectomy - Radical cervical lymphadenectomy - Modified radical cervical lymphadenectomy - Selective cervical lymphadenectomy - Extended cervical lymph node dissection 1.2.4 Complications of surgery for recurrent thyroid cancer - Parathyroidism - Recurrent nerve palsy - Bleeding after surgery - Acute respiratory failure - Chyle leak 12 CHAPTER RESULTS 3.1 Clinical characteristics of the study group of patients Table 3.4 TNM stage assessment Age < 55 Age ≥ 55 (n=72) (n=26) I 70 (97,2%) (19,2%) 75 (76,5%) II (2,8%) 11 (42,3%) 13 (13,3%) III (30,8%) (8,2%) IV 0 Undetermined (7,7%) (2,0%) Stage Overall Total 98 (100%) Comment: majority of patients in stage I (76,5%) Table 3.7 Number of treatments and cumulative dose 131I Number of treatments and cumulative dose Number of 131 treatment Cumulative dose (mCi) 131 131 of Tỷ lệ (%) Number I patitents (n) I ≤2 57 58,2 >2 41 41,8 Mean 2,7 ± 1,2 Median (1 - 9) I Mean 351,5 ± 181,4 Median 300 (100 - 1250) ≤ 300 62 63.3 300 - 600 27 27,5 ≥ 600 9,2 Comment: the average number of 131 I treatments was 2.7 ± 1.2, the average cumulative dose was 351.5 ± 181.4 mCi 13 Table 3.13 CT and PET/CT image results and other diagnostic methods Image characteristics Number patients Ratio (%) (n) CT 80 81,6 PET/CT 18 18,4 21 21,4 59 60,2 CT No contrast enhancement Contrast enhancement CT and Invasion 26 26,5 PET/CT No invasion 72 73,5 ≤ 10 47 48 > 10 51 52 Size (mm) Mean 12,9 ± 7,5 Median 11 (6 - 59) FNA positive 95 96,9 Vocal cord paralysis through 7* 18,5 laryngoscopy (* there were patients with vocal cord paralysis due to previous surgery and patients with laryngeal paralysis due to tumor invasion of the recurrent nerve and trachea) Comment: The mean lesion size was 12.9 ± 7.5 (6 - 59) mm, of which 52% of patients had lesion size > 10mm 14 Table 3.15 BRAF mutation results (n = 83) Pathology BRAF mutation Total Positive Negative Papillary 67 13 80 Folicular Oncocytic cell 0 69 (83,1%) 14 (16,9%) 83 Total Comment: the majority of patients had BRAF mutations (83.1%) 3.2 Result of surgery Table 3.19 Surgical method Surgical method Number of Ratio patitents (n) (%) 6,1 3,1 1 1 Cervical and mediastinal dissection 87 88,8 Total 98 100 Thyroid bed lesion removal + cervical dissection Thyroid bed lesion removal + tracheal resection Thyroid bed lesion removal + tracheal resection + cervical dissection Dissection of neck lymph nodes + removal of lung metastases Comment: cervical, mediastinal lymph node dissection accounted for the majority with 88.8% 15 Table 3.24 Location of cervical lymph node groups (n = 95) Position Right Left Subcutaneous lymph nodes (3,1%) Central VI 59 (60,2%) compartment VII (7,1%) Lateral II 23 (23,5%) 23 (23,5%) compartment III 23 (23,5%) 19 (19,4%) IV 23 (23,5%) 27 (27,6) V 10 (10,2%) (5,1%) Comment: group VI lymph nodes were removed the most (60.2%) Table 3.25 Number of lymph nodes removed (n = 95) Dissected Undissected Position Overall area area Number of Min 1 nodes Max 19 43 47 removed Mean 5,6 ± 4,6 16,9 ± 8,4 13,2 ± 10,6 Number of Min 1 metastatic Max 12 14 15 lymph Mean 2,8 ± 2,4 3,3 ± 2,8 3,9 ± 3,1 nodes Lymph Mean node ratio Median 0,43 ± 0,3 0,37 (0,06 - 1,0) Comment: the average number of removed lymph nodes was 13.2 ± 10.6, the average number of metastatic lymph nodes was: 3.9 ± 3.1 16 Table 3.28 Surgical complications (n = 98) Complications Number of Ratio (%) patitents (n) Bleeding 1 Chyle leak 3,1 Surgical site infection 0 Hypocalcimia 4,1 Recurrent nerve injury* 2 Total 10 10,2 (*excluding patients with active sacrifice recurrent nerve) Comment: the complication rate in surgery is 10.2% Table 3.29 Classification of surgical results (n = 98) Classification of surgical Number results of Ratio (%) patitents (n) Good 88 89,8 Satisfactory 10 10,2 Unsatisfactory 0 Total 98 100 Comment: 89.8% of patients had good surgical results There were no unsatisfactory patients 17 Chart 3.2 Recurrence-free survival curve Median recurrence-free survival: 37.06 ± 1.52 months The recurrence-free survival rates at year, years and years were 94.4%, 80.6% and 62.5%, respectively Table 3.31 Classification of response and treatment after surgery Response and treatment after surgery Number patitents (n) of Ratio (%) Response Complete 28 28,6 after Intermediate 20 20,4 surgery Biochemical Incomplete 42 42,9 Structural Incomplete 8,2 Post- Surveillance 86 87,8 surgery 131 9,1 3,1 treatment I treatment External beam radiation Comment: incomplete biochemical response accounted for the highest rate (42.9%) 18 Table 3.37 Univariate and multivariate analysis for recurrence-free survival Variables Gender Female Male ≤ 55 Age at thyroidectomy > 55 Age at this ≤ 55 surgery > 55 Risk of recurrence Cumulative dose 131I Low – Medium High ≤ 300mCi > 300mCi Size ≤ 10mm Invasion > 10mm No Tg Yes < 1ng/mL ≥ 1ng/mL Univariate Multivariate HR (95% CI) p HR (95% CI) p 0,31 (013 - 0,76) 0,01 0,50 (0,19 - 1,37) 0,179 1,89 (0,85 - 4,23) 0,12 – – 4,12 (1,71 - 9,94) 0,002 2,05 (0,81 - 5,23) 0,132 0,96 (0,38 - 2,43) 0,927 – – 2,81 (1,27 - 6,19) 0,011 1,11 (0,43 - 2,89) 0,202 14,16 (3,32 - 60,45) < 7,07 0,001 (1,53 - 32,72) 0,012 11,11 (3,80 - 32,43) < 3,72 0,001 (1,05 - 3,21) 0,043 5,10 (1,75 - 14,88) 0,003 0,202 2,35 (0,63 - 8,77) Comment: lesion invasion and lesion size >10mm are independent prognostic factors for survival without recurrence 19 CHAPTER DISCUSSION 4.1 Clinical and paraclinical features 4.1.1 General characteristics of the study group 4.1.1.1 Age, sex and histopathology The average age of patients in the study was 47.4 ± 14.9 years old (the lowest age was 17 years old, the highest age was 84 years old This result is similar to Le Ngoc Ha's study in 2021, the average age is 48 (17 - 81 years old) However, our results are different from some other authors such as Brose (2017), Schlumberger (2015) and Shobab (2019) Regarding gender, differentiated thyroid cancer is common in women, accounting for 87.8%; The female/male ratio in the study was 7.2/1 In the study of Shokoohi (2020) in Canada, the percentage of female patients predominates, respectively 76.0% 4.1.1.2 Evaluation of TNM stage and risk of recurrence - Initial tumor size According to AJCC 8, 59.2% of patients have tumor size T1 - 2, 15,% tumor at T3 stage and 15.3% at T4 stage This is similar to the study of Kalaitzidou (2020) when the tumors were mainly at T1 and T2 stages [93] However, the study of Lamartina (2017) showed that the tumor size at T1 and T2 stage was only 42% and 53% of the tumor size of T3 and T4 using the AJCC classification - Lymph node metastasis The rate of lymph node metastasis was 69.4%; in which, metastasis in one or more groups of lateral cervical lymph nodes (N1b) accounted for the highest rate (63.3%) In the study of So (2018), the rate of lymph node metastasis was only 20.9% in the group of 18,141 patients with papillary cancer 20 - Classification of disease stages According to the classification of AJCC 8, 76.5% of patients in the study were in phase I, 13.3% in stage II, in stage III with 8.2%, there were patients with undetermined stage Onuma (2019) a study on 70 cases of papillary thyroid cancer also showed the highest proportion of patients in stage I (91.4%) A previous study also at 108 Military Central Hospital classified according to AJCC found that stage I accounted for the highest rate of 37.7%, stage IV accounted for 24.6%, stage II and III were 14.5% and 4.3%, respectively - Risk of recurrence In our study, the rate of patients with low - medium risk of recurrence accounted for 33.7%, the rate of patients with high risk of relapse was 66.3% 4.1.1.3 First surgery and treatment 131I - First surgical method In this study, total thyroidectomy alone accounted for 20.4%, the rest were patients who had total thyroidectomy + prophylactic or therapeutic cervical lymphadenectomy accounted for 79.6 % This rate is similar to Lamartina (2017) with the rate of thyroidectomy alone is 29%, the rest is thyroidectomy and neck lymph node dissection However, in Dong's study (2019) with 466 papillary carcinoma patients operated in Tokyo from 1981 to 1991, the rate of thyroidectomy alone was very low (only 1.9%) - Treatment 131I The average number of 131 I treatments before surgery in our study was 2.76 ± 1.3 times The average total dose of 131I was 358.6 ± 221.6mCi (median 37 mCi, lowest 50mCi, highest 1425mCi) 21 Meanwhile, in Brose's study (2014), the median cumulative dose of 131 I before receiving Sorafenib was 400; Shobab's study (2019) had an average number of 131 I treatments of 2.19 ± 1.13mCi and a mean cumulative dose of 518 ± 313.5mCi 4.1.2 Clinical, paraclinical and diagnostic characteristics of radioactive-iodine refractory differentiated thyroid cancer 4.1.2.1 Clinical symptoms In our study, functional symptoms were uncommon, accounting for 11.2% Physical symptoms: palpable recurrence rate is 40.1% In this study, we did clinical examination to detect lesions in 40 patients This rate is similar to the Onkendi (2014) study in the Mayo Clinic 4.1.2.2 Paraclinical diagnosis - Ultrasound Our study found that ultrasound detected 94.9% of cases of radioactive-iodine refractory differentiated thyroid cancer In the studies by Onkendi (2014), 42% of patients had palpable nodules identified in the central compartment and 67% in the lateral neck region - Image analysation In this study, we performed ultrasound for 100% of cases and CT for 81.6% of patients and PET/CT for the remaining 18.4% We use a combination of methods to diagnose and locate lesions - Test for Tg, anti-Tg The mean preoperative Tg concentration was 33.61 ± 72.68 ng/mL, the median was 6.84 ng/mL (0.04 - 500 ng/mL), of which 44.9% of patients had the concentration Preoperative Tg ≥ 10 22 ng/mL Compared with the studies of Sun (2022), the median Tg concentration was 11.12ng/mL (0.1 - 1000 ng/mL) 4.2 Outcomes of surgical treatment 4.2.3 Result of surgery 4.2.3.2 Invasive recurrent lesions We found 32 patients (32.7%) with invasive Compared with Zhou (2021), the author's rate of extranodal invasion was 34/743 (4.58%) Sun (2022) found that the rate of extranodal invasion was 31.4% 4.2.3.3 Number of lymph nodes removed during surgery With 98 patients undergoing surgery, 95 patients had lymph node dissection The average number of lymph nodes removed was 13.2 ± 10.6 In which, the average number of metastatic lymph nodes was 3.9 ± 3.1 The average lymph node ratio metastasis was 0.43 ± 0.3 Lamartina (2015) reported that among 157 patients undergoing surgery for recurrent differentiated thyroid cancer, the median number of removed lymph nodes was 29 (1 - 98), with a median number of lymph node metastases of (1 - 41) The median size of the largest metastatic lymph node was 14 mm (4 - 70 mm) The average rate of lymph node metastasis was 0.17 (0.02 - 1) RiveraRobledo (2019) reported the results of lymphadenectomy in recurrent papillary carcinoma Lymph nodes were confirmed in the specimen in 98.8% of the patients, with a mean number of metastases and recovered lymph nodes of 2.43/4.5 in the central compartment (0 - 20 lymph nodes removed, - 20 metastatic nodes) and 2.41/14.4 in the lateral neck (0 - 46 lymph nodes removed, - 12 metastatic nodes) Kalaitzidou (2020) reported the results of lymph node dissection for recurrent papillary carcinoma The median number of lymph nodes at surgery was 26 (1 - 60) and the median number of metastatic nodes 23 was (1 - 13) The lymph node ratio at reoperation was 0.36 ± 0.33 (from 0.04 to 1.00) Thus, it can be seen that the number of removed lymph nodes and number of metastatic nodes in this study are similar to those of other authors 4.2.3.5 Complications after surgery Postoperative complications in our study were 10.2% Regarding the rate of complications after surgery, there are many studies showing that this rate ranges from 1.4 to 17.1% 4.2.4 Follow-up after surgery 4.2.4.1 Response after surgery In our 98 patients: 28.6% of patients had a complete response after resection; biochemical incomplete response was achieved in 42.9%; intermediate and structural incomplete response rates were 20.4% and 8.2%, respectively A study by Lamartina (2017) on 156 patients with differentiated thyroid cancer showed that, after recurrent cervical dissection, 63% achieved complete response, 10% achieved a biochemical incomplete response, 10 % structural incomplete response and 17% intermediate response Onuma's study (2019) on 60 papillary carcinoma patients who underwent cervical lymph node dissection showed the complete response rate was 19/60 (31.7%), the biochemical incomplete response was /60 (6%), structural incomplete response was 31/60 (51.7%) and intermediate response was 6/60 (10%) Kalaitzidou (2020) studied on 30 patients with papillary cancer, there were patients (23.3%) with complete response, (13.3%) biochemical incomplete response, (30.0%) patients with intermediate response and 10 (33.3%) structural incomplete responses With the study of Chiapponi (2021) on the results of cervical lymph node surgery on 30 patients with 131Iresistant differentiated thyroid cancer with positive 18F-FDG-PET The results showed 40% biochemical and structural responses, 20% 24 incomplete biochemical responses, and 6% structural incomplete responses 4.2.4.2 Recurrence events, progression and recurrence-free survival Median follow-up time after surgery was 24 months, mean follow-up was 24.7 months Recurrent or progressive events were observed in 25 patients (26.3%) Lee (2015) during the mean followup period of 57.5 months (from 21 to 196.2 months), 41 (27.2 %) patients relapsed after the first recurrence surgery Sun (2022) with a median follow-up time of 36 months, with 124 patients undergoing surgery for 131I-resistant and non-resistant papillary carcinoma, 32 patients had recurrent events The mean recurrence-free survival time of 95 patients in the study was 37.06 ± 1.52 months (median 46 months) 4.2.5 Factors related to recurrence-free survival time 4.2.5.8 Independent prognostic factors for recurrence-free survival Independent prognostic factors for recurrence-free survival are: lesion size > 10mm and lesions (tumors and lymph nodes) invading surrounding tissues Lee (2015) studied on recurrent papillary carcinoma, the independent prognostic factor for recurrence-free survival is high Tg concentration after surgery Molteni (2019) studied on subjects with recurrent papillary carcinoma in the central compartment, the independent prognostic factors for disease-specific survival were lymph node invasion and high malignancy histology Xu (2021), the independent prognostic factor of recurrence-free survival for recurrent papillary carcinoma is the age of recurrent surgery ≥ 55, primary thyroid tumor > cm and the number of recurrent metastatic nodes ≥ 10 Sun (2022) studied on subjects with both resistant and non-resistant 131I papillary cancers, the independent prognostic factors for recurrence-free survival were invasive lymph nodes and high Tg levels after surgery 25 CONCLUSION Clinical and paraclinical characteristics in patients with radioactive-iodine refractory differentiated thyroid cancer The mean age was 47.4 ± 14.9 Most are papillary cancers (96%) 66.3% of patients had a high risk of recurrence The average number of 131I treatments was 2.7 times with an average cumulative dose of 351.5mCi Time to relapse 44.02 ± 33.44 months The mean size of the recurrent lesion was 12.9 ± 7.5mm The mean preoperative Tg concentration was 33.61 ± 72.68ng/mL 83.1% of patients with radioactive-iodine refractory differentiated thyroid cancer have BRAF mutations Surgical outcomes and factors related factors in patients with radioactive-iodine refractory differentiated thyroid cancer The site of group VI lymph node recurrence was the highest, accounting for 60.2% The average number of lymph nodes removed: 13.2 ± 10.6 Average number of metastatic lymph nodes: 3.9 ± 3.1 Lymph node ratio: 0.43 ± 0.3 The complication rate was 10.2% Patients with biochemical incomplete response: 42.9%, complete response accounted for 28.6% and 8.2% of patients had structural incomplete response 26.3% of patients had recurrent events, progressed during the average follow-up of 24.7 months The recurrence-free survival time was 37.06 ± 1.52 months Univariate and multivariate analyzes showed that the size of recurrent lesions and gross invasion in recurrent/metastatic lesions were independent predictors of recurrence-free survival LIST OF WORKS RELATED TO THE THESIS Dung Trung Dang, Ha Ngoc Le, Hai Vi Ngo, Kiem Trong Tran, Son Hai Le, Thang Duc Nguyen, Ha Van Xuan Nguyen, Phuong Thi Nguyen, Nhung Thi Nguyen, Nhung Thi Tuyet Le, Son Hong Mai (2022) Outcomes of reoperation for locoregional recurrence in radioactive-iodine refractory papillary thyroid carcinoma patients: a singleinstitution experience Annals of Cancer Research and Therapy, 2022, Volume 30, Issue 2, Pages 67-73 Dang Trung Dung, Le Quoc Khanh, Nguyen Duc Thang, Le Hai Son, Nguyen Van Xuan Ha, Tran Trong Kiem, Ngo Vi Hai, Le Ngoc Ha (2022) Tracheal resection for recurrent radioactive iodine-refractory differentiated thyroid cancer involving the trachea: Two case reports Journal of 108 - Clinical Medicine and Pharmacy, Volume 17, No 2/2022; pp.129-133 Dang Trung Dung, Le Ngoc Ha, Tran Trong Kiem (2023) The outcomes of surgery for radioactive iodine-refractory differentiated thyroid cancer Journal of 108 - Clinical Medicine and Pharmacy, Volume 18, No 2/2023; pp.48-55 Dang Trung Dung, Le Ngoc Ha, Tran Trong Kiem (2023) Recurrence-free survival and related factors after reoperation of radioactive iodine-refractory differentiated thyroid cancer patients Journal of 108 - Clinical Medicine and Pharmacy, Volume 18, No 2/2023; pp.69-76