NcXHF

BENJAMIN ET AL
FIGURE 1. Continuous Disease-Free Survival by Tumor
Necrosis
FIGURE 2. Continuous Disease-Free Survival with
Tumor Necrosis of 90% or Less
will be needed in patients whose disease cannot be treated
surgically. 17
OSTEOSARCOMA
Our therapy for osteosarcoma is based on experience in a
group of patients treated from 1980 to 1991 with induction
therapy of 90 mg/m 2 of doxorubicin as a continuous intravenous
infusion over 48 to 96 hours and 120 to 160 mg/m 2 of
cisplatin intra-arterially. Initially, we found a marked difference
in postoperative continuous disease-free survival
(CDFS) between those with 90% or greater (i.e., good) tumor
necrosis and those with less than 90% (i.e., poor) tumor
necrosis. 20 (Fig. 1) We subsequently modifıed postoperative
chemotherapy, fırst adding high-dose methotrexate
and later, in addition, ifosfamide. We found no benefıt
from the addition of methotrexate to the good responders,
but we observed an increased CDFS in the poor responders
from 13% to 34%. The subsequent addition of ifosfamide
to the postoperative regimen further increased the
CDFS to 67% (Fig. 2), such that the difference between
good and poor responders was no longer statistically signifıcant.
21
Because we have not had additional good drugs to add to
our regimen, we have continued the practice established in
our 1988 to 1991 series of adding ifosfamide and highdose
methotrexate to patients who have poor tumor necrosis.
We recently reviewed a series of 46 patients with
primary osteosarcoma of the extremities who were treated
according to this approach. The median 10-year CDFS was
50%, and there was no difference between patients with
good or poor necrosis. The recent EURAMOS study concluded
that addition of ifosfamide was of no benefıt to
(largely) pediatric patients with osteosarcoma and poor
necrosis. 22 The initial approach with modifıed adjuvant
chemotherapy after poor response to neoadjuvant chemotherapy
came from the sequential studies of Rosen et al, 23
the inventor of the neoadjuvant approach. 23 Our data, together
with the early studies of Bacci et al from the Rizzoli Institute, 24
support adaptation of postoperative therapy to preoperative response,
despite the EURAMOS data. Our approach emphasizes
maximum doses of the individual drugs in the initial
doxorubicin-cisplatin doublet rather than adding methotrexate,
which overlaps in nephrotoxicity with cisplatin
and in mucositis with doxorubicin. We see no advantage
to adding methotrexate in good responders, and it can be a
diffıcult drug to use in older patients.
One factor that needs emphasis is that the spectrum of
histologic appearance in adult osteosarcoma is quite different
from that usually seen in pediatric series. Conventional
osteosarcoma (osteoblastic, chondroblastic, and
fıbroblastic subtypes) makes up the vast majority of cases
in typical pediatric series. Of the variants, only telangiectatic
osteosarcoma has a similar response to therapy and
prognosis. Patients with chondroblastic osteosarcoma had
a lower rate of good necrosis but a better prognosis despite
poor necrosis in our original series of patients, and that
observation appears to be true in the subsequent group we
analyzed, albeit with small numbers. Patients with variant
histology (dedifferentiated parosteal osteosarcoma, highgrade
surface osteosarcoma, small cell osteosarcoma)
other than telangiectatic osteosarcoma represented 12% of
our original series and had signifıcantly worse CDFS. Perhaps
because of the increasing age of patients currently seen
on our pediatric service, variant histology was even more
common in our recent group (28%). The patients in our current
group were older than in our original series. In our current
group, 46% are older than age 30, and 33% are older than
age 40, compared with 23% and 11%, respectively, in our initial
series.
PET-CT is the best imaging modality to assess response to
therapy. MRI is the best modality to defıne an anatomic abnormality
within bone, but it routinely overestimates the extent
of residual viable tumor. CT shows details of cortical
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