Abstract
Introduction
Thyroid cancer incidence is rising in the United States. Although overall thyroid cancer survival is high, prognostic stratification schemes have been developed to better delineate patients with poor prognoses.
Methods
A random sample that included 1,003 adult papillary thyroid cancer patients diagnosed in 2006 and reported to the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) program had their medical records re-abstracted and additional risk factor data collected. The distribution of patient demographics, medical histories, tumor characteristics and treatment modalities were assessed. Logistic regression was used to assess factors associated with total thyroidectomy (total, subtotal or near total) and radioiodine therapy. All analyses were conducted stratified by the Age, Metastases, Extent and Size (AMES) low/high risk classification.
Results
Receipt of total thyroidectomy was associated with family history of thyroid disease/cancer and larger tumor size among low-risk patients and smaller tumor size among high-risk patients. Among low-risk patients, the receipt of radioiodine was associated with family history of thyroid disease/cancer, larger tumor size, total thyroidectomy and positive lymph nodes. Among high-risk patients, the receipt of radioiodine was associated with intermediate tumor and hospital sizes.
Conclusions
This study provides insight into the patterns of papillary thyroid cancer care in the general population. The findings from this study indicate adherence to guideline recommendations in that family history of thyroid disease/cancer, in addition to tumor characteristics, does appear to inform treatment practices, especially among low-risk patients.
Keywords: Thyroid cancer, papillary carcinomas, epidemiology, treatment, thyroidectomy, radioiodine
Introduction
Thyroid cancer currently has the fastest-increasing incidence rate of all cancers in the United States.1 Incidence rates have increased from 4.9/100,000 in 1975 to 13.8/100,000 in 2010.2 The greatest increase has been observed among the smallest tumors leading some to conclude that the increase is due to improved diagnostics resulting in over-diagnosis.3, 4 However, others conclude that additional causes should be explored because improved diagnostics have been estimated to account for only 50% of the increase in incidence.5, 6
The American Cancer Society reported that 62,980 new thyroid cancer cases would be diagnosed in 2014;1 the vast majority of these new cases were expected to be diagnosed among women and individuals younger than 65 years. Incidence rates are notably high among Asians, twice as high among whites as blacks and are slightly higher among non-Hispanic whites than Hispanic whites.2, 5, 7 Although the distribution of histology varies by race and ethnicity, the predominant (≥80%) histology among all racial and ethnic groups is papillary adenocarcinoma.2 The majority (68%) of thyroid cancers are localized, confined to the thyroid capsule but not beyond, at diagnosis, resulting in a 98% overall 5-year relative survival.2 However, this is not the experience of all patients and treatment-related morbidity (e.g., hypocalcemia and laryngeal nerve paralysis) is not insignificant, especially given the uncertain clinical relevance of many small tumors and the often young age at diagnosis. Various risk classification schemes have, thus, been developed to better inform treatment decisions.8 The AMES classification, which takes into account patient age, metastasis status, and tumor extent and size, was selected to stratify patients in the current study because all relevant information was available and because it was able to sufficiently stratify risk into two categories.9, 10 The low risk group consists of young patients (women ≤50; men ≤40) with no metastases and older patients with intrathyroid papillary tumors that are <5cm. The high risk group consists of young patients with metastases and older patients who have metastases, extrathyroid papillary tumors or tumors ≥5cm. Based on the AMES risk classification, the 20-year survival rates have been predicted to be 98% among the low risk group and 54% among the high risk group.9
Although surgery is the primary treatment for thyroid cancer,11-13 variations in the extent of surgery and the associated survival times have been observed. Analyses of the Surveillance, Epidemiology and End-Results (SEER) data published in 2005 and 2010 found similar survival among patients with papillary adenocarcinoma who received total thyroidectomy compared to those who received lobectomy.14, 15 However, a 2007 study conducted within the National Cancer Data Base (NCDB) observed better survival among those who received total thyroidectomy.16 Additionally, although guidelines recommend post-surgical radioiodine treatment for papillary adenocarcinoma when there is primary tumor size of > 4cm., gross extrathyroidal extension, extensive vascular invasion, known or suspected distant metastases or known or suspected residual tumor,12, 13 receipt of radioiodine has been shown to vary by patient, provider and tumor characteristics.17, 18
The National Cancer Institute (NCI) conducts annual Patterns of Care (POC) studies to evaluate the administration of cancer therapies across the United States by collecting additional data on a random sample of cancer patients reported to the SEER registries. For the current study, POC data were used to examine treatment provided to patients diagnosed with papillary thyroid cancer in 2006 with vital status follow-up through 2010. The aims of the study were to identify factors associated with the receipt of total thyroidectomy (total, subtotal or near total) and radioactive iodine (I-131) among individuals diagnosed with papillary thyroid cancer. All analyses were conducted stratified by the AMES risk classification because it was hypothesized that assigned risk would affect treatment decisions.
Methods
Data source
Data from the POC study of thyroid cancer diagnosed in 2006 were included for the current analysis. Patients were eligible for the POC study if they were diagnosed with histologically confirmed thyroid cancer and were at least 20 years old at diagnosis. Patients were ineligible if they had a previous diagnosis of cancer, other than non-melanoma skin, were diagnosed with multiple concurrent primaries or were ascertained at autopsy or on death certificate only. Eligible patients were first stratified by SEER registry (the metropolitan areas of San Francisco/Oakland, San Jose/Monterey, Seattle, Atlanta, Detroit, Los Angeles County and the states of Connecticut, Iowa, New Mexico, Utah, Kentucky, Louisiana, New Jersey and the remainder of the state of California), age, sex, and race/ethnicity. A random sample (n=1233) was then drawn from each stratum.
SEER data are mainly obtained from hospital records. Adjuvant therapy is often provided in an out-patient setting, therefore, supplemental data was obtained for the POC study. Briefly, hospital medical records were re-abstracted for demographic data, tumor characteristics and treatment information. Additional data was abstracted regarding thyroid cancer risk factors (e.g. family history of thyroid disease/cancer, personal history of goiter, medical radiation to head and/or neck and environmental radiation) and comorbidities. Each patient’s treating physician was also asked to verify the thyroid cancer therapies and to provide the name and address of any other physician who may have treated the patient. Any additional physicians were then contacted. The primary abstractor from each registry attended a central training to assure consistency of abstracting and coding. Each SEER registry obtained institutional review board approval, as required, prior to initiating the POC study.
Study population
Patients were eligible for the current analyses if they had histologically confirmed papillary thyroid cancer (International Classification of Diseases for Oncology third edition (ICD-O-3): 8050, 8052, 8260, 8340-8344). Patients with non-papillary histologies (n=202) and patients with papillary thyroid cancer who did not have sufficient information to determine their AMES-risk group (n=28) were excluded.
Variables of interest
Demographics, tumor characteristics and personal/family medical history were determined based on hospital medical records. If ethnicity was unavailable the patient’s surname was used to determine Hispanic ethnicity. All comorbid conditions listed in the medical record at the hospital where the most definitive treatment was received were recorded and centrally coded at NCI. Comorbidity score, excluding thyroid cancer, was calculated based on the Charlson comorbidity index.19 Tumor stage was classified based on the American Joint Committee on Cancer 7th edition.20 Lymph node status was classified as 1) none examined or unknown if examined (n=3), 2) none positive and 3) at least one positive. Presence of a residency training program and number of beds at the hospital where the patient had their most definitive treatment were determined according to data from the American Hospital Association Annual Survey of Hospitals.21 The extent of surgery was categorized as thyroidectomy (total, subtotal, near total), lobectomy (partial lobectomy, lobectomy and/or isthmusectomy) and none. Surgical margins were classified as free of tumor, tumor at margins and unknown. The receipt of radioiodine (I-131), non-iodine radiotherapy and chemotherapy were determined via physician verification. Vital status and occurrence of thyroid-specific deaths were assessed through December 31, 2010.
Statistical analysis
Sample weights, defined as the inverse of the sampling proportion for each sampling stratum, were applied in order to obtain estimates that reflected all thyroid cancers diagnosed within the participating SEER areas in 2006. Black, Hispanic, Asian/Pacific Islanders (API), and American Indian/Alaska Native (AI/AN) patients were oversampled to obtain more stable estimates. Due to small numbers API and AI/AN patients were combined into ‘Other’ race. To account for the complex sample design and to correctly calculate the standard errors, all analyses were performed using SAS (version 9.3; SAS Institute Inc., Cary, NC) and SAS-callable SUDAAN (version 10.0.1; Research Triangle Institute, Research Triangle Park, NC).
Differences in patient demographic, tumor and health characteristics were evaluated using the chi-square test. The extent of surgery and receipt of radioiodine to treat papillary thyroid cancer was then assessed via multivariate logistic regression models. Variables that were associated with the treatment outcomes (p≤0.10) during bivariate analyses and remained significant (p≤0.05) in the regression model were retained and reported. All analyses were conducted stratified by the AMES risk classification.
Results
The current analysis included 1,003 papillary thyroid cancer patients (low risk: 834 and high risk: 169). As expected, the low-risk group included patients that were younger, had less advanced tumors and had better prognoses (Table 1). Patients in the low-risk group were also less likely to be male, to have had a history of environmental radiation exposure and to have been treated at a hospital with an approved residency program. As of December 31, 2010, 2.2% of the low-risk group and 17.7% of the high-risk group had died. Thyroid cancer accounted for an estimated 6.9% and 72.4% of the deaths among individuals in the low- and high-risk groups, respectively (data not shown).
Table 1.
Demographic, clinical and non-clinical characteristics among patients diagnosed with papillary thyroid cancer stratified by AMES-risk group1, Patterns of Care Study 2006.
| AMES risk-group1 | |||||
|---|---|---|---|---|---|
| Low | High | ||||
| Characteristic | N2 | %3 | N2 | %3 | p4 |
| Age at diagnosis | |||||
| 20-44 | 408 | 47.6 | 15 | 2.4 | <0.01 |
| 45-54 | 171 | 27.2 | 31 | 21.2 | |
| 55-64 | 127 | 15.6 | 45 | 39.1 | |
| 65-74 | 79 | 7.2 | 34 | 21.6 | |
| 75+ | 49 | 2.4 | 44 | 15.8 | |
| Sex | |||||
| Men | 280 | 19.1 | 94 | 35.4 | <0.01 |
| Women | 554 | 80.9 | 75 | 64.6 | |
| Race/Ethnicity | |||||
| Non-Hispanic white | 353 | 70.3 | 64 | 73.6 | 0.13 |
| Non-Hispanic black | 120 | 4.6 | 26 | 5.9 | |
| Hispanic | 175 | 14.4 | 50 | 14.4 | |
| Other | 186 | 10.7 | 29 | 6.0 | |
| Marital Status | |||||
| Married/Living as | 516 | 67.9 | 98 | 54.4 | 0.06 |
| Other | 318 | 32.1 | 71 | 45.6 | |
| Insurance status | |||||
| Private/HMO/Military | 669 | 86.3 | 116 | 72.3 | <0.01 |
| Any Medicaid | 84 | 8.0 | 24 | 7.7 | |
| Medicare only | 30 | 1.4 | 20 | 13.4 | |
| Unknown | 51 | 4.3 | 9 | 6.6 | |
| Family history of thyroid disease/cancer | |||||
| No, unknown | 740 | 87.1 | 153 | 79.2 | 0.32 |
| Yes | 94 | 12.9 | 16 | 20.8 | |
| History of goiter | |||||
| No, unknown | 611 | 71.7 | 125 | 68.8 | 0.76 |
| Yes | 223 | 28.3 | 44 | 31.2 | |
| History of radiation exposure to head and/or neck | |||||
| No, unknown | 821 | 97.4 | ~ | 97.5 | 0.89 |
| Yes | 13 | 2.6 | ~ | 2.5 | |
| History of environmental radiation exposure | |||||
| No, unknown | ~ | 99.8 | ~ | 98.9 | 0.05 |
| Yes | ~ | 0.2 | ~ | 1.1 | |
| Charlson comorbidity index | |||||
| 0 | 686 | 80.1 | 113 | 74.5 | 0.32 |
| >1 | 148 | 19.9 | 56 | 25.5 | |
| Tumor stage | |||||
| Stage I | 695 | 84.1 | 13 | 12.1 | <0.01 |
| Stage II | 56 | 4.9 | 6 | 1.6 | |
| Stage III | 53 | 7.0 | 72 | 45.4 | |
| Stage IV | 17 | 2.5 | 68 | 37.3 | |
| Unstaged | 13 | 1.4 | 10 | 3.5 | |
| Tumor size | |||||
| <1 cm or no mass found | 282 | 34.5 | 10 | 9.0 | <0.01 |
| 1.0-3.9cm | 476 | 59.0 | 91 | 65.9 | |
| 4.0+cm | 64 | 5.4 | 55 | 21.1 | |
| Unknown | 12 | 1.0 | 13 | 4.1 | |
| Number of lymph nodes examined | |||||
| 0 | 462 | 50.7 | 61 | 34.8 | 0.10 |
| 1-2 | 165 | 21.9 | 41 | 28.2 | |
| 3-4 | 70 | 9.2 | ~ | 7.9 | |
| 5-9 | 57 | 7.5 | 17 | 9.9 | |
| 10+ | 70 | 9.0 | 36 | 17.8 | |
| Unknown | 10 | 1.8 | ~ | 1.3 | |
| Nodal status | |||||
| None examined, unknown | 462 | 50.7 | 61 | 34.8 | 0.02 |
| None positive | 183 | 25.7 | 28 | 22.6 | |
| At least one positive | 189 | 23.6 | 80 | 42.5 | |
| Hospital bed size | |||||
| Unknown, out patient only, < 200 beds | 162 | 22.2 | 39 | 17.7 | 0.18 |
| 200-299 beds | 171 | 21.5 | 28 | 12.3 | |
| 300-399 beds | 144 | 17.4 | 27 | 27.0 | |
| 400+ beds | 357 | 39.0 | 75 | 43.1 | |
| Approved residency training program | |||||
| No/Unknown | 345 | 42.1 | 64 | 24.7 | <0.01 |
| Yes | 489 | 57.9 | 105 | 75.3 | |
| Vital Status (December 31, 2010) | |||||
| Alive | 813 | 97.8 | 134 | 82.3 | <0.01 |
| Dead | 21 | 2.2 | 35 | 17.7 | |
According to the Age, Metastases, Extent and Size (AMES) risk classification.9
Unweighted sample size.
Weighted percentage.
Chi-square p-value comparing low vs. high risk groups.
Due to small cell size, exact numbers were supressed.
Overall treatment
Regardless of risk group, surgery was the most common therapy and total thyroidectomy was the most common type of surgery (Table 2). Total thyroidectomy was, however, less common among low-risk patients (86.1%) than high-risk patients (89.9%; p=0.03). Among those who had surgery, low-risk patients (76.3%) were more likely to have clear surgical margins compared to high-risk patients (54.3%; p<0.01). The majority of patients, regardless of risk group, received radioiodine (I-131). However, radioiodine was less common among low-risk patients (63.0%) compared to high-risk patients (77.9%; p<0.01). The administration of radiotherapy and chemotherapy was also less common among low-risk patients (p<0.01).
Table 2.
Treatment among patients diagnosed with papillary thyroid cancer satrtified by AMES risk-group1, Patterns of Care Study 2006.
| AMES risk-group1 | |||
|---|---|---|---|
| Low | High | ||
| Treatment | %2 | %2 | p3 |
| Surgery | |||
| None | 0.2 | 1.4 | 0.03 |
| Partial lobectomy, lobectomy and/or isthmusectomy | 13.7 | 8.7 | |
| Total, subtotal, near total thyroidectomy | 86.1 | 89.9 | |
| Surgical margins3 | |||
| Margins free of tumor | 76.8 | 54.3 | <0.01 |
| Tumor at margins | 13.3 | 38.7 | |
| Unknown, not stated | 10.0 | 7.0 | |
| Radioiodine (I-131) | |||
| No/Unknown | 37.0 | 22.1 | <0.01 |
| Yes | 63.0 | 77.9 | |
| Radiotherapy | |||
| No/Unknown | 97.6 | 89.7 | <0.01 |
| Yes | 2.4 | 10.3 | |
| Chemotherapy | |||
| No/Unknown | 100.0 | 98.0 | <0.01 |
| Yes | 0.0 | 2.0 | |
According to the Age, Metastases, Extent and Size (AMES) risk classification.9
Weighted percentage.
Chi-square p-value comparing low vs. high risk groups.
Among patients who underwent surgery.
Total Thyroidectomy
Among low-risk patients, bivariate analyses indicated that receipt of total thyroidectomy versus partial thyroidectomy was associated with younger age, having a family history of thyroid disease/cancer, having a larger tumor size and being treated at a hospital with 200-299 beds and an approved registry program (Table 3). In multivariate analyses, having a family history of thyroid disease/cancer (odds ratio (OR):4.48; 95% confidence interval (CI): 1.69-11.93) and having a tumor >1cm (OR range: 3.51-3.76) remained significantly associated with having a total thyroidectomy. When stratified by tumor size, multivariate analyses indicated that the association between receipt of total thyroidectomy and family history of thyroid disease/cancer remained significant among patients with tumors <1cm (OR: 5.53; 95% CI: 1.12-27.25) and ≥1cm (OR: 4.22; 95% CI: 1.16-15.38; data not shown).
Table 3.
Factors associated with total thyroidectomy1 for the treatment of papillary carcinomas among patients who underwent surgery stratified by AMES risk-group2, Patterns of Care Study 2006.
| AMES risk-group2 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Low | High | |||||||
| No | Yes | No | Yes | |||||
| Characteristic | %3 | %3 | p 4 | OR5 | 95% CI | %3 | %3 | p 4 |
| Age at diagnosis | ||||||||
| 20-44 | 11.9 | 88.1 | 0.03 | 6.4 | 93.6 | 0.02 | ||
| 45-54 | 12.0 | 88.0 | 3.1 | 96.9 | ||||
| 55-64 | 17.1 | 82.9 | 4.9 | 95.1 | ||||
| 65-74 | 22.8 | 77.2 | 10.9 | 89.1 | ||||
| 75+ | 19.7 | 80.3 | 24.8 | 75.2 | ||||
| Sex | ||||||||
| Men | 11.7 | 88.3 | 0.29 | 12.0 | 88.0 | 0.30 | ||
| Women | 14.2 | 85.8 | 7.2 | 92.8 | ||||
| Race/Ethnicity | ||||||||
| Non-Hispanic white | 14.1 | 85.9 | 0.06 | 9.2 | 90.8 | 0.26 | ||
| Non-Hispanic black | 23.7 | 76.3 | 4.9 | 95.1 | ||||
| Hispanic | 10.4 | 89.6 | 11.2 | 88.8 | ||||
| Other | 11.2 | 88.8 | 3.7 | 96.3 | ||||
| Marital Status | ||||||||
| Married/Living as | 14.0 | 86.0 | 0.80 | 8.4 | 91.6 | 0.81 | ||
| Other | 13.1 | 86.9 | 9.5 | 90.5 | ||||
| Insurance status | ||||||||
| Private/HMO/Military | 13.6 | 86.4 | 0.53 | 8.1 | 91.9 | 0.03 | ||
| Any Medicaid | 15.1 | 84.9 | 10.0 | 90.0 | ||||
| Medicare only | 20.8 | 79.2 | 15.7 | 84.3 | ||||
| Unknown | 11.2 | 88.8 | 2.1 | 97.9 | ||||
| Family history of thyroid disease/cancer | ||||||||
| No/Unknown | 15.2 | 84.8 | <0.01 | 1.00 | ref | 9.2 | 90.8 | 0.85 |
| Yes | 3.7 | 96.3 | 4.48 | 1.69-11.93 | 7.8 | 92.2 | ||
| History of goiter | ||||||||
| No/Unknown | 14.0 | 86.0 | 0.76 | 11.6 | 88.4 | 0.02 | ||
| Yes | 13.1 | 86.9 | 3.0 | 97.0 | ||||
| Charlson comorbidity index | ||||||||
| 0 | 13.2 | 86.8 | 0.52 | 7.9 | 92.1 | 0.20 | ||
| ≥1 | 15.8 | 84.2 | 11.8 | 88.2 | ||||
| Tumor Stage | ||||||||
| Stage I | 14.2 | 85.8 | ~ | 1.1 | 98.9 | ~ | ||
| Stage II | 13.7 | 86.3 | 0.0 | 100.0 | ||||
| Stage III | 12.7 | 87.3 | 9.8 | 90.2 | ||||
| Stage IV | 0.0 | 100.0 | 10.8 | 89.2 | ||||
| Unstaged | 16.7 | 83.3 | 7.6 | 92.4 | ||||
| Tumor Size | ||||||||
| <1 cm or no mass found | 23.9 | 76.1 | <0.01 | 1.00 | ref | 2.8 | 97.2 | <0.01 |
| 1.0-3.9cm | 7.8 | 92.2 | 3.76 | 1.72-8.19 | 3.8 | 96.2 | ||
| 4.0+cm | 6.3 | 93.7 | 3.51 | 1.08-11.37 | 21.1 | 78.9 | ||
| Unknown | 49.5 | 50.5 | 0.34 | 0.06-2.02 | 50.0 | 50.0 | ||
| Hospital bed size | ||||||||
| Unknown, out patient only, < 200 beds | 15.8 | 84.2 | 0.02 | 7.6 | 92.4 | 0.14 | ||
| 200-299 beds | 6.9 | 93.1 | 3.9 | 96.1 | ||||
| 300-399 beds | 15.4 | 84.6 | 7.7 | 92.3 | ||||
| 400+ beds | 15.5 | 84.5 | 11.5 | 88.5 | ||||
| Approved residency training program | ||||||||
| No/Unknown | 10.2 | 89.8 | 0.03 | 9.1 | 90.9 | 0.90 | ||
| Yes | 16.3 | 83.7 | 8.8 | 91.2 | ||||
| Vital Status (December 31, 2010) | ||||||||
| Alive | 13.8 | 86.2 | 0.60 | 4.3 | 95.7 | 0.02 | ||
| Dead | 12.0 | 88.0 | 31.3 | 68.7 | ||||
OR: odds ratio; CI: Confidence interval
Total, subtotal, near total thyroidectomy compared to partial lumpectomy, lumpectomy and/or isthmusectomy.
According to the Age, Metastases, Extent and Size (AMES) risk classification.9
Weighted row percentage.
Bivariate Chi-Square test comparing those who did and did not have total thyroidectomy within each risk group.
Logistic regression model adjusted for listed variables; not calculated for the high risk group because tumor size was the only variable that remained significant during multivariate modeling.
Statistic not calculated because at least one cell size was zero.
Among high-risk patients, bivariate analyses indicated that receipt of total thyroidectomy was associated with younger age, insurance other than Medicare only, history of goiter, and smaller tumor size. Multivariate results were not reported because tumor size was the only variable that remained significant during multivariate modeling. As of December 31, 2010, bivariate analyses also revealed that total thyroidectomy was associated with better prognosis.
Radioiodine
Among low-risk patients, bivariate analyses indicated that receipt of postsurgical radioiodine was associated with younger age, insurance other than Medicare only, family history of thyroid disease/cancer, having a more advanced tumor (e.g., stage, size, and lymph node status), receipt of total thyroidectomy and positive tumor margins (Table 4). Multivariate analyses revealed that receipt of radioiodine was more likely among patients who had a family history of thyroid disease/cancer (OR: 1.89; 95% CI: 1.00-3.63), had tumors >1cm (OR range: 2.86-3.65), received a total thyroidectomy (OR: 5.47; 95% CI: 2.61-11.46) and had positive lymph nodes (OR: 3.41; 95% CI: 1.57-7.42). When stratified by tumor size, multivariate analyses indicated that the association between receipt of radioiodine and family history of thyroid disease/cancer remained significant among patients with tumors <1cm (OR: 3.71; 95% CI: 1.38-9.93) but not among those with tumors <1cm (OR: 1.09; 95% CI: 0.41-2.91; data not shown).
Table 4.
Factors associated with receipt of radioiodine (I-131) among patients diagnosed with papillary carcinoma who underwent surgery, Patterns of Care Study 2006.
| AMES risk-group1 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Low | High | |||||||||
| No | Yes | No | Yes | |||||||
| Characteristic | %2 | %2 | p 3 | OR4 | 95% CI | %2 | %2 | p 3 | OR4 | 95% CI |
| Age at diagnosis | ||||||||||
| 20-45 | 33.8 | 66.2 | <0.01 | 27.7 | 72.3 | <0.01 | ||||
| 45-54 | 31.3 | 68.7 | 4.3 | 95.7 | ||||||
| 55-64 | 47.8 | 52.2 | 15.8 | 84.2 | ||||||
| 65-74 | 52.0 | 48.0 | 25.9 | 74.1 | ||||||
| 75+ | 46.1 | 53.9 | 51.0 | 49.0 | ||||||
| Sex | ||||||||||
| Men | 35.8 | 64.2 | 0.75 | 15.3 | 84.7 | 0.13 | ||||
| Women | 37.2 | 62.8 | 24.3 | 75.7 | ||||||
| Race/Ethnicity | ||||||||||
| Non-Hispanic white | 37.3 | 62.7 | 0.78 | 17.0 | 83.0 | <0.01 | ||||
| Non-Hispanic black | 41.0 | 59.0 | 34.2 | 65.8 | ||||||
| Hispanic | 35.8 | 64.2 | 35.8 | 64.2 | ||||||
| Other | 34.5 | 65.5 | 26.3 | 73.7 | ||||||
| Marital Status | ||||||||||
| Married/Living as | 38.1 | 61.9 | 0.56 | 16.8 | 83.2 | 0.08 | ||||
| Other | 34.5 | 65.5 | 26.4 | 73.6 | ||||||
| Insurance status | ||||||||||
| Private/HMO/Military | 36.2 | 63.8 | 0.03 | 18.7 | 81.3 | <0.01 | ||||
| Any Medicaid | 41.4 | 58.6 | 38.8 | 61.2 | ||||||
| Medicare only | 68.8 | 31.2 | 28.2 | 71.8 | ||||||
| Unknown | 33.0 | 67.0 | 14.7 | 85.3 | ||||||
| Family history of thyroid disease/cancer | ||||||||||
| No/Unknown | 39.2 | 60.8 | 0.02 | 1.00 | ref | 23.4 | 76.6 | 0.18 | ||
| Yes | 21.9 | 78.1 | 1.89 | 1.00-3.63 | 12.5 | 87.5 | ||||
| History of goiter | ||||||||||
| No/Unknown | 36.2 | 63.8 | 0.70 | 26.6 | 73.4 | <0.01 | ||||
| Yes | 38.7 | 61.3 | 9.3 | 90.7 | ||||||
| Charlson comorbidity index | ||||||||||
| 0 | 37.8 | 62.2 | 0.35 | 23.7 | 76.3 | 0.02 | ||||
| ≥1 | 33.2 | 66.8 | 13.6 | 86.4 | ||||||
| Tumor Stage | ||||||||||
| Stage I | 40.5 | 59.5 | <0.01 | 4.8 | 95.2 | ~ | ||||
| Stage II | 22.3 | 77.7 | 0.0 | 100.0 | ||||||
| Stage III | 13.3 | 86.7 | 27.8 | 72.2 | ||||||
| Stage IV | 23.3 | 76.7 | 20.2 | 79.8 | ||||||
| Unstaged | 18.5 | 81.5 | 7.6 | 92.4 | ||||||
| Tumor Size | ||||||||||
| <1 cm or no mass found | 58.3 | 41.7 | <0.01 | 1.00 | ref | 48.8 | 51.2 | <0.01 | 1.00 | ref |
| 1.0-3.9cm | 25.9 | 74.1 | 2.86 | 1.60-5.10 | 10.1 | 89.9 | 11.83 | 2.03-68.86 | ||
| 4.0+cm | 17.8 | 82.2 | 3.65 | 1.49-8.91 | 43.2 | 56.8 | 1.55 | 0.17-14.41 | ||
| Unknown | 55.6 | 44.4 | 1.70 | 0.49-5.88 | 27.7 | 72.3 | 3.76 | 0.27-52.64 | ||
| Total Thyroidectomy5 | ||||||||||
| No | 77.3 | 22.7 | <0.01 | 1.00 | ref | 47.6 | 52.4 | 0.11 | ||
| Yes | 30.5 | 69.5 | 5.47 | 2.61-11.46 | 18.5 | 81.5 | ||||
| Nodal status | ||||||||||
| None examined, unknown | 48.9 | 51.1 | <0.01 | 1.00 | ref | 13.9 | 86.1 | 0.12 | ||
| None positive | 33.0 | 67.0 | 1.65 | 0.80-3.37 | 36.4 | 63.6 | ||||
| At least one positive | 15.6 | 84.4 | 3.41 | 1.57-7.42 | 18.7 | 81.3 | ||||
| Surgical margins | ||||||||||
| Margins free of tumor | 37.4 | 62.6 | 0.01 | 19.9 | 80.1 | 0.86 | ||||
| Tumor at margins | 23.3 | 76.7 | 21.1 | 78.9 | ||||||
| Unknown, not stated, not assessed | 51.6 | 48.4 | 30.4 | 69.6 | ||||||
| Hospital bed size | ||||||||||
| < 200 beds/Out patient only/Unknown | 35.2 | 64.8 | 0.40 | 42.4 | 57.6 | <0.01 | 1.00 | ref | ||
| 200-299 beds | 29.3 | 70.7 | 15.1 | 84.9 | 10.45 | 2.09-52.23* | ||||
| 300-399 beds | 38.4 | 61.6 | 6.1 | 93.9 | ||||||
| 400+ beds | 41.5 | 58.5 | 23.7 | 76.3 | 3.48 | 0.97-12.57 | ||||
| Approved residency training program | ||||||||||
| No/Unknown | 36.2 | 63.8 | 0.81 | 35.4 | 64.6 | <0.01 | ||||
| Yes | 37.5 | 62.5 | 16.4 | 83.6 | ||||||
| Vital Status (December 31, 2010) | ||||||||||
| Alive | 37.2 | 62.8 | 0.14 | 14.6 | 85.4 | <0.01 | ||||
| Dead | 26.1 | 73.9 | 52.9 | 47.1 | ||||||
OR: odds ratio; CI: Confidence interval
According to the Age, Metastases, Extent and Size (AMES) risk classification.9
Weighted row percentage.
Bivariate Chi-Square test comparing those who did and did not have total thyroidectomy within each risk group.
Logistic regression model adjusted for listed variables.
Total, subtotal, near total thyroidectomy compared to partial lumpectomy, lumpectomy and/or isthmusectomy.
Statistic not calculated because at least one cell size was zero.
Bed size 200-299 and 300-399 were collapsed due to small numbers.
Among high-risk patients, bivariate analyses indicated that receipt of postsurgical radioiodine varied significantly by age, race/ethnicity, insurance status, history of goiter, comorbidity level, tumor stage and size, hospital bed size and hospital residency program status. Multivariate analyses indicated that significant differences remained by tumor size (1.0-3.9 cm versus <1cm: OR: 11.83; 95% CI: 2.03-68.86) and hospital bed size (200-399 versus <200: OR: 10.45; 9%% CI: 2.09-52.23). As of December 31, 2010, bivariate analyses also revealed that postsurgical radioiodine was associated with better prognosis in high-risk patients.
Discussion
The majority of patients with papillary thyroid cancers undergo total thyroidectomy; high-risk patients were slightly more likely to undergo total thyroidectomy than low-risk patients. Among patients who undergo surgery, the majority have clear tumor margins. Clear margins were, however, more common among low-risk patients. Roughly two-thirds of low-risk patients and three-fourths of high-risk patients also received radioiodine. Family history of thyroid disease/cancer and extent of disease were the strongest predictors for treatment modality among low-risk patients. Among high-risk patients, tumor size and hospital characteristics were the strongest predictors. Significant variation in vital status was observed by treatment modality only among high-risk patients.
Regardless of risk-group status, the receipt of total thyroidectomy was found to be associated with greater extent of disease, which has previously been observed.14, 15 However, in contrast to these previous studies, patient demographics (i.e., age and sex) were not found to be associated with receipt of total thyroidectomy. To the best of our knowledge, the association between extent of surgery and family history of thyroid disease/cancer has not previously been assessed. The current data also indicated that this association was not dependent on tumor size. Family history of thyroid disease/cancer remained significantly associated with receipt of total thyroidectomy among low-risk patients when analyses were stratified by size (<1cm and ≥1cm; data not shown). Given a personal or family history of thyroid disease/cancer among low-risk patients, it is possible that the treating physician and/or the patient decided more aggressive therapy was warranted. Although total thyroidectomy is recommended for all high-risk patients, not all high risk patients in the current study underwent this procedure. During multivariate analyses the only variable that remained significantly associated with receipt of total thyroidectomy was tumor size. It cannot be ruled out though that the receipt of total thyroidectomy among high-risk patients may have also depended on other variables (e.g., age and comorbidity index) but that such associations were not significant in the current study due to insufficient statistical power.
In agreement with previous studies,17, 18 the receipt of postsurgical radioiodine was also associated with greater extent of disease regardless of risk-group status (e.g., size > 1 cm and/or positive lymph nodes). Total thyroidectomy was also found to be associated with receipt of radioiodine among low-risk patients in the current study, which was expected given that total thyroidectomy is recommended prior to radioiodine therapy.11, 12 In contrast to the study by Haymart et al.,17 which was restricted to patients who had undergone total thyroidectomy, in the current study, patient demographics (age, sex and race/ethnicity) were not associated with receipt of radioiodine. Although previous studies have found annual thyroid case volume to be associated with receipt of total thyroidectomy,17, 18 this variable was not available for assessment in the current study. In the current study, intermediate hospital bed size was found to be associated with receipt of radioiodine but only among high-risk patients. To the best of our knowledge this is the first study to report the association between family history of thyroid disease/cancer and radioiodine. When stratified by tumor size this association was observed only among patients who had tumors ≥1 cm. Again, a positive history of thyroid disease/cancer may prompt the treating physician(s) and/or the patient to opt for more aggressive therapy when the patient is otherwise considered low-risk.
Although this study had strengths, namely that it was conducted using a population-based sample that oversampled minority groups and ascertained personal and family medical history, it also had limitations. Although our results indicate that a family history of thyroid disease/cancer was associated with treatment modality choices among low-risk patients, based on how the data were abstracted it is not possible to delineate family history of thyroid disease from family history of thyroid cancer. It is unlikely that these patients truly had a familial syndrome; however, we believe that our findings provide incentive to further investigate the influence of family medical history on papillary thyroid cancer treatment choices. Additionally, while we were not able to ascertain physician and/or patient treatment preferences, we were able to investigate factors associated with treatment received. It is also possible that residual confounding by unmeasured factors, including physician type (e.g., endocrinologist or surgeon) and indication for surgery, may also have influenced our findings. Finally, the small sample size among the high-risk group often resulted in imprecise multivariate parameter estimates. In conclusion, this study provides insight into the patterns of papillary thyroid cancer care, in the general population. The findings from this study indicate adherence to guideline recommendations in that family history of thyroid disease/cancer, in addition to tumor characteristics, does appear to inform treatment practices.
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