2.7. Survival and follow-up
Median overall follow-up since diagnosis is 36 months
(range 4-354). Median progression-free survival is
12.5 months (range 1-284). Five-year overall survival is
83% (95% confidence interval, 60-100), and 5-year progres-
sion-free survival is 22% (95% confidence interval, 0-44)
(
Fig. 2
A and B).
There were trends in disease differences, and hence in
outcomes, between the 10 patients aged 16 years and
younger and the 10 patients aged 17 years and older. The
majority of the younger cohort (7/10 or 70%) had IRS group
I disease. In contrast, the majority of the older cohort (6/10
or 60%) had IRS group II to IV disease. Age did not
significantly impact time to progression.
Tumor size appeared to impact upon time to progression.
There was significantly longer progression-free survival for
those with primary tumors 5 cm or smaller, versus those
with tumors bigger than 5 cm ( P = .03) (
Fig. 2
C).
2.8. Deaths
Three patients are known to have died of disease. Patients
7 and 19 both had thigh primaries that progressed to widely
metastatic disease and both received multiple metastasec-
tomies, chemotherapy, and XRT. These 2 each had an
identifiable period when their disease was neglected: patient
7 presented to our hospital 7 years after diagnosis of unilateral
lung metastases, with no interim therapy, and had progressed
by then to bilateral metastases; patient 19 had a diagnostic
delay for 16 months and then had lung metastases at
presentation. Patient 17, though, already had an unresectable
chest wall mass at presentation, along with pulmonary
metastases. She died in hospice 16 months after diagnosis.
3. Discussion
Achievement of complete microscopic resection of
localized alveolar soft part sarcoma is of paramount
importance. Eighty percent of our IRS group I patients
remain NED, and 100% are free of local recurrence at last
follow-up. The few existing pediatric series of this disease in
the literature show similar results. A study of alveolar soft
part sarcoma in 19 pediatric patients from the Italian Soft-
Tissue Sarcoma Cooperative Group found that 9 of 9 IRS
group I patients remained NED, with follow-up ranging from
11 to 243 months, with many having received no adjuvant
therapy
[5]
. In another report on 11 pediatric patients, 4 of
5 IRS group I patients were NED with follow-up of 0.6 to
17.3 years
[4]
. Together, these are a compelling argument for
complete excision of the primary tumor with negative
margins. We could not show a benefit from chemotherapy
or radiation.
Initial management pitfalls were encountered commonly.
Four patients came to our center with positive margins after
attempted excisional biopsies. Another presented after
embolization, undertaken without prior biopsy. Eight
(40%) of 20 patients had no preoperative imaging
performed. Preoperative imaging, usually with magnetic
resonance imaging, is mandatory and fine-needle aspiration
or core needle biopsy should be considered before definitive
surgery. Because of the presence of intracellular crystals,
fine-needle cytology can be diagnostic
[11-15]
.
Larger tumor size (N5 cm) was associated with diminished
progression-free survival in this series. In the 1989 report
from our institution, Lieberman et al
[3]
also reported that
larger tumor size adversely impacted survival, as did the pre-
sence of metastases at diagnosis and higher age at diagnosis.
Fourteen (70%) of 20 patients in this series had regional
nodal or distant parenchymal metastases. Although this
tumor may spread to a remarkable variety of tissues, the
lung remains the principal site requiring surveillance. No
patient in our series had brain metastases without also
having lung lesions, as previously seen in a study of
70 patients of all ages from Portera et al
[16]
, but all 4 of our
patients with brain metastases had lesions in the cerebellum,
an association not noted before. Finally, the presence of
lymph node metastases in 2 (10%) of 20 patients should
prompt clinical consideration of the draining nodal basins
for these tumors.
The very short progression-free survival (median
12.5 months) but much longer time of overall follow-up
(median 36 months) suggests that long-term survival is
possible even with metastatic disease. Resection of metasta-
ses may play a role, although it cannot be proven that
metastasectomy--as opposed to the indolent nature of the
disease--is the cause of long survival. Patient 10 had a thigh
primary at age 16, has undergone 8 thoracotomies, and is now
NED almost 20 years after initial diagnosis. Patient 18 was
22 years old when a retroperitoneal alveolar soft part
sarcoma was resected; after 5 more laparotomies in 10 years,
she was rendered cancer-free for 20 years until, 30 years after
initial diagnosis, a CT scan showed liver lesions. Patient 1,
at age 6 the youngest in this series, had a calf primary excised,
then had 2 pulmonary resections, and is NED 11 years
after diagnosis.
Our approach allows for expectant observation when
metastatic disease is low volume, imageable, and dormant
over several time points. For example, patient 3 is being
followed with stable pulmonary nodules proven at thoraco-
scopy to be alveolar soft part sarcoma. Patient 15 has a
stable lung density that has been followed for 4 years, and
through a pregnancy.
In the past 10 years, molecular analyses have shown that
alveolar soft part sarcoma is associated with a chromosomal
translocation from band p11.2 on the X chromosome to
17q25
[17,18]
. Ladanyi et al
[19]
reported in 2001 that a
unique fusion gene transcript, ASPL-TFE3, was present in
12 of 12 cases evaluated. The emerging understanding that
there is a specific molecular defect associated with alveolar
soft part sarcoma makes this a potentially fruitful time for
the study of this rare tumor. By practicing appropriate
M.L. Kayton et al.
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