A Surveillance, Epidemiology and End Results (SEER) program comparison of adult and pediatric Wilms' tumor

Article (PDF Available)inCancer 118(9):2541-51 · May 2012with41 Reads
DOI: 10.1002/cncr.26554 · Source: PubMed
Abstract
To compare the characteristics and outcome of adults and children diagnosed with Wilms' tumor. The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients diagnosed with Wilms' tumor between 1973 and 2007. Patients were stratified into pediatric (<16 years) or adult (≥16 years) groups. Overall survival was the primary endpoint. A total of 2342 patients (2190 pediatric and 152 adult) with Wilms' tumor were identified. Adult patients were statistically more likely to be staged as localized than pediatric patients (62.5% vs 44.7%), to not receive any lymph node sampling (57.9% vs 16.2%), and to not receive any radiation treatment (74.3% vs 53.9%). Adults had a statistically worse overall survival (OS) than pediatric patients (5-year OS, 69% vs 88%, P<.001) despite the earlier tumor stage. When stratified by treatment era, the OS of all patients treated after 1981 was statistically higher than those treated before (5-year OS, 75% vs 89%, P<.001). Significant predictors of OS on univariate analysis for adults included treatment era, SEER stage, surgery, and radiation treatment. Significant predictors of OS on multivariate analysis of all patients included adult status (hazard ratio, 4.14; P<.001), treatment era, SEER stage, and surgery. Adults in the SEER database had statistically worse OS than pediatric patients despite previous studies showing comparable outcome when treated on protocol. The worse outcome of SEER adults likely stems from incorrect diagnosis, inadequate staging and undertreatment. We recommend lymph node samplings for all adult Wilms' tumor patients and collaboration with pediatric oncologists.
A Surveillance, Epidemiology and End
Results (SEER) Program Comparison of
Adult and Pediatric Wilms’ Tumor
Arif N. Ali, MD, MS
1,2
; Roberto Diaz, MD, PhD
1,2
; Hui-Kuo Shu, MD, PhD
1,2
; Arnold C. Paulino, MD
3
; and Natia Esiashvili, MD
1,2
PURPOSE: To compare the characteristics and outcome of adults and children diagnosed with Wilms’ tumor.
METHODS: The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients diagnosed
with Wilms’ tumor between 1973 and 2007. Patients were stratified into pediatric (<16 years) or adult (16 years)
groups. Overall survival was the primary endpoint. RESULTS: A total of 2342 patients (2190 pediatric and 152 adult)
with Wilms’ tumor were identified. Adult patients were statistically more likely to be staged as localized than pediat-
ric patients (62.5% vs 44.7%), to not receive any lymph node sampling (57.9% vs 16.2%), and to not receive any radia-
tion treatment (74.3% vs 53.9%). Adults had a statistically worse overall survival (OS) than pediatric patients (5-year
OS, 69% vs 88%, P<.001) despite the earlier tumor stage. When stratified by treatment era, the OS of all patients
treated after 1981 was statistically higher than those treated before (5-year OS, 75% vs 89%, P<.001). Significant pre-
dictors of OS on univariate analysis for adults included treatment era, SEER stage, surgery, and radiation treatment.
Significant predictors of OS on multivariate analysis of all patients included adult status (hazard ratio, 4.14; P<.001),
treatment era, SEER stage, and surgery. CONCLUSION: Adults in the SEER database had statistically worse OS than
pediatric patients despite previous studies showing comparable outcome when treated on protocol. The worse out-
come of SEER adults likely stems from incorrect diagnosis, inadequate staging and undertreatment. We recommend
lymph node samplings for all adult Wilms’ tumor patients and collaboration with pediatric oncologists. Cancer
2012;118:2541-51.
V
C
2011 American Cancer Society.
KEYWORDS: adult, Wilms, SEER, pediatric, outcome.
INTRODUCTION
Wilms tumor is the most common renal tumor in children and represents approximately 95% of all pediatric renal
malignancies. The diagnosis of Wilms’ tumor in adults, however, is exceedingly rare, with an estimated incidence of only
0.2 cases per million.
1,2
Kilton et al
3
created a strict definition for the diagnosis of adult Wilms’ tumor in 1980 that
included several histological criteria as well as an age requirement of >15 years.
Currently, there have been only case reports and a limited number of published series with relatively small popula-
tions of registered patients studying the treatment and outcome of this rare adult tumor.
4-18
The 2 primary multi-institu-
tional Wilms’ tumor cooperative groups, the National Wilms Tumor Study Group (NWTS) and the International
Society of Paediatric Oncology (SIOP), have each published analyses of adult Wilms’ tumor cases registered on their re-
spective trials.
19,20
The publications from these groups were based on adult (16 years) subsets that were treated identi-
cally to the children on protocol with overall and disease-free survival results comparable to those of the children. These
outstanding results, however, are in contrast to those of general population-based studies and mono-institutional series
that have observed significantly worse outcome for adults compared with children.
2,14,16
It has been hypothesized that this
difference in outcome stems from the relative unfamiliarity of adult oncologists with the specifics of the Wilms’ tumor pe-
diatric treatment protocols as well as difficulties and delays associated with diagnosis in adults.
2,20
Although the NWTS and SIOP adult subsets have the distinct advantage of having received a highly regimented
diagnostic evaluation and treatment program with standardized and detailed outcome measures, these trials accrued few
DOI: 10.1002/cncr.26554, Received: June 1, 2011; Revised: July 13, 2011; Accepted: August 2, 2011, Published online September 14, 2011 in Wiley Online
Library (wileyonlinelibrary.com)
Corresponding author: Arif N. Ali, MD, MS, 1365 Clifton Road NE, Suite A1300, Atlanta, GA, 30322; Fax: (404) 778-4139; aali24@emory.edu
1
Department of Radiation Oncology, Emory University, Atlanta, Georgia;
2
Winship Cancer Institute, Emory University, Atlanta, Georgia;
3
Department of Radiology
and Pediatrics, Division of Radiation Oncology, Baylor College of Medicine and Methodist Hospital, Houston, Texas
This study, either as a whole or a portion thereof, has not been presented as part of any other forum, venue , or publication.
Cancer May 1, 2012 2541
Original Article
adult patients and thus had relatively weak statistical
power. The recent NWTS report on adult Wilms’ tumor
had only 23 patients from the NWTS 4 and 5 trials, and
the recent SIOP retrospective review included only 30
patients.
19,20
A recent report on adult Wilms’ tumor from
the EUROCARE study, which consists of data from 67
cancer registries and 22 European countries, included 143
adult patients. Unfortunately, there was no inclusion of
any pediatric patient data from that database within the
analysis. Additionally, the study was quite limited in asso-
ciated database parameters and did not have staging infor-
mation for over two-thirds of the included patients.
2
Another report on adult Wilms’ tumor patients by Izawa
et al
21
combined previously published single case reports
and small case series (including the previously mentioned
SIOP adult Wilms’ series) to create a study group of 128
patients. Though they were unable to perform a direct sta-
tistical comparison against a correlated pediatric popula-
tion, they did conclude that the overall survival for adult
patients appeared to be worse than historical pediatric
patient overall survival rates. Additionally, they postulated
that one of the reasons for the worse outcome may be
lower rates of lymph node dissections in adult patients
compared with pediatric patients, although they were
unable to report any lymph node dissection data for the
adult patients included in their publication.
Given the relative lack of knowledge and conflicting
analyses regarding the clinical behavior and treatment
outcome of Wilms’ tumor in adults compared with chil-
dren, we pursued the Surveillance, Epidemiology and
End Results (SEER) database to provide a singular source
of data from one of the nation’s most extensive tumor
registries to provide long-term follow-up, strong statistical
power, and uniform pediatric and adult patient popula-
tions with which to study this rare disease.
22
MATERIALS AND METHODS
Database
Data used in the analysis were acquired from the SEER 17
Registry, which was released in April 2010 and includes
tumors diagnosed between 1973 and 2007.
22
This data-
base was accessed using SEER*Stat version 6.6.2. The
inclusion criteria for the case listing session required that
all cases have a known age and an adolescent and young
adult site recode diagnosis of 9.1.1 Wilms tumor. The
SEER adolescent and young adult classification scheme is
based on that proposed by Barr et al
22,23
and includes, by
definition, the International Classification of Diseases for
Oncology (ICD-O-3) histological diagnostic codes of
8959-8960 with a malignant ICD-O-3 behavior recode.
Cases included only a patient’s first diagnosis of Wilms’
tumor, and those registered as autopsy or death certificate
only were excluded from the analysis.
It should be noted that although the SEER database
does provide strong statistical power with a large uniform
population of both adult and pediatric patients tracked
across nearly 4 decades in addition to supplying a sizeable
array of prognostic variables, there are rather significant
limitations of the SEER database compared with a data-
base from a clinical trial group such as the NWTS or
SIOP. Specifically, the SEER database, by design, does
not have a central pathology review of tissue specimens.
Additionally, although it does track the type of surgery
and radiation treatment as well as surgical margin status,
number of lymph nodes dissected, and number of positive
lymph nodes, it does not provide more extensive surgical
details such as the type of surgical approach and operative
notes or radiation doses. Perhaps the most significant li-
mitation of the SEER database, however, is the exclusion
of chemotherapy details and lack of long-term toxicity
parameters.
Statistical Analysis
All statistical analyses were performed with SPSS version
17 (SPSS Inc., Chicago, IL). Patients were classified as ei-
ther ‘pediatric’’ (<16 years) or ‘adult’ (16 years)
depending on age at the time of diagnosis.
3,19,20
The
SEER staging system was used for staging purposes
because this categorization had standardized definitions
and consistent data dating back to 1973 for primary kid-
ney tumors. SEER staging defines ‘localized’ cancer as
that which is ‘limited to the organ in which it began,
without evidence of spread.’ ‘‘Regional’ cancer is defined
as that which has ‘spread beyond the primary site to
nearby lymph nodes or organs and tissues.’’ ‘Distant’
cancer is defined as that which has ‘spread from the pri-
mary site to distant organs or distant lymph nodes.’
22
The listed year of diagnosis was used to categorize the
patients into 1 of 4 treatment eras between 1973 and
2007 defined by the publication years of the NWTS 2, 3,
and 4 trials.
24-26
Patient parameters were statistically compared
between age groups to assess for variable heterogeneity.
The continuous variables were statistically compared with
the Student t test, and categorical variables were compared
with Pearson’s chi-square test except when the data set
Original Article
2542 Cancer May 1, 2012
Table 1. Patient Characteristics
Parameter Total (N 5 2342) Pediatric (n 5 2190) Adult (n 5 152) P
Age, y
Median
33 36
Mean (SD)
5.6 (10.8) 3.2 (2.8) 40.3 (19.7) <.001
a
Range
0-93 0-15 16-93
Sex
.089
b
Male
1080 (46.1) 1020 (46.6) 60 (39.5)
Female
1262 (53.9) 1170 (53.4) 92 (60.5)
Race
.777
b
White
1860 (79.4) 1740 (79.5) 120 (78.9)
Black
342 (14.6) 321 (14.7) 21 (13.8)
Other/unknown
140 (6.0) 129 (5.9) 11 (7.2)
Laterality
<.001
b
Right
1093 (46.7) 1019 (46.5) 74 (48.7)
Left
1076 (45.9) 1007 (46.0) 69 (45.4)
Bilateral
142 (6.1) 141 (6.4) 1 (0.7)
Unknown
31 (1.3) 23 (1.1) 8 (5.3)
Primary malignancies
First primary
2320 (99.1) 2184 (99.7) 136 (89.5) <.001
c
1 total
2295 (98.0) 2158 (98.5) 137 (90.1) <.001
c
2 total
41 (1.8) 29 (1.3) 12 (7.9)
>2 total
6 (0.3) 3 (0.1) 3 (2.0)
Later primaries
38 (1.6) 33 (1.5) 5 (3.3) .096
c
SEER stage
<.001
b
Localized
1073 (45.8) 978 (44.7) 95 (62.5)
Regional
643 (27.5) 623 (28.4) 20 (13.2)
Distant
534 (22.8) 510 (23.3) 24 (15.8)
Unstaged/blank
92 (3.9) 79 (3.6) 13 (8.6)
Regional lymph nodes examined
d
<.001
b
0
442 (18.9) 354 (16.2) 88 (57.9)
1-3
551 (23.5) 540 (24.7) 11 (7.2)
4-6
284 (12.1) 279 (12.7) 5 (3.3)
7-9
110 (4.7) 110 (5.0) 0 (0.0)
10-12
64 (2.7) 64 (2.9) 0 (0.0)
>12
109 (4.7) 100 (4.6) 9 (5.9)
Unknown
782 (33.4) 743 (33.9) 39 (25.7)
Regional lymph nodes positive
d
.314
c
0
996 (81.4) 975 (81.5) 21 (75.0)
1-3
185 (15.1) 180 (15.1) 5 (17.9)
>3
43 (3.5) 41 (3.4) 2 (7.1)
Tumor size
.017
a
Measured
1526 (65.2) 1433 (65.4) 93 (61.2)
Unknown
816 (34.8) 757 (34.6) 59 (38.8)
Mean size (SD), cm
10.6 (4.4) 10.6 (4.2) 9.5 (6.3)
Treatment era
.320
b
1973-1981
349 (14.9) 328 (15.0) 21 (13.8)
1982-1989
357 (15.2) 341 (15.6) 16 (10.5)
1990-1998
594 (25.4) 550 (25.1) 44 (28.9)
1999-2007
1042 (44.5) 971 (44.3) 71 (46.7)
Surgery
<.001
b
No primary site surgery or biopsy only
94 (4.0) 82 (3.7) 12 (7.9)
Partial nephrectomy
96 (4.1) 86 (3.9) 10 (6.6)
Simple nephrectomy
378 (16.1) 368 (16.8) 10 (6.6)
Radical nephrectomy
1206 (51.5) 1121 (51.2) 85 (55.9)
Nephrectomy, NOS
136 (5.8) 129 (5.9) 7 (4.6)
(Continued)
SEER Comparison of Adult and Pediatric Wilms’ Tumor/Ali et al
Cancer May 1, 2012 2543
was relatively small, in which case the Fisher exact test was
used.
The outcomes of the pediatric and adult patient
groups were primarily compared on the basis of overall
survival (OS) and disease-specific survival (DSS) end-
points. The latter was obtained using the SEER cause-spe-
cific death classification as defined by Howlader et al.
27
Relative survival was also calculated across the spectrum
of ages of patients with Wilms’ tumor.
22
The Kaplan-
Meier method was used to generate survival curves. Sur-
vival estimates are presented followed by the standard
error. The pediatric and adult patient groups were com-
pared through a univariate analysis on the basis of the log-
rank test and a multivariate analysis using Cox propor-
tional hazards regression. For the purposes of the multi-
variate analysis, the laterality parameter was consolidated
into unilateral versus bilateral, and the surgery parameter
was consolidated into no primary site surgery or biopsy
only versus surgery.
RESULTS
Patient Characteristics
The SEER 17 registry contained a total of 2352 patients
with a diagnosis of Wilms’ tumor. Ten of these patients
were registered on the basis of autopsy or death certificate
only and were excluded, leaving a total of 2342 patients
with 2190 (93.5%) pediatric patients ( <16 y ears) and
152 (6.5%) adult patients (16 years). As seen in Table
1, the pediatric and adult patients were fairly well bal-
anced with respect to sex and race. There was, however, a
statistically significant difference in tumor laterality,
because approximately 6.4% of the pediatric patients
were bilateral compared with only 0.7% of the adult
patients. In analyzing the association of the Wilms’ tu-
mor patients with other primary malignancies in the
same patient, it is observed that statistically more of the
adult patients had additional primary malignancies
(both before and after the Wilms’ diagnosis) than the pe-
diatric patients.
When the patients were stratified by treatment era
according to NWTS 2, 3, and 4 trial publication
dates, the pediatric and adult groups were well balanced
(Table 1). There is an increase in the number of cases in
later treatment eras due to the expanding geographical
coverage of the SEER program.
22
Comparison of the SEER stage at presentation
between children and adults revealed that the adult
patients were statistically lower stage than the pediatric
patients, with fewer metastatic presentations (15.8% vs
23.3%), fewer regional cases (13.2% vs 28.4%), and more
localized cases (62.5% vs 44.7%). In addition, the adult
group had statistically more cases without lymph node
samplings than the pediatric group (57.9% vs 16.2%).
Table 1. (Continued)
Parameter Total (N 5 2342) Pediatric (n 5 2190) Adult (n 5 152) P
Surgery, NOS
388 (16.6) 367 (16.8) 21 (13.8)
Unknown
44 (1.9) 37 (1.7) 7 (4.6)
Radiation treatment
<.001
c
None
1294 (55.3) 1181 (53.9) 113 (74.3)
External beam
1009 (43.1) 972 (44.4) 37 (24.3)
Other/NOS
9 (0.4) 9 (0.4) 0 (0.0)
Unknown
30 (1.3) 28 (1.3) 2 (1.3)
Radiation sequence
<.001
c
RT before surgery
87 (3.7) 84 (3.8) 3 (2.0)
RT after surgery
879 (37.5) 849 (38.8) 30 (19.7)
RT before and after surgery
14 (0.6) 14 (0.6) 0 (0.0)
Unknown/no RT or surgery
1362 (58.2) 1243 (56.8) 119 (78.3)
Vital status
<.001
b
Alive
2013 (86.0) 1913 (87.4) 100 (65.8)
Dead
329 (14.0) 277 (12.6) 52 (34.2)
NOS, not otherwise specified; RT, radiation treatment; SD, standard deviation; SEER, Surveillance, Epidemiology and End Results. All data are presented as
no. (%) unless indicated otherwise.
a
Student t test.
b
Pearson chi-square test.
c
Fisher exact test.
d
There were 109 patients who had unknown ‘regional lymph nodes examined’ status but reported positive lymph nodes, and there were 3 patients who had
‘regional lymp h nodes examined’ status but had an unknown posit ive lymph node status.
Original Article
2544 Cancer May 1, 2012
Regarding treatment, more adult patients had no
surgery or biopsy only compared with pediatric patients
(7.9% vs 3.7%). Additionally, adult patients were less
likely to receive radiation treatment than pediatric
patients (24.3% vs 44.4%). When radiation was adminis-
tered, it was after surgery in most pediatric and adult cases
(Table 1).
Survival Analysis
The survival for all patients was analyzed by treatment era
defined by NWTS 2, 3, and 4 trial publication dates
(1973-1981, 1982-1989, 1990-1998, and 1999-2007) in
Figure 1. There was a statistically significant improvement
in the OS of all patients treated after 1981 (5-year OS,
75% 2.3%, 89% 1.6%, 89% 1.3%, and 89%
1.1%; P<.001), which would correspond to the introduc-
tion of multiagent chemotherapy with doxorubicin. A
similar statistically significant improvement in the OS of
the adult patients treated after 1981 was also seen (Figure
2A) when the analysis was restricted to the adult group (5-
year OS, 38% 10.6%, 75% 10.8%, 72% 6.8%,
and 74% 6.8%; P ¼ .005). Figure 3A shows that there
Figure 1. Overall survival is shown for all patients, stratified by
treatment era corresponding to the publication dates of National
Wilms T umor Study Group 2 (1981), 3 (1989), and 4 (1998).
Figure 2. Overall survival is shown for adult patients, stratified by (A) treatment era, (B) Surveillance, Epidemiology and End
Results stage, (C) surgery, and (D) radiation in all stages.
SEER Comparison of Adult and Pediatric Wilms’ Tumor/Ali et al
Cancer May 1, 2012 2545
is a statistically significant worse OS for the adult group
compared with the pediatric group (P<.001). After a me-
dian follow-up of 7.1 years (range, 0-34.9 years), 87.4% of
pediatric patients were alive compared with only 65.8% of
adult patients. The 5-, 10-, and 15-year OS estimates for
the pediatric group were 88% 0.7%, 87% 0.8%, and
86% 0.9%, respectively. The corresponding OS rates for
the adult group were 69% 4.1%, 61% 4.7%, and
57% 5.3%, respectively. Similarly, the DSS rate for the
adult group was significantly worse than the pediatric
group (Figure 3B), with DSS estimates of 89% 0.7%,
88% 0.7%, and 88% 0.8%, respectively, for the pedi-
atric group and 73% 3.9%, 68% 4.5%, and 68%
4.5%, respectively, for the adult group (P<.001).
In Figure 4, the expected survival, relative survival,
and number of Wilms’ tumor patients in each age cate-
gory are displayed across the entire spectrum of ages. It is
seen that the youngest patients (<1 year) have the highest
relative survival and increasing age results in a decrease in
relative survival until a nadir is reached around the second
to third decade.
Univariate Analysis
Univariate analysis was performed using the log-rank test
to compare treatment era, sex, race, first primary, SEER
stage, lymph node sampling, surgery, and radiation treat-
ment within the adult patients on the basis of overall sur-
vival. As shown in Figure 2, only treatment era, SEER
stage, surgery, and radiation treatment were significant.
The 5-year OS for localized Wilms’ tumor was 90%
3.6%, regional was 32% 13.3%, and distant was 23%
9.4% (P<.001). Adult patients who underwent surgery
had a significantly better OS than those who had biopsy
only or received no surgery (5-year OS, 76% 4.0% vs
19.4% 12.2%; P<.001). Adult patients who did not
receive radiation treatment had significantly better OS
than those who did (5-year OS, 78% 4.3% vs 47%
8.8%; P ¼ .004). It should be noted, however, that when
radiation administration is analyzed within all distant
stage patients (pediatric and adult), there is a statistically
significant OS benefit to radiation treatment (5-year OS,
68% 4.6% vs 75% 2.3%; P ¼ .025) (Figure 5). In
Figure 6, the OS of the adult and pediatric groups are
compared by stage. The adult patients had a statistically sig-
nificant worse OS than pediatric patients for all stages
Figure 3. (A) Overall survival and (B) disease-specific survival
of the 2190 pediatric Wilms’ tumor patients compared with
the 152 adult Wilms’ tumor patients in the Surveillance, Epi-
demiology and End Results database are shown.
Figure 4. Estimated 5-year expected survival (based on gen-
eral population data), 5-year relative survival of the Surveil-
lance, Epidemiology and End Results Wilms’ tumor patients,
and number of patients in each age category are shown,
stratified by age. Error bars represent the standard error.
Original Article
2546 Cancer May 1, 2012
including localized (5-year OS, 90% 3.6% vs 94%
0.8%; P ¼ .001), regional (32% 13.3% vs 89%
1.4%; P<.001), and distant (23% 9.4% vs 76%
2.0%; P<.001). Additionally, the adult and pediatric
groups were compared via lymph node sampling status on
the basis of OS. The adult patients fared significantly worse
than the pediatric patients whether they received a lymph
node sampling (5-year OS, 74% 10.6% vs 92%
0.9%; P ¼ .001) or did not receive a lymph node sampling
(5-year OS, 75% 5.2% vs 85% 2.1%; P ¼ .010).
Multivariate Analysis
Multivariate analysis was performed using a Cox propor-
tional hazard model with OS as the endpoint. Only those
patients with complete information available for all varia-
bles were included (complete case analysis technique, n ¼
2173 total [2045 pediatric, 128 adult]).
28,29
Lymph node
sampling status was not included in the model because it is
correlated with stage, and there was a high proportion of
unknowns. As seen in Table 2, adult status (hazard ratio,
4.14; P<.001), SEER stage, and treatment era were signifi-
cant prognostic factors across all patient groups. Adult
patients diagnosed with Wilms’ tumor after another pri-
mary malignancy had worse OS than those in which the
Wilms’ tumor diagnosis was their first primary malignancy
(hazard ratio, 3.64; P ¼ .025). Surgery was of significant
benefit in pediatric patients (hazard ratio, 0.27; P<.001),
but was not statistically significant for adult patients,
though this is likely due to the limited number and reduced
statistical power of the patients that did not undergo resec-
tion (n ¼ 12). Radiation treatment was not a statistically
significant predictor for either the pediatric or adult group.
DISCUSSION
The analysis presented in this manuscript compares the
outcome of 2142 pediatric Wilms’ tumor patients with
152 adult Wilms’ tumor patients in the SEER database.
Adult patients were found to have a consistently worse
Figure 5. Overall survival in all distant stage patients
(pediatric and adults) is shown, stratified by radiation
administration.
Figure 6. (A) Localized stage, (B) regional stage, and (C) dis-
tant stage Wilms’ tumor are shown, stratified by age group.
SEER Comparison of Adult and Pediatric Wilms’ Tumor/Ali et al
Cancer May 1, 2012 2547
outcome than pediatric patients. The etiology of this
observed difference is likely multifactorial. It should be
noted, though, that the histology of adult Wilms’ tumors
are presumed to be identical to pediatric tumors and,
according to currently available literature, no biological
differences are apparent.
14,20,30
In fact, the 2 major
Wilms’ tumor trial groups, NWTS and SIOP, concluded
from their retrospective review of patients 16 years in
the NWTS 4-5 (n ¼ 23 þ 22) and SIOP 93-01 (n ¼ 30)
databases that adult patients, when treated on protocol in
a similarly risk-adapted strategy as pediatric patients, may
achieve outcomes comparable with pediatric patients
(adult 5-year OS, 82.6% and 83%, respectively).
19,20
A major difference between this report and the
NWTS and SIOP adult Wilms’ tumor data is the percent-
age of adult Wilms’ tumor patients within the database.
The SEER database contains 152 adult patients out of a
total 2342 Wilms’ tumor patients (6.5%). In contrast, the
NTWS report had 22 adult patients combined between
the NWTS 4 and 5 databases compared with 1638 and
2387 pediatric patients, representing approximately
0.5%. The SIOP report included only 30 adult patients
compared with 847 pediatric patients in the SIOP 93-01
trial publication, representing approximately 3%.
26,31
This difference in adult proportions between the SEER
and trial group databases likely stems from the reluctance
of adult oncologists, who may not have established insti-
tutional ties with either NWTS or SIOP, to register adult
patients on a specific protocol. The current study is based
on the SEER database, which includes a cohort of patients
from geographically diverse rural and urban areas treated
in academic and community practice settings and likely
not treated on any specific trial. As a result, the SEER
database appears to have captured a significantly higher
percentage of adult Wilms’ tumor patients than the pedi-
atric trial databases and is likely more representative of
community-based treatment practice trends for this rare
tumor.
In analyzing the SEER patient characteristics, adult
patients received far fewer lymph node samplings and
were significantly more likely to be staged lower than pe-
diatric patients, yet adults had a worse outcome on a
stage-for-stage basis. This is in contrast to the SIOP report
in which the SIOP adult patients generally presented at
higher stages than the SIOP pediatric patients and had
nearly twice the rate of irradiation as the SEER adult
patients (46% vs 24.3%).
20
As discussed, 74% of SEER
adult patients did not receive any radiation treatment
compared with only 54% of the SEER pediatric patients.
It should be noted that both pediatric trial groups,
NWTS and SIOP, require lymph node sampling in most
of their pediatric protocols.
32-36
If lymph node samplings
are not performed, it is likely that the number of patients
with regional disease would be underestimated, whereas
the localized patients would have a worse outcome. The
SEER data suggest that adult Wilms’ tumor patients,
when treated in the community and off protocol, tend to
be inadequately staged and are therefore undertreated
compared with their pediatric counterparts.
The inadequate staging of adult patients would also
be expected to affect chemotherapy administration as well
as radiation treatment. Although the SEER database does
not have chemotherapy data, when the patients are strati-
fied by treatment era, it is seen that those adult patients
treated after 1981 (NWTS 2 trial publication year, which
found a DSS benefit to the addition of doxorubicin) had a
significantly improved OS. Thus, it is apparent that adult
patients, like pediatric patients, benefit from modern
chemotherapy regimens. This finding is confirmed by
another study by Arrigo et al
37
that found an improve-
ment in the 3-year survival rate from 24% to 67% for a
series of 24 adults treated with modern 3-drug
chemotherapy, including doxorubicin. Current NWTS
treatment recommendations include a 2-drug chemother-
apy regimen for early stages and favorable histology and a
3-drug chemotherapy regimen plus radiation for
advanced stages and unfavorable histology.
19,38
Thus, if
adult patients were understaged, they might also be
expected to be undertreated with chemotherapy.
Another factor likely contributing to the worse out-
come of the SEER adult patients compared with protocol
adult and pediatric patients may be treatment delays and
inappropriate treatment regimens associated with the rela-
tive unfamiliarity of adult oncologists with established pe-
diatric Wilms’ tumor protocols. A recent mono-
institutional retrospective study on 17 adult Wilms’ tu-
mor patients found a ‘very low compliance with specific
diagnostic and therapeutic protocols’’ with a correspond-
ing worse outcome for the adult patients compared with
historical pediatric Wilms’ tumor results.
14
Additionally,
the minimization of radiation treatment delay has been
shown to be an important factor, because several studies
on pediatric patients have concluded that delays in the ini-
tiation of radiation beyond 10 days after surgery results in
a higher rate of recurrence.
39,40
It might also be expected
that there would be significant delay associated with the
pathological review of a rare Wilms’ tumor diagnosis in
an adult.
Original Article
2548 Cancer May 1, 2012
In addition to delays associated with a pathological
diagnosis, a misdiagnosis of more aggressive tumors as
Wilms’ tumor might also be expected to result in worse
outcomes for adults. Common tumors often pathologi-
cally confused with Wilms’ tumor include renal adenocar-
cinoma, clear cell sarcoma of the kidney, renal teratoma,
and malignant rhabdoid tumor of the kidney.
41
In fact, in
NWTS 4, it was found that 12 out of 1439 (0.8%)
patients originally diagnosed with favorable histology
Wilms’ tumor by their institution actually had clear cell
sarcoma of the kidney on central pathology review.
42
A
significant portion of the pediatric patients in the SEER
database likely have had central pathology review due to
concurrent registration on NWTS protocols; however, it
is probable that only a small portion of registered adult
cases would have received such a thorough examination. A
higher rate of pathological misdiagnosis might also result
in undertreatment and worse outcome for adult patients.
Additionally, a higher percentage of anaplastic tumors in
the adult patients would certainly account for the worse
outcome of the adult patient group. However, the report
by the SIOP group documented only 2 out of 30 adult
Wilms’ tumors (6.7%) that were anaplastic and only 3
tumors (10%) that were clear cell sarcoma of the kidney.
20
Notably, these rates were comparable to those of the pedi-
atric patients in that same SIOP 93-01 trial (7.0% high
Table 2. Multivariate Analysis
Parameter
All Patients Pediatric Patients Adult Patients
HR 95% CI P HR 95% CI P HR 95% CI P
Age category
Pediatric
1.00 Reference
Adult
4.14 2.81-6.10 <.001
Sex
Male
1.00 Reference 1.00 Reference 1.00 Reference
Female
0.91 0.72-1.15 .429 0.95 0.73-1.22 .667 0.71 0.34-1.49 .369
Race
White
1.00 Reference 1.00 Reference 1.00 Reference
Black
1.13 0.81-1.57 .468 1.00 0.70-1.44 .983 2.47 0.90-6.78 .080
Other/unknown
1.54 0.97-2.44 .068 1.53 0.93-2.52 .094 2.26 0.60-8.52 .228
Laterality
Unilateral
1.00 Reference 1.00 Reference 1.00 Reference
Bilateral
0.83 0.51-1.38 .477 0.87 0.52-1.45 .588 <0.001 NA
a
.987
a
Primary malignancies
First primary
1.00 Reference 1.00 Reference 1.00 Reference
Not first primary
1.86 0.77-4.46 .165 3.33 0.46-24.20 .235 3.64 1.17-11.28 .025
SEER stage
Localized
1.00 Reference 1.00 Reference 1.00 Reference
Regional
2.05 1.45-2.90 <.001 1.64 1.13-2.37 .009 10.25 3.91-26.87 <.001
Distant
4.16 2.92-5.94 <.001 3.35 2.31-4.87 <.001 43.40 11.72-160.6 <.001
Treatment era
1973-1981
1.00 Reference 1.00 Reference 1.00 Reference
1982-1989
0.40 0.27-0.59 <.001 0.40 0.26-0.60 <.001 0.38 0.10-1.38 .142
1990-1998
0.35 0.25-0.50 <.001 0.41 0.28-0.59 <.001 0.08 0.02-0.30 <.001
1999-2007
0.40 0.29-0.56 <.001 0.43 0.30-0.61 <.001 0.30 0.12-0.79 .015
Surgery
No surgery or biopsy only
1.00 Reference 1.00 Reference 1.00 Reference
Surgery
0.27 0.17-0.44 <.001 0.27 0.16-0.47 <.001 0.54 0.16-1.81 .315
Radiation
None
1.00 Reference 1.00 Reference 1.00 Reference
External beam
1.16 0.86-1.58 .336 1.21 0.87-1.67 .262 0.98 0.40-2.38 .958
CI, confidence int erval; HR, hazard ratio; NA, not available; SEER, Surveillance, Epidemiology and End Results.
a
There was only 1 patient with bilateral Wilms’ tumor in the adult group.
SEER Comparison of Adult and Pediatric Wilms’ Tumor/Ali et al
Cancer May 1, 2012 2549
risk histology and 5.0% clear cell sarcoma of the
kidney).
43
In conclusion, although previous studies have shown
comparable outcomes between adult and pediatric patient
populations when adults are treated on protocol, our analy-
sis of the SEER database finds that adults have significantly
worse outcome than pediatric patients. This worse out-
come likely stems from inadequate staging and incomplete
diagnostic evaluations in the general community resulting
in treatment delays and undertreatment with radiation as
well as possibly chemotherapy. Thus, this body of work
serves to support the recommendation for lymph node
sampling in all adult Wilms’ tumor patients, close collabo-
ration with pediatric surgeons and oncologists, and proto-
col-based treatment regimens. Additionally, it should be
noted that the Children’s Oncology Group (COG) has
recently raised the enrollment age for their trials to 30 years,
hence institutions should consider enrolling all eligible
adult patients on COG trials when possible.
FUNDING SOURCES
No specific funding was disclosed.
CONFLICT OF INTEREST
The authors made no disclosures.
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SEER Comparison of Adult and Pediatric Wilms’ Tumor/Ali et al
Cancer May 1, 2012 2551
    • "For example, a survey of adult and pediatric oncologists on the treatment of adult medulloblastoma patients similarly demonstrated substantial variation in practice, particularly with the choice of chemotherapeutic agents, likely reflecting the limited data available relevant to older adult population [22]. Likewise, population studies have demonstrated less aggressive protocols for diagnosis, staging, and treatment for adults with Wilms' Tumor relative to their pediatric counterparts and cited this less aggressive approach as an explanation for inferior survival outcomes among adults [23]. Together, these data call for renewed and continued collaboration across the artifactual divides of adult and pediatric oncology to define evidence-based treatment strategies and appropriate prospective trials across the age spectrum. "
    [Show abstract] [Hide abstract] ABSTRACT: Background. Whole lung irradiation (WLI) is a standard treatment component for children with metastatic Ewing Sarcoma (ES), but data on WLI for adults are sparse. Design. An email survey was sent to expert sarcoma-dedicated oncologists worldwide: An adult with excellent performance status presents with primary ES in the leg and multiple pulmonary metastases. The patient achieves complete radiographic response after chemotherapy and resection of the primary. Would you give bilateral WLI to (1) this adult patient?, (2) this patient if 20 years old (yo)?, (3) this patient if 45 yo?, or (4) this patient if 60 yo? Results. 38 experts responded, including 24 adult, 1 adolescent young adult, and 13 pediatric oncologists. 63%, 63%, 62%, and 50% of respondents offered WLI to the adult, 20-year-old, 45-year-old, and 60-year-old, respectively. Pediatric oncologists more likely endorsed WLI across all ages including the adult (í µí±ƒ = 0.01), 20-year-old (í µí±ƒ = 0.005), 45-year-old (í µí±ƒ = 0.01), and 60-year-old (í µí±ƒ = 0.08). There were no significant differences between medical and radiation oncologists or between European/Australian and American providers. Conclusions. Almost two-thirds of experts surveyed supported WLI for adults with metastatic ES up to age 45 and half supported WLI for a 60-year-old. Continued collaboration across adult and pediatric oncology is needed to define evidence-based strategies across the age spectrum.
    Full-text · Article · Jun 2015
    • "Up to 2% of these tumors were found in adults [10, 11] with more than 300 cases reported in the literature [11, 12]. In the SEER – Database almost 6.5% (152/2342 patients) were adults [11] . The presentation of adult Wilms' tumor differs from those in childhood with flank pain and loss of weight [12, 13]. "
    Full-text · Article · Apr 2013
  • [Show abstract] [Hide abstract] ABSTRACT: Secretory carcinoma of the breast is a rare breast cancer that is associated with incidence at a young age and an indolent course. The role for breast conservation and adjuvant radiation is unknown. The SEER database was reviewed and 83 patients were identified with secretory carcinoma of the breast between the years 1983 and 2007. Baseline characteristics were compared with χ(2) or Fisher's exact test. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan-Meier method. Analyses were performed using PASW Statistics, version 18. Median follow-up was 70 months. Median patient age was 53 years (range 11-86 years). 29 patients (34.9%) had involved regional lymph nodes. 39 patients (47.0%) underwent lumpectomy and 44 patients (53.0%) underwent mastectomy. 35 patients (42.2%) received radiation. Patients receiving radiation were more likely to have undergone lumpectomy, and the use of radiation increased over time. 5-year OS was 87.2%; 10-year OS was 76.5%. 5-year CSS was 94.4%; 10-year CSS was 91.4%. Among the lumpectomy patients, 25 patients (64.1%) received radiation. For lumpectomy patients, those who did not receive radiation had a 5-year OS of 92.9% and 10-year OS of 72.2% while patients who did receive radiation had a 5-year OS of 95.5% and 10-year OS of 85.9%. Only 1 patient treated with lumpectomy only died of cancer (92.9% CSS) and no patients treated with lumpectomy and radiation died of cancer (100% CSS). Secretory carcinoma of the breast commonly occurs at a later age than previously recognized, and is associated with good long-term survival.
    Article · Apr 2012
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