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RISK STRATIFICATION METHOD FOR THYROID CANCER Sunarto Reksoprawiro Division of Head & Neck Surgery, Department of Surgery Faculty of Medicine-Airlangga University/ Dr. Soetomo Hospital Surabaya, Indonesia INTRODUCTION THYROID CANCER Incidence : 1.2 to 2.6 per 100,000 (men) and 2.0 to 3.8 per 100,000 (women) >90% of tumors are differentiated thyroid cancer Some prognostic scoring systems do not differ between PTC and FTC PTC accounts for at least 70% of all DTC 10% of patients would eventually die of the disease and an even greater proportion would face the morbidity of recurrences. A number of studies have identified various clinicopathologic predictors for PTC and devised risk-group stratification or staging systems Age, gender, histological type, tumour size and extrathyroidal invasion have been found previously to be associated with a poor clinical outcome The prognostic impact of regional lymph node metastases is still a controversial issue Distant metastases is a recognized factor for a poor prognosis • There are conflicting thoughts over different aspects of treatment of differentiated thyroid cancer • The lack of consensus stems due to the absence of concrete data from randomized controlled trials • Surgery with or without radio-iodine therapy forms the mainstay of treatment of differentiated thyroid cancers STAGING SYSTEMS Many scoring or staging systems have been developed during the last two decades The most commonly used staging classifications are AMES , AGES , MACIS , EORTC , and UICC-TNM STAGING SYSTEMS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. European Organization for Research and Treatment of Cancer (EORTC) Mayo Clinic (Age, Grade, Extent, Size or AGES) Lahey Clinic (Age, Metastases, Extent, Size or AMES) University of Chicago (Clinical Class) Karolinska Hospital and Institute (DNA ploidy, Age, Metastases, Extent, Size or DAMES) Mayo Clinic (Metastases, Age, Complete resection, Invasion, Size or MACIS) University of Bergen (Sex, Age, Grade or SAG) Ohio State University (OSU) Noguchi Thyroid Clinic (Noguchi) Memorial Sloan Kettering (Grade, Age, Metastases, Extent, Size or GAMES) University of Munster (Munster) National Thyroid Cancer Treatment Cooperative Study (NTCTCS) University of Alabama and M.D. Anderson (UAB &MDA) Virgen de la Arrixaca University at Murcia (Murcia) AJCC/UICC 6th edition TNM (TNM) Cancer Institute Hospital in Tokyo (CIH) Ankara Oncology Training and Research Hospital in Turkey (Ankara) Degroot • There was no difference in the abilities of the top five classifications (AGES, TNM, EORTC, MACIS and AMES) to predict the prognosis for patients with differentiated thyroid carcinoma, and no statistically significant superiority of any system over the TNM classification was found • Brierley JD, Panzarella T, Tsang RW, Gospodarowicz MK & O’Sullivan B. A comparison of different staging systems predictability of patient outcome. Cancer 1997;79:2414–2423. There is no difference in tumor-specific survival between PTC and FTC when accounting for the presence of metastases, age, tumour size, and the presence of extrathyroidal invasion Verburg A, Mäder U, Luster M & Reiners C. Primary tumor diameter as a risk factor for advanced disease features of differentiated thyroid carcinoma. Clin Endocrinol 2009;71: 291–297 Age at presentation is a well-established strong prognostic factor for differentiated thyroid carcinoma Cady B & Rossi R. An expanded view of risk-group definition in differentiated thyroid carcinoma. Surgery 1988;104 :947–953. Gender proved to be of prognostic value for disease-free survival, which was shorter for males than for females Jukkola A, Bloigu R, Ebeling T & Salmela P. Prognostic factors in differentiated thyroid carcinomas and their implications for current staging classifications. Endocrine-Related Cancer 2004;11:571–579 Tumor extension beyond the thyroid capsule (pT4) is described as being one of the strongest prognostic factors in DTC, therefore resulting in its use in most staging systems Lerch H, Schober O, Kuwert T & Saur HB. Survival of differentiated thyroid carcinoma studied in 500 patients. J Clin Oncol 1997;15:2067–2075. • In some, but not all, studies, local lymph node involvement has been associated with an increased risk of tumour recurrence and also with DTC-related mortality • Mazzaferri EL & Young EL. Papillarythyroid carcinoma: a 10 year follow-up report of the impact of therapy in 576 patients. Am J Med 1981;70:511–51 • In patients > 45 years of age, involvement of cervical lymph nodes was associated with a poorer prognosis in PTC and FTC patients • Passler C, Scheuba C, Prager G, Kaczirek K, Kaserer K, Zettinig G, and Niederle B. Prognostic factors of papillary and follicular thyroid cancer: difference in an iodine-replate endemic goiter region. Endocrine-Related Cancer 2004;11:131-139 The diameter of the primary tumour is a determinant (independent predictor) for outcome in differentiated thyroid cancer. However, the delineation between low-risk and high-risk tumour size is unsettled. Mazzaferri & Kloos Machens et al. Verburg et al. : 4 cm : 2 cm : 1 cm Table 1. Risk of Death From Thyroid Cancer (Tuttle et al) Very Low risk Low Risk Intermediate Risk High Risk Age at diagnosis < 45 years < 45 years Young patients (< 45 years) Classic PTC > 4 cm Or vascular invasion Or extrathyroidal extension Or worrisome histology of any size‡ > 45 years Primary tumor size < 1 cm 1–4 cm Older patients (> 45 years) Classic PTC < 4 cm Or extrathyroidal extension Or worrisome histology < 1–2 cm confi ned to the thyroid‡ > 4 cm classic PTC Histology Classic PTC, confined Classic PTC, confined to Histology in conjunction Worrisome histology to the thyroid gland* the thyroid gland* with age as above > 1–2 cm‡ Completeness resection of Complete resection Lymph node None apparent involvement Distant metastasis None apparent Complete resection Complete resection Incomplete resection tumor Present or absent† Present or absent† Present or absent† None apparent None apparent Present REVISION SURGERY Pathology review USG neck Evidence of lobectomy + isthmectomy or large thyroid remnant Unfavorable histology Multifocal disease Positive margin Age > 50 years Male sex Nodule > 4 cm Nodule metastasis Completion thyroidectomy Low risk group (using presurgery criteria) observe If USG insignificant thyroid remnant RI scan Significant uptake >15% Completion thyroidectomy Low uptake <15%% RI ablation Frequency of thyroid carcinoma Dr.Soetomo Hospital Surabaya (2007-2011) N= 284 cases Fig.1. Sex distribution n = 284 Fig.2. Sex and age distribution n = 284 Fig.3. Metastases n = 284 Prognostic Factors AMES Low risk Age Metastases Extension Size : < 40 yrs (male); < 50 yrs (female) : None : No extrathyroid extension : < 4 cm Fig.4. Risk stratification n = 284 Fig.5. Treatment n = 284 Fig.6. Surgical treatment n = 221 Fig.7. Surgical complication 0.51% 0.51% 0.51% 0.51% 0.51% n = 195 Fig.8. Completion thyroidectomy n= 57 Fig.9. Histopathology n = 284 Fig.10. Mortality in hospital n = 284 SUMMARY A number of risk-group stratification have been found useful at stratifying patients with differentiated thyroid carcinoma into risk groups Significant risk factors were age, primary tumor size, histology, grade, local tumor extension, completeness of resection, and distant metastasis. Aggressive surgical resection was recommended for all gross disease in high risk and intermediate risk patients. The standard treatment for high risk patients are total thyroidectomy followed by I131 ablation and TSH suppression with thyroxin. Well-differentiated thyroid cancer in low risk patients has a favorable outcome and can be safely treated with unilateral thyroidectomy alone. Postoperatively, the patient’s operative and pathology records should be studied to re-assess the risk-group of the patients. Appropriate selection of surgical and adjuvant treatment should therefore be used based on prognostic factors and risk group stratification. Thank you