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7. Summary and conclusions
ter 3 presents a shorter but intensive treatment regimen for locally advanced ESTS,
consisting of HILP, preoperative EBRT and surgical resection of the tumor remnant.
This intensified treatment was found to be feasible and safe in locally advanced ESTS,
while the oncological outcome was found to be similar to the traditionally used regimen.
As highlighted in chapter 4, limb-salvage treatment is not or no longer feasible
for some patients. In these cases, limb-amputation is the only remaining treatment
option to obtain local tumor control. Non-resectability of the tumor caused by large
tumor size was found to be the main indication for a primary amputation, whereas
a local recurrence which could not be treated with a limb salvage treatment option
was the predominant indication to perform a non-primary amputation. Furthermore,
we showed in chapter 4 that while the time between diagnosis and amputation differs
significantly for primary and non-primary amputated patients, their oncological
outcome seems to be comparable.
not prognostic for oncological outcome. 14 Possibly, because the amount of treatmentinduced
necrosis cannot be distinguished from tumor necrosis already present, due
to tumor heterogeneity, prior to treatment. 15 Chapter 6 establishes that the European
Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma
Group response score 15 is applicable for the determination of the histopathological
tumor response in pretreated ESTS. However, it seems that neither local recurrence
free survival nor overall survival are predicted by this stainable, possibly viable, tumor
cell based response score.
In conclusion, the preceding chapters of this thesis address various aspects and advancements
in the treatment of, locally advanced, localized ESTS. Insights in the ongoing
and future research in the treatment of, locally advanced, localized ESTS will be
addressed in the following chapter; Chapter 8 – Future perspectives.
Part III - Metabolic and histopathological tumor responses in pretreated
extremity soft tissue sarcoma
The more routine use of neoadjuvant treatment modalities i.e. HILP, preoperative EBRT
and neoadjuvant systemic chemotherapy in localized ESTS has consequently led to
more research focusing on the assessment of neoadjuvant treatment-efficacy. Since
the 1990s, fluorine-18-fluorodeoxyglucose positron emission tomography with computed
tomography ( 18 F-FDG PET-CT) scans have been used to assess and quantify
the changes in metabolic tumor activity, commonly expressed as maximum standardized
uptake value (SUVmax) and SUVmean. 13 In chapter 5 we present the use of
various volume of interest (VOI) delineation techniques for the quantification of the
metabolic tumor activity of locally advanced ESTS during neoadjuvant multimodality
treatment, consisting of neoadjuvant HILP, preoperative EBRT and surgical resection.
In addition to the commonly used SUVmax and SUVmean, SUVpeak, total lesion
glycolysis (TLG) and metabolically-active tumor volume (MATV) were obtained for all
scans. Considering the VOI delineation techniques, the VOI grad+
delineation technique
was shown to be most reliable considering reproducibility when compared with the
three other delineation techniques. A significant decline in metabolic tumor activity
during this treatment was found, this decline was most pronounced following the
HILP. TLG was shown to be promising as predictor for histopathological response in
pretreated ESTS, however, it warrants further confirmation in larger patient-cohorts.
The histopathological response of pretreated ESTS was further studied in chapter 6.
The percentage tumor necrosis has been used commonly to express the extent of
the histopathological tumor response following neoadjuvant treatment. However,
the percentage tumor necrosis at histopathological examination in pretreated ESTS is
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