The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma

BACKGROUND: Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. METHODS: We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). RESULTS: Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors. CONCLUSION: Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00259-016-3494-2) contains supplementary material which is available to authorized users

A Modality-Adaptive Method for Segmenting Brain Tumors and Organs-at-Risk in Radiation Therapy Planning

In this paper we present a method for simultaneously segmenting brain tumors and an extensive set of organs-at-risk for radiation therapy planning of glioblastomas. The method combines a contrast-adaptive generative model for whole-brain segmentation with a new spatial regularization model of tumor shape using convolutional restricted Boltzmann machines. We demonstrate experimentally that the method is able to adapt to image acquisitions that differ substantially from any available training data, ensuring its applicability across treatment sites; that its tumor segmentation accuracy is comparable to that of the current state of the art; and that it captures most organs-at-risk sufficiently well for radiation therapy planning purposes. The proposed method may be a valuable step towards automating the delineation of brain tumors and organs-at-risk in glioblastoma patients undergoing radiation therapy.Comment: corrected one referenc

Dose painting based on tumor uptake of Cu-ATSM and FDG:a comparative study

BACKGROUND: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[(18) F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N(4))-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. METHODS: Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and (64)Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. RESULTS: Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. (64)Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. CONCLUSION: Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, (64)Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that (64)Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning

A modality-adaptive method for segmenting brain tumors and organs-at-risk in radiation therapy planning

In this paper we present a method for simultaneously segmenting brain tumors and an extensive set of organs-at-risk for radiation therapy planning of glioblastomas. The method combines a contrast-adaptive generative model for whole-brain segmentation with a new spatial regularization model of tumor shape using convolutional restricted Boltzmann machines. We demonstrate experimentally that the method is able to adapt to image acquisitions that differ substantially from any available training data, ensuring its applicability across treatment sites; that its tumor segmentation accuracy is comparable to that of the current state of the art; and that it captures most organs-at-risk sufficiently well for radiation therapy planning purposes. The proposed method may be a valuable step towards automating the delineation of brain tumors and organs-at-risk in glioblastoma patients undergoing radiation therapy

Patterns of failure for patients with glioblastoma following O-(2-[¹⁸F]fluoroethyl)-L-tyrosine PET- and MRI-guided radiotherapy

Background and purpose To evaluate the patterns of failure following clinical introduction of amino-acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET-guided target definition for radiotherapy (RT) of glioblastoma patients. Materials and methods The first 66 consecutive patients with confirmed histology, scanned using FET-PET/CT and MRI were selected for evaluation. Chemo-radiotherapy was delivered to a volume based on both MRI and FET-PET (PETvol). The volume of recurrence (RV) was defined on MRI data collected at the time of progression according to RANO criteria. Results Fifty patients were evaluable, with median follow-up of 45 months. Central, in-field, marginal and distant recurrences were observed for 82%, 10%, 2%, and 6% of the patients, respectively. We found a volumetric overlap of 26%, 31% and 39% of the RV with the contrast-enhancing MR volume, PETvol and the composite MRPETvol, respectively. MGMT-methylation (p = 0.03), larger PETvol (p < 0.001), and less extensive surgery (p < 0.001), were associated with larger PETvol overlap. Conclusion The combined MRPETvol had a stronger association with the recurrence volume than either of the modalities alone. Larger overlap of PETvol and RV was observed for patients with MGMT-methylation, less extensive surgery, and large PETvol on the RT-planning scans

Impact of [18F]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma

Background.We sought to assess the impact of amino-acid 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus the current standard using MRI alone. Specifically, we investigated the influence of tumor grade, MR-defined tumor volume, and the extent of surgical resection on PET positivity. Methods. Fifty-four consecutive high-grade glioma patients (World Health Organization grades III–IV) with confirmed histology were scanned using FET-PET/CT and T1 and T2/fluid attenuated inversion recovery MRI. Gross tumor volume and clinical target volumes (CTVs) were defined in a blinded fashion based on MRI and subsequently PET, and volumetric analysis was performed. The extent of the surgical resection was reviewed using postoperative MRI. Results. Overall, for90 % of the patients, the PET-positive volumes were encompassed by T1 MRI with contrast-defined tumor plus a 20-mm margin. The tumor volume defined by PET was larger for glioma grade IV (P,.001) and smaller for patients with more ex-tensive surgical resection (P .004). The margin required to be added to the MRI-defined tumor in order to fully encompass the FET-PET positive volume tended to be larger for grade IV tumors (P .018). Conclusion. With an unchanged CTV margin and by including FET-PET for gross tumor volume definition, the CTV will increase mod-erately for most patients, and quite substantially for a minority of patients. Patients with grade IV gliomawere found to be the primar