and overall survival between the 2 treatment
groups. 33 With regards to IMRT, a single institution cohort experience with 41 patients who
received IMRT following limb-sparing surgery
had similar local control rates when compared
to historical controls. 34
CASE CONTINUED
After discussion of the risks and benefits of
radiation therapy, the patient opts for preoperative radiation prior to resection of his liposarcoma. He receives 50 Gy of EBRT prior to
undergoing resection. Resection results in R1
margin consistent with microscopic disease. He
receives 16 Gy of EBRT as a boost after recovery
from his resection. 2
•;What;is;the;evidence;for;neoadjuvant;and
adjuvant;chemotherapy;for;stage;I;tumors?
CHEMOTHERAPY
Localized Sarcoma
For localized sarcoma, limb-sparing resection
with or without radiation forms the backbone
of treatment. Studies have evaluated chemotherapy in both the neoadjuvant and adjuvant
settings, with the vast majority of studies evaluating doxorubicin-based chemotherapy regimens
in the adjuvant settings. Due to the rare nature
of sarcomas, most studies are not sufficiently powered to detect significant benefit from
chemotherapy. Several trials evaluating chemotherapy regimens in the neoadjuvant and
adjuvant settings needed to be terminated prematurely due to inadequate enrollment into the
study. 35, 36
For stage IA (T1a-Tb, N0, M0, low grade)
tumors, no additional therapy is recommended
after limb-sparing surgery with appropriate sur-
gical margins. For stage IB (T2a-2b, N0, M0,
low grade) tumors with insufficient margins,
re-resection and radiation therapy should be
considered, while for stage IIA (T1a-1b, N0, M0,
G2-3) tumors preoperative or postoperative ra-
diation therapy is recommended. 2 Studies have
not found benefit of adjuvant chemotherapy
in these low-grade, stage I tumors in terms of
progression-free survival and overall survival. 37
•;At;what;stage;should;chemotherapy;be;con-
sidered?
For stage IIb and stage III tumors, surgery
and radiation therapy again form the backbone
of therapy; however, neoadjuvant and adjuvant
chemotherapy are also recommended as considerations. Anthracycline-based chemotherapy
with either single-agent doxorubicin or doxorubicin and ifosfamide in combination are considered first-line chemotherapy agents in locally
advanced STS. 2, 29, 37
Evidence regarding the efficacy of both neo-adjuvant and adjuvant chemotherapy regimens
in the setting of locally advanced high-grade
STS has been mixed. The Sarcoma Meta-analysis
Collaboration evaluated 14 trials of doxorubicin-based adjuvant chemotherapy and found a
trend towards overall survival in the treatment
groups that received chemotherapy. 37 All trials included in the meta-analysis compared
patients with localized resectable soft-tissue sarcomas who were randomized to either adjuvant chemotherapy or no adjuvant chemotherapy after limb-sparing surgery with or without
radiation therapy. None of the individual trials showed a significant benefit, and all trials
had large confidence intervals; however, the
meta-analysis showed significant benefit in the
chemotherapy treatment groups with regard
to local recurrence, distant recurrence, and
progression-free survival. No significant difference in overall survival was found. 37 Pervais et al
updated the Sarcoma Meta-analysis Collaboration’s 1997 meta-analysis with the inclusion of 4
new trials that evaluated doxorubicin combined
with ifosfamide and found that both patients
who received doxorubicin-based regimens or
doxorubicin with ifosfamide had significant
decreases in distant and overall recurrences.
Only the trials that utilized doxorubicin and
ifosfamide had an improved overall survival
that was statistically significant (hazard ratio
