Tryptophan PET-defined gross tumor volume offers better coverage of initial progression than standard MRI-based planning in glioblastoma patients

Abstract

Objective Glioblastoma is an infiltrative malignancy that tends to extend beyond the MRI-defined tumor volume. We utilized positron emission tomography (PET) imaging with the radiotracer alpha-[11C]methyl-L -tryptophan (AMT) to develop a reliable high-risk gross tumor volume (HR-GTV) method for delineation of glioblastoma. AMT can detect solid tumor mass and tumoral brain infiltration by increased tumoral tryptophan transport and metabolism via the immunosuppressive kynurenine pathway. Methods We reviewed all patients in our database with histologically proven glioblastoma who underwent preoperative AMT-PET scan prior to surgery and chemoradiation. Treated radiotherapy volumes were derived from the simulation CT with MRI fusion. High-GTV with contrast enhanced T1-weighted MRI alone (GTVMRI) was defined as the postoperative cavity plus any residual area of enhancement on postcontrast T1-weighted images. AMT-PET images were retrospectively fused to the simulation CT, and a high-risk GTVs generated by both AMT-PET alone (GTVAMT) was defined using a threshold previously established to distinguish tumor tissue from peritumoral edema. A composite volume of MRI and AMT tumor volume was also created (combination of MRI fused with AMT-PET data; GTVMRI+AMT). In patients with definitive radiographic progression, follow-up MRI demonstrating initial tumor progression was fused with the pretreatment images and a progression volume was contoured. The coverage of the progression volume by GTVMRI, GTVAMT, and GTVMRI+AMT was determined and compared using the Wilcoxon’s signed-rank test. Results Eleven patients completed presurgical AMT-PET scan, seven of whom had progressive disease after initial therapy. GTVMRI (mean, 50.2 cm3) and GTVAMT (mean, 48.9 cm3) were not significantly different. Mean concordance index of the volumes was 39±15 %. Coverage of the initial recurrence volume by HR-GTVMRI (mean, 52 %) was inferior to both GTVAMT (mean, 68 %; p =0.028) and GTVMRI+AMT (mean 73 %; p =0.018). The AMT-PET-exclusive coverage was up to 41 % of the recurrent volume. There was a tendency towards better recurrence coverage with GTVMRI+AMT than with GTVAMT alone (p =0.068). Addition of 5 mm concentric margin around GTVMRI, GTVAMT, and GTVMRI+AMT would have completely covered the initial progression volume in 14, 57, and 71 % of the patients, respectively. Conclusion We found that a GTV defined by AMT-PET produced similar volume, but superior recurrence coverage than the treated standard MRI-determined volume. A prospective study is necessary to fully determine the usefulness of AMT-PET for volume definition in glioblastoma radiotherapy planning.

Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival

“…14,15,[22][23][24] Our previous preliminary study also suggested that detection of such high-AMT uptake areas may improve the accuracy of radiation targeting. 32 Interestingly, contrast-enhancing tumor areas showing low amino acid uptake were also common in our study. In posttreatment cases, such combination is consistent with radiation injury.…”

Comparison of Amino Acid Positron Emission Tomographic Radiotracers for Molecular Imaging of Primary and Metastatic Brain Tumors

“…In a recent study of 10 patients with high-grade glioma who underwent tumor resection followed by radiotherapy, AMT-PET provided superior coverage of the recurrence volume when compared to the gross tumor volume defined by clinical MRI. 115 Certainly, the clinical value of AMT-PET for treatment planning has to be verified on a larger number of patients.…”

Molecular and Clinical Insights into the Invasive Capacity of Glioblastoma Cells

“…For instance, [18] fluorothymidine (FLT)-PET-CT, a proliferation marker, shows that the tumor infiltration can extend up to 24 mm beyond the MRI-based T2 abnormality volume and it was useful to distinguish between infiltrative tumor and peritumoral oedema [132]. Similar results have been described by using other PET amino acid markers as Fluoroethylthyrosine [133], Tryptophan [134], and methionine [135].…”

“…Other imaging methods, as Positron Emission Tomography (PET), have been used to assess the parenchymal response to tumor invasion [131] and, more recently, to assess the infiltrative tumor volume [132–134]. For instance, [18] fluorothymidine (FLT)-PET-CT, a proliferation marker, shows that the tumor infiltration can extend up to 24 mm beyond the MRI-based T2 abnormality volume and it was useful to distinguish between infiltrative tumor and peritumoral oedema [132].…”