Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients

Köcher, Martin; Jockwitz, Christiane; Lohmann, Philipp; Stoffels, Gabriele; Filß, Christian; Mottaghy, Felix M.; Ruge, Maximilian I.; Lucas, Carolin Weiß; Goldbrunner, Roland; Shah, N. Jon; Fink, Gereon R.; Galldiks, Norbert; Langen, Karl‐Josef; Caspers, Svenja

doi:10.3390/cancers13102373

Cited by 8 publications

(14 citation statements)

References 53 publications

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“…Moreover, pre-and postoperative volumes for CE and non-CE tumors were directly correlated suggesting that larger tumors are likely to invade eloquent areas, limiting extensive resection. 28,29 Although surgically induced neurologic deficits were not linked to less favorable outcome, deficits were generally mild. This might reflect the mindset that profound deficits jeopardize survival, 6,30,31 and preventing these should be prioritized over EOR.…”

Section: Discussionmentioning

confidence: 99%

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

et al. 2022

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Background Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (I) explore the prognostic utility of the classification system and (II) define how much removed non-CE tumor translates into a survival benefit. Methods The international RANO resect group retrospectively searched previously compiled databases from seven neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and post-operative MRI were collected. Results We collected 1008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC 26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm 3) were favorably associated with outcome: patients with ‘maximal CE resection’ (class 2) had superior outcome compared to patients with ‘submaximal CE resection’ (class 3) or ‘biopsy’ (class 4). Extensive resection of non-CE tumor (≤5 cm 3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 (‘supramaximal CE resection’). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. Conclusions The proposed “RANO categories for extent of resection in glioblastoma” are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such ‘supramaximal CE resection’.

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Section: Discussionmentioning

confidence: 99%

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

et al. 2022

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“…This problem cannot be completely eliminated by neither of the widely available registration algorithms. The misalignment can only be minimized to have the least effect on the results ( Kocher et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Predicting the true extent of glioblastoma based on probabilistic tractography

et al. 2022

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Glioblastoma is the most frequent type of primary brain tumors. Despite the advanced therapy, most of the patients die within 2 years after the diagnosis. The tumor has a typical appearance on MRI: a central hypointensity surrounded by an inhomogeneous, ring-shaped contrast enhancement along its border. Too small to be recognized by MRI, detached individual tumor cells migrate along white matter fiber tracts several centimeters away from the edge of the tumor. Usually these cells are the source of tumor recurrence. If the infiltrated brain areas could be identified, longer survival time could be achieved through supratotal resection and individually planned radiation therapy. Probabilistic tractography is an advanced imaging method that can potentially be used to identify infiltrated pathways, thus the real extent of the glioblastoma. Our study consisted of twenty high grade glioma patients. Probabilistic tractography was started from the tumor. The location of tumor recurrence on follow-up MRI was considered as the primary infiltrated white matter tracts. The results of probabilistic tractography were evaluated at thirteen different thresholds. The overlap with the tumor recurrence of each threshold level was then defined to calculate the sensitivity and specificity. In the group level, sensitivity (81%) and specificity (90%) were the most reliable at 5% threshold level. There were two outliers in the study group, both with high specificity and very low sensitivity. According to our results, probabilistic tractography can help to define the true extent of the glioblastoma at the time of diagnosis with high sensitivity and specificity. Individually planned surgery and irradiation could provide a better chance of survival in these patients.

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“…Controls were matched for gender (males, n=75; females, n=46), age (mean 51.7 ± 11.5 years), and educational status using propensity score matching ( 35 ). Both cohorts have been analyzed in an earlier study presented by our group ( 36 ).…”

Section: Methodsmentioning

confidence: 99%

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

et al. 2022

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BackgroundIn glioma patients, multimodality therapy and recurrent tumor can lead to structural brain tissue damage characterized by pathologic findings in MR and PET imaging. However, little is known about the impact of different types of damage on the fiber architecture of the affected white matter.Patients and methodsThis study included 121 pretreated patients (median age, 52 years; ECOG performance score, 0 in 48%, 1-2 in 51%) with histomolecularly characterized glioma (WHO grade IV glioblastoma, n=81; WHO grade III anaplastic astrocytoma, n=28; WHO grade III anaplastic oligodendroglioma, n=12), who had a resection, radiotherapy, alkylating chemotherapy, or combinations thereof. After a median follow-up time of 14 months (range, 1-214 months), anatomic MR and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET images were acquired on a 3T hybrid PET/MR scanner. Post-therapeutic findings comprised resection cavities, regions with contrast enhancement or increased FET uptake and T2/FLAIR hyperintensities. Local fiber density was determined from high angular-resolution diffusion-weighted imaging and advanced tractography methods. A cohort of 121 healthy subjects selected from the 1000BRAINS study matched for age, gender and education served as a control group.ResultsLesion types differed in both affected tissue volumes and relative fiber densities compared to control values (resection cavities: median volume 20.9 mL, fiber density 16% of controls; contrast-enhanced lesions: 7.9 mL, 43%; FET uptake areas: 30.3 mL, 49%; T2/FLAIR hyperintensities: 53.4 mL, 57%, p<0.001). In T2/FLAIR-hyperintense lesions caused by peritumoral edema due to recurrent glioma (n=27), relative fiber density was as low as in lesions associated with radiation-induced gliosis (n=13, 48% vs. 53%, p=0.17). In regions with pathologically increased FET uptake, local fiber density was inversely related (p=0.005) to the extent of uptake. Total fiber loss associated with contrast-enhanced lesions (p=0.006) and T2/FLAIR hyperintense lesions (p=0.013) had a significant impact on overall ECOG score.ConclusionsThese results suggest that apart from resection cavities, reduction in local fiber density is greatest in contrast-enhancing recurrent tumors, but total fiber loss induced by edema or gliosis has an equal detrimental effect on the patients’ performance status due to the larger volume affected.

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Lesion-Function Analysis from Multimodal Imaging and Normative Brain Atlases for Prediction of Cognitive Deficits in Glioma Patients

Cited by 8 publications

References 53 publications

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

Predicting the true extent of glioblastoma based on probabilistic tractography

Alterations in white matter fiber density associated with structural MRI and metabolic PET lesions following multimodal therapy in glioma patients

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