Thyroid Diseases: Grigsby PW

Dillehay GL, Ellerbroek NA, Balon H, Brill DR, Grigsby PW, Macklis RM, Mauch PM, Mian TA, Potters L, Silberstein EB, Williams TR, Wong JC, Gaspar LE, Anonymous00250. · American College of Radiology, Reston, VA, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #16472933 No free full text.

This publication has no abstract.

Showalter TN, Siegel BA, Moley JF, Baranski TJ, Grigsby PW. · Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA. · Cancer Biother Radiopharm. · Pubmed #18976119 No free full text.

Abstract: PURPOSE: Survival outcomes in patients presenting with well-differentiated thyroid cancer with pulmonary metastasis are variable. The aim of this study was to evaluate prognostic factors for outcome in this patient population. METHODS: A prospective registry database was searched to identify patients presenting with pulmonary metastasis from well-differentiated thyroid cancer. All patients underwent total thyroidectomy and postoperative I-131 therapy. Cox proportional hazards modeling was performed to evaluate prognostic factors for survival outcomes. RESULTS: Forty (40) patients were identified with well-differentiated thyroid cancer involving the thyroid and metastatic to cervical lymph nodes and lung at initial diagnosis. The median follow-up was 9.7 years for those alive at last follow-up. Cox proportional hazards modeling evaluated age at diagnosis, gender, primary tumor size, and vascular invasion on cause-specific and progression-free survivals. Age at diagnosis was the only significant independent prognostic factor (p = 0.0035). The 10-year cause-specific survivals were 100% in patient's < or =40 years, compared to 36% for those >40 years (p < 0.0001). The corresponding 10-year progression-free survivals were 69% and 12% (p = 0.0003). CONCLUSIONS: Patients < or =40 years of age presenting with pulmonary metastasis from well-differentiated thyroid cancer had an excellent prognosis. Older patients have a poor survival outcome. Postoperative I-131 therapy is recommended in all patients.

Finkelstein SE, Grigsby PW, Siegel BA, Dehdashti F, Moley JF, Hall BL. · Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA. · Ann Surg Oncol. · Pubmed #17882493 No free full text.

Abstract: BACKGROUND: Whole-body (131)I scintigraphy (WBS) and serial thyroglobulin measurement (Tg) are standard methods for detecting thyroid cancer recurrence after total/near total thyroidectomy and (131)I ablation. Some patients develop elevated Tg (Tg-positive) or there is clinical suspicion of recurrence, but WBS are negative (WBS-negative). This may reflect non-iodine-avid recurrence or metastasis. In 2002, the Centers for Medicare and Medicaid Services (CMS) approved positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) for Tg-positive/WBS-negative patients with follicular-cell-origin thyroid cancer. Limited data are available regarding the performance of combined FDG-PET/computed tomography (FDG-PET/CT) for detecting recurrent thyroid cancer in WBS-neg patients. METHODS: This retrospective review of prospectively collected data analyzed 65 patients who had FDG-PET/CT for suspected thyroid cancer recurrence (April 1998-August 2006). Patients were WBS-negative but were suspected to have recurrence based on Tg levels or clinical grounds. Suspected FDG-PET/CT abnormalities were reported as benign or malignant. Lesions were ultimately declared benign or malignant by surgical pathology or clinical outcome (disease progression). RESULTS: Of 65 patients who underwent FDG-PET/CT, 47 had positive FDG-PET/CT. Of the positive FDG-PET/CT, 43 studies were true positives, with 21 (49%) confirmed pathologically by surgical resection. The four false positives (3/4 confirmed pathologically) included an infundibular cyst, an inflamed supraclavicular cyst, pneumonitis, and degenerative disc disease. Of the 18 FDG-PET/CT studies that were negative, 17 were true negatives and one was a false negative (metastatic papillary carcinoma). Thus, FDG-PET/CT demonstrated a patient-based sensitivity of 98%, specificity of 81%, positive predictive value of 91%, and negative predictive value of 94%. CONCLUSIONS: FDG-PET/CT is useful for detecting thyroid cancer recurrence in WBS-negative patients, and can assist decision making.

Reddy RM, Grigsby PW, Moley JF, Hall BL. · Department of Surgery, Washington University School of Medicine, Saint Louis, MO 63110, USA. · Surgery. · Pubmed #17188156 No free full text.

Abstract: BACKGROUND: The goal of this study was to evaluate the presence of lymph node metastasis in patients with T1 differentiated thyroid cancer (DTC) and determine prognostic significance for tumor recurrence and cancer-related death. METHODS: From a prospective tumor registry, we reviewed data from 551 patients with DTC who underwent total or subtotal thyroidectomy and who had primary tumor size </=2 cm. Patients received standard radioactive iodine ablation. RESULTS: The proportion of patients with lymph node metastasis was 45%. This percentage remained the same in a comparison of tumors from 0 to 1 cm with tumors from 1 to 2 cm. Logistic regression analyses did not identify primary tumor size as a predictor of lymph node metastasis, but did show that histologic vascular invasion and soft tissue invasion correlated with positive lymph nodes. Multifocal disease approached significance. Actuarial estimates for first recurrence displayed a significant difference in patients who had positive cervical lymph nodes versus negative nodes: 56% versus 71% disease-free at 20 years. There was no difference in cancer-related death. CONCLUSIONS: In T1 DTC, lymph node metastasis does not correlate with tumor size but does correlate with vascular/soft tissue invasion. Patients with positive lymph nodes have a higher recurrence risk, but no significant increase in death.

Grigsby PW, Reddy RM, Moley JF, Hall BL. · Department of Radiation Oncology, Washington University School of Medicine, Saint Louis, MO 63110, USA. · Surgery. · Pubmed #17188155 No free full text.

Abstract: BACKGROUND: This study investigated the rate of contralateral papillary thyroid cancer (PTC) in low-risk PTC patients who had completion thyroidectomy, and were referred for radioactive iodine (RAI) therapy. The study sought predictors of contralateral disease and examined the impact of contralateral disease in RAI-treated patients. METHODS: We reviewed 20 years of data from a prospective registry for 150 patients with PTC. These patients had undergone thyroid lobectomy, followed by completion thyroidectomy, and had been referred for RAI. RESULTS: Of the 150 patients, 41% had PTC in the contralateral lobe. There was no difference in the rate of contralateral disease in low-risk patients (age <45 years, T1 tumors, lymph node-negative) compared with the remainder. There were no significant differences between patients with or without contralateral disease with respect to primary tumor size, mean age, time to completion thyroidectomy, or metastatic lymph node disease. Logistic regression analyses showed no histologic parameters that correlated with contralateral disease. There were no recurrence or survival differences in patients with or without contralateral disease after resection and RAI. CONCLUSIONS: The prevalence of tumor in the contralateral lobe of low-risk patients with PTC is significant and warrants consideration for completion thyroidectomy and radioiodine treatment. Our results, however, suggest that contralateral disease does not have an impact on recurrence or survival after treatment.

Grigsby PW, Siegel BA, Bekker S, Clutter WE, Moley JF. · Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri, USA. · J Nucl Med. · Pubmed #15073251 links to  free full text

Abstract: To assess whether the patient preparation procedure for (131)I scintigraphy could be streamlined, we evaluated the time course of thyroid-stimulating hormone (TSH) elevation after total thyroidectomy or after discontinuation of thyroxine (T(4)) in patients with thyroid cancer. METHODS: The clinical records of 284 patients with well-differentiated thyroid cancer were reviewed. All patients had undergone total thyroidectomy. Two groups of patients were evaluated. The immediate postoperative group consisted of 176 patients who were not given thyroid hormone replacement after surgery because of planned postoperative (131)I therapy. The surveillance group consisted of 108 patients in whom T(4) replacement was stopped (without triiodothyronine [T(3)] replacement) in preparation for surveillance whole-body (131)I scintigraphy. We recorded the first TSH measurement and number of days after surgery or without thyroid hormone for each patient. RESULTS: In the immediate postoperative group, TSH levels obtained 6-65 d (median, 17 d) after surgery ranged from 18.2 to 194.8 micro IU/mL (median, 46.6 micro IU/mL). The TSH values exceeded 30 micro IU/mL in 89% of patients evaluated at 1-2 wk, in 88% of those evaluated at 2-3 wk, and in 90% of those evaluated after 3 wk. In patients discontinuing T(4) (without T(3) replacement), TSH levels obtained from 6 to 35 d (median, 20 d) later ranged from 23.4 to 214.5 micro IU/mL (median, 61.1 micro IU/mL). The TSH levels exceeded 30 micro IU/mL in 100% of patients evaluated at 1-2 wk, in 89% of those evaluated at 2-3 wk, and in 96% of those evaluated after 3 wk. CONCLUSION: In most patients with thyroid cancer being prepared for (131)I imaging or therapy, a TSH level exceeding 30 micro IU/mL can be achieved by withdrawal of thyroid hormone therapy for 1-3 wk.

DiBiase SJ, Grigsby PW, Guo C, Lin HS, Wasserman TH. · Department of Radiation Oncology, University of Maryland, Baltimore, Maryland, USA. · Am J Clin Oncol. · Pubmed #15057158 No free full text.

Abstract: Previous reports have revealed modest results in the management of thyroid lymphoma with radiotherapy alone. This retrospective report evaluates the outcome of patients treated for thyroid lymphoma with radiotherapy alone and with combined modality therapy (chemotherapy and radiotherapy) at a single institution. Twenty-seven patients with stages IE and IIE non-Hodgkin's lymphoma of the thyroid gland were treated between 1960 and 1998 at Barnes-Jewish Hospital, of which 14 patients were stage IE and 13 patients were stage IIE. The median age at diagnosis was 67 years, and there were 21 females and 6 males evaluated. The median follow-up time was 38 months (range: 3-279 months). All patients had histologically proven non-Hodgkin's lymphoma, of which 22 patients (81%) were intermediate grade. Treatment consisted of radiotherapy alone in 19 patients and a combined modality therapy in 8 patients. The median radiation dose to the thyroid bed was 44 Gy, and most patients received a doxorubicin-containing regimen administered prior to radiotherapy. Patient, tumor, and treatment-related characteristics were evaluated using Cox regression analysis. Local-regional tumor control, disease-free survival (DFS), and overall survival (OS) were calculated using the Kaplan-Meier method. Four patients had local relapse in this series, with a crude local tumor control rate of 85%. No factor was determined to be significant for local tumor control. The actuarial 5-year DFS and OS for the entire cohort were 57%, and 56%, respectively. In terms of DFS, both age and stage were statistically significant. The 5-year actuarial DFS for patients less than age 65 years was 83% versus 37% for those more than this age (p = 0.024). Furthermore, the 5-year actuarial DFS for patients with stage I and II disease was 69% and 45%, respectively (p = 0.022). In multivariate analysis, age continued to be significant for DFS (p = 0.049). Overall survival analysis revealed age, local tumor control, and stage to be significant in univariate analysis. Multivariate analysis was further carried out using Cox proportional hazard model, and it revealed age (p = 0.006) and local tumor control (p = 0.007) to be significant. Primary thyroid gland lymphomas have a favorable outcome with appropriate therapy, but prognosis depends on both clinical stage and age at presentation. Because of the risk of both local-regional and distant failure, combined modality approaches that use chemotherapy with radiotherapy are warranted for intermediate- and high grade thyroid lymphoma.

Heron DE, Karimpour S, Grigsby PW. · Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA. · Am J Clin Oncol. · Pubmed #12393980 No free full text.

Abstract: Anaplastic thyroid carcinoma (ATC) is a highly aggressive neoplasm with a poor prognosis. Curative management of these tumors has been difficult secondary to delayed diagnosis and advanced disease at presentation. Treatment modalities including surgery and fractionated radiotherapy have had limited success in controlling these tumors. Median survival time is often measured in months. A review of all patients treated between 1952 and 1999 identified 32 patients with anaplastic or poorly differentiated thyroid carcinoma. Patients were divided into two groups: those treated between 1952 to 1980 (9 patients, group 1) and those treated between 1981 and 1999 (23 patients, group 2). Most group 1 patients received once-daily radiotherapy and most group 2 patients received twice-daily radiotherapy with concurrent chemotherapy. A variety of radiotherapy techniques were used. Chemotherapy consisted of doxorubicin, paclitaxel, vincristine, or cisplatin. Eleven patients presented with lymph node metastasis and two patients had distant metastases at diagnosis. The most common clinical presentation was a neck mass in 17 patients. In group 1, one patient was treated with surgery only, four with surgery and radiotherapy and four with radiotherapy alone. In group 2, 1 patient was treated with surgery only; 3 with surgery and radiotherapy; 10 with radiotherapy and chemotherapy; 5 with surgery, radiotherapy, and chemotherapy; and 5 with radiotherapy alone. Overall 2-year survival rates were 44% for group 1 and 52% for group 2. Two-year progression-free survival (PFS) was 53% for group 1 and 38% for group 2. Five (16%) patients died within 60 days of diagnosis. Severe side effects included skin sequelae (one patient) and osteoradionecrosis of the mandible (one patient). There were 10 (52%) long-term survivors (>2 years). Clinicopathologic features associated with extended survival were limited extent of disease and inclusion in group 2. Among patients with ATC surgery, hyperfractionated radiotherapy in conjunction with chemotherapy is associated with better survival but not PFS compared to conventional radiotherapy.

Grigsby PW, Gal-or A, Michalski JM, Doherty GM. · Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, Missouri 63110, USA. · Cancer. · Pubmed #12209714 links to  free full text

Abstract: OBJECTIVES: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. METHODS: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years. There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease confined to the thyroid, 34 (60%) had additional lymph node metastasis to the neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4 patients, and a lobectomy in 4 patients. All 56 patients received postoperative thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of patients after their initial surgery. RESULTS: The overall survival rate was 98% with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The one death that occurred in this patient population was the result of a congenital heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their thyroid carcinoma. The time to first recurrence of disease ranged from 8 months to 14.8 years (mean, 5.3 years). None of those with disease confined to the thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in patients with lymph node metastasis and 29% (2 of 7) in patients with lung metastasis (P = 0.02). Tumor characteristics were evaluated for time to first recurrence utilizing the logistic likelihood ratio test to predict disease recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03), positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02) were significant for developing recurrent disease. Patients younger than 15 years old at diagnosis were more likely to have more extensive tumor at diagnosis than patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma of the thyroid in children and adolescents has little risk of mortality but a high risk of recurrence. Younger patients present with a more advanced stage of disease and are more likely to have disease recurrence. Total thyroidectomy and lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone replacement (suppressive) administration, and diligent surveillance are warranted.

Grigsby PW, Siegel BA, Baker S, Eichling JO. · Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA. · JAMA. · Pubmed #10807387 links to  free full text

Abstract: CONTEXT: In May 1997, the US Nuclear Regulatory Commission (NRC) revised its patient release regulations, allowing for outpatient administration of larger activities of sodium iodide 131I than previously permitted. OBJECTIVE: To measure the radiation exposure to household members from patients receiving outpatient 131I therapy for thyroid carcinoma in accordance with the new regulations. DESIGN: Consecutive case series from October 1998 to June 1999. SETTING AND PATIENTS: Thirty patients who received outpatient 131I therapy following thyroidectomy for differentiated thyroid carcinoma were enrolled, along with their 65 household members and 17 household pets. MAIN OUTCOME MEASURE: Radiation exposure to household members and 4 rooms in each home, as monitored with dosimeters for 10 days following 131I administration. RESULTS: The patients received 131I doses ranging from 2.8 to 5.6 GBq (mean, 4.3 GBq). The radiation dose to 65 household members ranged from 0.01 mSv to 1.09 mSv (mean, 0.24 mSv). The dose to 17 household pets ranged from 0.02 mSv to 1.11 mSv (mean, 0.37 mSv). The mean dose to the 4 rooms ranged from 0.17 mSv (kitchen) to 0.58 mSv (bedroom). CONCLUSION: In our study, 131I doses to household members of patients receiving outpatient 131I therapy were well below the limit (5.0 mSv) mandated by current NRC regulations.

Grigsby PW, Baglan K, Siegel BA. · Radiation Oncology Center, Mallinckrodt Institute of Radiology, Washington University Medical Center, St. Louis, Missouri, USA. · Cancer. · Pubmed #10091774 links to  free full text

Abstract: BACKGROUND: The purpose of this study was to evaluate the utility of surveillance with annual whole-body iodine-131 (131I) scintigraphy for patients with recurrent thyroid carcinoma. METHODS: The records of patients with thyroid carcinoma were reviewed. The 76 patients included in this study had undergone thyroidectomy and postoperative 131I therapy, and had at least 1 negative whole-body 131I scintigraphy 1 year after 131I therapy. There were 59 females and 17 males (age range, 12-74 years). Surgery consisted of a total thyroidectomy for 84% of patients and a subtotal thyroidectomy for 16%. 131I was administered within 1 month of thyroidectomy and annually thereafter until complete ablation of remaining thyroid tissue occurred. Annual follow-up diagnostic whole-body 131I scintigraphy was performed at Years 1 and 2, and then every 3-5 years. Some patients also had scintigraphy performed in Years 3, 4, and 5. RESULTS: Patients received 1-4 annual administrations of 131I (median, 1). The administered activity per treatment was 30-211 mCi, and the total activity administered that was necessary to achieve complete ablation of functioning thyroid tissue ranged from 30 to 514 mCi (median, 100 mCi). The relapse free survival at both 5 and 10 years was 88%. By definition, all of these patients had a negative 131I scintigraphy at 1 year after their last therapeutic 131I administration. Seven patients had a positive 131I scintigraphy 1 year after the first negative scintigraphy. Two other patients had positive 131I images after 2 consecutive negative annual 131I scintigraphic studies. The predictive value for relapse free survival of 1 negative diagnostic 131I study of these patients was 91% (+/- 0.02), and for 2 consecutive annual negative 131I studies the value was 97% (+/- 0.02); these results were significantly different (P = 0.0197). A stepwise logistic regression analysis was performed in an effort to identify risk factors for disease recurrence after complete ablation. None of the variables assessed--age, gender, tumor histology, tumor size, vascular invasion, capsular invasion, surgical margin status, or lymph node status--was predictive of recurrence after complete ablation. CONCLUSIONS: A single negative 131I scintigraphic study after complete ablation has a lower predictive value for relapse free survival than do two consecutive annual negative studies. Annual 131I imaging is recommended for surveillance until 2 consecutive annual negative studies are obtained, after which repeat imaging at 3-5 years appears to be satisfactory.