|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4464-4471
Positron Emission Tomography in Non-Hodgkin's Lymphoma:
Assessment of Chemotherapy With Fluorodeoxyglucose
By
Wolfgang Römer,
Axel-R. Hanauske,
Sibylle Ziegler,
Ralf Thödtmann,
Wolfgang Weber,
Christoph Fuchs,
Wolfgang Enne,
Michael Herz,
Christoph Nerl,
Manfred Garbrecht, and
Markus Schwaiger
From Nuklearmedizinische Klinik, Klinikum rechts der Isar, Technische
Universität München, Munchen, Germany; I. Medizinische
Klinik, Abteilung Hämatologie und Onkologie, Klinikum rechts der
Isar, Technische Universität München, München,
Germany; Department of Oncology, Universitair Ziekenhuis Gasthuisberg,
Leuven, Belgium; IV. Medizinische Abteilung, Städtisches
Krankenhaus München-Neuperlach; I. Medizinische
Abteilung, Hämatologie, Onkologie und Immunologie,
Städtisches Krankenhaus München-Schwabing.
 |
ABSTRACT |
Positron emission tomography (PET) using F-18
fluorodeoxyglucose (FDG) was performed in non-Hodgkin's lymphoma
(NHL), which is known to be highly responsive to chemotherapy, but also
yields variable treatment results to answer the following questions: (1) What is the extent and time course of changes in FDG utilization in
response to chemotherapy? (2) Are the changes of FDG uptake at early
time points of chemotherapy predictive for therapy outcome? (3) Which
quantitative FDG parameter provides the most sensitive measures of
initial tumor response? Dynamic PET scans were performed in 11 patients
at baseline and 1 and 6 weeks after initiation of chemotherapy. Based
on attenuation corrected images acquired 30 to 60 minutes
postinjection, standardized uptake values (SUV) were determined.
Arterial input functions were estimated from vascular F-18 activity and
the metabolic rates for FDG (MRFDG) were calculated using Patlak
analysis. Before chemotherapy, high FDG uptake was found in all lesions
(SUV[max] 13.3 ± 4.2). Seven days after initiation of chemotherapy,
tumor FDG uptake decreased 60% (SUV[max]). A further decrease
of 42% was seen at day 42 resulting in a total decrease
of 79% from baseline to day 42. During a follow-up of 16.0 ± 4.2 months, six of the 11 patients continued to show complete remission.
Seven days after initiation of chemotherapy, this group of patients
displayed significantly lower mean MRFDG than the group of patients
with relapse. At day 42, all parameters of FDG uptake showed a
significant difference for both patient groups. The relative change of
MRFDG from baseline to day 42, as well as from day 7 to day 42, was
significantly larger as compared with SUV parameters. Standard
chemotherapy of patients with NHL causes rapid decrease of tumor FDG
uptake as early as 7 days after treatment, which continues to decline
during therapy, indicating the sensitivity of metabolic signals to
chemotherapeutic interventions. FDG uptake at 42 days after therapy was
superior in prediction of long-term outcome over day 7 parameters.
Dynamic data acquisition combined with Patlak analysis of FDG kinetics
may provide superior information in therapy monitoring.
| |
INTRODUCTION |
MALIGNANT TUMORS HAVE been shown to
display increased glucose metabolism.1 Positron emission
tomography (PET) with the radiolabeled glucose analog
fluorine-18-deoxyglucose (FDG) allows quantitative assessment of
glucose utilization in tumor tissue. The mechanism of cellular uptake
of FDG reflects both transport and phosphorylation of glucose. FDG is
phosphorylated by hexokinase and trapped intracellulary as FDG-6-PO4
with a slow rate of dephosphorylation in most tissues. Because the
majority of tissue activity represents FDG-6-phosphate at the time of
PET imaging, regional radioactivity will correlate with FDG
metabolism.2 The ability of FDG-PET to localize primary
carcinomas, regional lymph nodes, and distant metastatic sites is well
documented in the literature.3,4
Several studies on FDG uptake after radiotherapy, as well as after
chemotherapy in miscellaneous tumors, suggest the use of FDG for
assessment of therapeutic effects.5-8 Reduced numbers of
viable cells or reduced metabolism of the damaged cells might be
associated with decrease of tumor glucose utilization.9,10 Few data exist defining the time course and extent of changes in tumor
FDG uptake as response to chemotherapy. Data from cell culture and
animal studies suggest an initial enhancement of glucose uptake induced
by chemotherapy11,12 or radiotherapy.13 PET imaging in patients with breast cancer showed that chemotherapy leads
to a decrease of the glucose metabolism in solid tumor within 1 or 2 weeks.9,14,15
The purpose of this study was (1) to assess the incidence and time
course of changes of glucose utilization in response to chemotherapy
with FDG-PET; (2) to investigate the value of FDG uptake during
chemotherapy at early (day 7) and late (day 42) time points in
prediction of therapy outcome; and (3) to identify quantitative PET
parameters, which may provide sensitive measures of initial tumor
response.
To evaluate these questions, non-Hodgkin's lymphoma (NHL) has been
chosen as the tumor model because this tumor displays enhanced FDG
uptake.16-23 In addition, NHL is known to be highly
responsive to chemotherapy and shows a high variability of responses to
chemotherapy.24,25 A baseline PET was performed before
chemotherapy and was repeated 1 and 6 weeks after initiation of
chemotherapy.
| |
MATERIALS AND METHODS |
Patients.
Eleven patients with newly diagnosed high-grade NHL, who were scheduled
to undergo chemotherapy, were included in this study between July 1995 and July 1996. Mean age of the patients was 50 years, ranging from 21 to 77 years. Six patients were men and five were women. Patient
characteristics are listed in Table 1.
The lymphatic malignancy was histologically verified in all patients.
Exclusion criteria were pregnancy, known diabetes, or age younger than
18 years. No patient received prior therapy for NHL.
Details of the study were explained by a physician and written informed
consent was obtained from all patients. The study protocol was approved
by the institutional review board at the Technische Universität
München.
Histologic classification.
Histology of lymphomas was classified according to the updated Kiel
classification.26
Treatment protocol.
The patients underwent chemotherapy either with a standard
protocol27 using a combination of cyclophosphamide,
doxorubicin, vincristin, (etoposid), and prednisone (CHO(E)P) (CHOP: n = 4; CHOEP: n = 2) or were included in a phase 1 trial evaluating the polyamine pool depleting compound mitoguazone (MGBG, NSC 32946) in
combination with CHOP (sequence MGBG  CHOP: n = 2; CHOP MGBG: n = 3).
A baseline PET examination was performed within 1 week before
chemotherapy, together with other staging modalities (clinical examination, computed tomography [CT], or magnetic resonance imaging [MRI]). PET imaging was repeated at day 7 (range, day 6 to day 8)
after the first course of chemotherapy (day 1 to 5). A third PET study
was performed after completion of an additional course (day 22 to 26)
at day 42 (range, day 39 to day 47). At this time, restaging procedures
including morphologic imaging (CT or MRI) were scheduled. In one case
(patient no. 8), chemotherapy was repeated in 2-week intervals (day 15 to 19 and day 29 to 33).
PET imaging.
Patients were fasted at least 8 hours before PET imaging. The serum
glucose level was measured before each PET examination with blood
glucose reagent strips and photometric measurement (Glucometer II,
Glucostix, Bayer Diagnostics, Munich, Germany). Mean blood glucose
level summarizing all PET studies was 104.2 ± 14.2 mg/100 mL (mean ± standard deviation [SD]; range, 83 to 139).
F-18 was produced with a self-shielded 11 MeV cyclotron RDS 112 (Siemens/CTI, Knoxville, TN) by the acceleration of
protons onto an O-18 H2O target. FDG of high specific
activity was produced with a standard technique by means of
nucleophilic fluorination using a method modified from the synthesis of
Hamacher.28
PET scans were performed using a whole body PET scanner (ECAT 951R/31
or ECAT EXACT, Siemens CTI) over the largest known lesion. The ECAT
951R/31 scanner consists of 16 rings of bismuth germanate detectors
(BGO) yielding 31 transverse slices, 3.375 mm apart (axial
field-of-view 10.8 cm). The 24-ring ECAT EXACT yields 47 slices, 3.375 mm apart (axial field-of-view 16 cm). Emission data corrected for
randoms, dead time, and attenuation were reconstructed with filtered
back-projection (Hanning filter with cut-off frequency of 0.4 cycles/bin). Transmission measurements were acquired before tracer
injection with Germanium-68 rod sources yielding approximately 4 million counts per slice. The resulting in-plane image resolution of
transaxial images of both scanners was approximately 8 mm full width
half maximum (FWHM) with an axial width of approximately 5 mm FWHM.
In all patients, dynamic data acquisition was performed up to 60 minutes after intravenous bolus injection of 370 MBq F-18 FDG (30 frames: 12 × 10 seconds, 6 × 30 seconds, 5 × 60 seconds, 4 × 5 minutes, 3 × 10 minutes).
Data analysis.
Regional FDG uptake in tumor tissue from the PET image data was
quantified using the following methods. (1) Standardized uptake value
(SUV): SUV were calculated using the sum of the three last frames of
dynamic imaging (30 to 60 minutes postinjection [p.i.]). Standardized circular regions of interest (ROI) with a diameter of 12 mm were drawn on the slice displaying highest tumor activity concentration and the neighboring planes. SUV values represent the
average (SUV[avg]) or maximum (SUV[max]) radioactivity
concentration of each set of three ROIs normalized for injected dose
and body weight.3 (2) Patlak analysis: dynamic PET studies
allow the assessment of a FDG influx constant using the Patlak analysis approach29 if unidirectional transport between two
compartments can be assumed. This requirement is fulfilled during
approximately the first hour after FDG injection as long as
dephosphorylation is negligible. A graphical analysis of
tissue-time-activity curve and arterial blood activity curve results in
a measure for tracer uptake rate. The arterial input function was
obtained using 90% isocontour ROIs placed in a large vessel (aorta,
arteria carotis) in four consecutive planes in frames 3 or 4. During
follow-up, the ROIs were repositioned using the same vascular
structure. Tissue-time-activity curves were derived from standardized
circular ROIs with a diameter of 5 mm, which were drawn over the tumor in the plane displaying highest activity concentration and the neighboring planes. The tissue radioactivity concentration divided by
plasma activity was plotted against cumulative plasma radioactivity divided by plasma activity for each time point. The slope of this linear plot from 20 to 60 min p.i. determined the utilization constant
of FDG (influx constant K), expressed as mL/100g/minute. To indicate a
parameter of the quality of the influx constant K, the r value of the
linear regression was used. Furthermore, the metabolic rate of FDG
(MRFDG) in tumor was calculated by multiplication of the
influx constant K and the basic blood glucose concentration. Because
the lumped constant accounting for differences in the transport and
phosphorylation of FDG and glucose has not yet been determined in
tumors, the local glucose metabolic rate could not be
indicated.2
Clinical evaluation.
CT and MRI were performed as part of the routine clinical management of
the patients. The decision for CT and/or MRI was made by the clinician
depending on tumor locations.
Baseline CT and/or MRI of head and neck, thorax, abdomen, and
pelvis were performed in all patients before chemotherapy. After the
therapy protocols, the patients were reevaluated by means of CT
and/or MRI after two courses of chemotherapy around day 42. The
treatment response was classified as complete response (CR), partial
response (PR), no change (NC), or progressive disease (PD) according to
the criteria stated by Miller et al30 based on the
bidimensional diameters of corresponding tumor lesions measured by
ruler or caliper. Further evaluations of treatment response were done
according to standard protocols every 3 months. The patient management
was not influenced by the results of PET studies. Actual patient status
was recorded in all remaining patients between April and August 1997.
Statistical analysis.
Data were expressed as the mean ± SD. For intraindividual
comparison of the various FDG parameters at different time points, two
sided paired t-test was used. The Mann-Whitney U test was used
to evaluate the differences between the decreases from baseline to day
7 and 42 and from day 7 to day 42 and to test the differences between
the FDG parameters of patients with long-term response and relapsed
patients. All statistical tests were performed at the 5% level of
significance.
| |
RESULTS |
Responses to chemotherapy.
We studied 11 patients at baseline and 7 and 42 days after initiation
of chemotherapy. Conventional morphologic imaging after two courses of
chemotherapy showed partial (n = 8) or complete (n = 3) response in all
patients. As indicated in Table 1, at the
end of first-line chemotherapy, seven patients showed complete remission. Four of these (no. 2, 3, 7, and 10) received radiotherapy of
the main-bulk area after completion of chemotherapy. Over a follow-up
period of 16.0 ± 4.2 months (range, 10.9 to 23.2 months), six of 11 patients remained in complete remission based on clinical and
radiographic data. Patient no. 4 initially showed a local partial
response, but during the third course, this patient developed tumor
progression with additional new lesions in the central nervous system
(CNS). Histopathologic reevaluation showed that this
patient had a Burkitt's lymphoma. Patients no. 1 and no. 6 developed a relapse including CNS involvement during the sixth and fourth course of
chemotherapy, respectively. Patient no. 11 was progressive at the end of six courses of CHOP. One patient (no. 9), who showed CR
after two courses of chemotherapy, relapsed after a disease-free interval of 12 months. Three patients died of relapse 8 months (no. 1),
12 months (no. 4), and 10 months (no. 11) after the start of
therapy.
Time course of FDG-uptake during treatment.
Statistical comparisons of blood glucose levels at the time of PET
studies before chemotherapy (105.1 ± 16.0 mg/100 mL) and during
chemotherapy at day 7 (101.9 ± 9.9 mg/100 mL) and day 42 (105.8 ± 16.2 mg/100 mL) showed no significant differences.
Figure 1A (patient no. 5) shows an example
of bulky tumor in the left parahilar region with prominent FDG uptake.
Seven days after initiation of chemotherapy, PET imaging showed a
decrease of 77% of maximum SUV and 72% of MRFDG. On day 42, the tumor
region can hardly be differentiated from background activity. This
patient displayed CR over a follow-up period of 15 months. In contrast, the patient shown in Fig 1B (no. 6) exhibited partial remission at day
42, but relapsed during the third course of chemotherapy at multiple
locations including CNS. FDG-PET at day 42 showed residual viable tumor
mass in the left mediastinum and right lower lobe. The myocardial FDG
uptake at day 7 and day 42 does not reflect tumor involvement.
View larger version (57K):
[in this window]
[in a new window]
| Fig 1.
(A) Bulky high-grade NHL in the left parahilar region
with prominent FDG uptake. The patient (no. 5) showed CR over a
follow-up period of 15 months. (B) Extensive mediastinal tumor mass of
a high-grade NHL with an additional focal tumor lesion in the right lower lobe. The patient (no. 6) exhibited partial remission at day 42, but relapsed during the third course of chemotherapy. Myocardial FDG
uptake at day 7 and day 42 does not reflect tumor involvement.
|
|
All tumor lesions imaged before chemotherapy had increased FDG uptake
as compared with surrounding normal tissue (SUV[max] 13.3 ± 4.2).
In Table 1, the results of quantitative analysis of FDG uptake are
summarized. There was no significant difference notable between
SUV[max] and SUV[avg]. The metabolic rate MRFDG was 6.8 ± 2.8 mg/100 mL/minute. The linear fit of dynamic FDG data from 20 to 60 minutes p.i. at baseline showed an r value of 0.988 ± 0.021 (range,
0.927 to 0.999).
Seven days after initiation of chemotherapy, parameters of tumor FDG
uptake decreased by 60% (SUV[max]) and 67% (MRFDG) of initial
values. From day 7 to 42, all lesions exhibited a further decrease of
tracer uptake of 42% (SUV[max]) and 71% (MRFDG). The total decrease
from baseline to day 42 was 79% (SUV[max]) and 89% (MRFDG).
Statistical comparison of all baseline and day 7 parameters, as well as
day 7 and day 42 parameters, showed significant differences (P < .001). The relative decrease of FDG uptake did not correlate with
the initial uptake values either for SUV values or for accumulation
rates. No correlation was found concerning either patients' age or
tumor stage.
In five patients, there were two evaluable lesions within the
field-of-view. We correlated the decrease of SUV[max] of these two
lesions, intraindividually, from baseline to day 7, as well as from
baseline to day 42. The SUV decrease from baseline to day 7 (r = 0.563)
did not correlate as well, as compared with the decrease from baseline
to day 42 (r = 0.981). The intraindividual comparison of SUV[max] at
day 7 (lesion 1, 5.7 ± 2.0; lesion 2, 3.7 ± 1.9) and day 42 (lesion 1, 2.6 ± 1.1; lesion 2, 2.3 ± 1.3) showed no
statistically significant difference.
Correlation of FDG-PET data with therapy outcome.
FDG uptake parameters at day 7 and day 42 were correlated with
long-term clinical outcome (Fig 2). The
analysis of the parameters of FDG uptake at day 7 showed that the group
of patients with long-term remission had significantly lower mean
values of the MRFDG (1.46 ± 0.75 mg/100 mL/minute) as compared with
the group of patients with disease relapse (2.70 ± 1.10 mg/100
mL/minute; P = .045). Using the SUV parameters, there was no
notable difference between both groups (SUV[max] P = .235; SUV[avg] P = .201).
At day 42, we also found significantly lower mean values of MRFDG in
the group of patients with complete remission (0.24 ± 0.22 mg/100 mL/minute) as compared with the group of relapsed patients
(1.15 ± 0.62 mg/100 mL/minute; P = .018) and also the mean
values of maximum (2.1 ± 0.3 v. 3.3 ± 1.0;
P = .018) and average (1.5 ± 0.4 v 2.7 ± 0.9; P = .029) SUV showed significant differences for
both groups. Neither baseline parameters nor percentage decrease from
baseline to day 42 was significantly different in the two groups.
Comparison of various quantitative FDG parameters in therapy
monitoring.
Comparing the percentage change from baseline to day 7, there was no
statistically significant difference between different parameters of
FDG uptake. Considering the percentage decrease of FDG uptake
parameters from baseline to day 42, as well as from day 7 to day 42, the accumulation rates (influx constant K and MRFDG) showed the largest
decrease as compared with SUV parameters (P < .05). However,
the r value of linear regression at day 42 (0.628 ± 0.494; range,
0.720 to 0.983) was significantly lower than r values at
baseline (0.989 ± 0.020; range, 0.927 to 0.999; P = .012) and day 7 (0.950 ± 0.086; range, 0.685 to 0.996; P = .018).
| |
DISCUSSION |
Changes in FDG uptake have been correlated with response to antitumor
therapy by several investigators.31-33 To establish the extent and time course of changes in metabolic parameters that occur
during therapy, high-grade NHL was used as a tumor model to evaluate
FDG uptake in this study. As anticipated, these tumors displayed a high
FDG uptake as assessed with the SUV method in agreement with previous
studies.16 All patients responded to chemotherapy by
partial or complete remission after two courses of chemotherapy. This
response rate is in accordance with data from the
literature.25,34 A rapid and marked decrease of FDG uptake
paralleled this therapy response. However, patients with relapse
displayed higher residual FDG uptake after therapy, suggesting the
sensitivity of FDG to detect residual tumor tissue.
FDG-PET in lymphomas.
NHL are known to have increased FDG uptake before therapeutic
intervention indicating high metabolic activity.18-21
Rodriguez et al23 found an average SUV of 11.8 ± 4.7 (mean ± SD) in 10 patients with high-grade NHL in good agreement
with the average SUV found at the baseline in our patient population
(11.1 ± 3.5). In contrast, Lapela et al16 reported a
significantly higher average SUV in a group of 10 high-grade NHL (17.2 ± 8.2; P = .032), which may reflect methodologic
differences.
Time course of FDG uptake during treatment.
The immediate changes of glucose metabolism after initiation of
antitumor chemotherapy are not completely understood. In a homogeneous
population of 11 patients with high-grade NHL, we observed for the
first time that tumor FDG uptake as a marker of glucose metabolism
showed a marked decrease of 60% (SUV[max]) to 67% (MRFDG)
as early as 7 days after initiation of chemotherapy compared with
baseline. All lesions displayed further decrease of FDG uptake from day
7 to day 42 resulting in a total decrease of 79% (SUV[max]) to 90%
(MRFDG) from baseline to day 42. The observed changes of FDG parameters
cannot be explained by statistical variations. Recent data from our
laboratory showed that repeated measurements of FDG uptake in different
solid tumors are associated with variations of 8% to
14%.35 Minn et al36 found only 10% variation
of FDG uptake in 10 untreated lung cancer patients who were studied two
times within 1 week. Therefore, changes in FDG-parameters of more than
25% cannot be explained by statistical variations, but represent
definite change in metabolic parameters as a consequence of therapeutic
interventions.
In view of the rapid response to chemotherapy, the question may arise
whether the pronounced decrease of FDG uptake is a consequence of rapid
decrease of tumor size resulting in partial volume effects. Recovery of
radioactivity concentration in structures less than twice the spatial
resolution will be decreased (partial volume effect). For the scanner
system used in this study, the spatial resolution is 8 mm. However,
only two lesions displayed a diameter less than 16 mm at day 7, estimated from transaxial PET images. Therefore, it appears unlikely
that partial volume effects are responsible for the observed changes of
tumor FDG uptake.
It was shown by Lindholm et al,37 as well as by Langen et
al,38 that the FDG uptake is influenced by plasma glucose
levels. Significantly higher FDG uptake was measured in fasting
conditions as compared with oral glucose loading. Chemotherapeutic
agents may affect blood glucose level. However, comparison of blood
glucose levels before and during chemotherapy showed no difference.
Therefore, changes in FDG uptake are not correlated with
therapy-induced changes in blood glucose levels.
In 1993, Wahl et al14 described successful early tumor
response monitoring of chemohormonotherapy with FDG-PET in breast cancer. At day 8 of the first course of chemohormonotherapy, a significant decrease of 22% of maximum FDG tumor uptake was shown in
eight therapy responding patients with large primary breast cancer.
Three nonresponding tumors did not show significant decrease in FDG
uptake. Decreases of metabolic parameters preceded changes in tumor
size. Jones et al10 examined patients with soft tissue and
musculoskeletal sarcomas 1 to 3 weeks after initiation of chemotherapy.
In two responsive tumors, FDG uptake decreased by 38% and 36%,
whereas in a tumor progressive under therapy, FDG uptake increased by
71% within some weeks.
Hoekstra et al21 reported similar results in patients with
Hodgkin's disease (n = 3) and NHL (n = 8). In nine of 11 patients, they described a reduction of FDG uptake studied with planar
scintigraphy during the first cycle of chemotherapy. In five patients,
the second study was performed within 1 week after initiation of
treatment. Two patients who failed to respond to therapy exhibited
persistent high FDG uptake. These results were confirmed by
Dimitrakopoulou-Strauss et al18 in a group of 10 patients
with Hodgkin's disease and NHL who were studied at baseline and around
day 30 of chemotherapy.
In summarizing the indicated studies, we conclude that the decrease of
FDG-PET in NHL does reflect treatment-induced metabolic changes.
Correlation of functional and morphologic data with therapy outcome.
It was of particular interest that FDG uptake at day 42 correlated
closely with the patients' disease status. The group of patients with
stable, complete remission even 10 months or more after completion of
therapy exhibited significantly lower mean SUV values, as well as mean
FDG accumulation rates after two courses of chemotherapy compared with
the group of patients with transient tumor response followed by tumor
relapse. Furthermore, already at day 7, the group of patients with
long-term remission had significantly lower mean values of the
metabolic rate MRFDG than the group of patients with disease relapse.
In contrast, SUV parameters did not show significant differences.
Although more studies in larger patient populations are required, one
may speculate that PET represents a sensitive method to detect not only
early tumor response to therapy, but also predict long-term outcome.
Monitoring of antitumor chemotherapy is generally performed by
sequential determinations of tumor size using morphologic imaging modalities (ultrasound, CT, MRI). These assessments do not necessarily reflect the quantity of remaining viable tumor cells. Based on morphologic criteria alone, residual tumor mass cannot be
differentiated from scar. In addition, several courses of chemotherapy
must be administered before treatment effectiveness can be reliably
determined.39,40 However, there are no data showing that
cross-sectional imaging with CT or MRI, after completing one course of
chemotherapy in a highly responsive tumor like NHL, would predict the
result of treatment. Further studies comparing PET data and morphologic data are required to define the relative benefit of each modality in
early therapy monitoring.
In eight of 11 patients in this investigation, morphologic imaging
after two courses of chemotherapy showed residual tumor mass. Four of
these eight patients showed recurrence at later examinations. In three patients, there was no evidence of residual tumor mass. One of these patients relapsed after a disease-free interval of 12 months. Therefore, in this case, morphologic imaging after two courses was not predictive for long-term outcome. In contrast, using a maximum SUV of 2.5 as a cut-off value for
differentiating viable tumor from scar, FDG PET indicated no evidence
of residual viable tumor cells in seven of 11 patients at day 42. This
cut-off value was defined in previous studies to be well-suited for
differentiation of benign and malignant breast tumors.41
Only one of these seven patients relapsed. This was the same patient
who had shown CR by morphologic criteria after two courses of
chemotherapy. All patients displaying a maximum SUV = 2.5 (n = 4)
relapsed.
Our data are in accordance with the results recently published by
Janicek et al42 who studied the value of early restaging gallium-67 scans in predicting chemotherapy outcome in NHL. They found
that Ga-67 scans after two courses of chemotherapy accurately distinguished long-term complete responders from patients with relapsed
disease. At a median follow-up of 31 months, 94% of patients who had
negative Ga-67 scans after two courses of chemotherapy remained free
from progression, whereas only 18% of patients who had positive early
restaging Ga-67 scans remained in complete remission. Similar to FDG,
the tumor seeking radionuclide Ga-67 concentrates in viable tumor, but
lacks to accumulate in fibrotic and necrotic tissue. However, the use
of Ga-67 is limited by its unfavorable radiation properties. The long
half-life of 78 hours results in a relatively high radiation burden of
44 mSv (120 µSv/MBq) per examination using a standard dose of 370 MBq.43 This is in contrast to FDG-PET, which results in a
lower radiation burden of about 10 mSv per study (27 µSv/MBq). A
second disadvantage of Ga-67 is the length of time required for the
examination. Imaging is usually performed 48 to 96 hours after
administration to allow time for clearance of background activity. In
contrast, a FDG-PET examination takes a maximum of 90 minutes scanning
time. Finally, imaging with Ga-67 does not enable absolute
quantification of tracer uptake, allowing only qualitative assessment
of residual tumor mass. Therefore, FDG-PET seems to be the favorable
technique, as long as these first promising data can be confirmed in
larger patient populations.
Based on the data of this study, we postulate that a single PET study
after two courses of chemotherapy may be sufficient to separate patient
subgroups with good prognosis who can be cured with standard
chemotherapy from those with much poorer survival in whom more
aggressive approaches may be required. More aggressive, but also more
toxic regimens, are currently available, but clear criteria to define
the best suited treatment protocol are lacking.27,44,45 The
prognostic value of FDG-PET imaging in this clinical situation needs to
be further investigated.
Comparison of various quantitative FDG parameters in therapy
monitoring.
Several scintigraphic parameters have been suggested for the analysis
of FDG uptake in tumor tissue with respect to their value in monitoring
therapy effects.29,46-48 Dose uptake ratios have been
introduced to normalize tracer uptake to injected dose and body weight.
These simple methods allow comparison of regional tracer uptake in
sequential studies. We calculated maximum and average standardized
uptake values (SUV) of the tumor lesion.
SUV parameters only reflect the concentration of FDG in tumors at the
time of data acquisition, ie, from 30 to 60 minutes postinjection,
without indicating changes in the level of FDG accumulation during this
period. Accumulation parameters expressed as the influx constant K or
the MRFDG indicate the net rate of FDG transport and phosphorylation in
tumor tissue. In contrast to SUV parameters, these parameters include
information on the kinetics of FDG uptake and may possibly be more
sensitive to changes during therapy.
Comparison of SUV values and accumulation parameters suggested that the
influx constant K and MRFDG may be more sensitive in predicting the
tumor response to treatment. In contrast to SUV parameters, at day 7 the influx constant K and MRFDG were already significantly lower for
long-term responding patients as compared with patients with disease
relapse. The percentage decrease of the accumulation rates from
baseline to day 42, as well as from day 7 to day 42, was more
pronounced as compared with SUV parameters. However, because all tumors
showed effective response to therapy at day 42, the activity in the
lesions was low. Therefore, the Patlak graphical analysis at this time
resulted in very shallow curves causing large uncertainties in K, as
shown by the significantly lower r values. In reviewing our data, only influx constants K of more than 1.4 were associated with r values greater than 0.9. Thus, the accumulation rates at baseline and day 7 are more reliable than those at day 42. However, this does not affect
the principle applicability of Patlak analysis in therapy monitoring.
In contrast, SUV parameters may be more stable in areas with low FDG
uptake and may represent the preferable method to differentiate
long-term responders from patients with disease relapse. This
hypothesis has to be tested prospectively in a larger patient
population.
From our data, we conclude that a more demanding data acquisition
including the determination of the blood input curve may yield
additional information for therapeutic monitoring. On the other hand it
has to be taken into account that in lesions with very low FDG uptake,
the reliability of Patlak analysis will be limited. It needs to be
addressed in the future whether this conclusion is also valid for other
tumor types.
| |
CONCLUSION |
In conclusion, FDG uptake in successfully treated NHLs decreased by
60% to 67% from baseline to 7 days after the initiation of
chemotherapy. These results indicate that two thirds of the metabolic
effect of chemotherapy, as assessed by FDG uptake, occur within the
first 7 days of therapy. In addition, FDG uptake at day 42 showed
significantly lower values for long-term responders. Based on these
results, we hypothesize that primary outcome of chemotherapy may be
predicted using FDG-PET as early as 7 days after beginning of
treatment, while long-term prognosis is best correlated with the
results after completion of two courses of chemotherapy.
In NHL, dynamic data acquisition combined with Patlak analysis of FDG
kinetics may provide superior information in therapy monitoring.
Similar studies in solid tumors are needed to determine whether more
dynamic acquisition methods will improve the predictive value of
FDG-PET.
| |
FOOTNOTES |
Submitted August 28, 1997;
accepted January 30, 1998.
Address reprint requests to Wolfgang Römer, MD,
Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der
Isar, Technische Universität München, Ismaninger Stra e
22, 81675 München, Germany.
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U.S.C. section 1734 solely to indicate this fact.
| |
ACKNOWLEDGMENT |
We thank Sylvia Fürst, Claudia Kolligs, and Coletta Kruschke for
their excellent performance of the PET scans and Jodi Neverve for her
review of this manuscript. Furthermore, we gratefully acknowledge the
support of the cyclotron and radiochemistry staff. The authors
appreciate the assistance of Cornelia Pankalla in preparation of the
figures.
| |
REFERENCES |
1.
Warburg O:
The metabolism of tumors.
London, UK, Constable
, 1930
2.
Fischman AJ,
Alpert NM:
FDG-PET in oncology: There's more to it than looking at pictures.
J Nucl Med
34:6,
1993[Free Full Text]
3.
Strauss LG,
Conti PS:
The applications of PET in clinical oncology.
J Nucl Med
32:623,
1991[Abstract/Free Full Text]
4.
Rigo P,
Paulus P,
Kaschten BJ,
Hustinx R,
Bury T,
Jerusalem G,
Benoit T,
Foidart WJ:
Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose.
Eur J Nucl Med
23:1641,
1996[Medline]
[Order article via Infotrieve]
5.
Minn H,
Paul R,
Ahonen A:
Evaluation of treatment response to radiotherapy in head and neck cancer with fluorine-18 fluorodeoxyglucose.
J Nucl Med
29:1521,
1988[Abstract/Free Full Text]
6.
Minn H,
Soini I:
F-18-fluordeoxyglucose scintigraphy in diagnosis and follow up of treatment in advanced breast cancer.
Eur J Nucl Med
15:61,
1989[Medline]
[Order article via Infotrieve]
7.
Haberkorn U,
Strauss LG,
Dimitrakopoulou A,
Engenhart R,
Oberdorfer F,
Ostertag H,
Romahn J,
van Kaick G:
PET studies of fluorodeoxyglucose metabolism in patients with recurrent colorectal tumors receiving radiotherapy.
J Nucl Med
32:1485,
1991[Abstract/Free Full Text]
8.
Ichiya Y,
Kuwabara Y,
Otsuka M,
Tahara T,
Yoshikai T,
Fukumura T,
Jingu K,
Masuda K:
Assessment of response to cancer therapy using fluorine-18-fluorodeoxyglucose and positron emission tomography.
J Nucl Med
32:1655,
1991[Abstract/Free Full Text]
9.
Bassa P,
Kim EE,
Inoue T,
Wong FCL,
Korkmaz M,
Yang DJ,
Won W-H,
Hicks KW,
Buzdar AU,
Podoloff DA:
Evaluation of preoperative chemotherapy using PET with fluorine-18-fluorodeoxyglucose in breast cancer.
J Nucl Med
37:931,
1996[Abstract/Free Full Text]
10.
Jones DN,
McCowage GB,
Sostman HD,
Brizel DM,
Layfield L,
Charles HC,
Dewhirst MW,
Prescott DM,
Friedman HS,
Harrelson JM,
Scully SP,
Coleman RE:
Monitoring of neoadjuvant therapy response of soft-tissue and musculoskeletal sarcoma using fluorine-18-FDG PET.
J Nucl Med
37:1438,
1996[Abstract/Free Full Text]
11.
Haberkorn U,
Morr I,
Oberdorfer F,
Bellemann ME,
Blatter J,
Altmann A,
Kahn B,
van Kaick G:
Fluorodeoxyglucose uptake in vitro: Aspects of method and effects of treatment with gemcitabine.
J Nucl Med
35:1842,
1994[Abstract/Free Full Text]
12.
Schaider H,
Haberkorn U,
Berger MR,
Oberdorfer F,
Morr I,
van Kaick G:
Application of alpha-aminoisobutyric acid, L-methionine, thymidine and 2-fluoro-2-deoxy-D-glucose to monitor effects of chemotherapy in a human colon carcinoma cell line.
Eur J Nucl Med
23:55,
1996[Medline]
[Order article via Infotrieve]
13.
Higashi K,
Clavo AC,
Wahl RL:
In vitro assessment of 2-fluoro-2-deoxy-D-glucose, L-methionine and thymidine as agents to monitor the early response of a human adenocarcinoma cell line to radiotherapy.
J Nucl Med
34:773,
1993[Abstract/Free Full Text]
14.
Wahl RL,
Zasadny K,
Helvie M,
Hutchins GD,
Weber B,
Cody R:
Metabolic monitoring of breast cancer chemohormonotherapy using positron emission tomography: Initial evaluation.
J Clin Oncol
11:2101,
1993[Abstract/Free Full Text]
15.
Jansson T,
Westlin JE,
Ahlstrom H,
Lilja A,
Langstrom B,
Bergh J:
Positron emission tomography studies in patients with locally advanced and/or metastatic breast cancer: A method for early therapy evaluation?
J Clin Oncol
13:1470,
1995[Abstract]
16.
Lapela M,
Leskinen S,
Minn HR,
Lindholm P,
Klemi PJ,
Soderstrom KO,
Bergman J,
Haaparanta M,
Ruotsalainen U,
Solin O,
Joensuu H:
Increased glucose metabolism in untreated non-Hodgkin's lymphoma: A study with positron emission tomography and fluorine-18-fluorodeoxyglucose.
Blood
86:3522,
1995[Abstract/Free Full Text]
17.
Durig J,
Fiedler W,
de Wit M,
Steffen M,
Hossfeld DK:
Lactic acidosis and hypoglycemia in a patient with high-grade non-Hodgkin's lymphoma and elevated circulating TNF-alpha.
Ann Hematol
72:97,
1996[Medline]
[Order article via Infotrieve]
18.
Dimitrakopoulou-Strauss A,
Strauss LG,
Goldschmidt H,
Lorenz WJ,
Maier BW,
van Kaick G:
Evaluation of tumour metabolism and multidrug resistance in patients with treated malignant lymphomas.
Eur J Nucl Med
22:434,
1995[Medline]
[Order article via Infotrieve]
19.
Leskinen KS,
Ruotsalainen U,
Nagren K,
Teras M,
Joensuu H:
Uptake of carbon-11-methionine and fluorodeoxyglucose in non-Hodgkin's lymphoma: A PET study.
J Nucl Med
32:1211,
1991[Abstract/Free Full Text]
20.
Lindholm P,
Leskinen KS,
Minn H,
Bergman J,
Haaparanta M,
Lehikoinen P,
Nagren K,
Ruotsalainen U,
Teras M,
Joensuu H:
Comparison of fluorine-18-fluorodeoxyglucose and carbon-11-methionine in head and neck cancer.
J Nucl Med
34:1711,
1993[Abstract/Free Full Text]
21.
Hoekstra OS,
Ossenkoppele GJ,
Golding R,
van Lingen A,
Visser GW,
Teule GJ,
Huijgens PC:
Early treatment response in malignant lymphoma, as determined by planar fluorine-18-fluorodeoxyglucose scintigraphy.
J Nucl Med
34:1706,
1993[Abstract/Free Full Text]
22.
Hoekstra OS,
van Lingen A,
Ossenkoppele GJ,
Golding R,
Teule GJ:
Early response monitoring in malignant lymphoma using fluorine-18 fluorodeoxyglucose single-photon emission tomography.
Eur J Nucl Med
20:1214,
1993[Medline]
[Order article via Infotrieve]
23.
Rodriguez M,
Rehn S,
Ahlstrom H,
Sundstrom C,
Glimelius B:
Predicting malignancy grade with PET in non-Hodgkin's lymphoma.
J Nucl Med
36:1790,
1995[Abstract/Free Full Text]
24.
Llanos M,
Tabernero J,
Brunet J,
Amenedo M,
Pallares C,
de Andres L,
Lopez JJ:
CHOP chemotherapy of intermediate and high-grade non-Hodgkin's lymphoma.
Acta Oncol
33:935,
1994[Medline]
[Order article via Infotrieve]
25.
Meyer RM,
Browman GP,
Samosh ML,
Benger AM,
Bryant LD,
Wilson WE,
Frank GL,
Leber BF,
Sternbach MS,
Foster GA:
Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin's lymphoma.
J Clin Oncol
13:2386,
1995[Abstract/Free Full Text]
26.
Stansfeld AG,
Diebold J,
Noel H,
Kapanci Y,
Rilke F,
Kelényi G,
Sundström C,
Lennert K,
van Unnik JAM,
Mioduszewska O,
Wright DH:
Updated Kiel classification for lymphomas.
Lancet
1:292,
1988[Medline]
[Order article via Infotrieve]
27.
Fisher RI,
Gaynor ER,
Dahlberg S,
Oken MM,
Grogan TM,
Mize EM,
Glick JH,
Coltman CJ,
Miller TP:
Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma.
N Engl J Med
328:1002,
1993[Abstract/Free Full Text]
28.
Hamacher K,
Coenen HH,
Stöcklin G:
Efficient stereospecific synthesis of nocarrier-added 2-(F-18)-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution.
J Nucl Med
27:235,
1986[Abstract/Free Full Text]
29.
Patlak CS,
Blasberg RG:
Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data.
J Cereb Blood Flow Metab
3:1,
1983[Medline]
[Order article via Infotrieve]
30.
Miller AB,
Hoogstraten B,
Staquet M,
Winkler A:
Reporting results of cancer treatment.
Cancer
47:207,
1981[Medline]
[Order article via Infotrieve]
31.
Iosilevsky G,
Front D,
Bettman L,
Hardoff R,
Ben-Arieh Y:
Uptake of Gallium-67 citrate and 2-3H deoxyglucose in the tumor model, following chemotherapy and radiotherapy.
J Nucl Med
26:278,
1985[Medline]
[Order article via Infotrieve]
32.
Abe Y,
Matsuzawa T,
Fujiwara T,
Fukuda H,
Itoh M,
Yamada K,
Yamaguchi K,
Sato T,
Ido T:
Assessment of radiotherapeutic effects on experimental tumors using F-18-2-fluoro-2-deoxy-D-glucose.
Eur J Nucl Med
12:325,
1986[Medline]
[Order article via Infotrieve]
33.
Kubota K,
Ishiwata K,
Kubota R,
Yamada S,
Tada M,
Sato T,
Ido T:
Tracer feasibility for monitoring tumor radiotherapy: A quadruple tracer study with fluorine-18-fluorodeoxyglucose or fluorine-18-fluorodeoxyuridine, L-[methyl-14C]methionine, [6-3H]thymidine, and gallium-67.
J Nucl Med
32:2118,
1991[Abstract/Free Full Text]
34.
Fisher RI:
Treatment of aggressive non-Hodgkin' lymphomas. Lessons from the past 10 years.
Cancer
74:2657,
1994[Medline]
[Order article via Infotrieve]
35.
Weber W,
Thödtmann R,
Ziegler S,
Römer W,
Hanauske A,
Schwaiger M:
Reproducibility of FDG-PET in malignant tumors.
J Nucl Med
38:243,
1997[Abstract/Free Full Text]
36.
Minn H,
Zasadny KR,
Quint LE,
Wahl RL:
Lung cancer: Reproducibility of quantitative measurements for evaluating 2-[F-18]-fluoro-2-deoxy-D-glucose uptake at PET.
Radiology
196:167,
1995[Abstract/Free Full Text]
37.
Lindholm P,
Minn H,
Leskinen KS,
Bergman J,
Ruotsalainen U,
Joensuu H:
Influence of the blood glucose concentration on FDG uptake in cancer-a PET study.
J Nucl Med
34:1,
1993[Abstract/Free Full Text]
38.
Langen KJ,
Braun U,
Rota KE,
Herzog H,
Kuwert T,
Nebeling B,
Feinendegen LE:
The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas.
J Nucl Med
34:355,
1993[Abstract/Free Full Text]
39.
Canellos GP:
Residual mass in lymphoma may not be residual disease.
J Clin Oncol
6:931,
1988[Free Full Text]
40.
Thomas F,
Cosset JM,
Cherel P,
Renaudy N,
Carde P,
Piekarski JD:
Thoracic CT-scanning follow-up of residual mediastinal masses after treatment of Hodgkin's disease.
Radiother Oncol
11:119,
1988[Medline]
[Order article via Infotrieve]
41.
Avril N,
Dose J,
Jänicke F,
Bense S,
Ziegler S,
Laubenbacher C,
Römer W,
Pache H,
Herz M,
Allgayer B,
Nathrath W,
Graeff H,
Schwaiger M:
Metabolic characterization of breast tumors with positron emission tomography using F-18 fluorodeoxyglucose.
J Clin Oncol
14:1848,
1996[Abstract/Free Full Text]
42.
Janicek M,
Kaplan W,
Neuberg D,
Canellos GP,
Shulman LN,
Shipp MA:
Early restaging gallium scans predict outcome in poor-prognosis patients with aggressive non-Hodgkin's lymphoma treated with high-dose CHOP chemotherapy.
J Clin Oncol
15:1631,
1997[Abstract]
43.
Bartold SP,
Donohoe KJ,
Fletcher JW,
Haynie TP,
Henkin RE,
Silberstein EB,
Royal HD,
Van den Abbeele A:
Procedure guideline for gallium scintigraphy in the evaluation of malignant disease.
J Nucl Med
38:990,
1997[Free Full Text]
44.
Armitage JO,
Vose JM,
Bierman PJ,
Bishop MR:
Salvage therapy for patients with lymphoma.
Semin Oncol
21:82,
1994[Medline]
[Order article via Infotrieve]
45.
Vose JM,
Armitage JO:
What is the role of third generation regimens for initial therapy of non-Hodgkin's lymphomas?
Leuk Lymphoma
10:61,
1993
46.
Hawkins RA,
Choi Y,
Huang S-C,
Messa C,
Hoh CK,
Phelps ME:
Quantitating tumor glucose metabolism with FDG and PET.
J Nucl Med
33:339,
1992[Free Full Text]
47.
Zasadny KR,
Wahl RL:
Standardized uptake values of normal tissues at PET with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose: Variations with body weight and a method for correction.
Radiology
189:847,
1993[Abstract/Free Full Text]
48.
Hamberg LM,
Hunter GJ,
Alpert NM,
Choi NC,
Babich JW,
Fischman AJ:
The dose uptake ratio as an index of glucose metabolism: Useful parameter or oversimplification?
J Nucl Med
35:1308,
1994[Abstract/Free Full Text]
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Brepoels, S. Stroobants, G. Verhoef, T. De Groot, L. Mortelmans, and C. De Wolf-Peeters
18F-FDG and 18F-FLT Uptake Early After Cyclophosphamide and mTOR Inhibition in an Experimental Lymphoma Model
J. Nucl. Med.,
July 1, 2009;
50(7):
1102 - 1109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Terasawa, J. Lau, S. Bardet, O. Couturier, T. Hotta, M. Hutchings, T. Nihashi, and H. Nagai
Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography for Interim Response Assessment of Advanced-Stage Hodgkin's Lymphoma and Diffuse Large B-Cell Lymphoma: A Systematic Review
J. Clin. Oncol.,
April 10, 2009;
27(11):
1906 - 1914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Itti, C. Lin, J. Dupuis, G. Paone, D. Capacchione, A. Rahmouni, C. Haioun, and M. Meignan
Prognostic Value of Interim 18F-FDG PET in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment at 4 Cycles of Chemotherapy
J. Nucl. Med.,
April 1, 2009;
50(4):
527 - 533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Noy, H. Schoder, M. Gonen, M. Weissler, K. Ertelt, C. Cohler, C. Portlock, P. Hamlin, and H. W. D. Yeung
The majority of transformed lymphomas have high standardized uptake values (SUVs) on positron emission tomography (PET) scanning similar to diffuse large B-cell lymphoma (DLBCL)
Ann. Onc.,
March 1, 2009;
20(3):
508 - 512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Schwarz-Dose, M. Untch, R. Tiling, S. Sassen, S. Mahner, S. Kahlert, N. Harbeck, A. Lebeau, W. Brenner, M. Schwaiger, et al.
Monitoring Primary Systemic Therapy of Large and Locally Advanced Breast Cancer by Using Sequential Positron Emission Tomography Imaging With [18F]Fluorodeoxyglucose
J. Clin. Oncol.,
February 1, 2009;
27(4):
535 - 541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Seam, M. E. Juweid, and B. D. Cheson
The role of FDG-PET scans in patients with lymphoma
Blood,
November 15, 2007;
110(10):
3507 - 3516.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Lin, E. Itti, C. Haioun, Y. Petegnief, A. Luciani, J. Dupuis, G. Paone, J.-N. Talbot, A. Rahmouni, and M. Meignan
Early 18F-FDG PET for Prediction of Prognosis in Patients with Diffuse Large B-Cell Lymphoma: SUV-Based Assessment Versus Visual Analysis
J. Nucl. Med.,
October 1, 2007;
48(10):
1626 - 1632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Mankoff, J. F. Eary, J. M. Link, M. Muzi, J. G. Rajendran, A. M. Spence, and K. A. Krohn
Tumor-Specific Positron Emission Tomography Imaging in Patients: [18F] Fluorodeoxyglucose and Beyond
Clin. Cancer Res.,
June 15, 2007;
13(12):
3460 - 3469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Herrmann, H. A. Wieder, A. K. Buck, M. Schoffel, B.-J. Krause, F. Fend, T. Schuster, C. Meyer zum Buschenfelde, H.-J. Wester, J. Duyster, et al.
Early Response Assessment Using 3'-Deoxy-3'-[18F]Fluorothymidine-Positron Emission Tomography in High-Grade Non-Hodgkin's Lymphoma
Clin. Cancer Res.,
June 15, 2007;
13(12):
3552 - 3558.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. L. Zinzani, M. Tani, R. Trisolini, S. Fanti, V. Stefoni, M. Alifano, P. Castellucci, G. Musuraca, G. Dalpiaz, L. Alinari, et al.
Histological verification of positive positron emission tomography findings in the follow-up of patients with mediastinal lymphoma
Haematologica,
June 1, 2007;
92(6):
771 - 777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid, S. Stroobants, O. S. Hoekstra, F. M. Mottaghy, M. Dietlein, A. Guermazi, G. A. Wiseman, L. Kostakoglu, K. Scheidhauer, A. Buck, et al.
Use of Positron Emission Tomography for Response Assessment of Lymphoma: Consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma
J. Clin. Oncol.,
February 10, 2007;
25(5):
571 - 578.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. L. Kasamon, R. J. Jones, and R. L. Wahl
Integrating PET and PET/CT into the Risk-Adapted Therapy of Lymphoma
J. Nucl. Med.,
January 1, 2007;
48(1_suppl):
19S - 27S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. K. Buck, M. Bommer, S. Stilgenbauer, M. Juweid, G. Glatting, H. Schirrmeister, T. Mattfeldt, D. Tepsic, D. Bunjes, F. M. Mottaghy, et al.
Molecular Imaging of Proliferation in Malignant Lymphoma.
Cancer Res.,
November 15, 2006;
66(22):
11055 - 11061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid and B. D. Cheson
Positron-Emission Tomography and Assessment of Cancer Therapy
N. Engl. J. Med.,
February 2, 2006;
354(5):
496 - 507.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid
Utility of Positron Emission Tomography (PET) Scanning in Managing Patients with Hodgkin Lymphoma
Hematology,
January 1, 2006;
2006(1):
259 - 265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Hutchings, A. Loft, M. Hansen, L. M. Pedersen, T. Buhl, J. Jurlander, S. Buus, S. Keiding, F. D'Amore, A.-M. Boesen, et al.
FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma
Blood,
January 1, 2006;
107(1):
52 - 59.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Hawkins, S. M. Schuetze, J. E. Butrynski, J. G. Rajendran, C. B. Vernon, E. U. Conrad III, and J. F. Eary
[18F]Fluorodeoxyglucose Positron Emission Tomography Predicts Outcome for Ewing Sarcoma Family of Tumors
J. Clin. Oncol.,
December 1, 2005;
23(34):
8828 - 8834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tatsumi, C. Cohade, Y. Nakamoto, E. K. Fishman, and R. L. Wahl
Direct Comparison of FDG PET and CT Findings in Patients with Lymphoma: Initial Experience
Radiology,
December 1, 2005;
237(3):
1038 - 1045.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Avril, S. Sassen, B. Schmalfeldt, J. Naehrig, S. Rutke, W. A. Weber, M. Werner, H. Graeff, M. Schwaiger, and W. Kuhn
Prediction of Response to Neoadjuvant Chemotherapy by Sequential F-18-Fluorodeoxyglucose Positron Emission Tomography in Patients With Advanced-Stage Ovarian Cancer
J. Clin. Oncol.,
October 20, 2005;
23(30):
7445 - 7453.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. G. Mikhaeel, M. Hutchings, P. A. Fields, M. J. O'Doherty, and A. R. Timothy
FDG-PET after two to three cycles of chemotherapy predicts progression-free and overall survival in high-grade non-Hodgkin lymphoma
Ann. Onc.,
September 1, 2005;
16(9):
1514 - 1523.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Haioun, E. Itti, A. Rahmouni, P. Brice, J.-D. Rain, K. Belhadj, P. Gaulard, L. Garderet, E. Lepage, F. Reyes, et al.
[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in aggressive lymphoma: an early prognostic tool for predicting patient outcome
Blood,
August 15, 2005;
106(4):
1376 - 1381.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid, G. A. Wiseman, J. M. Vose, J. M. Ritchie, Y. Menda, J. E. Wooldridge, F. M. Mottaghy, E. M. Rohren, N. M. Blumstein, A. Stolpen, et al.
Response Assessment of Aggressive Non-Hodgkin's Lymphoma by Integrated International Workshop Criteria and Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography
J. Clin. Oncol.,
July 20, 2005;
23(21):
4652 - 4661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schoder, A. Noy, M. Gonen, L. Weng, D. Green, Y. E. Erdi, S. M. Larson, and H. W.D. Yeung
Intensity of 18Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes Between Indolent and Aggressive Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
July 20, 2005;
23(21):
4643 - 4651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Juweid and B. D. Cheson
Role of Positron Emission Tomography in Lymphoma
J. Clin. Oncol.,
July 20, 2005;
23(21):
4577 - 4580.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Kelloff, J. M. Hoffman, B. Johnson, H. I. Scher, B. A. Siegel, E. Y. Cheng, B. D. Cheson, J. O'Shaughnessy, K. Z. Guyton, D. A. Mankoff, et al.
Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development
Clin. Cancer Res.,
April 15, 2005;
11(8):
2785 - 2808.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Sun, T. J. Mangner, J. M. Collins, O. Muzik, K. Douglas, and A. F. Shields
Imaging DNA Synthesis In Vivo with 18F-FMAU and PET
J. Nucl. Med.,
February 1, 2005;
46(2):
292 - 296.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Mengiardi, H. Honegger, J. Hodler, U. G. Exner, M. D. Csherhati, and W. Bruhlmann
Primary Lymphoma of Bone: MRI and CT Characteristics During and After Successful Treatment
Am. J. Roentgenol.,
January 1, 2005;
184(1):
185 - 192.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kazama, S. C. Faria, V. Varavithya, S. Phongkitkarun, H. Ito, and H. A. Macapinlac
FDG PET in the Evaluation of Treatment for Lymphoma: Clinical Usefulness and Pitfalls
RadioGraphics,
January 1, 2005;
25(1):
191 - 207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. C. Detterbeck, J. F. Vansteenkiste, D. E. Morris, C. A. Dooms, A. H. Khandani, and M. A. Socinski
Seeking a Home for a PET, Part 3: Emerging Applications of Positron Emission Tomography Imaging in the Management of Patients With Lung Cancer
Chest,
November 1, 2004;
126(5):
1656 - 1666.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Yamane, O. Daimaru, S. Ito, K. Yoshiya, T. Nagata, S. Ito, and H. Uchida
Decreased 18F-FDG Uptake 1 Day After Initiation of Chemotherapy for Malignant Lymphomas
J. Nucl. Med.,
November 1, 2004;
45(11):
1838 - 1842.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Romer, M. Chung, A. Chan, D. W. Townsend, F. Torok, B. McCook, M. P. Federle, and N. Avril
Single-Detector Helical CT in PET-CT: Assessment of Image Quality
Am. J. Roentgenol.,
June 1, 2004;
182(6):
1571 - 1577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Rohren, T. G. Turkington, and R. E. Coleman
Clinical Applications of PET in Oncology
Radiology,
May 1, 2004;
231(2):
305 - 332.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schoder, Y. E. Erdi, K. Chao, M. Gonen, S. M. Larson, and H. W.D. Yeung
Clinical Implications of Different Image Reconstruction Parameters for Interpretation of Whole-Body PET Studies in Cancer Patients
J. Nucl. Med.,
April 1, 2004;
45(4):
559 - 566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Meyer, R. F. Ambinder, and S. Stroobants
Hodgkin's Lymphoma: Evolving Concepts with Implications for Practice
Hematology,
January 1, 2004;
2004(1):
184 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schoder, S. M. Larson, and H. W.D. Yeung
PET/CT in Oncology: Integration into Clinical Management of Lymphoma, Melanoma, and Gastrointestinal Malignancies
J. Nucl. Med.,
January 1, 2004;
45(90010):
72S - 81.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ott, U. Fink, K. Becker, A. Stahl, H.-J. Dittler, R. Busch, H. Stein, F. Lordick, T. Link, M. Schwaiger, et al.
Prediction of Response to Preoperative Chemotherapy in Gastric Carcinoma by Metabolic Imaging: Results of a Prospective Trial
J. Clin. Oncol.,
December 15, 2003;
21(24):
4604 - 4610.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G J R Cook
Oncological molecular imaging: nuclear medicine techniques
Br. J. Radiol.,
December 1, 2003;
76(suppl_2):
S152 - S158.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Friedberg and V. Chengazi
PET Scans in the Staging of Lymphoma: Current Status
Oncologist,
October 1, 2003;
8(5):
438 - 447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Guay, M. Lepine, J. Verreault, and F. Benard
Prognostic Value of PET Using 18F-FDG in Hodgkin's Disease for Posttreatment Evaluation
J. Nucl. Med.,
August 1, 2003;
44(8):
1225 - 1231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Chesnay, E. Babin, J. M. Constans, D. Agostini, A. Bequignon, A. Regeasse, F. Sobrio, and S. Moreau
Early Response to Chemotherapy in Hypopharyngeal Cancer: Assessment with 11C-Methionine PET, Correlation with Morphologic Response, and Clinical Outcome
J. Nucl. Med.,
April 1, 2003;
44(4):
526 - 532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Kostakoglu, H. Agress Jr, and S. J. Goldsmith
Clinical Role of FDG PET in Evaluation of Cancer Patients
RadioGraphics,
March 1, 2003;
23(2):
315 - 340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Kostakoglu and S. J. Goldsmith
18F-FDG PET Evaluation of the Response to Therapy for Lymphoma and for Breast, Lung, and Colorectal Carcinoma
J. Nucl. Med.,
February 1, 2003;
44(2):
224 - 239.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Downey, T. Akhurst, D. Ilson, R. Ginsberg, M. S. Bains, M. Gonen, H. Koong, M. Gollub, B. D. Minsky, M. Zakowski, et al.
Whole Body 18FDG-PET and the Response of Esophageal Cancer to Induction Therapy: Results of a Prospective Trial
J. Clin. Oncol.,
February 1, 2003;
21(3):
428 - 432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Jerusalem, Y. Beguin, M. F. Fassotte, T. Belhocine, R. Hustinx, P. Rigo, and G. Fillet
Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease
Ann. Onc.,
January 1, 2003;
14(1):
123 - 130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M Schwaiger
Functional imaging for assessment of therapy
Br. J. Radiol.,
November 1, 2002;
75(90009):
S67 - 73.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. J. Hoekstra, O. S. Hoekstra, S. G. Stroobants, J. Vansteenkiste, J. Nuyts, E. F. Smit, M. Boers, J. W.R. Twisk, and A. A. Lammertsma
Methods to Monitor Response to Chemotherapy in Non-Small Cell Lung Cancer with 18F-FDG PET
J. Nucl. Med.,
October 1, 2002;
43(10):
1304 - 1309.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Spaepen, S. Stroobants, P. Dupont, P. Vandenberghe, J. Thomas, T. de Groot, J. Balzarini, C. De Wolf-Peeters, L. Mortelmans, and G. Verhoef
Early restaging positron emission tomography with 18F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma
Ann. Onc.,
September 1, 2002;
13(9):
1356 - 1363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.B. Bomanji, R. Syed, C. Brock, P. Jankowska, A. Dogan, D.C. Costa, P.J. Ell, and S.M. Lee
Challenging Cases and Diagnostic Dilemmas: Case 2. Pitfalls of Positron Emission Tomography for Assessing Residual Mediastinal Mass After Chemotherapy for Hodgkin's Disease
J. Clin. Oncol.,
August 1, 2002;
20(15):
3347 - 3349.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Kostakoglu, M. Coleman, J. P. Leonard, I. Kuji, H. Zoe, and S. J. Goldsmith
PET Predicts Prognosis After 1 Cycle of Chemotherapy in Aggressive Lymphoma and Hodgkin's Disease
J. Nucl. Med.,
August 1, 2002;
43(8):
1018 - 1027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. J. Lowe and G. A. Wiseman
Assessment of Lymphoma Therapy Using 18F-FDG PET
J. Nucl. Med.,
August 1, 2002;
43(8):
1028 - 1030.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schoder, J. Meta, C. Yap, M. Ariannejad, J. Rao, M. E. Phelps, P. E. Valk, J. Sayre, and J. Czernin
Effect of Whole-Body 18F-FDG PET Imaging on Clinical Staging and Management of Patients with Malignant Lymphoma
J. Nucl. Med.,
August 1, 2001;
42(8):
1139 - 1143.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. A. Weber, K. Ott, K. Becker, H.-J. Dittler, H. Helmberger, N. E. Avril, G. Meisetschlager, R. Busch, J.-R. Siewert, M. Schwaiger, et al.
Prediction of Response to Preoperative Chemotherapy in Adenocarcinomas of the Esophagogastric Junction by Metabolic Imaging
J. Clin. Oncol.,
June 15, 2001;
19(12):
3058 - 3065.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Spaepen, S. Stroobants, P. Dupont, S. Van Steenweghen, J. Thomas, P. Vandenberghe, L. Vanuytsel, G. Bormans, J. Balzarini, C. De Wolf-Peeters, et al.
Prognostic Value of Positron Emission Tomography (PET) With Fluorine-18 Fluorodeoxyglucose ([18F]FDG) After First-Line Chemotherapy in Non-Hodgkin's Lymphoma: Is [18F]FDG-PET a Valid Alternative to Conventional Diagnostic Methods?
J. Clin. Oncol.,
January 15, 2001;
19(2):
414 - 419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. P. Frush, L. F. Donnelly, and H. G. Chotas
Contemporary Pediatric Thoracic Imaging
Am. J. Roentgenol.,
September 1, 2000;
175(3):
841 - 851.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Skehan, A. L. Brown, M. Thompson, J. E. M. Young, G. Coates, and C. Nahmias
Imaging Features of Primary and Recurrent Esophageal Cancer at FDG PET
RadioGraphics,
May 1, 2000;
20(3):
713 - 723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Sweetenham, A. M. Carella, G. Taghipour, D. Cunningham, R. Marcus, A. D. Volpe, D. C. Linch, N. Schmitz, and A. H. Goldstone
High-Dose Therapy and Autologous Stem-Cell Transplantation for Adult Patients With Hodgkin's Disease Who Do Not Enter Remission After Induction Chemotherapy: Results in 175 Patients Reported to the European Group for Blood and Marrow Transplantation
J. Clin. Oncol.,
October 1, 1999;
17(10):
3101 - 3109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Cheson, S. J. Horning, B. Coiffier, M. A. Shipp, R. I. Fisher, J. M. Connors, T. A. Lister, J. Vose, A. Grillo-Lopez, A. Hagenbeek, et al.
Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas
J. Clin. Oncol.,
April 1, 1999;
17(4):
1244 - 1244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract
) and
the metabolic rate of FDG (MRFDG) (
) at (A) day 7 and (B) day 42 in
patients with relapse (n = 5) and complete response
(CR; n = 6).
