NcXHF

PAOLO G. CASALI
ever, this trial showed a clear superiority of the combination
in terms of antitumor activity (response rate and
progression-free survival). Thus, it is logical to resort to most
active regimens in the adjuvant setting, aside from their superiority
in terms of survival in the setting of advanced disease.
Therefore, if the decision is made to use adjuvant
chemotherapy in the single patient, in the absence of a personalized
choice in favor of an histology-driven regimen, a
full-dose combination of an anthracycline and ifosfamide
can be regarded as the most logical selection today. In many
institutions, this means doses of doxorubicin in the range of
60 to 75 mg/m 2 , or equivalents, plus ifosfamide in the range
of 6,000 to 7,500 mg/m 2 .
CONCLUSION
The rarity and the heterogeneity of STS have been formidable
obstacles to generating reliable evidence in favor of or against
adjuvant and neoadjuvant chemotherapy. Available data are
consistent with a limited degree of effectiveness, but a lack of
benefıt cannot be ruled out. In fact, several institutions worldwide
propose systemic therapy to selected patients with STS in a
shared decision-making process in conditions of uncertainty.
Eligible patients are those with a high risk of relapse, which
largely is dictated by the malignancy grade and the clinical
presentation. There are some rare histologies that are poorly
sensitive to chemotherapy: in patients who have these histologies,
adjuvant chemotherapy usually is not proposed, even
when the risk would be high enough to justify adjuvant treatment,
if available.
There is some evidence that systemic therapy may be
placed before or after surgery with similar results, with the
obvious advantage for preoperative chemotherapy to exert a
local effect, which sometimes may be benefıcial for the quality
of surgical margins. Chemotherapy may be combined
with radiation therapy preoperatively so that the local effect
is maximized. Evidence provided by one randomized trial
would support a short course of three cycles of chemotherapy,
which clearly is more acceptable for decision making in
a setting of so much uncertainty over its effıcacy.
Overall, chemotherapy has a limited antitumor activity in
STS. Although this explains the diffıculty in fınding any major
effect of adjuvant chemotherapy, it is clear that systemic
therapy is undergoing improvements in STS. A major way
forward seems to lie in histology-driven approaches. Thus,
an ongoing, randomized trial is comparing three cycles of
full-dose epirubicin plus ifosfamide with three cycles of an
histology-driven chemotherapy regimen (i.e., gemcitabine
plus dacarbazine in leiomyosarcoma; trabectedin in myxoid
liposarcoma; high-dose continuous-infusion ifosfamide in
synovial sarcoma; ifosfamide plus etoposide in malignant peripheral
nerve sheath tumors; gemcitabine plus docetaxel in
pleomorphic sarcomas). Likewise, an above-mentioned randomized
trial that is ongoing in uterine leiomyosarcoma is
histology-driven. In principle, molecularly targeted agents
shown to be active in STS might be tested in the adjuvant
setting, though they face all of the limitations that targeted
therapy may encounter in solid tumors when used as an adjuvant,
as demonstrated with gastrointestinal stromal tumors.
19,20
Thus, there is room to test the effectiveness of more variegated
medical therapies in the adjuvant treatment of STS, but
standard practice continues to face a high degree of uncertainty.
All the rules of rational decision making in conditions
of uncertainty should be exploited while we look forward to
the implementation of new methods for clinical studies in
rare cancers. 21
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: Paolo G. Casali, Novartis, Pfizer, PharmaMar.
Consulting or Advisory Role: Paolo G. Casali, Amgen Dompé, ARIAD/Merck, Bayer, Blueprint Medicines, GlaxoSmithKline, Lilly, Merck Serono, Merck Sharp
& Dohme, Novartis, Pfizer, PharmaMar. Speakers’ Bureau: None. Research Funding: Paolo G. Casali, Amgen Dompé (Inst), Bayer (Inst), Eisai (Inst),
GlaxoSmithKline (Inst), MolMed S.p.A. (Inst), Novartis (Inst), Pfizer (Inst), PharmaMar (Inst). Patents, Royalties, or Other Intellectual Property: None.
Expert Testimony: None. Travel, Accommodations, Expenses: Paolo G. Casali, Novartis, PharmaMar. Other Relationships: None.
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