Supplementary Appendix

Transcription

1 Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Schlumberger M, Catargi B, Borget I, et al. Strategies of radioiodine in patients with low-risk thyroid cancer. N Engl J Med 2012;366:

2 SUPPLEMENTARY FILES TABLE OF CONTENTS Table 1: Hypothyroid symptoms and Patient Quality of Life at Radioiodine Ablation... Page 2 Table 2: Sensitivity analyses... Page 4 Definitions of TNM stage in differentiated thyroid cancer... Page 5 Stage grouping for differentiated thyroid cancer... Page 6 Assays and functional sensitivities used for serum thyroglobulin and thyroglobulin-antibody determinations performed at individual sites... Page 7 Members of the TUTHYREF (TUmeurs de la THYroide REFractaires) network who participated in the trial... Page 8 1

3 Table 1: Hypothyroid symptoms and Patient Quality of Life at Radioiodine Ablation rhtsh- 1.1GBq rhtsh- 3.7 GBq THW 1.1 GBq THW 3.7 GBq % of patients with hypothyroid symptoms (Billewicz scale) Diminished sweating 14 (8%) 22 (12%) 31 (18%) 38 (21%) Dry skin 58 (33%) 56 (31%) 76 (43%) 87 (46%) Cold intolerance 60 (33%) 53 (29%) 98 (56%) 108 (61%) Weight increase 71 (38%) 65 (36%) 115 (66%) 117 (66%) Constipation 52 (28%) 36 (20%) 65 (38%) 67 (38%) Hoarseness 45 (24%) 44 (24%) 68 (39%) 73 (41%) Paresthesia 42 (23%) 41 (23%) 68 (39%) 76 (43%) Deafness 27 (15%) 15 (8%) 32 (19%) 40 (22%) Slow movements 28 (15%) 20 (11%) 84 (47%) 81 (46%) Coarse skin 12 (6%) 14 (7%) 26 (15%) 29 (16%) Cold skin 15 (8%) 20 (11%) 49 (28%) 54 (31%) Periorbital puffiness 13 (7%) 11 (6%) 82 (46%) 109 (61%) Slow pulse heart 19 (11%) 18 (11%) 40 (23%) 47 (28%) Patient quality of life score at radioiodine (SF-36 scale) mean score ± std Physical Functioning 86 ± ± ± ± 22 Role Physical 75 ± ± ± ± 29 Bodily Pain 77 ± ± ± ± 27 General Health 67 ± ± ± ± 20 Vitality 54 ± ± ± ± 23 Social Functionning 76 ± ± ± ± 26 2

4 Emotionnal role 78 ± ± ± ± 27 Mental health 66 ± ± ± ± 22 Mental summary component 44 ± ± ± ± 13 Physical summary component 52 ± 7 52 ± 8 48 ± 9 47 ± 10 Legend rhtsh: recombinant human thyrotropin (Thyrogen ) THW: thyroid hormone withdrawal 3

5 Table 2: Sensitivity analyses Stimulation method Iodine activity n Complete rate in rhtsh groups Complete rate in THW groups Difference in complete rate ( ) 95% CI of difference in rate (rhtsh minus THW) Complete rate in 1.1 GBq groups Complete rate in 3.7 GBq groups Differenc e in complete rate ( ) 95% CI of difference in rate (1.1 GBq minus 3.7 Per protocol analysis % 92.9 % % -4.5% to 2.2% 91.1 % 93.5 % % -5.8% to 0.9% Per protocol analysis, using central Tg determinations and a Tg % 92.8 % % -4.3% to 2.5% 91.2 % 93.4 % % -5.7% to 1.2% cut-off at 1 ng/ml Per protocol analysis, using central Tg determinations and a Tg % 93.1 % % -3.6% to 3.0% 91.8 % 94.1 % % -5.5% to 1.1% cut-off at 1.4 ng/ml Intention to treat analysis % 88.9 % 0.2 % -3.6% to 4.1% 89.0 % 89.0 % 0 % -3.8% to 3.8% Intention to treat analysis - Maximal Bias % 93.9 % -6.9 % Legend rhtsh: recombinant human thyrotropin (Thyrogen ) THW: thyroid hormone withdrawal CI: confidence interval -10.4% to - 3.3% GBq) 86.9 % 93.3 % % -10% to 2.8% 4

6 DEFINITIONS OF TNM STAGE IN DIFFERENTIATED THYROID CANCER AJCC CANCER STAGING MANUAL 6 TH EDITION 2002 In: Springer, ed. American Joint Committee on Cancer. New-York; 2002: Primary tumor (T) Tx Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor 2 cm or less in greatest dimension limited to the thyroid T2 Tumor more than 2 cm but no more than 4 cm in greatest dimension limited to the thyroid T3 Tumor more than 4 cm in greatest dimension limited to the thyroid or any tumor with minimal extrathyroid extension (e.g. extension to the sternothyroid muscle or perithyroid soft tissues) T4a Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, oesophagus, or recurrent laryngeal nerve T4b Tumor invades pervertebral fascia or encases carotid artery or mediastinal vessels Regional Lymph nodes (N) Regional lymph nodes are the central compartment, lateral cervical and upper mediastinal lymph nodes. Nx Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Regional lymph node metastasis N1a Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/delphian lymph nodes) N1b Metastasis to unilateral, bilateral or contralateral cervical or superior mediastinal lymph nodes Distant metastasis (M) Mx Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis 5

7 STAGE GROUPING FOR DIFFERENTIATED (PAPILLARY OR FOLLICULAR) THYROID CANCER Age under 45 years Stage I Any T Any N M0 Stage II Any T Any N M1 45 years and older Stage I T1 N0 M0 Stage II T2 N0 M0 Stage III T3 N0 M0 T1 N1a M0 T2 N1a M0 T3 N1a M0 Stage IVA T4a N0 M0 T4a N1a M0 T1 N1b M0 T2 N1b M0 T3 N1b M0 T4a N1b M0 Stage IVB T4b Any N M0 Stage IVC Any T Any N M1 6

8 Assays and functional sensitivities used for serum thyroglobulin and thyroglobulinantibody determinations performed at individual sites The kits used in the study were Tg-Kryptor (B.R.A.H.M.S., Berlin, Germany), Immulite TG (Diagnostic Products Corporation, Los Angeles, CA), Thyro (Cis Bio International, Gif-sur-Yvette, France), Tg Advantage (Nichols Institute Diagnostics, San Clemente, CA), DYNOtest Tg-Plus (B.R.A.H.M.S.), Tg Access (Beckman-Coulter, Fullerton, CA), and e-iason TgCa (Iason, Graz- Seierberg, Austria). Functional sensitivity, described by the manufacturers is 0.9 ng/ml for three assays (Tg Kryptor, Immulite Tg, and Thyro), 0.3 ng/ml for Tg Advantage, 0.2ng/ml for Dynotest Tg-Plus, 0.11 ng/ml for Tg Access, and 0.02 ng/ml for e-iason TgCa. 7

9 Members of the TUTHYREF (TUmeurs de la THYroide REFractaires) Network who participated in the trial Archambeaud Françoise, MD, Endocrinology, Limoges; Giraudet Anne-Laure, MD, Nuclear Medicine, Institut Curie, Paris; Schneegans Olivier, MD, Nuclear Medicine, Centre Strauss, Strasbourg; Toubeau Michel, MD, Nuclear Medicine, Centre Leclerc, Dijon; Bouin-Pineau Marie- Hélène, MD, Nuclear Medicine, Poitiers; Raingeard Isabelle, MD, Endocrinology, Montpellier; Prost Annie, MD, Nuclear Medicine, Le Mans; Bouchard Philippe, MD, PHD, Endocrinology, Hôpital Saint-Antoine, Paris. 8