A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma

Kim, Michelle M.; Sun, Yilun; Aryal, Madhava; Parmar, Hemant; Piert, Morand; Rosen, Benjamin; Mayo, Charles S.; Balter, James M.; Schipper, Matthew J.; Gabel, Nicolette; Briceño, Emily M.; You, Daekeun; Heth, Jason; Al-Holou, Wajd N.; Umemura, Yoshie; Leung, Denise; Junck, Larry; Wahl, Daniel R.; Lawrence, Theodore S.; Cao, Yue

doi:10.1016/j.ijrobp.2021.01.033

Cited by 29 publications

(29 citation statements)

References 59 publications

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“…This hypothesis, which remains to be validated clinically, is supported by evidence provided by a recent phase II clinical trial. 18 Using a combination of diffusion- and perfusion-weighted MRI-derived parameters to guide dose escalation to 76 Gy – a similar approach to the one used in our study – Kim et al 18 demonstrated a 27% improvement in 12-month overall survival in the dose escalation arm compared to historical controls.…”

Section: Discussionmentioning

confidence: 76%

“…Importantly, in a phase II trial they showed that escalating the dose to 76 Gy in these regions improved 1-year overall survival rate by 27% compared to standard treatment outcomes from historical controls. 18 As such, the combination of these two advanced MRI techniques could represent the best approach for DP adaptive planning strategies that aim to adjust the radiotherapy plan over the course of treatment in response to the evolving physiology in the tumor microenvironment.…”

mentioning

confidence: 99%

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An investigation of the conformity, feasibility, and expected clinical benefits of multiparametric MRI-guided dose painting radiotherapy in glioblastoma

Brighi

Keall

Holloway

et al. 2022

Neuro-Oncology Advances

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Background New technologies developed to improve survival outcomes for glioblastoma (GBM) continue to have limited success. Recently, image-guided dose painting (DP) radiotherapy has emerged as a promising strategy to increase local control rates. In this study, we evaluate the practical application of a multiparametric MRI model of glioma infiltration for DP radiotherapy in GBM by measuring its conformity, feasibility and expected clinical benefits against standard of care treatment. Methods Maps of tumour probability were generated from perfusion/diffusion MRI data from 17 GBM patients via a previously developed model of GBM infiltration. Prescriptions for DP were linearly derived from tumour probability maps and used to develop dose optimised treatment plans. Conformity of DP plans to dose prescriptions was measured via a quality factor. Feasibility of DP plans was evaluated by dose metrics to target volumes and critical brain structures. Expected clinical benefit of DP plans was assessed by tumour control probability. The DP plans were compared to standard radiotherapy plans. Results The conformity of the dose painting plans was >90%. Compared to the standard plans, DP a) did not affect dose delivered to organs at risk; b) increased mean and maximum dose and improved minimum dose coverage for the target volumes; c) reduced minimum dose within the radiotherapy treatment margins; d) improved local tumour control probability within the target volumes for all patients. Conclusions A multiparametric MRI model of GBM infiltration can enable conformal, feasible and potentially beneficial dose painting radiotherapy plans.

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Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

An investigation of the conformity, feasibility, and expected clinical benefits of multiparametric MRI-guided dose painting radiotherapy in glioblastoma

Brighi

Keall

Holloway

et al. 2022

Neuro-Oncology Advances

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“…In contrast, dose painting radiotherapy guided by functional imaging, such as functional MR and PET, is expected to achieve a safe dose boost. Kim et al [22] investigated the region of hyperperfused/hypercellular (TV HCV /TV CBV ) >1 cm 3 in high b-value diffusion-weighted MRI and dynamic enhanced perfusion MRI (DCE) for glioblastoma with dose boosting (75 Gy/30 f) and found that it resulted in good survival rates (12-month OS rate of 92% (P=0.03) and median OS of 20 months) with fair function and quality of life.…”

Section: Discussionmentioning

confidence: 99%

A Study of Dose Painting Radiotherapy Guided by Three-Dimensional Arterial Spin labeling Perfusion Magnetic Resonance Imaging for Non-Enhancing Low-Grade Gliomas

Zhu

Gong

Wang

et al. 2021

Preprint

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Background: The purpose of this study was to investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL) perfusion magnetic resonance imaging.Methods: Eighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid attenuated inversion recovery (T2 FLAIR) and contrast-enhanced T1-weight magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 FLAIR. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The planning target volume (PTV), PTV-ASL and PTV-SUB were developed by expanding the external margins of the GTV, GTV-ASL and GTV-SUB, respectively. Three plans were established for each patient: in plan 1, the traditional homogeneous prescription dose to the PTV was 45-60 Gy; in plan 2 and plan 3, the dose to the PTV-ASL increased by 10-20% based on plan 1, without the maximum dose constraint to the PTV-ASL in plan 3. The dosimetric differences among the three plans were compared.Results: Compared with plan 1, the dose to 2% (D2%), 98% (D98%) and 50% (Dmean) of PTV-ASL volumes increased by 14.67%, 16.17% and 14.31% in plan 2 and 19.84%, 15.52% and 14.27% in plan 3, respectively (P < 0.05); the D2% of the PTV, PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P< 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In Plan 2 and plan 3, the conformity indexs decreased by 18.60% and 12.79%; while the homogeneity indexs increased by 1.43 and 2 times (P<0.05). Compared with plan 1, the D0.1cc of brain stem and Dmax of optic chiasma slightly increased in plan 2 and plan 3, but the absolute doses met the dose constraint. The other organs at risk were similar among the three plans (P > 0.05).Conclusions: The sub-volume with hyper-perfusion for NE-LGG radiotherapy can be segmented based on the perfusion difference guided by 3D-ASL. And the radiation dose to the hyper-perfusion area increased safely by 10-20% through dose painting.

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“…The median proportion of the overlapping volume (i.e., both restricted diffusion and increased perfusion) that developed progression during follow-up was 77%, indicating that regions with restricted diffusion and increased perfusion are likely to show progression in the future. This overlapping volume has been targeted in a phase II dose escalation study that showed significantly improved 12-month overall survival (92%) compared to historical control ( p = 0.03) [ 38 ].…”

Section: Vascular Leakinessmentioning

confidence: 99%

“…Based on these results, the authors imply that regions that display both restricted diffusion and increased perfusion harbor resistant disease that is likely to progress in the future, but most failures will spatially occur in regions characterized by neither restricted diffusion nor increased perfusion. At the same institute, Kim et al conducted a phase II study in which patients with glioblastoma received dose intensification against regions with restricted diffusion and elevated perfusion resulting in improved overall survival [ 38 ]. Chang et al used computational big-data modeling to evaluate the potential of ADC and FLAIR signal pre-radiotherapy to predict future recurrence [ 106 ].…”

Section: Hypercellularitymentioning

confidence: 99%

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

Tang

Romero

Jaspers

et al. 2022

Magn Reson Mater Phy

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As microscopic tumour infiltration of glioblastomas is not visible on conventional magnetic resonance (MR) imaging, an isotropic expansion of 1–2 cm around the visible tumour is applied to define the clinical target volume for radiotherapy. An opportunity to visualize microscopic infiltration arises with advanced MR imaging. In this review, various advanced MR biomarkers are explored that could improve target volume delineation for radiotherapy of glioblastomas. Various physiological processes in glioblastomas can be visualized with different advanced MR techniques. Combining maps of oxygen metabolism (CMRO2), relative cerebral blood volume (rCBV), vessel size imaging (VSI), and apparent diffusion coefficient (ADC) or amide proton transfer (APT) can provide early information on tumour infiltration and high-risk regions of future recurrence. Oxygen consumption is increased 6 months prior to tumour progression being visible on conventional MR imaging. However, presence of the Warburg effect, marking a switch from an infiltrative to a proliferative phenotype, could result in CMRO2 to appear unaltered in high-risk regions. Including information on biomarkers representing angiogenesis (rCBV and VSI) and hypercellularity (ADC) or protein concentration (APT) can omit misinterpretation due to the Warburg effect. Future research should evaluate these biomarkers in radiotherapy planning to explore the potential of advanced MR techniques to personalize target volume delineation with the aim to improve local tumour control and/or reduce radiation-induced toxicity.

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A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma

Cited by 29 publications

References 59 publications

An investigation of the conformity, feasibility, and expected clinical benefits of multiparametric MRI-guided dose painting radiotherapy in glioblastoma

An investigation of the conformity, feasibility, and expected clinical benefits of multiparametric MRI-guided dose painting radiotherapy in glioblastoma

A Study of Dose Painting Radiotherapy Guided by Three-Dimensional Arterial Spin labeling Perfusion Magnetic Resonance Imaging for Non-Enhancing Low-Grade Gliomas

The potential of advanced MR techniques for precision radiotherapy of glioblastoma

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