Cau

Clinicopathologic
Characteristics

Among all patients, 528 (72.8%) presented with local

dis- ease, compared with 197 (27.2%) patients with
metasta- sis. Tumor size was known for 406 patient cases
(56.0%), with 164 (22.6%) patient cases having tumor
size <8 cm, and 242 (33.4%) patient cases having tumor
size equal to or greater than 8 cm. Patient cases with
metastatic disease had a higher proportion of large
tumors (8 cm and greater) than did patient cases
without metastatic disease (76.8% vs 54.3%, P < .
0001). Furthermore, a greater proportion of whites had
tumor size smaller than 8 cm, as compared with Others
and Hispanics (46.6% vs 31.8% and 33.6%,
respectively, P .02). Large tumor size was not
associated with rate of low SES, chemotherapy, radiation therapy, or surgical intervention. Location of
disease at initial presentation was as follows: 34
(4.9%) head/ neck, 121 (17.4%) chest/abdomen, 301
(43.3%) extrem- ities, 61 (8.8%) spine, and 178
(25.6%) pelvis, which include the sacrum according to
CCR site coding. There were 544 (75%) patient cases
with skeletal involvement and 181 (25%) with
nonskeletal involvement. Patient cases with pelvic
involvement had a statistically higher fre- quency of
metastasis at diagnosis compared with patient cases
with extremity or other location involvement
(36.5% vs 19.6% and 25.9%, respectively; P .0002).
Pelvic involvement also had a higher rate of large tumor
size than did patient cases of extremity or other location
involvement (73.0% vs 60.5% and 45.1%, respectively, P
< .0001).
Treatment profile for all patients included 339
(46.7%) who did not receive radiation, and 386 (53.2%)
who did receive radiation. Similar rate of radiation therapy was seen across the major racial/ethnic groups (45.7%
Others vs 56.5% white vs 49.8% Hispanic, P .1).
There was no significant difference in rate of surgical
interven- tion (P .12), metastatic disease (P .
09), SES (P .23), or tumor size (P .5) between
patient cases that received radiation and those that did
not. However, radiation was given more commonly to
patient cases with pelvic and axial involvement,
compared with extremity involvement (58.43% and
57.41% vs 48.5%, respec- tively, P .048). The
majority of patient cases received chemotherapy, 664
(93%), with only 50 (7.0%) patient cases that did not.
When comparing the 2 age groups, a significantly
greater proportion of the adult group did not receive
chemotherapy (12.7% adults vs 1.6% children, P

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< .0001). Across the race/ethnic groups, a greater

propor- tion of Others did not receive chemotherapy
(14.5% vs
6.2% white and 6.3% Hispanic, P .04). For patient
cases that received chemotherapy compared with those
that did not receive chemotherapy, no significant difference was found in the rate of surgical intervention
(56.65% vs
52.08%,
respectively, P .54),
SES (P .52), tumor size (P .32), or tumor
location (P .30). However, there was a significantly
lower rate of radiation therapy (24% vs 56%, P < .
0001) and meta- static disease (12% vs 28.2%, P .
01) among patient cases that did not receive
chemotherapy
versus those that did receive
chemotherapy, respectively.
In terms of surgical intervention, 318 (44.4%) did
not receive any surgery. Among patients who did receive
surgery, 105 (14.7%) underwent local excision or
destruc- tion, 159 (22.2%) had radical resection or
limb salvage procedure, and 60 (8.4%) underwent
amputation. Sixty- nine (9.6%) patients had surgery
that were not otherwise specified, and in 5 (0.7%)
patient cases, it is unknown if any surgical intervention
was done.
se of Death Analysis

Three hundred twenty-one (44.3%) of the 725 Ewing

sar- coma patient cases died. Of these deaths,
72.3% (n 232) were attributed to Ewing
sarcoma-related causes. Cause of death was unknown
for 40 of the 321 patient cases (12.5%). There was no
significant difference in cause of death between the
different race/ethnicity groups (P .233).
Univariate Survival Analysis

For all patients, 5-year OS was 53.8% and 10-year OS

was 48.3%. Five year Ewing-specific survival was 63.5%
and 10 year was 59.9%. Compared with children, adults
had significantly decreased OS as well as Ewing-specific
survival (P < .0001, and P .0006, respectively).
Ewing- specific survival curves by age are shown in
Figure 1. A subset analysis was done on adult patients
by eliminating patients age 0-19 years. Among the adult
age Groups 2039, 40-49, 50-59, 60-69, and 70 , there was no
signifi- cant difference in survival (P .466).
Furthermore, there was no difference in survival
between male and female patient cases. When the
major ethnic groups were exam- ined, Hispanics had the
poorest OS (P .03). For Ewing- specific survival
however, this survival difference was not significant (P
.24). Ewing-specific survival curves by race are shown
in Figure 2. Among the SES categories, the lowest SES
had the poorest OS and Ewing-specific
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Figure 1. Ewing-specific survival of adults versus children is

stratified by stage of disease.

Figure 2. Shown is Ewing-specific survival by race/ethnicity;

P .24.

survival (P .002 and P .005, respectively). Ewingspe- cific survival among different SES groups is shown in
Fig- ure 3.
Patient cases that presented with metastatic disease
had significantly poorer survival than those with local
dis- ease (P < .0001). Comparisons were made with
regard to location of disease, and patient cases with
pelvic involve- ment were found to have the poorest OS
and Ewing-spe- cific survival (P < .0001). This is
illustrated in Figure 4. Patient cases with tumor size
equal to or greater than 8 cm had poorer OS and Ewingspecific survival than patient cases with tumor size
smaller than 8 cm (P < .0001). There was no
significant difference in OS and Ewing-spe- cific survival
between axial versus nonaxial patient cases, or between
skeletal versus nonskeletal patient cases (P .05 and
P .49, respectively).

Figure 3. Ewing-specific survival by socioeconomic status

(SES) is depicted. Lowest SES quintile compared with other
quintiles; P .0003.

Figure 4. Ewing-specific survival is stratified by anatomic site

of disease; P .0001.

There was no difference in survival found

between patient cases that received chemotherapy or
radiation, and those that did not (OS, P .18 and
P .35, Ewing-specific survival P .54 and P .
31, respectively). Patient cases that did not receive any
sur- gery had the poorest OS and Ewing-specific
survival, compared with patient cases that did receive
surgery (P
< .0001). Three treatment groups were formed that
comprised patient cases that received surgery without
radiation, surgery with radiation, and radiation without
surgery. Survival among these groups were compared,
and the groups that received surgery without radiation
and surgery with radiation were found to have
signifi- cantly better survival than the group that
received

Table 2. Multivariate Analysis (Cox Models) of OS and Ewing-Specific Survival

OS Analysis
a

Ewing-Specific Survival

HR (95% CI)

HRa (95% CI)

1.00b
1.71 (1.35-2.17)

<.0001

1.00b
1.64 (1.24-2.16)

.0005

1.00b
1.00 (0.79-1.26)

.99

1.00b
0.91 (0.68-1.2)

.5

1.00b
1.33 (1.01-1.75)
0.99 (0.65-1.49)

.04
.95

1.00b
1.2 (0.86-1.67)
0.85 (0.5-1.43)

.29
.54

1.00b
0.54 (0.38-0.78)
0.57 (0.40-0.82)
0.75 (0.51-1.08)
0.67 (0.45-0.99)

.001
.002
.12
.04

1.00b
0.55 (0.36-0.84)
0.41 (0.26-0.64)
0.65 (0.42-1.00)
0.61 (0.39-0.96)

.005
<.0001
.05
.03

1.00b

1.00b

2.74 (2.14-3.49)

<.0001

2.85 (2.13-3.80)

<.0001

1.00b
1.65 (1.17-2.34)

.005

1.61 (1.05-2.48)

.03

1.00b
1.27 (0.95-1.68)
0.85 (0.63-1.15)

.1
.3

1.00b
1.21 (0.87-1.69)
0.85 (0.59-1.22)

.26
.37

1.00b
0.82 (0.65-1.03)

.09

1.00b
0.75 (0.57-0.99)

.04

1.00b
0.67 (0.42-1.07)

.09

1.00b
1.09 (0.55-2.15)

.81

1.00b
0.53 (0.35-0.79)
0.65 (0.47-0.91)
0.78 (0.51-1.21)
0.82 (0.57-1.19)

.002
.012
.27
.32

1.00b
0.45 (0.27-0.75)
0.54 (0.35-0.82)
0.71 (0.42-1.20)
0.81 (0.53-1.25)

.002
.004
.2
.79

1.00b
0.95 (0.73-1.24)

.7

1.00b
0.72 (0.51-1.00)

.053

Age
Children (<18 y)
Adult

Sex
Male
Female

Race/ethnicity
White
Hispanic
Others

SES
Lowest
Second lowest
Middle
High
Highest

Stage
Local disease
Metastasis

Tumor size
<8 cm
8 cm and greater

Anatomic site
Extremity
Pelvis
Other

Radiation
No
Yes

Chemotherapy
No
Yes

Surgery
None
Local excision/destruction
Radical excision/limb salvage
Amputation
Surgery NOS

Year of diagnosis
Before 2001
2001 and after

OS indicates overall survival; CI, confidence interval; SES, socioeconomic status; NOS, not otherwise specified.
a
Hazards ratios indicate values after adjustment for each of the listed variables in the table.
b
Reference group.

radiation without surgery (OS P .0002, Ewing-specific survival P .0004). There was no difference in
survival between the the group that received surgery
without radiation and the group that received
surgery with radiation (OS, P .5646, Ewing-specific
survival P .8832).

Survival in different time periods was examined by

categorizing patient cases into 3 groups based on their
year of diagnosis: 1989-1994, 1995-2000, and 20012007. We restricted the analysis to events that occurred in
the first 72 months to adjust for the shorter follow-up
times for patient cases diagnosed more recently. Five
year

survival improved during the most recent time period, with Ewing-specific survival being 61.5% for 1989-1994,
60.5% for 1995-2000, and 71.4% for 2001-2007. For patient cases diagnosed 2001 and after, Ewing-specific
survival was significantly better than those diagnosed before 2001 (P .02). For the earlier time periods, a significantly higher rate of radiation therapy was given (1989-1994: 60%, 1995-2000: 56.1%, 2001-2007:
44.4%, P .002). Metastatic disease was also seen at a significantly higher rate during the earlier time periods
(1989-1994: 32.7%, 1995-2000: 32%, 2001-2007:
17.5%, P < .0001).

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