Second Malignant Neoplasms in Survivors of Childhood Cancer

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Running Title: Second Malignant Cancers
Second Malignant Neoplasms in Survivors of Childhood Cancer
Ray M. Merrill and Arielle A. Sloan
Department of Health Science, College of Life Sciences, Brigham Young University,
Provo, Utah
Corresponding author:
Ray M. Merrill, Professor, Department of Health Science, College of Life Sciences,
Brigham Young University, Provo, UT 84602, USA. Telephone: 801-422-9788; Fax:
801-422-9713
RMM: ray_merrill@byu.edu
BCA: bcault@gmail.com
AAS: ellesloan@yahoo.com
Abstract word count: 212
Text word count: 4,113
Figures and tables: 1 (figure), 3 (tables)
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Abstract
Introduction: Individuals who survive a first primary cancer in childhood are at increased risk of a second
malignant neoplasm.
Study design: This cohort study updates a previous long-term report with 10 additional years of data to
verify and add to our existing knowledge about subsequent primary cancer risk.
Materials and Methods: Analyses are based on a cohort of 40,337 children (age < 20 years) who survived
cancer for at least two months from 1973 through 2010 in the Surveillance, Epidemiology, and End Results
(SEER) program. Each member of this cohort was followed for an average of 17.6 years.
Observed/expected ratios based on cancer rates in the general population were calculated based on primary
and second primary cancer types and with/without radiation treatment.
Results: Follow-up of the cohort identified 1,081 second malignant neoplasms, which represented a 4.2fold increase in incidence compared with the general population (O/E=4.2, 95% CI=4.0-4.5). O/E ratios for
subsequent cancer were consistently lower than in the first study, with the exception of Hodgkin’s
lymphoma. Our study also found a heightened risk of esophageal, cecum, corpus uteri, and kidney cancers
among Hodgkin’s lymphoma survivors, increased risk for salivary gland tumors among CNS patients, and
increased risk of the oral cavity and pharynx, respiratory system, and soft tissue second primaries among
bone cancer survivors. O/E risk of subsequent neoplasm was higher among radiation-treated individuals in
our sample than in the original study.
Conclusion: The increased risk and latency periods for second malignant cancer among childhood cancer
patients depends on the cancer type and treatment, but risk of subsequent cancer lowers over time.
Keywords: Childhood cancer, radiotherapy, secondary neoplasms, subsequent malignancies, treatment
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Background
Childhood cancer represents a major public health issue in the United States, and
it is responsible for more child deaths from age 1-14 than any other cause except for
motor vehicle accidents [1]. While lymphoid leukemia, lymphoma, and central nervous
system (CNS) tumors account for over half of all childhood cancers, over a dozen forms
of cancer manifest themselves commonly in childhood [2, 5]. Regardless of type, the
prevalence of childhood cancer is generally highest among males and whites [3, 4] and
among who are either younger than five or between 15 and19 years of age [5].
Advances in cancer recognition, tracking, and treatment have improved child
cancer survival rates in recent years [5, 6]. Since 1990, five-year survival for childhood
cancers has increased in the United States from 75.1% to 83.3% and ten-year survival
from 71.9% to 76.6% [5]. Now that children with cancer are surviving longer, it is
essential to understand their risk for subsequent malignant neoplasms later in life.
Previous research has assessed short- and long-term risks of subsequent primary
cancer among survivors of childhood cancer [2, 7-12]. A comprehensive body of
information assembled on childhood cancer and risk of subsequent primary malignancies
began in January 1970 and is called the Childhood Cancer Survivor Study [13]. The
British Childhood Cancer Survivor Study identified individuals diagnosed with childhood
cancer in Britain during 1940 through 1991 who had survived at least 5 years to conduct
a population-based study of late mortality and the risks of second primary cancers [11].
The Surveillance, Epidemiology and End Results (SEER) Program of the
National Cancer Institute has also studied new malignancies following childhood cancers
diagnosed from 1973 to 2000 [2]. Our study will update their report with ten additional
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years of data with the intent to verify and add to our existing knowledge about
subsequent primary cancer risk. Site-specific latency periods will also be presented and
results will be compared with the existing literature, which will have implications for
patient follow-up monitoring.
Methods
Childhood Cancer Definition
The Childhood Cancer Survivor Study classifies childhood and adolescent
cancers as those cases diagnosed before the age of 21 [13]. However, other organizations
classify childhood cancers as those involving individuals younger than 20, including the
SEER program of the National Cancer Institute, the Environmental Protection Agency,
and the American Childhood Cancer Organization [1, 10-11]. In the United States, the
definitive source of cancer incidence and survival data comes from the Surveillance
Epidemiology and End Results (SEER) Program of the National Cancer Institute [5, 6].
SEER data are currently available from 1973 to 2010 [1]. The SEER program and the
International Classification for Childhood Cancer (ICCC) have provided the following
list of childhood cancers: leukemia, lymphomas, CNS tumors, neuroblastoma,
retinoblastoma, renal tumors, hepatic tumors, malignant bone tumors, soft tissue
sarcomas, germ cell tumors, and other and unspecified malignant neoplasms [5, 14, 15].
SEER*Stat
SEER*Stat is a statistical software product that provides a mechanism for SEER
data analysis [16]. We used this software to compute multiple primary standardized
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incidence ratios, which represent the observed divided by the expected number of cancer
cases subsequent to a first primary cancer diagnosis. The observed is the actual count of
events resulting in the cohort. The expected number of events is what we expect to be
experienced, based on the data in general population and accumulated person-time at risk
for this cohort. Included with our ratios are 95% confidence intervals.
For our analysis, we also obtained excess risk, mean age at diagnosis, and mean
age when the subsequent cancer occurred. Excess absolute cancer risk is cancer incidence
beyond what we normally expect. We express this as the number of excess cases of
cancer per 10,000 at-risk individuals per year. Only malignant neoplasms are considered
in the current study, and cases based only on death certificates or autopsies have been
excluded.
The data-use agreement for accessing the SEER 1973-2010 research data files
was entered into April, 24, 2013. The SEER program subsequently provided the authors
with internet access to the cancer data files. We accordingly use the suggested SEER*Stat
citation [16].
The SEER Program was initiated in 1973, when it began gathering and publishing
population-based cancer incidence and survival data from seven tumor registries
(Connecticut, Detroit [Metropolitan], Hawaii, Iowa, New Mexico, San FranciscoOakland, and Utah). In 1975, two additional tumor registries joined the SEER Program
(Seattle [Puget Sound] and Atlanta [Metropolitan]). The nine tumor registries routinely
obtained cancer data in their catchment areas from the records of all cancer patients
identified by hospitals, clinics, nursing homes, private pathology laboratories,
radiotherapy units, death certificates, and other health service units that provide
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diagnostic or treatment services. The current analysis is based on SEER data collected
from 1973 through 2010.
Literature Review Selection Criteria
We performed an extensive literature review to compare our results with previous
research. Peer-reviewed articles published in English on second and subsequent
malignant neoplasms in childhood cancer survivors during 1993-2011 were identified
from electronic databases – PubMed, Wiley Online Library, ScienceDirect, American
Association for Cancer Research, and CA: A Cancer Journal for Clinicians. The search
terms used to identify all relevant published data in the above mentioned databases were:
childhood cancers, second primary cancers from childhood cancer, subsequent cancers
from childhood cancer, retinoblastoma, leukemia, neuroblastoma, hepatic tumor, central
nervous system (CNS) tumors, lymphoma, renal tumors, malignant bone tumor, soft
tissue sarcoma, germ cell tumors, thyroid tumor, skin carcinoma.
Results and Discussion
Table 1 provides a general overview of the demographic characteristics of the
sample population. This study extended the study period of the 1973-2000 original SEER
report by 10 years, and, consequently, included almost twice the number of individuals as
the first study (40,337 children, as opposed to 23,819) and followed them for twice as
long, on average (17.6 years versus 8.3). Consequently, the results of this study generally
reflected findings from the 1973-2000 SEER report, such as the fact that acute
lymphocytic leukemia remained the most common type of first cancer (accounting for
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19% of cases, similar to the originally reported 21%), while 17% were CNS cancers (as
opposed to 18% in the first study) [2]. Mean age at first cancer diagnosis also remained
similar to the first study, both overall and stratified by gender [2]. The shortest latency
period involved first primary melanoma, and the longest latency period involved first
primary Hodgkin lymphoma. However, a number of differences were noted between this
study and the original, which will be described in detail in this section.
Tables 2 and 3 show the risk of subsequent cancer based on first cancer diagnosis
and use of radiation treatment. Subsequent cancer risk among childhood cancer
survivors—especially among patients who underwent radiation treatment—was greater
than cancer risk in the general population, as reported in the original study [2]. Still, in
several cases, higher O/E ratios were not statistically significant, and in other cases, small
counts influenced reported associations.
In our study, there was a 4.2-fold higher subsequent cancer incidence among
childhood cancer survivors compared with the general population (O/E = 4.2, 95% CI =
4.0-4.5), which is significantly lower than the 6-fold O/E ratio observed in the previous
study [2]. Cancer-specific O/E ratios were generally lower for cancers in this analysis
regardless of whether or not radiation treatment was used, although these differences
were generally non-significant. Two exceptions included Hodgkin’s lymphoma, which
had a 6.9 subsequent cancer O/E ratio if treated with radiation and 5.0 without, as
opposed to 1.2 and 0.35, respectively; and non-Hodgkin’s lymphoma without radiation
treatment, which had a 4.3 O/E ratio as opposed to 2.85 [2]. The general decrease in the
O/E ratio would be expected not only because cancer treatments and early detection have
improved but because the impact of childhood cancer on subsequent cancer risk tends to
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lower with age [2]. More longitudinal analysis should be conducted to determine whether
the O/E ratio among Hodgkin’s lymphoma survivors and among non-Hodgkin’s
lymphoma survivors who did not undergo radiation treatment will continue to increase.
Concerning gender disparities, the male:female ratio of first cancer cases
remained 54:46, and females in our study were still overrepresented for melanoma and
Wilms’ tumor [2]. However, rather than outnumbering males for fibrosarcoma and
carcinoma, as was the case in the original study, females outnumbered males for renal
and thyroid cancers. Mean age at diagnosis was similar between males and females (10.1
versus 10.2 for females), as found previously, but mean age at a subsequent event was
lower for males than for females (25.6 vs. 28.8). Increased risk of subsequent cancer was
influenced by follow-up time (O/E = 5.6 [3.8-8.0] for 2-11 months, 7.3 [6.2-8.5] for 1259 months, 6.9 [6.0-7.9] for 60-119 months, and 3.4 [3.2-3.7] for 120+ months).
The original SEER study did not include O/E ratios for esophageal and cecal
cancer among Hodgkin’s disease survivors, salivary gland tumors among CNS survivors,
or oral cavity, pharynx, respiratory and soft tissue cancers among bone cancer patients. In
addition, no studies from our literature review identified specific links between these
primary and second primary cancers. In our study, however, there was a significant
association observed for each.
The fact that this study found these and other associations among cancers for the
first time may be due in part to the 10 years of follow-up that have been added since the
original SEER report. Both Hodgkin’s and bone cancer, for example, were diagnosed at
later ages in our study (15.8 years and 13.8, respectively), with latency periods of 19.1
and 13.5 years before the subsequent primary cancer [Table 1]. In the original study,
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patients were followed up on average for only 8.3 years [2]. Regardless, further research
on each of these subjects would prove valuable, especially because the second primary
cancers described above are all most commonly diagnosed after middle age [68].
Several studies have emphasized the importance of long-term follow-up when
investigating second malignant neoplasms [10, 18, 19, 34, 42, 49, 56, 57]. In our study,
typically 15.2 years separated the first and subsequent neoplasm. The previous SEERbased study of new malignancies following childhood cancer included 10 fewer years in
its analysis and failed to observe some of the findings observed in the current study,
especially among individuals who were diagnosed with cancers later in childhood. The
latency periods presented in this study should guide further research on the length of
follow-up needed, and continued follow-up on this population should determine how risk
of subsequent cancer changes over time.
Conclusion
The current study verifies several previous studies showing that children who
survive various types of cancer are at increased risk of developing certain second
malignant neoplasms. With follow-up, these excess cancer rates remain higher than the
general population but may either lower or increase during specific ages.
In addition to confirming several of the previously shown results, children with a
first primary Hodgkin lymphoma were at increased risk for cancers of the esophagus,
cecum, corpus uteri, and kidney; children with a first primary CNS were at increased risk
for salivary gland tumors; children with a first primary bone tumor were at increased risk
for cancers of the oral cavity and pharynx, respiratory system, and soft tissue; children
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with a first primary soft tissue tumor were at increased risk for kidney carcinoma and
lymphatic and hematopoietic diseases; children with a first primary germ
cell tumor were at increased risk for cancers of the CNS and lymphatic
and hematopoietic diseases; and children with a first thyroid tumor were
at increased risk for cancers of the salivary gland and kidney.
Further research regarding connections among these cancer types
as well as further follow-up in this population are warranted in order to
understand subsequent cancer risk over the life span among childhood
cancer survivors.
Competing Interests
The authors have no conflicts of interest.
Authors’ Contributions
RMM: Analyzed and described the data, assisted in the literature review, and wrote the
paper.
AAS: Assisted in the literature review and writing the paper.
Authors’ Information
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RMM: Professor of Cancer Epidemiology and Biostatistics at Brigham Young
University. Former Visiting fellow at the International Agency for Research on Cancer in
Lyon, France, and former fellow at the National Cancer Institute, Rockville, Maryland.
AAS: Student of Public Health at Brigham Young University.
Abbreviations
O = observed number of subsequent (2nd, 3rd, etc.) primary cancers; E = expected number
of cancers in the general population; O/E = ratio of observed to expected cancers; CI:
confidence interval; SEER: Surveillance, Epidemiology and End Results; CNS = central
nervous system, including brain; Excess absolute risk (excess cancers per 10,000 person
years, calculated as [(O-E)/person-years at risk] × 10,000).
Acknowledgements
We would like to thank Elizabeth Brutsch for her comments on the manuscript and
suggestion of additional references.
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Hawkins M, Zucker JM, de Vathaire F. Role of radiotherapy and chemotherapy in
the risk of secondary leukemia after a solid tumour in childhood. Eur J Cancer
2006;42:2757-2764.
56. Laverdière C, Liu Q, Yasui Y, Nathan PC, Gurney JG, Stovall M, Diller LR, Cheung
NK, Wolden S, Robison LL, Sklar CA. Long-term outcomes in survivors of
neuroblastoma. J Natl Cancer Inst 2009;101:1131-1140.
57. Rubino C, Adjadj E, Guérin S, Guibout C, Shamsaldin A, Dondon MG, ValteauCouanet D, Hartmann O, Hawkins M, de Vathaire F. Long-term risk of second
malignant neoplasms after neuroblastoma in childhood: role of treatment. Int J Cancer
2003;107:791-796.
58. Bluhm EC, Ronckers C, Hayashi RJ, Neglia JP, Mertens AC, Stovall M, Meadows
AT, Mitby PA, Whitton JA, Hammond S, Barker JD, Donaldson SS, Robison LL,
Inskip PD: Cause-specific mortality and second cancer incidence after non-Hodgkin
lymphoma: A report from the Childhood Cancer Survivor Study. Blood J
2008;111:4014-4021.
59. Leung W, Sandlund JT, Hudson MM, Zhou Y, Hancock ML, Zhu Y, Ribeiro RC,
Rubnitz JE, Kun LE, Razzouk B, Evans WE, Pui CH. Second malignancy after
treatment of childhood non-Hodgkin lymphoma. Cancer 2001;92(7):1959-1966.
60. The Childhood Brain Tumor Foundation. Brain stem gliomas in childhood
[http://www.childhoodbraintumor.org/index.php?view=article&catid=34%3Abraintumor-types-and-imaging&id=57%3Abrain-stem-gliomas-in-
21
childhood&format=pdf&option=com_content&Itemid=53]. 2010-2013 [updated
2010; retrieved 2012 October 1].
61. Ceha HM, Balm AJ, de Jong D, van 't Veer LJ. Multiple malignancies in a patient
with bilateral retinoblastoma. J Laryngol Otol. 1998;112(2):189-192.
62. Bhagia P, Colanta AB, Abramson DH, Carlson DL, Kleinerman RA, Kraus D,
Dunkel IJ. Sinonasal adenocarcinoma: A rare second malignancy in long term
retinoblastoma survivors. Pediatr Blood Cancer 2011;57(4):693-695.
63. Bataille V, Hiles R, Bishop JA. Retinoblastoma, melanoma and the atypical mole
syndrome. Br J Dermatol. 1995;132(1):134-138.
64. Wong FL, Boice JD Jr, Abramson DH, Tarone RE, Kleinerman RA, Stovall M,
Goldman MB, Seddon JM, Tarbell N, Fraumeni JF Jr, Li FP. Cancer incidence after
retinoblastoma. Radiation dose and sarcoma risk. JAMA 1997;278(15):1262-1267.
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2013 January 11; cited 2013 May 11].
66. MD Anderson Cancer Center. Childhood melanoma
[http://www.mdanderson.org/patient-and-cancer-information/cancerinformation/cancer-types/childhood-melanoma/index.html].
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childhood as potential risk factor for second thyroid cancer. Panminerva Med
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68. NCI [http://seer.cancer.gov/archive/csr/1975_2003/results_single/sect_01_table.11_2
pgs.pdf]. Median age of cancer patients at diagnosis. [n.d.].
22
23
Table 1: Descriptive characteristics of persons diagnosed with different histopathologic types of malignant childhood cancer (ages 019 years), both sexes, 1973-2010
Histopathology type*
Total
Number
(%)
Male
Female
Rate per
100,000
Male/Female
(Ratio)
Mean
Mean
Age at
First
Primary
Diagnosis
7.0
9.5
15.8
12.8
8.9
2.9
1.8
4.5
5.5
13.8
11.0
14.3
16.5
16.3
3.9
Age at
Latency
Subsequent Period
Primary
Diagnosis
22.1
15.1
25.1
15.6
34.9
19.1
25.9
13.1
22.9
14.0
19.9
17.0
13.0
11.2
21.3
16.8
23.4
17.9
27.3
13.5
24.3
13.3
29.7
15.4
34.6
18.1
26.7
10.4
22.1
18.2
Acute lymphocytic leukemia
7,578 4,328 (57) 3,250 (43) 3.1/2.5 (1.3)
Acute Myeloid leukemia
1,705
888 (52)
817 (48) 0.6/0.6 (1.0)
Hodgkin lymphoma
3,535 1,821 (52) 1,714 (48) 1.3/1.3 (1.0)
Non-Hodgkin lymphoma
2,752 1,863 (68)
889 (32) 1.3/0.7 (1.9)
Brain, CNS tumors
7,036 3,876 (55) 3,160 (45) 2.8/2.4 (1.2)
Neuroblastoma
2,154 1,136 (53) 1,018 (47) 0.8/0.8 (1.0)
Retinoblastoma
824
414 (50)
410 (50) 0.3/0.3 (1.0)
Renal tumors
1,754
838 (48)
916 (52) 0.6/0.7 (0.9)
Hepatic tumors
515
299 (58)
216 (42) 0.2/0.2 (1.0)
Bone tumors
2,277 1,330 (58)
947 (42) 1.0/0.7 (1.4)
Soft tissue sarcoma
3,008 1,621 (54) 1,387 (46) 1.2/1.0 (1.2)
Germ cell tumors
2,759 1,640 (59) 1,119 (41) 1.2/0.8 (1.5)
Thyroid carcinoma
1,546
307 (20) 1,239 (80) 0.2/0.9 (0.2)
Melanoma
1,329
533 (40)
796 (60) 0.4/0.6 (0.7)
Wilms’ tumor
1,565
741 (47)
824 (53) 0.5/0.6 (0.8)
Data source: Surveillance, Epidemiology, and End Results (SEER).
Note: Includes children surviving 2 months or more after diagnosis. CNS: Central Nervous System.
*
Categories and ordering based on International Classification of Childhood Cancer [15].
Mean
24
Table 2: Childhood malignant cancer (ages 0-19 years) according to subsequent cancer risk (all sites) according to radiation treatment,
1973-2010
Age at
Latency
Bone
Brain, Thyroid Leukemia
First
Period
CNS
Primary
Diagnosis
Histopathology type*
95%
95% Mean
Mean
O/E
O/E
O/E
O/E
O/E
CI
CI
No.
%
Lower Upper
Acute lymphocytic leukemia
No
71 68
4.0
3.1
5.1
6.6
14.2
6.8
8.1
7.4
4.8
Yes
33 32
3.1
2.1
4.3
8.2
16.8
13.0
12.5
7.9
Acute myeloid leukemia
No
12 50
3.2
1.6
5.6
9.5
26.8
7.4
Yes
12 50 10.2
3.8
22.3
10.0
12.7
26.5
27.6
Hodgkin lymphoma
No
78 26
5.0
3.9
6.2
15.7
16.7
10.8
7.7
9.2
18.1
Yes
217 74
6.9
6.1
7.9
15.8
20.0
12.9
8.0
7.5
Non-Hodgkin lymphoma
No
29 50
4.3
2.9
6.2
12.6
11.5
8.3
12.1
Yes
29 50
5.9
3.9
8.4
13.1
14.7
23.6
19.4
8.2
Brain, CNS tumors
No
58 33
3.7
2.8
4.7
8.4
12.0
18.1
6.5
Yes
116 67
6.5
5.4
7.8
9.3
14.8
20.4
47.7
8.5
11.9
Neuroblastoma
No
14 45
3.5
1.9
5.8
2.5
14.0
25
Yes
17 55
8.6
5.0
13.8
3.8
18.9
Retinoblastoma
No
13 39
5.1
2.7
8.8
1.8
7.9
51.3
Yes
20 61 29.6
18.1
45.7
1.4
13.7
311.6
Renal tumors
No
13 42
3.3
1.7
5.6
4.4
15.4
Yes
18 58
4.5
2.7
7.1
4.7
17.8
Hepatic tumors
No
3 100
3.7
0.8
10.8
5.4
18
Yes
0
0
Bone tumors
No
48 67
4.3
3.1
5.7
13.9
14.5
11.7
Yes
24 33
8.4
5.4
12.5
13.5
11.7
102.0
Soft tissue sarcoma
No
22 33
1.6
1.0
2.4
11.4
12.8
15.1
Yes
45 67
7.3
5.4
9.8
10.6
13.7
48.7
Germ cell tumors
No
60 80
2.5
1.9
3.2
14.2
13.8
Yes
15 20
2.8
1.6
4.6
14.6
22.2
Thyroid carcinoma
No
26 67
1.5
1.0
2.2
16.5
19.7
Yes
13 33
1.8
1.0
3.1
16.5
14.9
Melanoma
No
48 100
2.9
2.1
3.8
16.3
10.4
Yes
0
0
Wilms’ tumor
No
10 37
3.0
1.5
5.8
3.3
16.9
Yes
17 63
4.4
2.5
7.0
4.6
18.7
Data source: Surveillance, Epidemiology, and End Results (SEER).
Note: Includes children surviving 2 months or more after diagnosis. CNS: Central Nervous System.
21.8
29.4
7.1
5.0
6.0
5.2
19.5
35.5
15.3
5.9
18.6
7.1
26
*
Categories and ordering based on International Classification of Childhood Cancer [15].
Table 3: Childhood malignant cancer (ages 0-19 years) according to subsequent cancer risk based on multiple primary standardized
incidence ratios, 1973-2010
Histopathology type*
Subsequent Cancer Site
Observe
Observed
d
/Expected
95%
95%
CI
CI
Lower
Upper
Excess
Cancers
Per
10,000
Mean
Latency
Period
Supporting
References
Acute Lymphocytic Leukemia
Oral Cavity and Pharynx
9
16.0
7.3
30.4
1.0
15.7
2, 36
Salivary Gland
8
45.6
19.7
89.9
0.9
16.2
2, 32, 36
Bones and Joints
7
8.5
3.4
17.6
0.7
8.4
2, 31, 34
Soft Tissue including Heart
7
7.6
3
15.6
0.7
8.4
31, 37
24
9.3
6.0
13.9
2.5
14.2
2, 31, 33, 34,
Brain, CNS
35
Thyroid
21
7.6
4.7
11.6
2.1
20.0
2, 31, 33, 34
27
Leukemia
13
4.6
2.4
7.8
1.2
9.0
Non-Lymphocytic Leukemia
13
12.1
6.4
20.6
1.4
9.0
Acute Non-Lymphocytic Leukemia
11
13.8
6.9
24.7
1.2
9.9
Myeloid and Monocytic Leukemia
13
13.2
7.0
22.6
1.4
9.0
Acute Myeloid Leukemia
11
16.3
8.1
29.1
1.2
9.9
31, 32, 38
Brain, CNS
3
9.7
2.0
28.4
2.5
17.7
31
Thyroid
3
6.8
1.4
19.9
2.4
17.4
31
Salivary Gland
7
32.1
12.9
66
1.2
21.1
2
Esophagus
4
27.3
7.4
69.9
0.7
26.9
Colon excluding Rectum
9
6.3
2.9
12
1.4
29.6
(ANLL)
34
Acute Myeloid Leukemia
Hodgkin Lymphoma
2, 7, 27, 47,
49
Stomach
7
18.5
7.4
38.2
1.2
19.1
2, 7, 49
Cecum
3
13.2
2.7
38.6
0.5
30.2
Soft Tissue including Heart
19
23.7
14.3
37
3.3
15.7
2, 31, 51
Melanoma of the Skin
12
2.2
1.1
3.8
1.2
17.3
2, 7, 17, 43,
47, 50
Female Breast
96
11.4
9.2
13.9
15.9
20.9
2, 7, 8, 10,
17, 27, 31, 32,
28
38, 42-48
Pancreas
Lung and Bronchus
Bones and Joints
4
11.1
3
28.4
0.7
18.8
2
12
8.2
4.2
14.3
1.9
24.3
2, 49, 51
6
12.1
4.4
26.4
1.0
9.5
2, 7, 17, 27,
31, 49, 51
Corpus Uteri
4
3.9
1.1
10
0.5
19.4
Kidney
7
6.6
2.7
13.7
1.1
30.9
Brain, CNS
6
3.3
1.1
7.2
0.8
16.7
2, 7, 17, 27,
31, 49, 51
Thyroid
37
8.4
5.9
11.6
5.9
16.4
2, 7, 17, 27,
31, 32, 43
Non-Hodgkin Lymphoma
18
6.7
3.9
10.5
2.8
18.2
2, 7, 17, 27,
31, 32, 39
Leukemia
19
11.3
6.8
17.7
3.1
5.6
2, 7, 17, 27,
31, 48
Non-Lymphocytic Leukemia
18
17.2
10.2
27.3
3.1
5.6
Acute Non-Lymphocytic Leukemia
17
25.1
14.6
40.2
3.0
5.5
Myeloid and Monocytic Leukemia
16
16.5
9.5
26.9
2.7
5.4
Acute Myeloid Leukemia
15
25.4
14.2
41.8
2.6
5.1
2
(ANLL)
Non-Hodgkin Lymphoma (except Burkitt Lymphoma)
31
29
Female Breast
7
5.8
2.3
12
2.7
25.3
2, 7, 13, 17,
31, 35, 47, 51,
58, 59
Brain
3
4.9
1
14.3
1.1
2.1 17, 41, 51, 58,
59
Thyroid
13
12.8
6.8
21.8
5.6
16.4
2, 7, 13, 17,
31, 32, 47,51,
52
Lymphoma
11
6.8
3.4
12.2
4.4
8.3
7, 17, 31, 53,
Non-Hodgkin Lymphoma
6
7.3
2.7
15.8
2.4
9.4
31, 48, 58
Leukemia
7
10.7
4.3
22
3.0
1.7
2, 7, 59
Non-Lymphocytic Leukemia
7
20.0
8.0
41.2
3.1
1.7
Acute Non-Lymphocytic Leukemia (ANLL)
6
25.5
9.4
55.6
2.7
0.6
Myeloid and Monocytic Leukemia
7
21.6
8.7
44.5
3.1
1.7
Acute Myeloid Leukemia
4
19.6
5.3
50.1
1.8
1.5
Salivary Gland
4
21.3
5.8
54.6
0.5
17
Rectum and Rectosigmoid Junction
3
5.7
1.2
16.7
0.3
13.8
58, 59
2
59
Brain, CNS tumors
2, 47, 49, 53,
54
Liver
3
13.7
2.8
39.9
0.4
18.1
53
30
Pancreas
2
10.1
1.2
36.5
0.2
12
2
Bones and Joints
9
12.7
5.8
24.1
1.1
9.1
2, 7, 17, 31,
34, 51, 54
Soft Tissue including Heart
13
14.8
7.9
25.3
1.7
11.1
2, 31, 51, 53
Brain, CNS
72
32.3
25.3
40.7
9.5
15.4
2, 7, 13, 17,
31, 34, 40, 41,
48, 51, 52, 54
Thyroid
17
5.4
3.1
8.6
1.9
18.2
7, 13, 17, 31,
34, 48, 49, 51,
52, 53
Leukemia
21
9.1
5.6
13.8
2.6
4.8
7, 17, 31, 34,
51, 54
Lymphocytic Leukemia
7
5.5
2.2
11.3
0.8
6.5
Acute Lymphocytic Leukemia
6
5.1
1.9
11.1
0.7
2.9
Non-Lymphocytic Leukemia
14
13.4
5.6
13.8
2.6
2.9
Acute Non-Lymphocytic Leukemia (ANLL)
12
16.3
8.4
28.4
9.8
4.1
Myeloid and Monocytic Leukemia
14
14.6
8.0
24.4
1.8
3.9
Acute Myeloid Leukemia
12
18.9
9.8
33.1
1.6
4.1
53, 54
6
18.9
6.9
41.2
2.5
16.9
2
2, 33
Neuroblastoma and Other Peripheral
Nervous Cell Tumors
Digestive System
31
Kidney
7
35.5
14.3
73.1
3.0
16.3
2, 56
Thyroid
4
8.2
2.2
21.1
1.6
16.3
2, 7, 13, 31,
33, 48, 49, 51,
56, 57
Retinoblastoma
Nose, Nasal Cavity and Middle Ear
Bones and Joints
3
325.5
67.1
951.1
2.4
11
49, 61, 62
11
109.5
54.7
196
8.7
9
2, 15, 16, 49,
51, 54
Eye and Orbit - Non-Melanoma
4
107.2
29.2
274.5
3.2
9.6
2
Soft Tissue including Heart
3
22.4
4.6
65.6
2.3
16.2
2, 49, 51, 62
Leukemia
4
8.6
2.4
22.1
2.8
9
Acute Lymphocytic Leukemia
4
12.8
3.5
32.8
2.9
9
Kidney
5
25.0
8.1
58.4
1.9
12.3
Soft Tissue including Heart
5
18.2
5.9
42.5
1.9
12.7
31
Thyroid
4
4.9
1.3
12.5
1.3
20.4
31, 54
Leukemia
4
4.8
1.3
12.3
1.1
7.4
52
Non-Lymphocytic Leukemia
3
9.8
2
28.7
1.1
6.2
Acute Non-Lymphocytic Leukemia (ANLL)
3
13.2
2.7
38.5
1.1
6.2
Myeloid and Monocytic Leukemia
3
10.8
2.2
31.7
1.1
6.2
Acute Myeloid Leukemia
3
15.6
3.2
45.7
1.1
6.2
2
Renal Tumors
32
Bone Tumors
Oral Cavity and Pharynx
3
8.9
1.8
26.0
1.2
31.8
Colon excluding Rectum
3
7.1
1.5
20.8
1.2
19.5
Respiratory System
3
5.7
1.2
16.8
1.1
17.2
Bones and Joints
7
31.8
12.8
65.6
3.1
4.1
7, 13, 52
7, 34, 48, 52,
54, 60
Soft Tissue including Heart
8
27.2
11.7
53.6
3.5
10.7
Kidney
3
9.5
2
27.7
1.2
18.7
Thyroid
5
3.9
1.3
9.1
1.7
14.1 13, 17, 34, 51,
52, 54
Female Breast
14
6.6
3.6
11.1
5.4
19
7, 10, 13, 17,
31, 34, 47, 52,
60
Leukemia
15
23
12.9
37.9
6.5
4.5
7, 34, 48, 52,
54, 55
Non-Lymphocytic Leukemia
14
37.5
20.5
62.9
6.2
3.9
Acute Non-Lymphocytic Leukemia (ANLL)
14
55.9
30.6
93.8
6.3
3.9
Myeloid and Monocytic Leukemia
14
40.4
22.1
67.8
6.2
3.9
Acute Myeloid Leukemia
11
50.2
25.1
89.9
4.9
4.9
3
178.9
36.9
522.9
1.4
0.3
Acute Monocytic Leukemia
Soft Tissue Sarcomas
33
Oral Cavity and Pharynx
5
10.7
3.5
25.1
1.3
17.7
2
Tongue
3
25.8
5.3
75.4
0.8
12.6
9, 49
Lung and Bronchus
3
5.4
1.1
15.8
0.7
22
9, 49
Bones and Joints
9
28
12.8
53.2
2.5
9.4
2, 7, 17, 31,
34, 49, 51, 52,
54
Soft Tissue including Heart
9
20.2
9.2
38.4
2.5
11.6
Kidney
3
6.3
1.3
18.4
0.7
12.9
Brain, CNS
6
5.7
2.1
12.5
1.4
17.6
Lymphatic and Hematopoietic Diseases
9
2.5
1.2
4.8
1.6
5.7
Leukemia
8
7.4
3.2
14.6
2.0
6.3
9, 31, 34, 51
7, 13, 17, 34,
31, 41, 54
7, 9, 17, 31,
34, 48, 49, 54
Non-Lymphocytic Leukemia
8
14.6
6.3
28.9
2.2
6.3
Acute Non-Lymphocytic Leukemia (ANLL)
7
18.8
7.6
38.8
1.9
6.6
Myeloid and Monocytic Leukemia
8
15.9
6.9
31.3
2.2
6.6
Acute Myeloid Leukemia
7
21.8
8.7
44.8
1.9
6.6
9
28
13.1
8.7
19
6.9
12
2, 52
6
4.8
1.8
10.5
1.3
5.5
11
2.4
1.2
4.3
1.7
18.9
Germ Cell Tumors
Testis
Brain, CNS
Lymphatic and Hematopoietic Diseases
34
Leukemia
7
5.7
2.3
11.7
1.5
12.5
54
Non-Lymphocytic Leukemia
6
8.6
3.1
18.6
1.4
12.6
Acute Non-Lymphocytic Leukemia (ANLL)
5
10.9
3.5
25.4
1.2
11.5
Myeloid and Monocytic Leukemia
6
9.2
3.4
20.1
1.4
12.6
Acute Myeloid Leukemia
4
10
2.7
25.5
1.0
13.2
Salivary Gland
4
35.6
9.7
91.1
1.6
8.0
Kidney
3
6.6
1.4
19.2
1.1
25.7
38
18.3
13.0
25.1
19.7
9.6
5
19.7
6.4
45.9
2.0
13.3
34, 51
1.4
21.0
7, 13, 34, 51
Thyroid Carcinomas
Malignant Melanomas
Melanoma of the Skin
Wilms’ Tumor
Soft Tissue including Heart
Thyroid
4
5.4
1.5
13.8
Data source: Surveillance, Epidemiology, and End Results (SEER).
Note: Includes children surviving 2 months or more after diagnosis. CNS: Central Nervous System.
*
Categories and ordering based on International Classification of Childhood Cancer [15].