Prognostic Impact of Direct 131I Therapy After Detection of Biochemical Recurrence in Intermediate or High-Risk Differentiated Thyroid Cancer: A Retrospective Cohort Study

Background: Patients treated for intermediate- or high-risk differentiated thyroid carcinoma (DTC) and Thyroglobulin (TG) elevation during follow-up, require a diagnostic whole-body scan (DWBS) and if positive, 131I treatment. This approach can lead to a delay in treatment and increased costs. The purpose of this study is to compare the oncologic outcomes associated to administration of direct therapy with 131I at first biochemical recurrence. Methods: Retrospective cohort study of patients with intermediate- or high-risk DTC treated with total thyroidectomy, 131I ablation and who developed TG elevation during follow-up, between January 2007 and December 2015. Cohort A included patients who underwent a DWBS with 5 mCi of 131I, and if negative an MRI and/or 18FDG PET-CT prior to the therapeutic dosage, and cohort B included those who only received a therapeutic dosage of 131I, without a DWBS or extensive image studies. Main outcomes were second recurrence (SR) and disease-free survival (DFS). The diagnostic accuracy of DWBS was analyzed. Results: Cohorts A and B had 74 and 41 patients, each. By multivariate analysis, age, differentiation grade, TN classification, ablation dose, and performed DWBS (odds ratio 55.1; 95% CI 11.3–269) were associated with SR (p < 0.0001); age, male gender, ablation dose and performed DWBS (hazard ratio 7.79; 95% CI 3.67–16.5) were independent factors associated with DFS (p < 0.0001). DWBS diagnostic accuracy was 36.48%. Conclusion: 131I treatment in patients with DTC biochemical recurrence and no DWBS or extensive image studies is associated with a significantly lower frequency of SR and an increased DFS. The diagnostic accuracy of DWBS is low, and its clinical efficiency should be defined in prospective phase III studies.

[1]  J. Maciejewski,et al.  Reply to A. Piccardo et al, E. Hindié et al, M.C. Kreissl et al, M. Doss, J. Buscombe, R. Fisher, M. Sollini et al, M. Lichtenstein, and M. Tulchinsky et al. , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  J. Tie,et al.  Clinical guidance for radioiodine refractory differentiated thyroid cancer , 2018, Clinical endocrinology.

[3]  Peter Angelos,et al.  Growing incidence of thyroid carcinoma in recent years: Factors underlying overdiagnosis , 2018, Head & neck.

[4]  Rui Gao,et al.  Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level , 2018, Scientific Reports.

[5]  D. Chadwick Hypocalcaemia and permanent hypoparathyroidism after total/bilateral thyroidectomy in the BAETS Registry. , 2017, Gland surgery.

[6]  I. Ganly,et al.  Post-treatment surveillance of thyroid cancer. , 2017, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[7]  E. Blackstone,et al.  Cancer of the esophagus and esophagogastric junction—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual , 2017, CA: a cancer journal for clinicians.

[8]  A. Ho,et al.  Selective use of radioactive iodine (RAI) in thyroid cancer: No longer "one size fits all". , 2017, European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology.

[9]  Nitin A. Pagedar,et al.  Radioiodine Ablation following Thyroidectomy for Differentiated Thyroid Cancer: Literature Review of Utility, Dose, and Toxicity
 , 2017, European Thyroid Journal.

[10]  A. Piccardo,et al.  18F-FDG-PET/CT in Patients Affected by Differentiated Thyroid Carcinoma with Positive Thyroglobulin Level and Negative 131I Whole Body Scan. It's Value Confirmed by a Bicentric Experience. , 2016, Current radiopharmaceuticals.

[11]  K. Woliński,et al.  The usefulness of fluorine-18 fluorodeoxyglucose PET in the detection of recurrence in patients with differentiated thyroid cancer with elevated thyroglobulin and negative radioiodine whole-body scan , 2016, Nuclear medicine communications.

[12]  S. Chen,et al.  A quantitative study about thyroid stunning after diagnostic whole-body scanning with 74 MBq 131I in patients with differentiated thyroid carcinoma. , 2015, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[13]  H. Harada,et al.  Characteristics and prognosis of patients with thyroglobulin-positive and radioactive iodine whole-body scan-negative differentiated thyroid carcinoma. , 2015, Japanese journal of clinical oncology.

[14]  P. Vigneri,et al.  The changing epidemiology of thyroid cancer: why is incidence increasing? , 2015, Current opinion in oncology.

[15]  P. Rosário,et al.  Is empirical radioactive iodine therapy still a valid approach to patients with thyroid cancer and elevated thyroglobulin? , 2014, Thyroid : official journal of the American Thyroid Association.

[16]  D. Penson,et al.  Epidemiology of Vocal Fold Paralyses after Total Thyroidectomy for Well-Differentiated Thyroid Cancer in a Medicare Population , 2014, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[17]  V. Beral,et al.  Incidence of thyroid cancer in England by ethnic group, 2001–2007 , 2014, British Journal of Cancer.

[18]  J. Perkins,et al.  Appropriate dosing of adjuvant radioactive iodine for differentiated thyroid cancer , 2014, Current opinion in oncology.

[19]  J. Shah,et al.  Thyroid cancer: surgery for the primary tumor. , 2013, Oral oncology.

[20]  Hiroshi Honda,et al.  Incremental diagnostic value of SPECT/CT with 131I scintigraphy after radioiodine therapy in patients with well-differentiated thyroid carcinoma. , 2012, Radiology.

[21]  E. Silberstein The problem of the patient with thyroglobulin elevation but negative iodine scintigraphy: the TENIS syndrome. , 2011, Seminars in nuclear medicine.

[22]  M. Chao Management of differentiated thyroid cancer with rising thyroglobulin and negative diagnostic radioiodine whole body scan. , 2010, Clinical oncology (Royal College of Radiologists (Great Britain)).

[23]  S. Mandel,et al.  2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. , 2009, Thyroid : official journal of the American Thyroid Association.

[24]  E. Hindié,et al.  Thyrotropin variations may explain some positive radioiodine therapy scans in patients with negative diagnostic scans , 2009, Journal of endocrinological investigation.

[25]  Chao Ma,et al.  Radioiodine therapy for differentiated thyroid carcinoma with thyroglobulin positive and radioactive iodine negative metastases. , 2009, The Cochrane database of systematic reviews.

[26]  David W. Hosmer,et al.  Applied Survival Analysis: Regression Modeling of Time-to-Event Data , 2008 .

[27]  Chao Ma,et al.  Is empiric 131I therapy justified for patients with positive thyroglobulin and negative 131I whole-body scanning results? , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  Rodney X. Sturdivant,et al.  Applied Logistic Regression: Hosmer/Applied Logistic Regression , 2005 .

[29]  Stephanie L. Lee,et al.  A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma. , 2003, The Journal of clinical endocrinology and metabolism.

[30]  Eun Sook Kim,et al.  Effects of therapeutic doses of 131I in thyroid papillary carcinoma patients with elevated thyroglobulin level and negative 131I whole‐body scan: comparative study , 2003, Clinical endocrinology.

[31]  A. Pinchera,et al.  Outcome of differentiated thyroid cancer with detectable serum Tg and negative diagnostic (131)I whole body scan: comparison of patients treated with high (131)I activities versus untreated patients. , 2001, The Journal of clinical endocrinology and metabolism.

[32]  I. McDougall,et al.  Is serum thyroglobulin a useful marker for thyroid cancer in patients who have not had ablation of residual thyroid tissue? , 1997, Thyroid : official journal of the American Thyroid Association.

[33]  E. Baudin,et al.  131I therapy for elevated thyroglobulin levels. , 1997, Thyroid : official journal of the American Thyroid Association.

[34]  D. Hosmer,et al.  Applied Logistic Regression , 1991 .

[35]  Nancy D Perrier,et al.  Differentiated and anaplastic thyroid carcinoma: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual , 2018, CA: a cancer journal for clinicians.

[36]  Kaliszewski,et al.  American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer : The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer , 2017 .

[37]  J. Shah,et al.  Thyroid – Differentiated and Anaplastic Carcinoma , 2017 .

[38]  Roger A. Erich,et al.  Regression Modeling of Time to Event Data Using the Ornstein-Uhlenbeck Process , 2012 .

[39]  Evon M. O. Abu-Taieh,et al.  Comparative study , 2003, BMJ : British Medical Journal.

[40]  R. Galen,et al.  Beyond Normality: The Predictive Value and E ciency of Medical Diagnoses , 1975 .