Predicting the Location of Glioma Recurrence After a Resection Surgery

International audienceWe propose a method for estimating the location of glioma recurrence after surgical resection. This method consists of a pipeline including the registration of images at different time points, the estimation of the tumor infiltration map, and the prediction of tumor regrowth using a reaction-diffusion model. A data set acquired on a patient with a low-grade glioma and post surgery MRIs is considered to evaluate the accuracy of the estimated recurrence locations found using our method. We observed good agreement in tumor volume prediction and qualitative matching in regrowth locations. Therefore, the proposed method seems adequate for modeling low-grade glioma recurrence. This tool could help clinicians anticipate tumor regrowth and better characterize the radiologically non-visible infiltrative extent of the tumor. Such information could pave the way for model-based personalization of treatment planning in a near future

Full Issue: Volume 13, Issue 1 - Winter 2018

Full Issue: Volume 13, Issue 1 - Winter 201

An Open-Source Tool for Anisotropic Radiation Therapy Planning in Neuro-oncology Using DW-MRI Tractography.

There is evidence from histopathological studies that glioma tumor cells migrate preferentially along large white matter bundles. If the peritumoral white matter structures can be used to predict the likely trajectory of migrating tumor cells outside of the surgical margin, then this information could be used to inform the delineation of radiation therapy (RT) targets. In theory, an anisotropic expansion that takes large white matter bundle anatomy into account may maximize the chances of treating migrating cancer cells and minimize the amount of brain tissue exposed to high doses of ionizing radiation. Diffusion-weighted MRI (DW-MRI) can be used in combination with fiber tracking algorithms to model the trajectory of large white matter pathways using the direction and magnitude of water movement in tissue. The method presented here is a tool for translating a DW-MRI fiber tracking (tractography) dataset into a white matter path length (WMPL) map that assigns each voxel the shortest distance along a streamline back to a specified region of interest (ROI). We present an open-source WMPL tool, implemented in the package Diffusion Imaging in Python (DIPY), and code to convert the resulting WMPL map to anisotropic contours for RT in a commercial treatment planning system. This proof-of-concept lays the groundwork for future studies to evaluate the clinical value of incorporating tractography modeling into treatment planning

Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme

Objectives Tumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy. Design Retropective cohort study. Setting Primary level of care with two participating centres. The geographical location was central Germany. Participants From January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression. Interventions This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. Primary and secondary outcome measures Median survival, progression free survival and complication rate. Results Median survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively. Conclusions CT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated

Diffusion MR Characteristics Following Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma.

The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADCL and ADCH were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADCL value of 1.0 um2/ms and ADCH value of 1.6 um2/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADCL had significantly shorter PFS (Cox Hazard Ratio = 0.12, P = 0.0006). OS was significantly shorter with low ADCL tumors, showing a median OS of 407 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADCH was not predictive of PFS or OS when accounting for age and ADCL. In summary, newly diagnosed glioblastoma patients with low ADCL after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADCL. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ

The role of Allee effect in modelling post resection recurrence of glioblastoma

Resection of the bulk of a tumour often cannot eliminate all cancer cells, due to their infiltration into the surrounding healthy tissue. This may lead to recurrence of the tumour at a later time. We use a reaction-diffusion equation based model of tumour growth to investigate how the invasion front is delayed by resection, and how this depends on the density and behaviour of the remaining cancer cells. We show that the delay time is highly sensitive to qualitative details of the proliferation dynamics of the cancer cell population. The typically assumed logistic type proliferation leads to unrealistic results, predicting immediate recurrence. We find that in glioblastoma cell cultures the cell proliferation rate is an increasing function of the density at small cell densities. Our analysis suggests that cooperative behaviour of cancer cells, analogous to the Allee effect in ecology, can play a critical role in determining the time until tumour recurrence

Surgery for Recurrent Glioblastoma

Recurrence of glioblastoma (GB) is inevitable. As the optimal management for recurrent glioblastoma continues to evolve, clear treatment guidelines for are lacking. Existing literature does not clarify the role that second surgery plays in the treatment of these patients. Although few studies report that second surgery is beneficial in select patients and leads to longer overall survival (OS), other studies have demonstrated the limited impact that repeat surgery has on the eventual patient outcome. Maximal safe resection (high extent of resection—EOR) has been proven to improve the OS at reoperation, even when undertaken for cases where the first surgery achieved only a limited EOR. Karnofsky Performance Score (KPS) and age at presentation are valuable prognostic factors that predict better OS and aid in better patient selection for surgical management. The true value of reoperation versus systemic treatment, their effects the patient’s QoL and the added increase in overall survival is better judged after detailed investigation by means of a prospective, randomized trial

Neurosurgical Applications of Magnetic Resonance Diffusion Tensor Imaging

Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) is a rapidly evolving technology that enables the visualization of neural fiber bundles, or white matter (WM) tracts. There are numerous neurosurgical applications for MR DTI including: (1) Tumor grading and staging; (2) Pre-surgical planning (determination of resectability, determination of surgical approach, identification of WM tracts at risk); (3) Intraoperative navigation (tumor resection that spares WM damage, epilepsy resection that spares WM damage, accurate location of deep brain stimulation structures); (4) Post-operative assessment and monitoring (identification of WM damage, identification of tumor recurrence). Limitations of MR DTI include difficulty tracking small and crossing WM tracts, lack of standardized data acquisition and post-processing techniques, and practical equipment, software, and timing considerations. Overall, MR DTI is a useful tool for planning, performing, and following neurosurgical procedures, and has the potential to significantly improve patient care. Technological improvements and increased familiarity with DTI among clinicians are next steps

Early postoperative MRI overestimates residual tumour after resection of gliomas with no or minimal enhancement

Standards for residual tumour measurement after resection of gliomas with no or minimal enhancement have not yet been established. In this study residual volumes on early and late postoperative T2-/FLAIR-weighted MRI are compared. A retrospective cohort included 58 consecutive glioma patients with no or minimal preoperative gadolinium enhancement. Inclusion criteria were first-time resection between 2007 and 2009 with a T2-/FLAIR-based target volume and availability of preoperative, early (<48 h) and late (1-7 months) postoperative MRI. The volumes of non-enhancing T2/FLAIR tissue and diffusion restriction areas were measured. Residual tumour volumes were 22% smaller on late postoperative compared with early postoperative T2-weighted MRI and 49% smaller for FLAIR-weighted imaging. Postoperative restricted diffusion volume correlated with the difference between early and late postoperative FLAIR volumes and with the difference between T2 and FLAIR volumes on early postoperative MRI. We observed a systematic and substantial overestimation of residual non-enhancing volume on MRI within 48 h of resection compared with months postoperatively, in particular for FLAIR imaging. Resection-induced ischaemia contributes to this overestimation, as may other operative effects. This indicates that early postoperative MRI is less reliable to determine the extent of non-enhancing residual glioma and restricted diffusion volumes are imperativ

Practical prognostic score for predicting the extent of resection and neurological outcome of gliomas in the sensorimotor area

OBJECTIVE: In this prospective study, we assessed the utility of a novel prognostic score (PS) in guiding the surgical strategy of patients with sensorimotor area gliomas. PATIENTS AND METHODS: Form December 2012 to April 2016, we collected data from patients diagnosed with brain gliomas in the sensorimotor area. All the patients had intraoperatively confirmed contiguity or continuity with sensorimotor cortical and subcortical structures. Several clinical and radiological factors were analyzed to generate a PS for each patient (range 1-8). The end-points included the extent of resection (EOR) and neurological outcome (modified Rankin Score; mRS). We assessed the predictive power of the PS using different analyses. Crosstabs analyses and Fisher's exact test (Fet) were used to evaluate the possible predictive parameters, and for the classification of positive or negative outcomes for the chosen proxies; the significance threshold was set at p<0.05. RESULTS: Using independent t-tests, we compared the mRS at different time points (pre, post, and at 6 months) for 2 subgroups from the total sample using a cut-off PS value of 4. For the EOR, a PS value of ≥5 was predictive of successful outcome, a value of 4 indicated an uncertain outcome, and a value of ≤3 predicted a worse outcome. CONCLUSIONS: This PS value can be easily used in clinical settings to help predict the functional outcome and EOR in sensorimotor area tumors. Integration with information from fMRI, DTI, and TMS, along with MRI spectroscopy could further enhance the value of this P