الفهرس 
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Abstract
Studying the impact of different imaging approaches on the accuracy of
staging, monitoring response, prognosis and detection of early relapse in children
suffering from HL is mandatory to achieve better therapy and better prognosis in
such age group.
Positron emission tomography using 18F-fluoro-deoxy-glucose (FDG-PET) is
considered an excellent tool for staging and monitoring disease status in patients
with lymphoma.
In our study, 53.7% of patients showed discrepant findings between PET and
conventional imaging modalities. Nevertheless, therapy was modified in only
20.4% of patients according to the change in their stage. FDG-PET modified
therapy in 7/54 patients (about 13%) and CIMs modified therapy in 4/54 patients
(about 7%).
This study was planned to assess the effectiveness of 18F-FDG PET performed
before starting therapy (staging PET or PET1) and early after two cycles of
chemotherapy (interim PET or PET2) in pHL patients emphasizing on in their
different pathological subgroups. Different risk factors and therapy groups were
also tested for their correlation to the patients’ outcome.
Only bone marrow infiltration was significantly related to the patient’s
outcome (p value = 0.0007).
Different visual and semiquantitative techniques were used to evaluate their
potential prognostic role to assess response to therapy measured from staging,
interim PET, and the combined results of both PETs.
A comparison of different PET data analyses was performed applying
individualized standardized uptake values (SUV), PET-derived metabolic tumor
volume (MTV), and the product of both parameters, termed total lesion
glycolysis (TLG).
One-hundred-eight PET datasets (PET1, n=54; PET2, n=54) of 54 children
were analysed by visual and semi-quantitative means. SUVmax, SUVmean,
MTV, and TLG were obtained. Results of both PETs and the relative change
from PET1 to PET2 (Δ in %) were compared for their capability of identifying
responders and non-responders using receiver operating characteristics (ROC)-
curves.
All semi-quantitative SUV estimates obtained at PET2 were significantly
superior to the visual PET2 analysis. However, ΔSUVmax revealed the best
results (area under the curve, 0.92; P<0.001; sensitivity 100%; specificity 85.4%;
PPV 46.2%; NPV 100%; accuracy, 87.0%) but was not significantly superior to
SUVmax-estimation at PET2 and ΔTLGmax.
In summary, elaborated techniques of semi-quantitative reading of FDG-PET
data for early response-to-therapy assessment in pHL such as SUV correction for
body surface area or metabolically guided volumetric analyses (e.g., MTV, TLG)
fail to improve the PPV to a clinically acceptable minimum of at least 80% while
preserving maximum NPV. Instead, SUVmax estimation of the interim PET or—
in order to increase the PPV—the ΔSUVmax from the staging PET to the interim
PET demonstrate equivalent results whereas their calculation is much faster in aclinical setting.
We may conclude that the high rate of false positive cases is not necessarily aweakness of FDG PET but in turn is owed to the strength of the optimized
subsequent treatment and the disproportional time points of treatment success
estimation: after two cycles of chemotherapy in case of PET2 against full course
of chemo-/ radio-chemotherapy in case of outcome estimation. Considering this,
a positive interim PET2 is not an optimal base to draw a treatment escalation
decision from, e.g. adding or omitting radiotherapy, respectively.
from a clinical point of view the high NPV provides an option to avoid
radiotherapy in interim PET-negative pHL patients regardless of their initially
attributed disease-related risk.
Recommendations:
Prospective patient collection with larger sample size and longer follow
up periods are recommended to validate the predictive value of negative
interim PET along years of close follow up.
Larger sample sizes are needed to draw valuable results regarding
different pathological subgroups of paediatric HL and to get deeper
insight about the characteristics of each pathological subtype.
A multidisciplinary tumor board is necessary for better reading of the
results of patients’ clinical data along with the findings of all
conventional imaging modalities (CIM) side by side with FDG-PET/CT
in pediatric lymphomas. A team should include pediatric hematologists,
diagnostic radiologists, nuclear medicine physicians, and radiation
oncologists.
Sstandardized and reproducible methods for PET scanning and
reporting should be respected as guidelines between PET/CT centers for
standardization of the results visual or semiquantitative analysis
techniques.
More sophisticated semi-quantitative techniques should not replace the
simple and fast analytical measures like SUVmax. Meanwhile, built in
calculation algorithms of the best performing semiquantitative measures
should be provided by the commercial workstations and analytical
programs used for display and quantification of PET/CT studies to
achieve more accurate prediction of the patient’s outcome and hence
achieve better prognosis.
Negative PET2 provides an option to omit radiotherapy regardless of
patient initial staging. Meanwhile, a positive PET2 is not an optimal
base to add radiotherapy, but indicates the need for additional
investigation by molecular imaging using new tracers such as:
11C-methionine
18F fluorothymidine (FLT).