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Journal of Nuclear Medicine Vol. 43 No. 12 1667-1673
© 2002 by Society of Nuclear Medicine

Basic Science Investigations

Volumetric Analysis of 18F-FDG PET in Glioblastoma Multiforme: Prognostic Information and Possible Role in Definition of Target Volumes in Radiation Dose Escalation

Kevin S. Tralins, MD1, James G. Douglas, MD, MS1, Keith J. Stelzer, MD, PhD1, David A. Mankoff, MD2, Daniel L. Silbergeld, MD3, Robert Rostomilly, MD3, Sharon Hummel, MS1, Jeff Scharnhorst, BS4, Kenneth A. Krohn, PhD2 and Alexander M. Spence, MD4

1 Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington
2 Department of Nuclear Medicine, University of Washington Medical Center, Seattle, Washington
3 Department of Neurosurgery, University of Washington Medical Center, Seattle, Washington
4 Department of Neuro-Oncology, University of Washington Medical Center, Seattle, Washington


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
The use of 18F-FDG PET for brain tumors has been shown to be accurate in identifying areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme (GBM) may lead to improved disease control. On the basis of these premises, we initiated a pilot study to investigate the use of 18F-FDG PET for the guidance of radiation dose escalation in the treatment of GBM. Methods: Patients were considered eligible to participate in the study if they had a diagnosis of GBM, were at least 18 y old, and had a score of at least 60 on the Karnofsky Scale. Patients were treated with standard conformal fractionated radiotherapy (1.8 Gy per fraction, to 59.4 Gy), with volumes defined by MRI. At a dose of 45–50.4 Gy, patients underwent 18F-FDG PET for boost target delineation. Final noncoplanar fields (3–4) were designed to treat the volume of abnormal 18F-FDG uptake plus a 0.5-cm margin for an additional 20 Gy (2 Gy per fraction), to a total dose of 79.4 Gy. If no abnormal 18F-FDG uptake was observed, treatment was stopped after the conventional course of 59.4 Gy. Age, Karnofsky score, MRI-based volumes, and 18F-FDG PET volume were analyzed as prognostic variables for time to tumor progression (TTP) and overall survival. 18F-FDG PET volumes and MRI-based volumes were compared to assess concordance. Results: For the 27 patients who could be evaluated, median actuarial TTP was 43 wk, and median actuarial survival was 70 wk. On univariate analysis, 18F-FDG PET, T1-weighted MRI gadolinium enhancement (excluding nonenhancing resection cavity), and T2-weighted MRI volumes were significantly predictive of TTP. On multivariate analysis, only 18F-FDG PET volume retained significance for predicting TTP. Similar results were obtained on analysis of these variables as prognostic factors for survival. When 18F-FDG PET-based volumes were compared with MRI-based volumes, a difference of at least 25% was detected in all patients, with all but 2 having smaller 18F-FDG PET volumes. Of patients in whom 18F-FDG uptake was initially present but treatment subsequently failed, 83% demonstrated the first tumor progression within the region of abnormal 18F-FDG uptake. Conclusion: In comparison with MRI, 18F-FDG PET defined unique volumes for radiation dose escalation in the treatment of GBM. 18F-FDG PET volumes were predictive of survival and time to tumor progression in the treatment of patients with GBM.

Key Words: glioblastoma multiforme • PET • radiation dose escalation


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Glioblastoma multiforme (GBM) remains one of the most uniformly fatal of all solid tumors. Radiotherapy treatment of GBM has been shown to increase median survival (1–3). However, even with treatment, the overall prognosis remains extremely poor. Trials of radiation dose escalation beyond 60 Gy have not proven beneficial in the treatment of GBM (4–8). Presumably, any enhancement of tumor control is undermined by increased toxicity to normal brain tissue. Risk of brain injury after radiation is a function of the volume of brain included within radiation fields, and the most likely site of first recurrence is near the original tumor site. Therefore, there is interest in using conformal techniques to escalate radiation dose to a limited volume containing the highest tumor cell burden.

In previous treatment trials, the volume designated for dose escalation has generally been determined by conventional anatomic imaging such as CT or MRI (9). A typical volume for dose escalation beyond 60 Gy has been defined as the operative bed plus the area of gadolinium enhancement on a postoperative T1-weighted MR image. However, the optimal volume to receive the boost dose of radiation has not been determined.

An incremental improvement in survival by radiation dose escalation will require an expansion of the therapeutic window by targeting the volume at greatest risk for first recurrence while minimizing radiation exposure to functional brain tissue. Newer functional imaging modalities such as PET have been postulated to be more accurate in determining target volumes to guide the radiation treatment of malignancies (10). 18F-FDG PET of brain tumors has been shown to be accurate in identifying areas of active disease (11,12). 18F-FDG uptake correlates with tumor grade and aggressiveness (11,12), and the level of 18F-FDG uptake in primary brain tumors predicts survival (13–15). On the basis of these premises, we initiated a prospective phase I/II trial using 18F-FDG PET uptake as a metabolic marker of the most malignant regions of GBM in determining high-dose-radiation boost volumes for conventionally fractionated conformal external-beam radiation. A comparison of boost target volumes between those determined by 18F-FDG PET and those determined by MRI, along with an analysis of the utility of 18F-FDG PET volume in predicting time to tumor progression (TTP) and survival in GBM patients, is emphasized in this initial evaluation. Our hypotheses are that 18F-FDG PET target volumes are different from MRI-based volumes and that 18F-FDG PET volumes identify foci of active residual tumor. Proving these hypotheses would be of significant clinical relevance, as these foci may represent the source of treatment failure.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Study Design and Treatment
Patients were considered eligible to participate in the study if they had a diagnosis of GBM, were at least 18 y old, and had a score of at least 60 on the Karnofsky Scale. In a thermoplastic head immobilization mask, patients underwent CT for 3-dimensional computerized radiation treatment planning. Patient positioning was the same for CT as for postoperative MRI. For patients on whom postoperative MRI was performed at a University of Washington institution, MR and CT images were fused within the computerized system, called Prism, that the University of Washington has developed for radiation treatment planning. The initial planning target volume was defined as the T2-weighted MRI signal abnormality plus a 2.5- to 3-cm margin. The initial planning target volume was treated to a dose of 50.4 Gy (1.8 Gy per fraction), usually through 3 noncoplanar fields designed by the beams-eye-view tool of Prism. Fields were then reduced to the second planning target volume, designated as the T2-weighted MRI abnormality plus a 1.5-cm margin. An additional 9 Gy (1.8 Gy per fraction) was delivered to this second planning target volume, bringing the total initial dose to the standard 59.4 Gy. At a dose of between 45 and 50.4 Gy, patients underwent 18F-FDG PET. Because the operative bed anatomy may have changed over the course of radiation, an additional MRI study was performed at the time of the 18F-FDG PET scan for correlation with the 18F-FDG PET images.

All 18F-FDG PET studies were performed on an Advance tomograph (General Electric Medical Systems, Waukesha, WI). Images were acquired in 3 dimensions onto 35 x 128 x 128 matrices using 4-mm transverse and 8.5-mm axial filters. The result was images with 4- to 6-mm spatial resolution in both axial and transverse directions (16). 18F-FDG was prepared using the method of Hamacher et al. (17) and had radiochemical purity in excess of 95% and specific activity greater than 47 GBq/mmol in all cases. The patients fasted for at least 6 h before the PET study. After plasma glucose measurement to rule out hyperglycemia (glucose less than 150 mg/dL), 259–370 MBq of 18F-FDG were infused over 1–2 min. Starting at approximately 45 min after injection, a 15-min 3-dimensional emission acquisition was obtained, followed by a transmission study 25 min after injection (16). Images were acquired with the patients in their radiotherapy head immobilization mask to facilitate coregistration of the PET scans with the treatment-planning CT scans. Images were reconstructed using the manufacturer’s implementation of the 3-dimensional reprojection algorithm (18). Images were reconstructed in a 30-cm transverse plane by a 14.5-cm axial image field of view onto 128 x 128 x 35 matrices using 4-mm transverse and 8.5-mm axial filters. The resulting image spatial resolution was between 5.5 and 6.5 in full width at half maximum in both axial and transverse directions.

Identification of 18F-FDG-avid areas of tumor and delineation of the 18F-FDG PET-positive contours took place in 2 steps. First, the 18F-FDG-avid tumor areas were determined using MRI as an adjunct to 18F-FDG PET interpretation. Second, 18F-FDG PET images were coregistered to the radiotherapy-planning CT scans, and 18F-FDG-avid tumor contours were drawn on the reformatted 18F-FDG scans. Because patients underwent both PET and CT in the radiotherapy immobilization mask, which firmly constrains head positioning, the reformatted 18F-FDG PET scans used for treatment planning differed only in transverse slice width from the original PET images.

MRI performed close to the time of 18F-FDG PET was used to aid in the interpretation of the 18F-FDG PET studies. When MR images were obtained at the University of Washington and were therefore available in electronic form, the MR and 18F-FDG PET images were software coregistered to aid image interpretation. For MR images obtained elsewhere and available as hard-copy films only, the 18F-FDG PET images were resliced to match the MRI presentation. All 18F-FDG PET images were interpreted by a single observer with expertise in PET imaging of brain tumors. The interpreting physician was aware of patients’ clinical characteristics but was generally unaware of patients’ conditions over the course of radiotherapy. In accord with prior published studies (13–15), 18F-FDG PET images were interpreted by comparing uptake in the tumor region with average uptake in normal white matter, defined as the centrum semiovale contralateral to the tumor.

Areas meeting any of 3 criteria were considered to represent metabolically active tumor. The first criterion was the presence of greater uptake of 18F-FDG in tumor than in normal white matter. To facilitate this determination, images were displayed with both standard gray-scale windowing and with the setting of windowing thresholds to normal white matter uptake levels, as defined above.

The second criterion was the presence of abnormal 18F-FDG uptake within the boundaries of the abnormal region on T2-weighted MR images. Elevated 18F-FDG uptake in areas appearing normal on MRI was considered to be functional rather than tumor based. An example is increased uptake in the visual cortex when it appeared normal on MRI.

The third criterion, applied to the special case of tumor sites in gray matter, when both normal brain and metabolically active tumor can have uptake greater than that of white matter, was that only regions with uptake greater than that of white matter and also within the boundaries of MRI contrast enhancement were considered positive. Areas of 18F-FDG uptake in gray matter abnormal only on T2-weighted MRI cannot be reliably classified as tumor versus damaged or edematous gray matter and were therefore not included in the 18F-FDG-avid tumor volume. In contrast, areas with increased 18F-FDG uptake with contrast enhancement indicate tumor, as opposed to the alternate possibilities for a contrast-enhancing region: postsurgical changes or necrosis.

Contours were placed for the 18F-FDG PET-positive boost region by coregistering the 18F-FDG PET images to the treatment planning CT scan using the image manipulation software of Prism. Because patients were scanned in the same head immobilization mask for PET as for CT, only translation and not rotation was allowed in the coregistration process. All coregistrations were confirmed visually by a single experienced observer. Estimated coregistration accuracy, by a comparison of common visualized structures (eye musculature, outer cortical boundaries, etc.), was 1–2 pixels (2–4 mm).

18F-FDG PET tumor volume contours were drawn on the CT-coregistered 18F-FDG PET images using the Prism software and with reference to the original 18F-FDG PET images. The sites of 18F-FDG-avid tumor, identified as described above, were delineated by contours with the following considerations. Contours were drawn to closely encircle all sites of 18F-FDG-avid disease. For lesions with a cold center by 18F-FDG PET, contours were drawn to include the outer rim of increased uptake and to exclude areas in the center without increased uptake. Whenever possible, contours were made to be contiguous within a slice. However, for lesions in which separate, noncontiguous sites of 18F-FDG uptake were seen in the tumor bed, noncontiguous contours were drawn, and the 18F-FDG PET tumor volume was taken as the sum of the volumes of the noncontiguous contours. Once contours were drawn on the individual slices, they were checked for slice-to-slice consistency and adjusted as necessary. In addition, the 18F-FDG PET contours were checked for consistency with the T2-weighted MRI contours to make sure the 18F-FDG PET contours were within the T2-weighted MRI contours to meet the criteria for identifying areas of abnormal tumor uptake.

Final noncoplanar fields (3–4) were designed to treat the volume of abnormal 18F-FDG uptake plus a 0.5-cm margin (the third planning target volume). This final boost volume was treated for an additional 20 Gy (2 Gy per fraction), for a total dose of 79.4 Gy in 43 fractions. When critical structures such as the optic chiasm or optic nerve abutted the final boost volume, margins were adjusted to respect tolerance of these critical structures. If no abnormal 18F-FDG uptake was observed, the treatment was stopped after the conventional course of 59.4 Gy. After completing radiation therapy, patients were followed every 3 mo by clinical examination and MRI. If increased gadolinium enhancement was observed, patients were strongly encouraged to undergo a repeated 18F-FDG PET scan to verify disease progression. 18F-FDG PET confirmed progression if the areas of new contrast enhancement on MRI also had 18F-FDG uptake greater than that of white matter and either not seen on the planning study or qualitatively worse than on the planning study.

Analysis of Correlation Between PET and MRI Volumes
18F-FDG PET volumes were analyzed for size and location and were compared with the MRI-based volumes. Volumes were determined by summation of digitized contours from axial images in Prism. Volumes included in the analysis were T2-weighted MRI signal abnormality, T1-weighted MRI gadolinium enhancement, T1-weighted MRI gadolinium enhancement plus operative cavity, and 18F-FDG PET abnormal activity. Differences in volumes were initially assessed by size criteria using a simple ratio between volumes (i.e., PET volume to MRI volume). When absolute volumes were similar (<25% difference), volume locations were assessed and the degree of volume overlap was determined by a concordance index (CI) as CI = ([P + M]/X) - 1, in which P is the boost target volume determined by PET, M is the boost target volume determined by MRI, and X is the volume encompassing the combined 18F-FDG PET (P) and MRI (M) abnormalities. Complete concordance, or equivalence between volumes P, M, and X, would yield a CI of 1 (i.e., P + M/X = 2). Conversely, complete nonconcordance would yield a CI of 0 (i.e., volume P and volume M would be entirely separate, and thus P + M/X = 1). For example, if the MRI volume measured 10 cm3 and the PET volume also measured 10 cm3, by absolute volume the targets would be equivalent. However, to assess volume overlap (concordance), the CI would be applied. If the MRI volume and PET volume were indeed identical, the CI would result in a value of 1 [([10 + 10]/10) - 1 = 1]. Alternatively, if the volumes were entirely discordant (no overlap), the CI formula would yield a value of zero [([10 + 10]/20) - 1 = 0]. For all other scenarios, the CI would yield a value between 0 and 1, with higher values meaning greater concordance. Values of CI less than 0.75 indicate discordance exceeding 25%. A CI of 1 was assigned if both P and M equaled 0.

Analysis of Potential Prognostic Factors
Age, Karnofsky Scale, T2-weighted MRI volume, T1-weighted MRI gadolinium enhancement volume (both with and without inclusion of the resection cavity), and 18F-FDG PET volume were analyzed as prognostic variables for TTP and survival from date of diagnosis using the Cox proportional hazards model for continuous variables. Statistical analyses were performed using the StatView (1986 version; Abacus Concepts, Inc., Berkeley, CA) software package.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Thirty-eight patients were enrolled in this trial from March 1997 through June 2000. Eight patients either were on treatment or had not received their first follow-up examination and imaging at the time of this analysis. Two patients could not undergo MRI: one because of an MRI-incompatible aneurysm clip and the other because of a cardiac pacemaker. The disease of 1 patient progressed before the 18F-FDG PET examination, and the patient was removed from the study. All patients will be included in the final analysis of TTP and survival, but the 27 patients who could be evaluated for MRI and 18F-FDG PET volumes are the focus of this interim analysis. The characteristics of these 27 patients are shown in Table 1.


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  		TABLE 1 Characteristics of Patients Who Could Be Evaluated for Volume Analysis

 
The comparison of abnormal 18F-FDG PET volume and T1-weighted MRI gadolinium enhancement volume (with and without resection cavity) was of interest to determine whether 18F-FDG PET provided a radiation boost target that was different from that which would have been delineated by MRI. The mean ratio of abnormal 18F-FDG PET uptake to T1-weighted MRI gadolinium enhancement was 0.72, with a range of 0–3.9. The mean ratio of abnormal 18F-FDG PET uptake to T1-weighted MRI gadolinium enhancement plus resection cavity was 0.45, with a range of 0–1.9. The mean abnormal 18F-FDG PET volume was significantly smaller than the T1-weighted MRI gadolinium enhancement volume (P = 0.0018) and the T1-weighted MRI gadolinium enhancement plus resection cavity volume (P = 0.0001). Often, abnormal 18F-FDG uptake was found within a portion, but not all, of the region of gadolinium enhancement (Fig. 1). Occasionally, 18F-FDG uptake extended outside regions of gadolinium enhancement and partially into regions of T2-weighted MRI signal abnormality (Fig. 2). An example of the PET-delineated volume is shown in Figure 3. The ratio of 18F-FDG PET abnormality volume to T1-weighted MRI gadolinium enhancement volume was outside the range of 0.76–1.24 (i.e., exceeded 25% difference) in all but 4 patients. The CI of the volumes for those 4 patients had a range of 0.47–0.50. The ratio of 18F-FDG PET abnormality volume to T1-weighted MRI gadolinium enhancement plus resection cavity volume was outside the range of 0.76–1.24 for all but 5 patients. The CI of the volumes for those 5 patients had a range of 0.41–0.52. Therefore, the abnormality defined by 18F-FDG PET for escalated radiation dose differed by more than 25% from the volumes that would have been targeted by MRI in all patients who could be evaluated.



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  		FIGURE 1. (A) Postoperative T1-weighted MR image shows gadolinium-enhanced region. (B) 18F-FDG PET scan after 50.4 Gy of treatment shows activity corresponding to only part of gadolinium-enhanced region. (C) MRI 3 mo after 79.4 Gy of treatment shows diminished gadolinium enhancement in portion of resection cavity that was excluded from boost field on basis of 18F-FDG PET, suggesting that enhancement in this region in A is likely related to postsurgical change as opposed to active tumor.

 


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  		FIGURE 2. (A) T2-weighted MR image obtained at dose of approximately 50 Gy. (B) Corresponding T1-weighted MR image with gadolinium enhancement. (C) PET scan obtained at time of MRI. On PET scan, region of increased uptake extends medially beyond T1-weighted gadolinium enhancement but is contained within region of T2-weighted signal abnormality on MR image.

 


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  		FIGURE 3. (A) T2-weighted MR image obtained at dose of approximately 50 Gy. (B) Corresponding T1-weighted MR image with gadolinium enhancement. (C) PET scan obtained at time of MRI, with PET boost volume outlined.

 
Median actuarial TTP for the patients who could be evaluated was 43 wk after diagnosis, and median actuarial survival was 70 wk after diagnosis. Variables of potential prognostic significance for TTP are shown in Table 2. On univariate analysis, 18F-FDG PET, T1-weighted MRI gadolinium enhancement (excluding nonenhancing resection cavity), and T2-weighted MRI volumes were significantly predictive of TTP. Between the 2 potential volumes for guidance of a boost dose of radiation, only the 18F-FDG PET volume retained significance on being entered in a multivariate analysis with T1-weighted MRI gadolinium enhancement volume. Similar results were obtained on analysis of these variables as prognostic factors for survival (Table 3).


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  		TABLE 2 Analysis of Potential Prognostic Variables for Tumor Progression After Radiation Therapy for Glioblastoma Multiforme

 

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  		TABLE 3 Analysis of Potential Prognostic Variables for Survival After Radiation Therapy for Glioblastoma Multiforme

 
Of the 27 patients who could be evaluated, 21 initially demonstrated increased uptake on 18F-FDG PET and 6 did not. Sixteen of the 27 patients who could be evaluated have had tumor progression after radiation. Of patients with tumor progression, 12 initially exhibited abnormal 18F-FDG uptake. Of these 12 patients, the first site of tumor progression was within the region of abnormal 18F-FDG uptake in 10 patients (83%). Of the 6 patients who did not initially have an identifiable region of abnormal 18F-FDG uptake on PET, 4 went on to exhibit tumor progression.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
Local tumor progression in the vicinity of the original site of GBM remains the most prevalent form of failure after treatment. Consequently, there has been great interest in selectively escalating radiation dose to the region of highest risk for subsequent tumor progression. Previous radiation dose escalation trials in the treatment of GBM have used CT and MRI volumes to define targets to receive the highest dose (9). These approaches have largely proven unsatisfactory, with no survival benefit demonstrated in multiple trials using a variety of dose-escalation, altered-fractionation, or particle-beam techniques (4–9,19–24). The use of biologic imaging, such as PET, magnetic resonance spectroscopy, and SPECT, has been proposed for integration with physical imaging in radiation treatment planning (25–27). Our ongoing radiation dose escalation trial has combined biologically guided target definition with computerized 3-dimensional treatment planning for delivery of conformal dose distributions to the volume of interest. This study’s hypotheses were that 18F-FDG PET would provide a target for high-dose radiation that differs from that based on anatomic imaging, such as MRI, and that the target defined by 18F-FDG PET would be at significant risk for tumor progression.

The first hypothesis was affirmed by comparing the volumes actually targeted for radiation dose escalation in these patients using 18F-FDG PET with the volumes that would have been defined using gadolinium-enhanced MRI. Volumes defined by 18F-FDG PET were, on average, less than half those defined by the resection cavity plus MRI gadolinium enhancement (the most common technique for defining high-dose radiation volumes in GBM) (9). Even if the non-gadolinium-enhancing resection cavity was excluded in defining the MRI volumes, 18F-FDG PET volumes were still an average of 38% smaller. Furthermore, among the minority of patients for whom 18F-FDG PET and MRI volumes were quantitatively similar (less than 25% deviation), the concordance was low. The low CI verified the qualitative observation that 18F-FDG PET regions of interest overlapped some (but not all) regions of gadolinium enhancement on MRI but in some cases also extended outside the gadolinium enhancement into regions of abnormal T2-weighted signal on MRI. Such discordance has recently been described by other investigators and may be of prognostic significance (28).

Given the uniqueness of the 18F-FDG PET target volume, a further question is whether this volume actually represents the region most likely to result in improved clinical outcome by an escalating radiation dose in GBM. Ultimately, a randomized clinical trial would be needed to prove a clinical benefit from 18F-FDG PET guidance for radiation dose escalation. However, our preliminary analysis supported theprinciple of this technique by demonstrating that 18F-FDG PET volume was more significant than MRI volumes for predicting survival and TTP. This finding confirms those of other investigators. Goldman et al. (11) determined that areas of increased 18F-FDG PET activity corresponded well to biopsy-proven anaplastic tumor. Delbeke et al. (12) also found that the level of 18F-FDG PET activity corresponded well to pathologic tumor grade. Alavi et al. (13) found that 18F-FDG PET was predictive of survival in high-grade glioma, with patients having hypermetabolic lesions on PET imaging surviving a mean of 7 mo, versus 19 mo for patients with hypometabolic lesions. Likewise, in a study of 45 patients with grade III or IV gliomas imaged by 18F-FDG PET (14), a mean survival of 5 mo for hypermetabolic lesions was found, versus 19 mo for lesions with lower 18F-FDG uptake. A study performed by Barker et al. (15) of patients with recurrent high-grade gliomas showed 18F-FDG PET imaging to be predictive of survival on both univariate and multivariate analysis. In addition to these prior studies showing the level of 18F-FDG uptake in tumor to be predictive of survival, ours is the first study to show that the volume of 18F-FDG-avid tumor is also predictive of outcome. Although the 18F-FDG PET volumes were an indicator of a longer disease-free survival in our study, the rate of false-negative PET studies is worrisome. Four of the 6 patients with a negative PET scan after 45–50 Gy had progressive disease. These 4 represented 25% (4/16) of all patients who progressed, suggesting that PET may identify a smaller cell burden than does MRI but is not an absolute indicator of absent disease.

Because 18F-FDG PET was used for targeting the extra 20 Gy of radiation, it was possible that an enhanced tumor kill could have masked the significance of the 18F-FDG PET volume as a prognostic variable. This potential confounding factor could have been exacerbated by the fact that 6 patients did not have an identifiable region of abnormal 18F-FDG uptake and did not receive the extra radiation dose beyond 59.4 Gy. However, even under these potentially confounding conditions, the volume of abnormal 18F-FDG uptake remained the most significant prognostic variable, strengthening the findings of this preliminary analysis.

Completion of accrual and further follow-up analysis will be needed to determine whether 18F-FDG PET-guided high-dose radiation treatment will be of greater benefit than standard radiotherapy in patients with GBM. The current results support the uniqueness of 18F-FDG PET targeting and confirm the significance of 18F-FDG PET volume as a prognostic variable for patients undergoing treatment for GBM.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
In comparison with MRI, 18F-FDG PET defined unique volumes for radiation dose escalation in the treatment of GBM. 18F-FDG PET volumes were predictive of survival and TTP in the treatment of patients with GBM.


   ACKNOWLEDGMENTS
 
This work was supported by grant P01-CA42045 from the National Institutes of Health.


   FOOTNOTES
 
Received Oct. 12, 2001; revision accepted Aug. 8, 2002.

For correspondence or reprints contact: James G. Douglas, MD, Department of Radiation Oncology, University of Washington, 1959 N.E. Pacific St., Box 356043, Seattle, WA 98195-6043.

E-mail: drjay{at}u.washington.edu


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

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