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Keywords:

  • pediatric rhabdomyosarcoma;
  • incidence;
  • survival;
  • trends

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References

BACKGROUND:

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents aged <20 years; its etiology remains largely unknown. It is believed that embryonal (ERMS) and alveolar rhabdomyosarcoma (ARMS), the most common subtypes, arise through distinct biologic mechanisms. The authors of this report evaluated incidence and survival trends by RMS demographic subgroups to inform future etiologic hypotheses.

METHODS:

Incidence and survival trends in RMS among children and adolescents aged <20 years were analyzed using data from the Surveillance, Epidemiology, and End Results Program. Frequencies, age-adjusted incidence and survival rates, and joinpoint regression results, including annual percentage change (APC) and 95% confidence interval (CI), were calculated.

RESULTS:

Between 1975 and 2005, the incidence of ERMS was stable, whereas a significant increase in the incidence of ARMS was observed (APC, 4.20%; 95%CI, 2.60%-5.82%). This trend may have been attributable in part to shifts in diagnosis, because a significant negative trend in RMS, not otherwise specified was observed concurrently. A bimodal age peak for ERMS was observed, with the second, smaller peak in adolescence noted for males only; ARMS incidence did not vary by age or sex. Five-year survival rates for RMS and ERMS increased during the period from 1976 to 1980 (52.7% and 60.9%, respectively) to the period from 1996 to 2000 (61.8% and 73.4%, respectively), whereas there was little improvement for ARMS (40.1% and 47.8%, respectively).

CONCLUSIONS:

Observed differences in incidence and survival for 2 major RMS subtypes across sex and age subgroups further supported the hypothesis that there are unique underlying etiologies for these tumors. Exploration of these differences presents an opportunity to increase current knowledge of RMS. Cancer 2009. © 2009 American Cancer Society.

Soft tissue sarcomas (STS) comprise approximately 7% of all malignancies in children and adolescents aged <20 years, and rhabdomyosarcoma (RMS) accounts for approximately 40% of pediatric STS.1 The incidence of RMS is 4.5 cases per million children/adolescents per year, and, in >50% of cases, RMS occurs during the first decade of life.2 RMS originates from tissue that imitates normal striated muscle.3 Because of its origin in embryonal mesenchyme, RMS can arise virtually anywhere in the body, often in sites where striated muscle is not ordinarily found. Very little is known about the etiology of RMS, primarily because of its rarity and diagnostic diversity.

Several environmental exposures have been associated with increased RMS risk, including paternal cigarette smoking,4 advanced maternal age and x-ray exposure in utero,5 antibiotic use by mother4 and/or child,6 stillbirths,7 and maternal recreational drug use.8 The largest case-control study of childhood RMS to date was conducted in the United States in the middle 1980s and included 249 RMS cases.9 The majority of associations between environmental exposures and risk for RMS found in the literature result from that study.4, 5, 8 Other associations between environmental exposures and risk of RMS were reported in very small epidemiologic studies (<100 cases).

In addition to environmental exposures, genetic changes may play an important role in RMS development. Although the majority of RMS cases appear to be sporadic, familial syndromes associated with inherited gene defects, such as neurofibromatosis and Li-Fraumeni syndrome, have been associated with RMS.10 Within Li-Fraumeni families that carry germ-line mutations in the tumor protein p53 gene TP53, RMS is the most frequently observed childhood cancer.11 Similarly, NF1 gene mutations of the neurofibromatosis 1 gene (NF1) associated with neurofibromatosis lead to 20-fold increased risk of RMS compared with the general population.12 In addition, several patients with Beckwith-Wiedeman syndrome13 and as many as 10% of patients with Costello syndrome subsequently developed RMS.14 Cancer is observed more often in the families of children affected by STS than in families with healthy children; mothers of children with STS develop breast cancer more frequently,11, 15 whereas their siblings have an increased incidence of brain tumors and adrenocortical carcinoma.16 An analysis of 338 childhood RMS cases indicated that 21% of them had a family history of cancer.17 Moreover, congenital malformations are observed more frequently (32%) in children and adolescents with RMS18 compared with the general population, in which the frequency of such malformations is approximately 3%.19 Taken together, the greater incidence of cancer in the families of RMS children, the higher frequency of malformations in these children, and the clear link between the genetic syndromes described above and RMS collectively suggest that genetic predisposition also may play an important role in RMS development.

RMS is classified based on the histologic and biologic features of the tumor. The 2 largest subgroups are embryonal (ERMS) and alveolar (ARMS). ERMS has an earlier age of onset (the majority of cases occur before age 10 years) and is associated with a better prognosis. In contrast, ARMS is distributed more evenly throughout childhood and adolescence (half of the cases occur after age 10 years) and has different primary sites than ERMS.1 Translocations t(2;13) and t(1;13) often are observed in ARMS, whereas allelic loss on chromosome 11 is frequent in ERMS. Because of these clinical and pathologic differences between ERMS and ARMS, it has been hypothesized that these 2 subtypes occur as a result of different biologic mechanisms of tumorigenesis.20

We recently analyzed trends in childhood cancer incidence and produced no evidence of an overall increase in RMS incidence during the last decade (1992-2004) in data obtained from 13 registries of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program.21 However, a more detailed and larger analysis is required to include a sufficient number of RMS cases to allow analyses by subtype. Therefore, we examined SEER Program data, including 9 registries with a longer follow-up (1975-2005), to examine incidence and survival trends by RMS subtype. Differences in incidence and survival trends of these subtypes may provide further clues into the etiology of these tumors.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References

SEER Program data22 were analyzed to evaluate incidence and survival rates of pediatric and adolescent RMS in the United States between 1975 and 2005. The SEER Program actively collected information on demographics, tumor site and morphology, stage at diagnosis, treatment, and vital status during this period from 9 registries encompassing 5 states (Connecticut, Hawaii, Iowa, New Mexico, and Utah) and 4 metropolitan areas (Detroit, San Francisco-Oakland, Seattle-Puget Sound, and Atlanta). These SEER 9 registries represent approximately 9% of the total US population2 and have an estimated case ascertainment rate of 98%.23 The SEER Program added 4 registries by 1992 (Los Angeles, San Jose-Monterey, rural Georgia, and the Alaskan Native Tumor Registry)22; the expanded SEER 13 dataset allowed for the analysis of incidence and survival rates among Hispanic children.

All primary cases of RMS among the pediatric and adolescent population (ages 0-19 years) were included. International Classification of Disease for Oncology, 3rd edition (ICD-O-3)24 morphology codes that were included in the International Classification of Childhood Cancer, 3rd edition (ICCC-3)25 category IXa-RMS were analyzed overall and separately and included 8900/3 (RMS, not otherwise specified [NOS]), 8901/3 (pleomorphic), 8902/3 (mixed type), 8910/3 (ERMS), 8912/3 (spindle cell RMS), 8920/3 (ARMS), and 8991/3 (embryonal sarcoma). All morphologies were included in data presented as RMS overall. ERMS and ARMS also were presented separately, whereas small sample sizes precluded this for other RMS morphologies. Nearly all RMS diagnoses were confirmed by histology (99.4%).

Statistical Analysis

SEER*STAT software26 was used to evaluate frequencies and incidence rates in RMS during the period from 1975 to 2005; whereas, for Hispanics, the evaluation period was from 1992 to 2005. Incidence rates were calculated per 1,000,000 person-years of follow-up and were age-adjusted to the 2000 US Standard Population. Annual population estimates used to calculate incidence rates were obtained from the US Census Bureau by the SEER Program. Incidence trends were evaluated by using weighted least-squares regression in Joinpoint software,27 in which the independent variable was calendar year and the dependent variable was the natural logarithm of the age-adjusted incidence rate, resulting in average annual percentage changes (APCs) in incidence rates and corresponding 95% confidence intervals (CIs); joinpoints were not permitted. Trend calculations that included 1 or more years with <10 cases are noted and should be interpreted with caution.

Five-year relative survival rates and corresponding standard errors among 5 5-year diagnostic cohorts (1976-1980, 1981-1985, 1986-1990, 1991-1995, and 1996-2000) were computed using the life tables method in SEER*STAT.26, 28 The cohorts included all individuals who were diagnosed with a first malignancy during the given period who were followed actively though 2005. Relative survival rates are ratios of observed-to-expected survival and are reported as percentages. The use of expected rates, derived from mortality data of the National Center for Health Statistics, takes into account the population distribution of age, sex, race, and calendar year. Relative rates were adjusted if they exceeded 100%, increased over time, or involved heterogeneity in withdrawal (exact method) within a survival function. The 95% CIs were calculated from standard errors to display the amount of variability in the rates, and Z tests were used to compare the relative survival functions across 3 cohorts (1976-1980, 1986-1990, and 1996-2000).29 Relative 5-year survival rates and corresponding 95% CIs also were evaluated for Hispanic children who were diagnosed during 1996 through 2000; the survival functions were compared with those among non-Hispanic white and black children (data not shown) using Z tests.29

Incidence and survival rates were examined overall and with respect to the following demographic groups: sex (males and females), age group (ages 0-4 years, 5-9 years, 10-14 years, and 15-19 years), and race (white, black, and American Indian/Alaskan Native and Asian/Pacific Islander combined). Cases with an unspecified or unknown race were excluded from subgroup analyses because of small sample sizes.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References

Incidence

In total, 987 children ages 0 to 19 years were newly diagnosed with RMS between 1975 and 2005 in the SEER 9 registries. These included 564 patients (57%) with ERMS, 227 patients (23%) with ARMS, 22 patients (2%) with embryonal sarcoma, 15 patients (1.5%) with pleomorphic RMS, 14 patients (1.4%) with mixed type RMS, 6 patients (0.6%) with spindle cell RMS, and 139 patients (14%) with RMS, NOS. The corresponding incidence rates for RMS overall, ERMS, and ARMS are shown in Table 1.

Table 1. Frequencies and Incidence Rates of Rhabdomyosarcoma in the Surveillance, Epidemiology, and End Results Registries
 RMS OverallEmbryonal RMSAlveolar RMS
VariableNo. (%)Incidence Rate*No. (%)Incidence Rate*No. (%)Incidence Rate*
  • RMS indicates rhabdomyosarcoma; SEER, Surveillance, Epidemiology, and End Results; APC, annual percentage change; CI, confidence interval.

  • *

    Incidence rate per 1,000,000 person-years, age-adjusted to the 2000 U.S. Standard population.

  • The APC: Annual percentage change calculated via weighted least squares regression.

  • The rate among females differed significantly from the rate among males (P < .0001).

  • §

    This trend calculation involved 1 or more years with <10 cases and should be interpreted with caution.

  • The statistic could not be calculated.

Reference period, 1975-2005: SEER 9 registries
 Total987 (100)4.5564 (100)2.6227 (100)1
 APC [95% CI]0.52 [−0.25-1.31] −0.41 [−1.52-0.71] 4.20 [2.60-5.82] 
 Sex      
  Male581 (58.9)5.2345 (61.2)3.1118 (52)1.1
  Female406 (41.1)3.8219 (38.8)2§109 (48)1
 Age, y      
  0-4352 (35.7)6.5236 (41.8)4.359 (26)1.1
  5-9259 (26.2)4.8155 (27.5)2.955 (24.2)1
  10-14171 (17.3)3.181 (14.4)1.551 (22.5)0.9
  15-19205 (20.8)3.792 (16.3)1.662 (27.3)1.1
 Race      
  White775 (78.5)4.6453 (80.3)2.7171 (75.3)1
  Black146 (14.8)4.982 (14.5)2.739 (17.2)1.3
  American Indian/Alaskan Native, Asian/Pacific Islander64 (6.5)2.929 (5.1)1.316 (7)0.7
Reference period, 1992-2005: SEER 13 registries
 Ethnicity      
 Hispanic148 (100)3.681 (54.7)1.939 (26.4)1
 APC [95% CI]1.54 [−1.73-4.92]§   

Males had a higher incidence of RMS than females (5.2 of 1,000,000 vs 3.8 of 1,000,000, respectively), with a rate ratio of 1.37 (95% CI, 1.21-1.56). This male predominance in RMS was comprised almost solely of ERMS, with a male/female rate ratio of 1.51 (95% CI, 1.27-1.80). ERMS was most common in the youngest children ages 0 to 4 years (42%), whereas ARMS was distributed nearly equally among all 4 age groups examined (Table 1). It is noteworthy that a bimodal age distribution was observed for RMS and ERMS, including a larger peak between ages 0 to 5 years and a smaller peak in adolescence (Fig. 1). Upon further examination, this second peak was observed only in males (data not shown).

thumbnail image

Figure 1. Rhabdomyosarcoma (RMS) incidence rates are illustrated by age for the period 1975 to 2005.

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When the incidence rates were analyzed by race/ethnicity, black children had slightly higher rates of ARMS than white children (1.3 of 1,000,000 vs 1.0 of 1,000,000, respectively). The American Indian/Alaskan Native/Asian/Pacific Islander group had somewhat lower RMS incidence rates (2.9 of 1,000,000) than white or black children; however, this combined group represented only 6.5% of all children. The data available for Hispanic children covered a shorter reference period; rates for these children were lower than the rates for non-Hispanic white and black children.

Incidence Trends

Although the APC in incidence of overall RMS and ERMS did not change significantly, we observed a statistically significant increase in ARMS incidence (APC, 4.20; 95% CI, 2.60%-5.82%) (Table 1). Furthermore, a significant negative trend was observed for RMS, NOS (APC, −3.05; 95% CI, −4.73% to −1.34%; data not shown). However, caution in the interpretation of this finding is warranted, because both ARMS and RMS, NOS included <10 cases in several years.

Survival Rates

ARMS relative 5-year survival rates have not increased significantly over the past 25 years; rates increased from 40.1% (95% CI, 22.5%-57.7%) during 1976 to 1980 to 47.8% (95% CI, 33.9%-61.7%) during 1996 to 2000 (Table 2). ERMS relative 5-year survival rates improved from 60.9% (95% CI, 50.2%-71.5%) to 73.4% (95% CI, 64.2%-82.6%) over this period, although the increase was not statistically significant (data not shown). Five-year survival rates for 5 diagnostic periods between 1976 and 2000 are shown in Figure 2. On visual inspection, the largest improvements in survival were achieved between the 1976 to 1980 cohort and the 1981 to 1985 cohort. Thereafter, survival rates for ERMS tended to stabilize around 70%, whereas ARMS survival rates had a small but continuous rise until the most recent period (1996-2000), when rates stabilized or possibly decreased.

thumbnail image

Figure 2. Relative 5-year survival of pediatric rhabdomyosarcoma (RMS) are illustrated for 5 consecutive 5-year periods.

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Table 2. Relative 5-Year Survival Rates of Rhabdomyosarcomas in the Surveillance, Epidemiology, and End Results Registries for the Diagnostic Period 1996-2000
 RMS OverallEmbryonal RMSAlveolar RMS
VariableNo. (%)5-Year Survival Rate (%)*95% CINo. (%)5-Year Survival Rate (%)*95% CINo. (%)5-Year Survival Rate (%)*95% CI
  • RMS, indicates rhabdomyosarcoma; CI, confidence interval; SEER, Surveillance, Epidemiology, and End Results.

  • *

    The 5-year relative survival rate was calculated using the actuarial method.

  • None of the survival curves for 1996 through 2000 differed significantly from the curves for 1986 through 1990.

  • The survival curve was significantly different from the curve for 1976 through 1980 (P < .05).

  • §

    The 1986 through 1990 survival curve differed significantly from the 1976 through 1980 curve (P < .05).

  • ∥, ||

    The upper confidence level was truncated at 100%.

  • The survival curve was statistically significantly different from the curve for non-Hispanic white children (P < .02).

SEER 9 registries         
 Total166 (100)61.8§54.3-69.291 (100)73.464.2-82.6)50 (100)47.833.9-61.7
  Sex         
   Male96 (57.8)64.4§54.8-74.153 (58.2)73.3§61.2-85.4)27 (54)55.636.8-74.4
   Female70 (42.2)5846.3-69.738 (41.8)73.459.1-87.6)23 (46)37.917.6-58.2
  Age, y         
   0-465 (39.2)70.559.3-81.842 (46.2)7662.9-89.1)16 (32)68.144.8-91.5
   5-946 (27.7)60.245.8-74.524 (26.4)78.5§61.8-95.3)16 (32)37.513.8-61.3
   10-1427 (16.3)59.340.8-77.911 (12.1)72.846.4-99.2)10 (20)409.6-70.5
   15-1928 (16.9)46.628-65.114 (15.4)57.331.3-83.3)8 (16)37.6§3.9-71.2
  Race         
   White121 (72.9)59§50.1-67.868 (74.7)7362.3-83.8)35 (70)39.423-55.8
   Black30 (18.1)66.849.9-83.814 (15.4)78.757.1-100||10 (20)50.119-81.2
   American Indian/Alaskan Native, Asian/Pacific Islander14 (8.4)71.547.8-95.29 (9.9)66.735.9-97.64 (8)100100-100
SEER 13 registries         
 Ethnicity         
 Hispanic48 (100)50.235.7-64.628 (58.3)57.338.9-75.713 (27.1)33.46.7-60.1

Table 2 shows 5-year survival rates for the diagnostic period from 1996 to 2000 by sex, age, and race/ethnicity. Adolescents ages 15 years to 19 years had the poorest overall survival rates (1996-2000: 46.6%; 95% CI, 28.0%-65.1%) compared with children ages 0 to 4 years (70.5%; 95% CI, 59.3%-81.8%). Boys had better 5-year survival rates compared with girls, which was reflected primarily in higher survival rates among the ARMS group (1996-2000: 55.6% vs 37.9%, respectively). Exploration of racial/ethnic differences indicated that black children may have better 5-year survival rates compared with whites, particularly for the ARMS subtype (1996-2000: 50.1% vs 39.4%, respectively). Hispanic children had lower relative 5-year survival rates compared with non-Hispanic white and black children, and the difference achieved statistical significance for ERMS compared with non-Hispanic whites. It is noteworthy that the observed differences by race and ethnicity were based on a small number of children in each category and, thus, should be interpreted with caution.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References

We have analyzed incidence and survival rates as well as trends, for 2 major RMS subtypes in children and adolescents diagnosed at aged <20 years from 1975 to 2005 using SEER Program data. We are not aware of any previous SEER reports that specifically addressed trends in incidence and survival of pediatric and adolescent RMS subtypes. We observed a 4.20% annual increase (95% CI, 2.60%-5.82%) in the incidence of ARMS. Furthermore, and unexpectedly, we observed that 5-year survival rates for ARMS have not improved significantly over the last 30 years, rising only 7.7% during this entire period. For ERMS, incidence rates have not changed significantly, whereas 5-year survival rates largely have improved (from 60.9% during 1976-1980 to 73.4% during 1996-2000).

Many changes in the classification and diagnosis of RMS were introduced over the last 3 decades.24, 30, 31 In 1995, a consensus classification of RMS, the International Classification of RMS (ICR) was established,32 thus improving the reproducibility of classification as well as prediction of outcome.33 A review of 800 cases of different RMS subtypes revealed high concordance between the review using the new ICR criteria and initial diagnosis established at individual institutions for the ERMS subtype. However, there was a “disturbing level” of discordant diagnosis (37%) reported for the ARMS subtype, which the authors believed reflected poor recognition of some of ARMS histologies.33 For example, a solid form of ARMS resembles ERMS morphologically and is associated with a misdiagnosis rate of about 20%.34 Because we examined the incidence of RMS during the period from 1975 to 2005, the vast majority of diagnoses were based on histology. Only within the last decade has the biology of tumors been taken into consideration during diagnosis by relying on advances in immunologic and molecular methods. Although immunologic studies are not necessary to establish a histologic diagnosis in the majority of cases, approximately 20% of cases require such analyses to establish or confirm diagnosis.33 In addition, the application of molecular methods to detect translocations t(1, 13) and t(2, 13), which are characteristic for ARMS,35 is useful in confirming the diagnosis. These changes in classification and application of novel methods over the last decade may have contributed in part to the rise in incidence rates of ARMS, the decrease in RMS, NOS and, to a lesser extent, the decrease in ERMS we have observed. However, given the relatively smaller number of RMS, NOS cases in any given period, this change in classification would attenuate, but probably would not eliminate, the annual increase in ARMS we observed.

Many of our findings affirm previous incidence reports of RMS, including early age of onset (>50% of RMS cases are diagnosed before age 10 years) and a strong male predominance. We demonstrated that this male predominance was driven by ERMS, whereas there were no sex differences in ARMS incidence. Furthermore, we observed slightly higher incidence rates of RMS and ARMS for black children compared with white children.

We also observed a bimodal distribution of ERMS incidence rates with a larger peak during the first 5 years of life and a smaller peak between ages 12 years and 17 years. It is noteworthy that this second peak was observed only in males. It is not clear why males would experience an increased incidence of ERMS in adolescence compared with females. Anecdotally, a recent study showed that prepubertal girls and boys have similar muscle size, whereas androgens have a strong impact on muscle enlargement, resulting in larger muscle gain in males during puberty.36 Therefore, it is plausible that the smaller peak of ERMS incidence rates observed during adolescence in males may be related to only these sex-specific hormonal differences; it would be interesting to investigate this further.

Our analyses of racial/ethnic differences in RMS incidence and survival were exploratory, because many of the categories that were compared were comprised of relatively small numbers. In a previous analysis of childhood STS in the SEER 9 registries during the period from 1975 to 1995,2 only white and black race were considered. Whereas black children had higher incidence rates of all STS, the authors reported no differences by histologic subgroups, acknowledging that this may be because of small numbers. The strengths of our current analysis include evaluation of an additional 10 years of data, inclusion of both RMS subtypes, and exploration of additional races/ethnicities. Compared with white children, black children and American Indian/Alaskan Native/Asian/Pacific Islander children had better 5-year survival rates, most strikingly for ARMS; there were notably few cases among these subgroups, however. The only exception was Hispanic children, who tended to fare more poorly than non-Hispanic white and black children, most notably for the ERMS subtype (1996-2000: 57.3% survival, compared with 79.2% in non-Hispanic whites and 82.5% in non-Hispanic blacks).

The observed differences in 5-year survival rates among black and white children are noteworthy. Ries et al2 observed that white children had slightly better 5-year survival rates for STS compared with black children. Those authors analyzed all STS together for the period from 1985 to 1994, whereas we focused on 1996 to 2000 and explored the histologic subtypes of RMS, which may account for differences in findings.

The considerable variation in incidence patterns that we observed for the 2 major subtypes of RMS strengthens the notion that these tumors are etiologically diverse. Molecular evidence comparing ERMS and ARMS gene expression further indicates that these tumors have distinct gene signatures.37, 38 ERMS frequently has loss of the chromosome 11p15 locus, resulting in loss of heterozygosity (LOH) in the region that contains several imprinted genes that have been implicated in oncogenesis, including the imprinted maternally expressed transcript (nonprotein coding) gene H19 and the insulin-like growth factor-2 gene IGF-2.39 In contrast, translocations are a hallmark of ARMS, are present in 80% of all cases40 and most commonly involve the paired box gene 3-forkhead box O1 (PAX3-FOXO1) fusion or the PAX7-FOXO1 fusion.41 Such translocations can arise in somatic muscle cells independently throughout adulthood; it is noteworthy that we observed no significant variation in ARMS incidence by age. Several studies have implicated DNA repair pathways in neoplastic transformation involving translocations,42, 43 but this has not been explored in ARMS.

There are a few limitations to this study. Our review of children with RMS and its 2 main subtypes reported to a population-based registry does not suffer from ascertainment biases reflecting referral patterns to regional centers that may be present in other epidemiologic studies. However, cancer registry data are limited by the information they are provided. These reports are based on diagnoses rendered by multiple pathologists and oncologists with variable expertise and equipment44 over an extended period; this may be especially pertinent for RMS, in which molecular classification has changed over the past several decades. However, as diagnostic techniques have improved for RMS, there is higher confidence in the most recent decade regarding accurate diagnosis. New cases registered using ICD-O-3 (begun on January 1, 2001) include more information on RMS subtypes. These data hold promise for future explorations of the relation between RMS subtypes, race/ethnicity, incidence, and survival.

In summary, the observed sex, age, and racial/ethnic differences in incidence and survival of 2 major RMS subtypes further support the view that these tumors have a distinct underlying etiology. Exploration of these differences presents the opportunity to increase our knowledge of RMS. Because improvements in cure rates of RMS, especially ARMS, are slowing, progress will depend at least in part on an improved understanding of tumor and host biology.40

Conflict of Interest Disclosures

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References

Supported by the Children's Cancer Research Fund (Minneapolis, Minn) and by National Institutes of Health Grant T32 CA099936.

References

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Conflict of Interest Disclosures
  7. References
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