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Comparison of secondary and primary thyroid cancer in adolescents and young adults (AYA)

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Comparison of secondary and primary thyroid cancer in adolescents and young adults (AYA)

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Content 1
COMPARISON OF SECONDARY AND PRIMARY THYROID CANCER IN
ADOLESCENTS AND YOUNG ADULTS (AYA)

Melanie Goldfarb MD
1
and David R. Freyer, DO, MS
2

1
University of Southern California Keck School of Medicine, Los Angeles, CA
2
Children’s Hospital Los Angeles, University of Southern California Keck School of Medicine,
Los Angeles, CA

Corresponding Author
Melanie Goldfarb, M.D.
Assistant Professor of Surgery
University of Southern California Keck School of Medicine
Division of Breast/Soft Tissue and Endocrine Surgery, Department of Surgery
1510 San Pablo St Suite 412k
Los Angeles, CA 90033
(Ph) 323-865-3535
Melanie.Goldfarb@med.usc.edu
2
Table of Contents

1 Title Page
2 TOC
3 Abstract
4 Manuscript
12 References
13 Tables I-V
19 Figure 1

3
Abstract

COMPARISON OF SECONDARY AND PRIMARY THYROID CANCER IN
ADOLESCENTS AND YOUNG ADULTS (AYA)

Background: Thyroid cancer is one of the five most common malignancies in AYA patients
(ages 15-39) and may develop de novo or in patients previously treated for cancer. We seek to
compare the tumor characteristics, treatment, and overall survival (OS) of secondary (SMN) vs.
primary thyroid cancer in AYA patients.
Methods: All cases of AYA thyroid cancer contained in the 1998-2010 American College of
Surgeons National Cancer Database were divided into two cohorts according to primary or
secondary occurrence. Comparisons using appropriate statistical methods were performed.
Results: Of 41,062 cases, 1349 (3.3%) had experienced a prior malignancy. Compared with
cases of primary thyroid cancer, SMNs were more likely multifocal (OR:1.173, CI:1.049-1.313)
microcarcinomas <1cm (OR:1.496, CI:1.327-1.687) with tell/columnar cells (OR:2.187,
CI:0.534-0.692), of White race (2.643, CI:1.310-5.331) and age 35-39 (OR:1.239, CI:1.093-
1.404) and less likely female (OR:0.608, CI:0.534-0.692), Hispanic (OR:0.779, CI:0.642-0.946)
age 15-19 (OR:0.624, CI:0.510-0.763) or 25-29 (OR:0.711, CI:0.604-0.837), or less likely >4cm
in size (OR:0.610, CI:0.493-0.758). There was a 6.63-fold (CI:4.97-8.86, p<0.001) relative risk
of death for secondary vs. primary thyroid cancers after adjusting for demographic, tumor and
thyroid treatment factors. Only Hispanic origin, tall/columnar cell histology and distant
metastases decreased OS for SMNs.
Conclusion: AYAs who develop thyroid cancer as a SMN have a significantly decreased OS
compared to AYAs with primary thyroid cancer. Multiple demographic and tumor differences
exist between these two cohorts. Whether the outcome disparity results from previous cancer
treatment or differences in biology, environment, or access to care are areas needing further
investigation.

4
Introduction

Thyroid cancer is one of the five most common malignancies in adolescent and young
adults (AYA: ages 15-39) and may develop de novo or in individuals previously treated for
cancer. The most recent SEER incidence rates show that for female AYAs, thyroid cancer is the
most common cancer in age groups 15-19, 20-24, and 25-29 years and the second most common
cancer for ages 30-34 and 35-39.
1
Overall, it is the fourth most common cancer for ages 15-19
but the second most common for ages 20-39. Although the majority are primary thyroid cancers,
a subset are secondary tumors (SMNs) arising in survivors of pediatric or other AYA
malignancies including ALL, CNS tumors, or bone and soft tissue sarcomas. The greatest risk is
for patients diagnosed at a younger ages (≤ 17 years for ALL and CNS tumors; ≤ 18 years for
bone and soft tissue sarcomas).
2,3,4
These patients may have experienced toxic and environmental
exposures such as chemotherapy and/or radiation therapy, which have the potential to cause
secondary cancers during their young adult life.
5,6
Influences such as family history, lifestyle
behaviors, and comorbid health conditions may also play a role in secondary cancer development
for AYAs.
7, 8
However, little is known about how these associations apply to thyroid cancer.
Therefore, the purpose of this study is to determine whether demographic, clinical, pathologic, or
survival differences exist between primary and secondary thyroid malignancies in AYA patients.

Methods

Data source
The National Cancer Database (NCDB) is a joint project of the American College of
Surgeons (ACoS) Commission on Cancer and the American Cancer Society. The NCDB
contains data elements on patient demographics, insurance status, tumor characteristics, first
course of treatment, ZIP code–level socioeconomic factors, and facility-level characteristics. A
recent analysis showed that 76.1% of all thyroid cancers in the United States are included in this
database and 71.1-77.4% of adolescent and young adult cancers.
9
Data reporting to NCDB is
highly standardized and similar to other federal cancer registry data systems. After a patient was
diagnosed and treated at an ACoS-accredited cancer program, the hospital registrar was
responsible for documenting care, even when the patient was transferred to another facility.
10

5
The data are then coded and reported according to nationally established protocols coordinated
by the North American Association of Central Cancer Registries.
11
Because all patient
information is de-identified, this study was determined by our institutional review board to be
exempt from approval.

Study cohort and measures
All 41,062 cases of AYA thyroid cancer contained in the 2004-2010 NCDB were
included in this study. Patients were divided into two cohorts according to whether their thyroid
cancer was a primary or SMN. Demographic variables included age, gender, race, ethnicity,
insurance and socioeconomic status. Age categories within the AYA population were divided
into five-year intervals as follows: ages 15-19, 20-24, 25-29, 30-34, and 35-39. Insurance status
was classified as “uninsured” or “any insurance,” and low socioeconomic status as < $46,000
annual income, as defined by the NCDB. Patient race was categorized by the NCDB as white,
black, Asian/Pacific Islanders, Native American, or Other, and ethnicity as Hispanic or non-
Hispanic. Race and ethnicity were included in the analysis because they have been shown to
influence outcome following treatment/response to treatment.
12
Tumor characteristics included
histology (Differentiated thyroid cancer (DTC) including all variants vs. non-DTC), grade
(moderate-well differentiated vs. poor or undifferentiated that is coded as a separate variable than
histological subtype), tumor focality (solitary or multiple nodules), tumor size (< 1cm, > 4cm),
lymph node status (unknown or negative lymph nodes vs. documented positive nodes), and
distant metastases at presentation (present or absent; unknown were excluded). Treatment
variables included extent of surgery (total thyroidectomy or less than total thyroidectomy), any
lymph nodes examined, post-operative radioiodine (RAI) or radiation (XRT), and less than 24-
hour hospital stay. Last date of contact was used for the amount of follow-up time; those with
“0” months or missing follow-up data were excluded from the survival analyses.

Statistical Analysis
Nominal categorical variables were compared using Fisher exact test and ordered
categorical variables were analyzed using the Mantel–Haenszel chi-square test to analyze the
demographic, pathologic, and treatment characteristics of the study cohort. Stepwise binary
logistic regression was employed to identify independent factors associated with primary or
6
secondary thyroid cancer. The model goodness of fit was assessed by evaluating model
discrimination (c-statistic) and calibration (Hosmer-Lemeshow chi-square). Odds ratios and
95 % confidence intervals were calculated to evaluate the strength of association between each
variable and the occurrence of a secondary thyroid malignancy. Kaplan–Meier analysis with the
log rank test was used to determine if any demographic or clinical variable differences
significantly impacted overall survival (OS). Analyses were also performed after stratification by
primary or secondary malignancy status. Cox proportional hazards regression modeling with
forward regression was performed to identify independent factors associated with OS. All
variables that were significant (p<.1) on univariate Kaplan Meir analysis in addition to tumor
sequence were entered into the regression model and only those with a p < .05 were retained in
the final model. Hazard ratios and 95 % confidence intervals were calculated to evaluate the
strength of association between each variable and survival.
Data analyses were performed with the Statistical Package for the Social Sciences (SPSS)
software (version 20.0; SPSS Inc., Chicago, IL) and SAS version 9.3 (SAS Institute, Inc, Cary,
NC); all tests were two-sided, and a p value of <0.05 was considered to be statistically
significant.

Results

Of 41,062 AYA thyroid cancer cases, 1349 (3.3%) had experienced a prior malignancy.
Within this cohort of SMNs, 23.7% were male, 90.5% white, 8.5% Hispanic, and 13.8% between
ages 15-25. Most (83.2%) had some form of insurance though 55% were considered of low
socioeconomic status. Compared with cases of primary thyroid cancer, those with secondary
cancers had a higher proportion of whites (p < 0.001), males (p < 0.001), non-Hispanics
(p=0.001), and significantly different age (p < 0.001) and race distributions (p < 0.001).
Secondary cancers were more common 15-19 and 35-39 year-olds and less common in 20-24
and 25-29 year-olds as well as in Asians and those of Other race. Pathologic tumor (p < 0.001)
and nodal (p=0.048) staging was different between the two groups: secondary cancers were
smaller (both microcarcinomas< 1cm [p < 0.001] and < 4cm [p < 0.001]) but more likely
multifocal (p=0.005) and with tall/columnar cell histology if a DTC. There was no difference in
7
the frequency of positive lymph nodes in patients that had nodes examined, the proportion of
DTC histology or moderate to well-differentiated grade (p=NS). Additionally, there was no
difference in rates of distant metastases at presentation between groups (p=NS). There was also
no significant difference in extent of surgery or use of external beam radiation between the two
cohorts. However, secondary cancers waited a mean of 2.7 days longer (p=0.009) for surgery and
were less likely to receive RAI therapy (p=0.0005). (Table I)
Stepwise multivariate regression demonstrated that SMNs occurred more commonly in
Whites and in individuals aged 35-39. SMNs were more likely microcarcinomas< 1cm and
multifocal with tall/columnar cell histology (model c-statistic 0.631, CI: 0.617-0.646; H-L
0.702). Patients with secondary thyroid cancers were less likely female, Hispanic, ages 15-19 or
24-29 at the time of this diagnosis less likely to have a tumor size > 4cm. (Table II)
Mean follow-up after thyroid cancer diagnosis was 35.5±24.0 months (1-96.1 months)
and was not different between those with primary (35.5 ± 24.1 months) and secondary (34.9 ±
23.1 months) DTC. Multiple demographic, pathologic, and clinical treatment factors impacted
OS on univariate Kaplan-Meir analyses. (Table III) However, after stratification by secondary
malignancy status, Hispanic origin, Other race, differentiated thyroid cancer histology,
tall/columnar cell histology, thyroid hormone replacement, any lymph nodes examined, and
distant metastases at presentation negatively impacted overall survival on univariate analysis.
(Table IV)
Multivariate cox regression showed that for all AYA thyroid cancer patients, female sex
and RAI therapy improved OS whereas secondary malignancy status, Hispanic ethnicity, low
SES, age 35-39, having lymph nodes examined or positive lymph nodes, and distant metastases
at presentation decreased OS. (Table V) The remaining variables (insurance status, metropolitan
treatment location, DTC, tumor focality and size <1cm, TTx, XRT, thyroid hormone
replacement, White and Asian race, and ages 15-19, 20-24, and 25-29) did not reach significance
in the final model. After adjusting for demographic, tumor and thyroid treatment factors, there
was a still a 6.63-fold (CI 4.97-8.86; p < 0.001) relative risk of death for secondary vs. primary
thyroid cancers. (Figure I) Additionally, for those with a secondary thyroid malignancy, only
Hispanic ethnicity, tall/columnar cell histology, and distant metastases decreased overall
survival. (Table V)

8
Discussion

The current study indicates that secondary malignancy status is an independent risk factor
for decreased overall survival among AYAs diagnosed with thyroid cancer. Patients for who
thyroid cancer is a SMN have a 6.63-fold risk of death independent of demographic, tumor, and
treatment factors compared to patients with primary thyroid cancer over a short follow-up period.
This is an important new observation for the 3-4% of this population that are already survivors of
pediatric or other AYA cancers. These numbers are not insignificant considering that thyroid
cancer is one of the most common AYA cancers, especially among females, and patients need to
be counseled appropriately. Additionally, differences in thyroid cancer survival usually require
15-20 years of follow-up rendering the results of this study quite significant. Future research
should explore possible disease-specific, biologic, environmental, or access to care explanations
for these findings. Additionally, since the difference in OS among primary and secondary
malignancy patients over a short follow-up period persisted even after controlling for various
clinical and thyroid cancer treatment factors, the overall treatment strategy for prior cancer
survivors with a secondary DTC should be a focus for future clinical investigation.
Only one study has looked at differential gene expression patterns in AYAs compared to
older individuals.{Vriens, 2011 #2896} The authors hypothesized that differences in the extent
of disease at presentation and survival of patients with papillary thyroid carcinoma that existed
between AYAs and older patients have a biologic/genetic basis. However, they were unable to
find a difference in the frequency or type of somatic mutations between the two groups though
six genes (extracellular matrix protein 1 [ECM1], v-erb-2 erythroblastic leukemia viral oncogene
homolog 2 [ERBB2], urinary plasminogen activator [UPA], 6-phosphofructo-2-kinase/fructose-
2,6-biphosphatase 2 [PFKFB2], meis homeobox 2 [MEIS2], and carbonic anhydrase II [CA2])
had significant differential expression between the AYA and older patients. They did not
comment upon SMNs in either group of patients.
Primary thyroid cancers occurred more often in AYAs in their twenties compared to
those 15-19 or over the age of thirty, where secondary thyroid cancers were more common. This
may be a consequence of a long latency in developing clinically apparent thyroid cancer after
radiation or chemotherapy, which may be up to thirty years after initial pediatric cancer
treatment. Alternatively, older patients have had more time to develop an assortment of
9
secondary thyroid conditions such as multinodular goiter or hyperthyroidism and finally undergo
thyroidectomy as treatment for these conditions, only to discover incidental, secondary thyroid
cancer in a final pathology specimen. Not surprisingly, age category within AYAs did not impact
OS on multivariate cox regression, inasmuch as the prognosis is excellent for patients with
thyroid cancer under the age of 45.
5,13,14
In AYA thyroid cancer patients, SMNs were more likely microcarcinomas < 1cm and
less likely to have a tumor > 4cm. This could be a consequence of increased surveillance and
thyroid screening in previous cancer survivors. In North America, monitoring of childhood
cancer survivors is largely guided by the Children’s Oncology Group Long-Term Follow-Up
Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers.
15,16
These risk-
adapted guidelines are developed on the basis of published evidence where available and
supported by expert consensus opinion. For childhood cancer survivors who received irradiation
to or in proximity with the thyroid gland, current surveillance recommendations consist of an
annual physical examination; ultrasound and fine needle aspiration (FNA) or biopsy are limited
to patients who have palpable nodules. Since microcarcinomas would generally not be
discovered by palpation, the most plausible explanations are that clinicians are screening more
aggressively with ultrasound than current COG guidelines recommend, that small nodules are
detected as part of routine surveillance for the patient’s original primary tumor, or that these
microcarcinomas are only discovered incidentally when the thyroid is removed for another
reason, such as hyperthyroidism or multinodular goiter. In regard to screening practices for
secondary thyroid cancer, it is of interest that in the current COG guidelines (version 3.0) routine
thyroid ultrasound is no longer recommended as it was in past versions because of the high
frequency of FNA, biopsy and thyroidectomy triggered by non-palpable nodules that later
proved to be histologically benign. The increased prevalence and negative impact of
tall/columnar cell histology in SMNs is an interesting finding that could be a consequence of
prior cancer treatments causing de-differentiation of latent DTCs or an inherent biologic/genetic
tendency to develop more aggressive tumors as a SMN. Prior studies in Chernobyl, Hodgkin’s
disease, and Childhood Cancer Surveillance Study cohorts that have some SMN thyroid cancers
after radiation did not comment on tall/columnar cell variants.
Patients with secondary thyroid malignancies were also more likely to be male, white,
and non-Hispanic. However, only Hispanic ethnicity, tall/columnar cell histology, and distant
10
metastases at presentation decreased OS for these patients. Gender, ethnicity, and SES also
impacted OS for the entire cohort, similar to previous studies in other thyroid cancer
cohorts.
13,14,17
In addition, age 35-39 and certain tumor characteristics decreased survival in the
larger group. Whether biologic or environmental explanations for these characteristics make
these patients more vulnerable to a second malignancy or worse overall outcomes is an area for
further study.
A recent study developed and validated a risk model, based on self-reported data, for
developing secondary thyroid cancer in survivors who had been diagnosed with cancer at less
than 18 years of age.
18
In that population, females, those with prior thyroid nodules, primary
cancer before age 15, treatment with an alkylating chemotherapy and/or radiation, and birth year
after 1970 all contributed to a patient’s risk for developing secondary thyroid cancer.
Interestingly, type of primary cancer was not included in the final model. History of thyroid
nodules conferred the greatest risk for subsequent thyroid cancer development, which may have
reflected more frequent referral for surgery and detection of incidental microcarcinomas.
Unfortunately, the report did not provide information on the tumor size or clinical significance of
the diagnosed thyroid cancers. Replicating these findings in AYA patients that receive radiation
as part of an initial cancer treatment would a valuable addition towards providing screening
guidelines for the AYA cancer survivor population and might provide insight into the increased
prevalence of a thyroid SMN in 35-39 year olds.
Although the NCDB captures the largest number of cancer cases in the United States,
long-term survival data is presently limited due to the infancy of the database. Therefore, this
study’s reported survival outcomes will need to be verified with another large database that has
longer follow-up data, or at a later date when the NCDB has more follow-up information.
Disease-free survival is also not part of the NCDB and would be another important clinical
outcome variable to measure and may be not as significant as the difference in OS since thyroid
cancer has an overall excellent prognosis. Moreover, for patients with secondary thyroid cancers
no information is available on the primary tumor type or prior cancer treatment exposures, which
and could influence both thyroid cancer characteristics and survival. Additionally, causes of
death are not captured in the NCDB. Although the present study appeared to have an appropriate
distribution of ethnicities (11% of the patients were Hispanic), the NCDB has been shown to
only capture 51.1% of Hispanic cancer cases, so that data may be skewed.
9
Additionally, other
11
post-operative outcomes specific to thyroid surgery that influence disease morbidity, such as
hypoparathyroidism or recurrent laryngeal nerve injury, are not captured in any database but
would be important considerations in evaluating the role of thyroid procedures in managing
AYAs with secondary thyroid nodules.

Conclusion
AYAs that develop thyroid cancer as a SMN have a significantly decreased OS compared
to AYAs with primary thyroid cancer. Secondary malignancies were more likely
microcarcinomas < 1cm, multifocal, with tall/columnar histology and occurred more often in
males, non-Hispanics, those of non-white race, and AYAs in their 20’s. Additionally, OS for
secondary thyroid cancers was impacted by Hispanic origin, tall/columnar cell histology and the
presence of distant metastases at presentation. Whether this is a direct consequence of previous
cancer treatment, biologic, environmental, or access to care disparity is an area that needs further
investigation.

12
References
1. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008, National
Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2008/, based on November 2010 SEER
data submission, posted to the SEER web site, 2011.
2. Curtis RE, Freedman DM, Ron E, et al, eds. New malignancies among cancer survivors: SEER Cancer
Registries, 1973–2000. National Cancer Institute, NIH Publ. No. 05-5302. Bethesda, MD, 2006.
3. Nagarajan R, Kamruzzaman A, Ness KK, et al. Twenty years of follow-up of survivors of childhood
osteosarcoma: a report from the Childhood Cancer Survivor Study. Cancer. 2011;117: 625-634.
4. Ginsberg JP, Goodman P, Leisenring W, et al. Long-term survivors of childhood Ewing sarcoma:
report from the childhood cancer survivor study. J Natl Cancer Inst. 2010;102: 1272-83
5. Waguespack S WS, Ross J. Thyroid cancer. SEER AYA monograph. Cancer Epidemiology in Older
adolescents and young adults 15-29 years of age, Including SEER Incidence and Survival 1975-2000.:
NCI, 2006:NIH NOO. -5767.
6. Ng AK, Travis LB. Subsequent malignant neoplasms in cancer survivors. Cancer J. 2008;14: 429-34
7. Oeffinger KC, Tonorezos ES. The cancer is over, now what?: Understanding risk, changing outcomes.
Cancer. 2011;117: 2250-2257.
8. Coccia PF, Altman J, Bhatia S, et al. Adolescent and young adult oncology clinical practice guidelines
in oncology. JNCCN Journal of the National Comprehensive Cancer Network. 2012;10: 1112-1150.
9. Lerro CC, Robbins AS, Phillips JL, Stewart AK. Comparison of Cases Captured in the National Cancer
Data Base with Those in Population-based Central Cancer Registries. Ann Surg Oncol. 2013;20: 1759-
1765.
10. Raval MV, Bilimoria KY, Stewart AK, Bentrem DJ, Ko CY. Using the NCDB for cancer care
improvement: an introduction to available quality assessment tools. J Surg Oncol. 2009;99: 488-90
11. Phillips JK, Stewart AK, ed. Facility Oncology Registry Data Standards. Chicago: Commission on
Cancer; 2011.
12. Smedley BD, ed, Stith AY, ed, Nelson AR, ed. Unequal Treatment: Confronting Racial and Ethnic
Disparities. Washington, DC: National Academies Press; 2003
13. Yu GP, Li JC, Branovan D, McCormick S, Schantz SP. Thyroid cancer incidence and survival in the
national cancer institute surveillance, epidemiology, and end results race/ethnicity groups. Thyroid.
2010;20: 465-473.
14. Stroup AM, Harrell CJ, Herget KA. Long-term survival in young women: hazards and competing
risks after thyroid cancer. J Cancer Epidemiol. 2012;2012: 641372.
15. http://www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf
16. Landier W, Bhatia S, Eshelman DA, et al. Development of risk-based guidelines for pediatric cancer
survivors: the Children's Oncology Group Long-Term Follow-Up Guidelines from the Children's
Oncology Group Late Effects Committee and Nursing Discipline. Journal of clinical oncology : official
journal of the American Society of Clinical Oncology. Dec 15 2004;22(24):4979-4990.
17. Jonklaas J, Nogueras-Gonzalez G, Munsell M, et al. The impact of age and gender on papillary
thyroid cancer survival. J Clin Endocrinol Metab. 2012;97: E878-887.
18. Kovalchik SA, Ronckers CM, Veiga LH, et al. Absolute risk prediction of second primary thyroid
cancer among 5-year survivors of childhood cancer. J Clin Oncol. 2013;31: 119-127.

13
Table I: Patient and Disease Characteristics by Type of Thyroid Cancer Occurrence
n=41,062 (unless otherwise noted) Primary Thyroid
Cancer (%)
Secondary
Thyroid Cancer (%)
P value
Demographics
Male Gender 16.4 23.7 <.001
Age category
15-19
20-24
25-29
30-34
35-39

4.9
14.4
21.7
29.7
29.2

5.0
8.8
15.6
31.1
39.5
<.001
<.001
<.001
<.001
0.153
<.001
Ethnicity
White/Caucasian
Black
American Indian
Asian
Other
Hispanic origin

86.0
6.7
0.3
5.4
1.6
11.4

90.5
5.1
0.1
3.7
0.6
8.5
<.001
<.001
0.011
0.061
0.003
0.003
0.001
Insured 82.7 83.2 0.63
Low Socioeconomic status 56.0 55.0 0.45
Tumor characteristics
Papillary/Follicular histology
Tall/Columnar cell variant
84.7
1.1
86.3
2.1
0.12
0.001
Well Differentiated (n=6667) 96.3 96.5 0.92
Size < 1cm
Size > 4cm
27.3
12.1
38.3
6.9
<.001
<.001
Multifocality 36.3 40.0 0.005
Positive lymph nodes 27.9 26.1 0.16
Distant Metastases (n=40257) 0.3 0.7 0.56
Treatment
Surgical treatment
Any nodes examined
Total thyroidectomy

58.4
86.1

56.2
86.8

0.11
0.26
Post-op therapy
Radioiodine
Beam radiation

55.5
0.3

50.7
0.2

<.001
0.51
< 24hour stay 78.8 77.0 0.11
14
Table II: Multivariate Predictors of Secondary Thyroid Cancers

N=41,062 Odds Ratio 95% Confidence Interval
Lower Upper
P-value
Female Sex 0.608 0.534 0.692 <.001
Tall/Columnar cell histology 2.187 1.489 3.210 <.001
Age 15-19 0.624 0.510 0.763 <.001
Age 25-29 0.711 0.604 0.837 <.001
Age 35-39 1.239 1.093 1.404 0.001
White race 2.643 1.310 5.331 0.007
Tumor size < 1cm 1.496 1.327 1.687 <.001
Tumor size >4cm 0.610 0.492 0.758 <.001
Multifocality 1.173 1.049 1.313 0.005
Hispanic Origin 0.779 0.642 0.946 0.012

15
Table III: Univariate predictors of Overall Survival
N Mean Survival
(months)
P
(log-rank)
Demographics
Tumor order
Primary thyroid cancer
Secondary thyroid cancer

39552
1367

35.689
35.919
0.569
Sex
Female
Male

34228
6834

35.38
34.65
0.17
Race
White/Caucasian
Black
American Indian
Asian
Other

35358
2733
133
2216
622

35.860
35.847
35.878
33.950
32.069
<0.001
0.001
0.617
0.426
<.001
<.001
Socioeconomic status
Low
Normal

22991
18071

36.199
35.303
.002
Insurance status
No
Yes

33965
7097

38.781
35.053
<0.001
Hispanic origin
No
Yes

4636
36426

35.917
33.961
<0.001
Age category
15-19
20-24
25-29
30-34
35-39

2006
5844
8837
12222
12153

34.360
35.463
34.836
35.903
36.453
<0.001
0.745
0.745
0.001
0.163
0.004
Metropolitan location
Urban
Rural

39340
1722

35.780
33.829

0.005
Tumor Characteristics
Tumor differentiation
Well-differentiated
Poorly differentiated

6423
244

33.866
35.324
0.507
Differentiated thyroid carcinoma
histology
No
Yes
Tall/Columnar cell histology
No
Yes

34812
6250

446
40473

40.472
34.841

33.0
35.5

<0.001

0.52
Tumor focality
Multifocal
Solitary

14961
26101

35.449
35.841
0.059

16
Table III continued: Univariate predictors of Overall Survival
N Mean Survival
(months)
P
(log-rank)
Tumor Characteristics
Tumor size > 4cm
No
Yes

4896
36166

35.631
36.194
0.147
Microcarcinoma (< 1cm)
No
Yes

11358
29704

36.330
34.037
<0.001
Documented pathologic lymph node
involvement
No
Yes

11432
29639

35.978
34.971

<0.001
Distant Metastases
No
Yes

40116
141

36.12
30.83
0.01
Treatment Factors
Extent Surgery
Total thyroidectomy (TTx)
Less than TTx

35377
5685

35.517
36.833
<0.001
Any lymph nodes examined
No
Yes

23938
17124

37.132
34.674
<0.001
Radioiodine therapy
No
Yes

22709
18353

33.849
37.180

<0.001
External beam irradiation
No
Yes

130
40932

35.652
49.968
<0.001
Thyroid hormone replacement
No
Yes

18860
22202

37.071
34.092
<0.001

17
Table IV: Univariate predictors of survival for patients with secondary thyroid cancers
(only significant predictors (p < 0.1) displayed)
N Mean Survival
(months)
p-value
(log rank)
Other race
No
Yes

1359
8

36.003
21.956
0.034
Hispanic origin
No
Yes

1250
117

36.324
31.416
0.045
Distant metastases at presentation
Yes
No

1337
9

36.31
37.37
0.01
Tall/Columnar Cell histology
No
Yes

1338
29

36.059
28.610
0.037

Differentiated Thyroid Carcinoma
No
Yes

188
1179

40.776
35.133
0.004
Thyroid Hormone Replacement
No
Yes

677
690

37.659
34.213
0.017
Any lymph nodes examined
No
Yes

597
770

38.749
33.715
<.001
Tumor size > 4cm
No
Yes

1272
95

35.570
40.681
0.077
Positive lymph nodes
No
Yes

1009
358

36.328
34.741
0.085
18
Table V: Multivariate Cox Regression Predictors of Decreased Overall Survival
N=39139
Hazard
Ratio
P-value

95.0% Confidence Interval
Lower Upper
All AYA Thyroid Cancer patients
Hispanic Origin 2.214 <0.001 1.680 2.918
Lymph Nodes Examined 1.376 .025 1.103 1.933
Positive Lymph Nodes 1.382 .027 1.038 1.8240
Low Socioeconomic Status 1.921 <0.001 1.504 2.454
Radioiodine Therapy 0.502 <0.001 0.400 0.631
Second Malignancy 6.438 <0.001 4.827 8.587
Distant Metastases at
presentation
9.820 <0.001 5.322 18.120
Female Sex 0.591 <0.001 0.459 0.762
Age 35-39 1.489 0.001 1.185 1.871
Only Secondary Thyroid Cancer patients
N=1326
Hispanic Origin 4.230 <0.001 2.266 7.898
Distant Metastases at
presentation
13.032 <0.001 4.010 42.350
Tall/Columnar cell histology 5.295 0.001 1.898 14.773

19
Figures
Figure I: Product-Limit Overall Survival Estimates of Primary and Secondary AYA
Thyroid Cancers (n=39693)

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Asset Metadata

Creator Goldfarb, Melanie (author)

Core Title Comparison of secondary and primary thyroid cancer in adolescents and young adults (AYA)

School Keck School of Medicine

Degree Master of Science

Degree Program Clinical and Biomedical Investigations

Publication Date 03/05/2014

Defense Date 03/05/2014

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag adolescent and young adult cancer,OAI-PMH Harvest,secondary malignancy,thyroid cancer

Format application/pdf (imt)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Azen, Stanley P. (committee chair), Freyer, David (committee member), Sener, Stephen (committee member)

Creator Email melanie.goldfarb@med.usc.edu,meli999@aol.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-c3-367576

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