Special Issue Postoperative Adjuvant Therapy and Follow Up of Thyroid Carcinoma Ka Hee Yi, M.D. Department of Internal Medicine Korea Cancer Center Ho

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1 Special ssue Postoperative Adjuvant Therapy and Follow Up of Thyroid Carcinoma Ka Hee Yi, M.D. Department of nternal Medicine Korea Cancer Center Hospital khyi@kcch.re.kr Abstract Differentiated thyroid cancer is usually a curable disease, for which treatment modalities such as surgery, radioiodine, and thyroid hormone have been used for the last 50 years, yet little consensus has been established due to the lack of prospective randomized controlled therapeutic trials. After an initial surgery, the patients' outcome can be predicted by staging classification on the basis of several parameters such as the age of the patient, tumor size, tumor grade or differentiation, presence of local invasion, and regional or distant metastases. However, regardless of the pathologic stage, most patients(except those with micopapillary or minimally invasive follicular carcinomas who underwent only a lobectomies) are supposed to receive radioiodine therapy for ablation of any remnant thyroid tissue, which increases the sensitivity of serum Tg and 131 whole body scan used to detect recurrence or metastasis during a longterm followup. Until recently, a high dose of 131 has been preferred, however, low dose therapy(30mci) is a new trend nowadays, which decreases the incidence of both acute and late complications of radioiodine with the same ablation rate. All patients take thyroid hormone after surgery and radioremnant ablation to suppress the level of serum TSH, which is thought to stimulate tumor cell growth.the T 4 dose should be adjusted according to the age of the patient, other medical conditions and the risk of recurrence. During the followup, the serum Tg level with antitg antibody and the TSH level and 131 whole body scan should be checked regularly. Recently the serum Tg level stimulated by T 4 withdrawal or rhtsh injection is suggested to be the most sensitive marker for the detection of recurrence or metastasis. When the stimulated Tg is undetectable (< 2ng/mL), residual or metastatic cancer can be nearly excluded; when it is higher than 10ng/mL, a high dose 131 therapy and posttherapy 131 whole body scan are needed. n cases where the localization fails(tgpositive/ 131 scannegative cases), other imaging studies such as highresolution ultrasonography of the neck, spiral CT of chest, bone Xray or 99m Tc MDP bone scan and 18 FFDG PET scan can be useful. 18 FFDG PET is especially sensitive to detect poorly differentiated thyroid cancers that have lost the ability to uptake radioiodine. Keywords : Thyroid cancer; Staging; Radioiodine; Thyroid hormone; Follow up 1183

2 Special ssue (AJCC) Stage 4545 M0 T1 T1 M1 T2 T2~4 VA VB VC T3N0M0 T13N1aM0 T4a N1b T4b M1 N1 M1 1184

3 Staging or Scoring System EORTC AGES AMES U of C MACS OSU MSKCC (1979) (1987) (1988) (1990) (1993) (1994) (1995) :, :, : EORTC = European Organization for Research and Treatment of Cancer AGES ; Lahey clinic AMES, MACS ; Mayo clinic U of C = University of Chicago OSU = Ohio State University MSKCC = Memorial SloanKettering Cancer Center ü 1185

4 Special ssue National Thyroid Cancer Treatment Cooperation Study Registry (cm) < 1 1~4 > , V V 1186

5 1187

6 Special ssue 1188

7 1189

8 Special ssue 1190

9 1191

10 Special ssue 1192

11 SpringerVerlag, 2002 : Ain KB. Papillary thyroid carcinoma : etiology, assessment, and therapy. Endocrinol Metab Clin North Am 1995 ; 24 : Byar DP, Green SB, Dor P, Williams ED, Colon J, van Glabbeke M, et al (Thyroid Cancer Cooperative Group). A prognostic index for thyroid carcinoma : a study of the E.O.R.T.C. Eur J Cancer 1979 ; 15 : Hay D, Grant CS, Taylor WF, McConahey WM. psilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma : a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987 ; 102 : Cady B, Rossi R. An expanded view of riskgroup definition in differentiated thyroid carcinoma. Surgery 1988 ; 104 : DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment, and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1990 ; 71 : Mazzaferri EL, Jhiang SM. Longterm impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994 ; 97 : Gilliand FD, Hunt WC, Orris DM, Key CR. Prognostic factors for thyroid carcinoma : a population based study of 15,698 cases from the surveillance, epidemiology and end results (SEER) program 1973~1991. Cancer 1997 ; 79 : Tsang TW, Brierley JD, Simpson WJ, Panzarella T, Gospodarowicz MK, Sutcliffe SB. The effects of surgery, radioiodine and external radiation therapy on the clinical outcome of patients with differentiated thyroid carcinoma. Cancer 1998 ; 82 : Greene FL, Page DL, et al. eds. AJCC(American Joint Committee on Cancer) Cancer Staging Manual. 6th ed. New York : 10. Hay D, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma : development of a reliable prognostic scoring system in a cohort of 1,779 patients surgically treated at one institution during 1940 through Surgery 1993 ; 114 : Shaha AR, Loree TR, Shah JP. Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery 1995 ; 118 : Sherman S, Brierley JD, Sperling M, Ain KB, Blgos ST, Maxon HR 3rd, et al (National Thyroid Cancer Treatment Cooperative Study Registry Group). Prospective multicenter study of thyroid carcinoma treatment : initial analysis of staging and outcome. Cancer 1998 ; 83 : Dulgeroff AJ, Hershman JM. Medical therapy for differentiated thyroid carcinoma. Endocr Rev 1994 ; 15 : Burman KD. How serious are the risks of thyroid hormone overreplacement? Thyroid Today 1995 ; 18 : Cobin RH. Thyroid hormone excess and bone. a clinical review. Endocr Pract 1995 ; 1 : Sawin CT, Geller A, Wolf PA, Belanger AJ, Baker E, D Agosti- 1193

12 Special ssue no RB, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994 ; 331 : Mazzaferri EL. An overview of the management of papillary and follicular thyroid carcinoma. Thyroid 1999 ; 9 : Schlumberger M, Mancusi F, Baudin E, Pacini F. 131 therapy for elevated thyroglobulin levels. Thyroid 1997 ; 7 : Wartofsky L, Sherman S, Gopal J, Schlumberger M, Hay D. The use of radioactive iodine in patients with papillary and follicular thyroid cancer. J Clin Endocrinol Metab 1998 ; 83 : Mazzaferri EL. Thyroid remnant 131 ablation for papillary and follicular thyroid carcinoma. Thyroid 1997 ; 7 : Solomon BL, Wartofsky L, Burman KD. Currents trends in the management of well differentiated papillary thyroid carcinoma. J Clin Endocrinol Metab 1996 ; 81 : Brierley J, Maxon HR. Radioiodine and external radiation therapy. n : Fagin JA, ed. Thyroid cancer. Boston/Dordrecht London : Kluwer Academic Publishers, 1998 : Pacini F, Molinaro E, Castagna MG, Agate L, Elisei R, Pinchera A, et al. Recombinant human thyrotropinstimulated serum thyroglobulin combined with neck ultrasonography has the highest sensitivity in monitoring differentiated thyroid carcinoma. J Clin Endocrinol Metab 2003 ; 88 : DeGroot LJ, Reilly M. Comparison of 30and 50mCi doses of iodine131 for thyroid ablation. Ann ntern Med 1982 ; 96 : Johansen K, Woodhouse NJ, Odugbesan O. Comparison of 1,073 MBq and 3,700 MBq iodine131 in postoperative ablation of thyroid tissue in patients with differentiated thyroid cancer. J Nucl Med 1991 ; 32 : Beierwaltes WH, Rabbani R, Dmuchowski C, Lloyd RV, Eyre P, Mallette S. An analysis of ablation of thyroid remnants with 131 in 511 patients from 1947~1984 : Experience at University of Michigan. J Nuc Med 1984 ; 25 : Maxon HR, Englaro EE, Thomas SR, Hertzberg VS, Hinnefeld JD, Aden MD, et al. Radioiodine131 therapy for welldifferentiated thyroid cancera quantitative radiation dosimetric approach : Outcome and validation in 85 patients. J Nuc Med 1992 ; 33 : Park HM, Perkins OW, Edmondson JW, Schnute RB, Manatunga A. nfluence of diagnostic radioiodines on the uptake of ablative dose of iodine131. Thyroid 1994 ; 4 : Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Ridgway EC, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab 1999 ; 84 : Robbins RJ, Tuttle M, Sonenberg M, Shaha A, Sharaf R, Larson SM, et al. Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin. Thyroid 2001 ; 11 : Koong SS, Reynolds JC, Movius EG, Keenan AM, Ain KB, Robbins J, et al. Lithium as a potential adjuvant to 131 therapy of metastatic, well differentiated thyroid carcinoma. J Clin Endocrinol Metab 1999 ; 84 : Burmeister LA, ducret RP, Mariash CN. Local reactions to radioiodine in the treatment of thyroid cancer. Am J Med 1991 ; 90 : Alexander C, Bader JB, Schaefer A, Finke C, Kirsch CM. ntermediate and longterm side effects of highdose radioiodine therapy for thyroid carcinoma. J Nucl Med 1998 ; 39 : Creutzig H. Sialadenitis following iodine131 therapy for thyroid carcinoma. J Nucl Med 1985 ; 26 : Datz FL. Cerebral edema following iodine131 therapy for thyroid carcinoma metastatic to the brain. J Nucl Med 1986 ; 27 : Sweeney DC, Johnson GS. Radioiodine therapy for thyroid cancer. Endocrinol Metab Clin North Am 1995 ; 24 :

13 37. Chiu AC, Delpassand ES, Sherman S. Prognosis and treatment of brain metastases in thyroid carcinoma. J Clin Endocrinol Metab 1997 ; 82 : Van Nostrand D, Neutze J, Atkins F. Side effects of rational dose iodine131 therapy for metastatic welldifferentiated thyroid carcinoma. J Nucl Med 1986 ; 27 : Raymond JP, zembart M, Marliac V, Dagousset F, Merceron RE, Vallee G, et al. Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine. J Clin Endocrinol Metab 1989 ; 69 : Vini L, Hyer S, AlSaadi A, Prztt B, Harmer C. Prognosis for fertility and ovarian function after treatment with radioiodine for thyroid cancer. Postgrad Med J 2002 ; 78 : Edmonds CJ, Smith T. The longterm hazards of the treatment of thyroid cancer with radioiodine. Br J Radiol 1986 ; 59 : Pacini F, Gasperi M, Fugazzola L, Ceccarelli C, Lippi F, Pinchera A, et al. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine. J Nucl Med 1994 ; 35 : Sarkar SD, Beierwaltes WH, Gill SP, Cowley BJ. Subsequent fertility and birth histories of children and adolescents treated with 131 for thyroid cancer. J Nucl Med 1976 ; 17 : Maxon H. The role of 131 in the treatment of thyroid cancer. Thyroid Today 1993 ; 16 : Maxon H, Smith HS. Radioiodine131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin North Am 1990 ; 19 : Wong JB, Kaplan MM, Meyer KB, Pauker SG. Ablative radioactive iodine therapy for apparently localized thyroid carcinoma. A decision analytic perspective. Endocrinol Metab Clin North Am 1990 ; 19 : Maheshwari YK, Hill Jr CS, Haynie 3rd TP, Hickey RC, Samaan NA. 131 therapy in differentiated thyroid carcinoma : M.D. Anderson Hospital experience. Cancer 1981 ; 47 : Brown AP, Greening WP, McCready VR, Shaw HJ, Harmer CL. Radioiodine treatment of metastatic thyroid carcinoma : the Royal Marsden Hospital experience. Br J Radiol 1984 ; 57 : Simpson WJ, Panzarella T, Carruthers JS, Gospodarowicz MK, Sutcliffe SB. Papillary and follicular thyroid cancer : impact of treatment in 1,578 patients. nt J Radiat Oncol Biol Phys 1988 ; 14 : Droz JP, Schlumberger M, Rougier P, Ghosn M, Gardet P, Parmentier C. Chemotherapy in metastatic nonanaplastic thyroid cancer : experience at the nstitut GustaveRoussy. Tumori 1990 ; 76 : Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, De- Conti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer 1985 ; 56 : De Besi P, Busnardo B, Toso S, Girelli ME, Nacamulli D, Fiorentino MV, et al. Combined chemotherapy with bleomycin, adriamycin, and platinum in advanced thyroid cancer. J Endocrinol nvest 1991 ; 14 : Santini F, Bottici V, Elisei R, Montanelli L, Mazzeo S, Pacini F, et al. Cytotoxic effects of carboplatinum and epirubicin in the setting of an elevated serum thyrotropin for advanced poorly differentiated thyroid cancer. J Clin Endocrinol Metab 2002 ; 87 : AACE/AAES medical/surgical guidelines for clinical practice : management of thyroid carcinoma. Endocr Pract 2001 ; 7 : Spencer CA, Takeuchi M, Kazarosyan M, Wang CC, Guttler RB, Nicoloff JT, et al. Serum thyroglobulin autoantibodies prevalence, influence on serum thyroglobulin measurement, and prognostic significance in patients with differentiated thyroid carcinoma. J Clin Endocrinol Metab 1998 ; 83 : Rubello D, Casara D, Girelli ME, Piccolo M, Busnardo B. Clinical meaning of circulating antithyroglobulin antibodies in 1195

14 Special ssue differentiated thyroid cancer : a prospective study. J Nucl Med 1992 ; 33 : Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Pinchera A, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for lowrisk patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 2003 ; 88 : Schlumberger M, Berg G, Cohen O, Duntas L, Jamar F, Wiersinga WM, et al. Followup of lowrisk patients with differentiated thyroid carcinoma : a European perspective. Eur J Endocrinol 2004 ; 150 : Park HM, Perkins OW, Edmondson JW, Schnute RB, Manatunga A. nfluence of diagnostic radioiodines on the uptake of ablative dose of iodine131. Thyroid 1994 ; 4 : Schlumberger M, Mancusi F, Baudin E, Pacini F. 131 therapy for elevated thyroglobulin levels. Thyroid 1997 ; 7 : Cailleux AF, Baudin E, Travagli JP, Ricard M, Schlumberger M. s diagnostic iodine131 scanning useful after total thyroid ablation for differentiated thyroid cancer? J Clin Endocrinol Metab 2000 ; 85 : Antonelli A, Miccoli P, Ferdeghini M, Di Coscio G, Alberti B, Baschieri L, et al. Role of neck ultrasonography in the follow up of patients operated on for thyroid cancer. Thyroid 1995 ; 5 : Naidich DP. Helical computed tomography of the thorax : clinical applications. Radiol Clin North Am 1994 ; 32 : Feine U, Lietzenmayer R, Hanke JP, Held J, Wohrle H, Müller Schauenburg W. Fluorine18FDG and iodine131iodide uptake in thyroid cancer. J Nucl Med 1996 ; 37 : Grunwald F, Schomburg A, Bender H, Klemm E, Menzel C, Biersack HJ, et al. Fluorine18 fluorodeoxyglucose positron emission tomography in the followup of differentiated thyroid cancer. Eur J Nucl Med 1996 ; 23 : Chung JK, So Y, Lee JS, Choi CW, Lim SM, Cho BY, et al. Value of FDG PET in papillary thyroid carcinoma with negative 131 wholebody scan. J Nucl Med 1999 ; 40 : Petrich T, Borner AR, Otto D, Hofmann M, Knapp WH. nfluence of rhtsh on [(18)F]fluorodeoxyglucose uptake by differentiated thyroid carcinoma. Eur J Nucl Med Mol maging 2002 ; 29 : Wang W, Larson SM, Fazzari M, Tickoo SK, Kolbert K, Robbins RJ, et al. Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 2000 ; 85 :

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