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Patient-Specific Planning for Thermal Magnetic Resonance of Glioblastoma Multiforme.

ABSTRACT: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. This drives research into optimization algorithms for treatment planning as well as radiofrequency (RF) applicator design for treatment delivery. In this work, nine clinically realistic GBM target volumes (TVs) for thermal intervention are compared using three optimization algorithms and up to ten RF applicator designs for thermal magnetic resonance. Hyperthermia treatment planning (HTP) was successfully performed for all cases, including very small, large, and even split target volumes. Minimum requirements formulated for the metrics assessing HTP outcome were met and exceeded for all patient specific cases. Results indicate a 16 channel two row arrangement to be most promising. HTP of TVs with a small extent in the cranial-caudal direction in conjunction with a large radial extent remains challenging despite the advanced optimization algorithms used. In general, deep seated targets are favorable. Overall, our findings indicate that a one-size-fits-all RF applicator might not be the ultimate approach in hyperthermia of brain tumors. It stands to reason that modular and reconfigurable RF applicator configurations might best suit the needs of targeting individual GBM geometry.

SUBMITTER: Oberacker E

PROVIDER: S-EPMC8070230 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM).Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival.The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%.This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Project description:ObjectivesThe aim of this study was to develop and verify a method to obtain good temporal resolution T2-weighted 4-dimensional (4D-T2w) magnetic resonance imaging (MRI) by using motion information from T1-weighted 4D (4D-T1w) MRI, to support treatment planning in MR-guided radiotherapy.Materials and methodsTen patients with primary non-small cell lung cancer were scanned at 1.5 T axially with a volumetric T2-weighted turbo spin echo sequence gated to exhalation and a volumetric T1-weighted stack-of-stars spoiled gradient echo sequence with golden angle spacing acquired in free breathing. From the latter, 20 respiratory phases were reconstructed using the recently developed 4D joint MoCo-HDTV algorithm based on the self-gating signal obtained from the k-space center. Motion vector fields describing the respiratory cycle were obtained by deformable image registration between the respiratory phases and projected onto the T2-weighted image volume. The resulting 4D-T2w volumes were verified against the 4D-T1w volumes: an edge-detection method was used to measure the diaphragm positions; the locations of anatomical landmarks delineated by a radiation oncologist were compared and normalized mutual information was calculated to evaluate volumetric image similarity.ResultsHigh-resolution 4D-T2w MRI was obtained. Respiratory motion was preserved on calculated 4D-T2w MRI, with median diaphragm positions being consistent with less than 6.6 mm (2 voxels) for all patients and less than 3.3 mm (1 voxel) for 9 of 10 patients. Geometrical positions were coherent between 4D-T1w and 4D-T2w MRI as Euclidean distances between all corresponding anatomical landmarks agreed to within 7.6 mm (Euclidean distance of 2 voxels) and were below 3.8 mm (Euclidean distance of 1 voxel) for 355 of 470 pairs of anatomical landmarks. Volumetric image similarity was commensurate between 4D-T1w and 4D-T2w MRI, as mean percentage differences in normalized mutual information (calculated over all respiratory phases and patients), between corresponding respiratory phases of 4D-T1w and 4D-T2w MRI and the tie-phase of 4D-T1w and 3-dimensional T2w MRI, were consistent to 0.41% ± 0.37%. Four-dimensional T2w MRI displayed tumor extent, structure, and position more clearly than corresponding 4D-T1w MRI, especially when mobile tumor sites were adjacent to organs at risk.ConclusionsA methodology to obtain 4D-T2w MRI that retrospectively applies the motion information from 4D-T1w MRI to 3-dimensional T2w MRI was developed and verified. Four-dimensional T2w MRI can assist clinicians in delineating mobile lesions that are difficult to define on 4D-T1w MRI, because of poor tumor-tissue contrast.

Project description:One of the most common and aggressive malignant brain tumors is Glioblastoma multiforme. Despite the multimodality treatment such as radiation therapy and chemotherapy (temozolomide: TMZ), the median survival rate of glioblastoma patient is less than 15 months. In this study, we investigated the association between measures of spatial diversity derived from spatial point pattern analysis of multiparametric magnetic resonance imaging (MRI) data with molecular status as well as 12-month survival in glioblastoma. We obtained 27 measures of spatial proximity (diversity) via spatial point pattern analysis of multiparametric T1 post-contrast and T2 fluid-attenuated inversion recovery MRI data. These measures were used to predict 12-month survival status (≤12 or >12 months) in 74 glioblastoma patients. Kaplan-Meier with receiver operating characteristic analyses was used to assess the relationship between derived spatial features and 12-month survival status as well as molecular subtype status in patients with glioblastoma. Kaplan-Meier survival analysis revealed that 14 spatial features were capable of stratifying overall survival in a statistically significant manner. For prediction of 12-month survival status based on these diversity indices, sensitivity and specificity were 0.86 and 0.64, respectively. The area under the receiver operating characteristic curve and the accuracy were 0.76 and 0.75, respectively. For prediction of molecular subtype status, proneural subtype shows highest accuracy of 0.93 among all molecular subtypes based on receiver operating characteristic analysis. We find that measures of spatial diversity from point pattern analysis of intensity habitats from T1 post-contrast and T2 fluid-attenuated inversion recovery images are associated with both tumor subtype status and 12-month survival status and may therefore be useful indicators of patient prognosis, in addition to providing potential guidance for molecularly-targeted therapies in Glioblastoma multiforme.

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Patient-Specific Planning for Thermal Magnetic Resonance of Glioblastoma Multiforme.

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