The time for the triggering event in neoplasms can be estimated using incubation period modeling techniques. We applied these techniques to primary osteosarcoma and Ewing’s sarcoma of bone using the Surveillance Epidemiology and End Results database for all cases of osteosarcoma or Ewing’s sarcoma of bone from 1993 through 2010. Secondary neoplasms were excluded. The age at diagnosis, gender, ethnicity, and anatomic location were collected. The time (
Osteosarcoma and Ewing’s sarcoma are the most common primary osseous malignancies, especially in children and young adults [
The time of the triggering event which starts the development of these neoplasms is unknown. An estimation of such time can be determined using incubation period modeling techniques. This modeling has been applied to malignancies [
The Surveillance Epidemiology and End Results (SEER) Program of the National Cancer Institute database was queried for all patients with osteosarcoma or Ewing’s sarcoma diagnosed from 1993 through 2010 [
Discrete data are reported as frequencies and percentages and continuous data as the mean
Incubation period modeling was used to determine the time of the insult/triggering event [
Subgroups were created since it is well known that there are differences in the epidemiology/demographics between conventional osteosarcoma (osteosarcoma not otherwise specified; chondroblastic, fibroblastic, telangiectatic osteosarcoma) separated by long and short bones; central and small cell medullary osteosarcoma; parosteal osteosarcoma; and osteosarcoma involving the mandible, skull, pelvis, and rib/sternum/clavicle [
There were 4,356 patients with osteosarcoma; 3,998 (91.8%) were conventional and 225 parosteal (5.2%). The remaining types accounted for 3%. There was a slight male predominance (55.6% male, 44.4% female). Statistically significant differences between the conventional and parosteal types by age, gender, race, and anatomic location were noted (Table
Demographics for conventional and parosteal osteosarcoma.
Variable | Total | Conventional | % | Parosteal | % |
|
---|---|---|---|---|---|---|
Average age (yrs) | 28.0 ± 20.3 | 28.1 ± 20.8 | — | 28.4 ± 13.0 | — | <0.0001 |
Median age (yrs) | 19 | 19 | 26 | |||
Geographic location in the USA | ||||||
Midwest | 727 | 679 | 17.0 | 48 | 21.3 | 0.39 |
Northeast | 553 | 526 | 13.2 | 27 | 12.0 | |
South | 589 | 561 | 14.1 | 28 | 12.4 | |
West | 2344 | 2222 | 55.7 | 122 | 54.2 | |
Sex | ||||||
Male | 2338 | 2235 | 56.0 | 103 | 45.8 | 0.003 |
Female | 1875 | 1753 | 44.0 | 122 | 54.2 | |
Race | ||||||
White | 3217 | 3051 | 77.3 | 166 | 75.1 | 0.28 |
Black | 607 | 568 | 14.4 | 39 | 17.6 | |
Indo-Malay | 247 | 238 | 6.0 | 9 | 4.1 | |
Amerindian | 37 | 34 | 0.9 | 3 | 1.4 | |
Indo-Mediterranean | 25 | 22 | 0.6 | 3 | 1.4 | |
Polynesian | 37 | 36 | 0.9 | 1 | 0.5 | |
Primary site | ||||||
Long bone | 3142 | 2942 | 75.2 | 200 | 88.9 | <0.0001 |
Short bone | 98 | 90 | 2.3 | 8 | 3.6 | |
Mandible | 179 | 175 | 4.5 | 4 | 1.8 | |
Pelvis | 316 | 316 | 8.1 | 0 | 0.0 | |
RSTCl | 89 | 83 | 2.1 | 6 | 2.7 | |
Skull | 215 | 209 | 5.3 | 6 | 2.7 | |
Vertebral | 98 | 98 | 2.5 | 1 | 0.4 |
RSTCl: rib, sternum, clavicle.
Demographics of conventional osteosarcoma by anatomic location.
Total | Long bone | Mandible | Pelvis | RSTCl | Short bone | Skull | Vertebral |
|
|
---|---|---|---|---|---|---|---|---|---|
|
3988 | 2942 | 175 | 316 | 83 | 90 | 209 | 98 | |
Age (yrs) | 23.1 ± 17.4 | 40.6 ± 20.0 | 43.1 ± 23.3 | 37.5 ± 22.7 | 33.2 ± 22.5 | 39.2 ± 20.5 | 44.0 ± 23.2 | <0.0001 | |
Median age (yrs) | 19 | 17 | 38 | 41 | 33 | 29 | 39 | 42 | |
Gender | |||||||||
Male | 2190 | 1679 | 71 | 175 | 50 | 53 | 109 | 53 | 0.0021 |
Female | 1263 | 104 | 141 | 33 | 37 | 100 | 45 | ||
Geographic Location in the USA | |||||||||
Midwest | 663 | 506 | 23 | 57 | 13 | 18 | 35 | 11 | 0.078 |
Northeast | 512 | 364 | 24 | 51 | 10 | 19 | 25 | 19 | |
South | 552 | 403 | 36 | 47 | 8 | 11 | 33 | 14 | |
West | 2186 | 1669 | 92 | 161 | 52 | 42 | 116 | 54 | |
Race | |||||||||
White | 2989 | 2217 | 116 | 272 | 75 | 69 | 163 | 77 | 0.0001 |
Black | 562 | 436 | 39 | 29 | 2 | 12 | 33 | 11 | (<0.0001)∧ |
Indo-Malay | 235 | 192 | 10 | 10 | 4 | 4 | 7 | 8 | |
Amerindian | 33 | 30 | 1 | 0 | 1 | 1 | 0 | 0 | |
Indo-Mediterranean | 22 | 15 | 3 | 1 | 0 | 3 | 0 | 0 | |
Polynesian | 35 | 27 | 1 | 4 | 0 | 0 | 2 | 1 |
RSTCl: rib, sternum, clavicle.
∧The 3 most common races, White, Black, and Indo-Malay.
Incubation period modeling was performed separately for each subgroup of osteosarcoma. The Pearson IV and log normal distributions were excellent fits for long bone osteosarcoma (Table
Incubation period modeling results for osteosarcoma and Ewing’s sarcoma of bone.
Type of malignancy |
|
Average age (yrs) | Pearson IV distribution | Log normal distribution | ||||
---|---|---|---|---|---|---|---|---|
|
|
|
|
|
|
|||
Conventional osteosarcoma | ||||||||
Long bone | 3142 | 23.1 ± 17.4 | 0.977 | 2.2 | 0.45 | 0.971 | 2.95 | 0.3 |
Short bone | 98 | 33.2 ± 22.5 | 0.41 | 0.32 | ||||
Mandible | 179 | 40.6 ± 20.0 | — | 0.39 | ||||
Pelvis | 316 | 43.1 ± 23.3 | — | 0.39 | ||||
RSTCl | 89 | 37.5 ± 22.7 | — | 0.32 | ||||
Skull | 215 | 39.2 ± 20.5 | 0.38 | 0.36 | ||||
Vertebral | 98 | 44.0 ± 23.2 | — | — | ||||
Parosteal long bone osteosarcoma | 200 | 27.7 ± 12.5 | 0.77 | 8.6 | 7.65 | 0.77 | 8.6 | 7.65 |
Ewing’s sarcoma of bone | 1832 | 18.4 ± 11.4 | 0.985 | 0.4 | −0.7 | 0.946 | ND | ND |
RSTCl: rib, sternum, clavicle.
ND: function not definable, since
Asymmetric single peak distribution function fits for long bone conventional osteosarcoma with the Pearson IV (a) and log normal distribution (b). The log normal distribution is a slightly better fit at the young ages but does not capture the peak age of 15 years as well as the Pearson IV distribution.
Single asymmetric peak distribution function fits for parosteal long bone sarcoma with the Pearson IV (a) and log normal (b) distributions. Although the
There were 1,832 patients with primary osseous Ewing’s sarcoma; the average age at diagnosis was
Single asymmetric peak distribution function fits of Ewing’s sarcoma of bone with the Pearson IV distribution (a) and the log normal distribution (b). Note that the log normal distribution poorly fits the younger ages, making it difficult to determine
This is the largest series to date of the demographics for these two primarily pediatric osseous malignancies. Our results are similar to others (Table
Demographics of osteosarcoma and Ewing’s sarcoma from the literature.
Study | Year | Time span | Location |
|
M | F | % M | W | B | Hispanic | Asian | % W | % B |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Osteosarcoma | |||||||||||||
Present study | — | 1993–2010 | USA | 4594 | 2535 | 2059 | 55.2 | 3508 | 663 | 41 | 273 | 77.1 | 14.4 |
Bovill Jr. et al. [ |
1975 | 1969–1972 | Malaysia | 68 | 40 | 28 | 58.8 | ||||||
Young Jr. and Miller [ |
1975 | 1969–1972 | USA | 61 | 32 | 29 | 52.5 | 51 | 10 | 83.6 | 16.4 | ||
Buckley et al. [ |
1998 | 1982-1983 | USA/Canada | 152 | 75 | 77 | 49.3 | 127 | 15 | 10 | 0 | 83.6 | 9.9 |
Jensen and Drake [ |
1970 | 1940–1968 | USA (AFIP) | 677 | 595 | 82 | 87.9 | 12.1 | |||||
Fraumeni Jr. and Glass [ |
1970 | 1960–1966 | USA | 819 | 452 | 367 | 55.2 | 692 | 84.5 | — | |||
Bassin et al. [ |
2006 | 1989–1992 | USA | 103 | 60 | 43 | 58.3 | 81 | 16 | 3 | 78.6 | 15.5 | |
Finkelstein [ |
1994 | 1950–1983 | Ontario, Canada | 20 | 15 | 5 | 75.0 | ||||||
Operskalski et al. [ |
1987 | 1972–1982 | Los Angeles, CA | 64 | 34 | 30 | 53.1 | 43 | 13 | 8 | 67.2 | 20.3 | |
Eyre et al. [ |
2009 | 1981–2002 | Northern England and West Midlands | 206 | 95 | 111 | 46.1 | — | — | — | — | — | — |
Stiller et al. [ |
1991 | 1981–1990 | UK | 150 | 130 | 7 | 86.7 | 0.0 | |||||
Stiller et al. [ |
2006 | 1978–1997 | Europe | 1609 | 889 | 720 | 55.3 | 0.0 | |||||
Cotterill et al. [ |
2000 | 1968–1995 | Northern England | 131 | 77 | 54 | 58.8 | — | — | — | — | — | — |
Ewing’s Sarcoma | |||||||||||||
Present study | — | 1993–2010 | USA | 2321 | 1420 | 90 | 61.2 | 2098 | 70 | 22 | 75 | 90.4 | 3.0 |
Young Jr. and Miller[ |
1975 | 1969–1972 | USA | 26 | 15 | 11 | 57.7 | — | |||||
Buckley et al. [ |
1998 | 1982-1983 | USA/Canada | 153 | 89 | 64 | 58.2 | 139 | 1 | 10 | 3 | 90.8 | 0.7 |
Jensen and Drake [ |
1970 | 1940–1968 | USA (AFIP) | 239 | 237 | 2 | 99.2 | 0.8 | |||||
Fraumeni Jr. and Glass [ |
1970 | 1960–1966 | USA | 482 | 265 | 217 | 55.0 | 456 | — | — | — | 94.6 | — |
Linden and Dunn [ |
1970 | — | California, USA | 149 | 147 | 2 | 98.7 | 1.3 | |||||
Finkelstein [ |
1994 | 1950–1983 | Ontario, CA | 15 | 9 | 6 | 60.0 | ||||||
Moore et al. [ |
2005 | 1983–1985 | USA | 196 | 120 | 76 | 61.2 | 184 | 93.9 | 0.0 | |||
Holly et al. [ |
1992 | 1978–1986 | San Francisco, CA | 43 | 28 | 15 | 65.1 | 0.0 | — | ||||
Eyre et al. [ |
2009 | 1981–2002 | Northern England and West Midlands | 144 | 74 | 70 | 51.4 | 0.0 | — | ||||
Stiller et al. [ |
1991 | 1981–1990 | UK | 172 | 0.0 | 156 | 8 | 90.7 | — | ||||
Stiller [ |
2006 | 1978–1997 | Europe | 1182 | 647 | 535 | 54.7 | — | — | — | — | — | |
Cotterill et al. [ |
2000 | 1968–1995 | Northern England | 81 | 53 | 28 | 65.4 | — | — | — | — | — |
Ewing’s sarcoma is nearly always associated with a t(11;22)(q24;q12) translocation [
Osteosarcoma has been associated with various genetic abnormalities [
A weakness of this study is that the histologic specimens used to make the diagnosis were not reviewed by the same pathologist, which could introduce bias. There are no studies addressing this question for osteosarcoma, although there have been studies addressing other malignancies [
Incubation period modeling markedly confirms the genetic etiology of Ewing’s sarcoma. Long bone osteosarcoma is not completely genetic in etiology, as
Incubation period modeling originated with infectious diseases [
The mechanics of such modeling is to first find a frequency distribution possessing an excellent fit of the data for the entire population afflicted with the disease in question. When
The distribution first used historically for incubation period modeling and infectious diseases was the log normal distribution [
The mathematical equations for these distributions are as follows.
(1) The lognormal distribution is mathematically expressed as
Note that, for any
(2) The Pearson IV distribution is mathematically expressed as
The authors declare that they have no conflict of interests.
This study was supported in part by the Garceau Professorship Endowment, Department of Orthopaedic Surgery, Indiana University School of Medicine, and the George Rapp Pediatric Orthopaedic Research Endowment, Riley Children’s Foundation, Riley Children’s Hospital, Indianapolis, Indiana.