A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation

Martin, Ting; Grimm, Jimm; McIntyre, Riley; Anderson-Keightly, Heather; Kleinberg, Lawrence; Hales, Russell K.; Moore, Joseph A.; Vannorsdall, Tracy D.; Redmond, Kristin J.

doi:10.1016/j.radonc.2017.09.035

Cited by 65 publications

(55 citation statements)

References 42 publications

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“…Studies on tissue-dose interaction, as the current one, aid in understanding radiation-induced cognitive decline, which may be the consequence of, but not restricted to, demyelination and loss of axonal integrity with increasing radiation doses. Research in neuroscience, especially on aging [47,48] and cognitive impairment [49,50] ROIs receiving certain dose levels or aim to avoid PVE by restricting the masking to connected voxels that only include WM structure by excluding voxels with FA lower than 0.2 [17,29,55].…”

Section: Discussionmentioning

confidence: 99%

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

Dávid

Mesri

Bodiut

et al. 2019

Preprint

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Background and purpose: Radiation-induced changes in brain tissue may relate to post-radiotherapy (RT) cognitive decline. Our aim is to investigate changes of the brain microstructural properties after exposure to radiation during clinical protocols of RT using diffusion MRI (dMRI). Methods and Materials: The susceptibility of tissue changes to radiation was investigated in a clinically heterogenic cohort (age, pathology, tumor location, type of surgery) consisting of 121 scans of 18 patients (10 females). The imaging dataset included 18 planning CTs and 103 dMRI scans (range 2-14, median = 6 per patient) assessing pre-operative, post-operative pre-RT and post-RT states. Diffusion tensor imaging (DTI) metrics were estimated from all scans for a region-of-interest based linear relation analysis between mean dose and change in DTI metrics, while partial volume effects were regressed out. Results: The largest regional dose dependency with mean diffusivity appear in the white matter of the frontal pole in the left hemisphere by an increase of 2.61 %/(Gy x year). Full brain-wise, pooled results for white matter show fractional anisotropy to decrease by 0.85 %/(30Gy x year); mean diffusivity increase by 9.17 %/(30Gy x year); axial diffusivity increase by 7.30%/(30Gy x year) and radial diffusivity increases by 10.63%/(30Gy x year). Conclusions: White matter is susceptible to radiation with some regional variability where diffusivity metrics demonstrate the largest relative sensitivity. This suggests that dMRI is a promising tool in assessing microstructural changes after RT, which can help in understanding treatment-induced cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

Dávid

Mesri

Bodiut

et al. 2019

Preprint

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“…46 This and similar studies have quantified the likelihood of neurotoxicity as a function of dose to the healthy brain parenchyma and have identified clinically meaningful benchmarks with implications for treatment planning. 46 , 47 , 48 Given the potential benefits of treating resection cavities with SRS at higher doses, particularly when employing fractionated regimens, continued quantification of adverse radiation effects is needed to assess the therapeutic index of this modality.…”

Section: Discussionmentioning

confidence: 99%

A Dose-Response Model of Local Tumor Control Probability After Stereotactic Radiosurgery for Brain Metastases Resection Cavities

Gui

Grimm

Kleinberg

et al. 2020

Advances in Radiation Oncology

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Purpose Recent randomized controlled trials evaluating stereotactic surgery (SRS) for resected brain metastases question the high rates of local control previously reported in retrospective studies. Tumor control probability (TCP) models were developed to quantify the relationship between radiation dose and local control after SRS for resected brain metastases. Methods and Materials Patients with resected brain metastases treated with SRS were evaluated retrospectively. Melanoma, sarcoma, and renal cell carcinoma were considered radio-resistant histologies. The planning target volume (PTV) was the region of enhancement on T1 post-gadolinium magnetic resonance imaging plus a 2-mm uniform margin. The primary outcome was local recurrence, defined as tumor progression within the resection cavity. Cox regression evaluated predictors of local recurrence. Dose-volume histograms for the PTV were obtained from treatment plans and converted to 3-fraction equivalent doses (α/β = 12 Gy). TCP models evaluated local control at 1-year follow-up as a logistic function of dose-volume histogram data. Results Among 150 cavities, 41 (27.3%) were radio-resistant. The median PTV volume was 14.6 mL (range, 1.3-65.3). The median prescription was 21 Gy (range, 15-25) in 3 fractions (range, 1-5). Local control rates at 12 and 24 months were 86% and 82%. On Cox regression, larger cavities (PTV > 12 cm 3 ) predicted increased risk of local recurrence ( P = .03). TCP modeling demonstrated relationships between improved 1-year local control and higher radiation doses delivered to radio-resistant cavities. Maximum PTV doses of 30, 35, and 40 Gy predicted 78%, 89%, and 94% local control among all radio-resistant cavities, versus 69%, 79%, and 86% among larger radio-resistant cavities. Conclusions After SRS for resected brain metastases, larger cavities are at greater risk of local recurrence. TCP models suggests that higher radiation doses may improve local control among cavities of radio-resistant histology. Given maximum tolerated doses established for single-fraction SRS, fractionated regimens may be required to optimize local control in large radio-resistant cavities.

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“…There are only a few prospective evaluations of hippocampal radiation dose volume effect and memory deficit [ 38 – 41 ]. Currently, two phases III randomized trials are ongoing and evaluating HA-WBRT.…”

Section: Discussionmentioning

confidence: 99%

Quality assurance analysis of hippocampal avoidance in a melanoma whole brain radiotherapy randomized trial shows good compliance

et al. 2018

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BackgroundMelanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. An ongoing randomised phase III trial (NCT01503827 – WBRT-Mel) evaluates the role of adjuvant whole brain radiotherapy (WBRT) following local treatment of MBM. Hippocampal avoidance during WBRT (HA-WBRT) has shown memory and neurocognitive function (NCF) preservation in the RTOG-0933 phase II study. This study assessed the quality assurance of HA-WBRT within the WBRT-Mel trial according to RTOG-0933 study criteria.MethodsHippocampal avoidance was allowed in approved centres with intensity-modulated radiotherapy capability. Patients treated by HA-WBRT were not randomized within the WBRT arm. The RTOG 0933 contouring Atlas was used to contour hippocampi. In the trial co-ordinating centre, patients were treated with volumetric modulated arc therapy using complementary arcs; similar techniques were used at other sites. Dosimetric data were extracted retrospectively and analysed in accordance with RTOG 0933 study constraints criteria.ResultsAmong the 215 patients accrued to the WBRT-Mel study between April 2009 and September 2017, 107 were randomized to the WBRT arm, 22 were treated by HA-WBRT in 4 centers. Eighteen patients were treated in the same centre. The median age was 65 years. The commonest (91%) HA-WBRT schema was 30 Gy in 10 fractions. Prior to HA-WBRT, 10 patients had been treated by surgery alone, six by radiosurgery alone, four by surgery and radiosurgery and two exclusively by simultaneous integrated boost concurrent to HA-WBRT. Twenty patients were treated with intention to spare both hippocampi and two patients had MBM close to one hippocampus and were treated with intention to spare the contralateral hippocampus. According to RTOG-0933 study criteria, 18 patients (82%) were treated within constraints and four patients (18%) had unacceptable deviation in just one hippocampus.ConclusionsThis dosimetric quality assurance study shows good compliance (82%) according to RTOG-0933 study dosimetric constraints. Indeed, all patients respected RTOG hippocampal avoidance constraints on at least one hippocampus. In the futureanalysis of the WBRT-Mel trial, the NCF of patients on the observation arm, WBRT arm and with HA-WBRT arm will be compared.

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A prospective evaluation of hippocampal radiation dose volume effects and memory deficits following cranial irradiation

Cited by 65 publications

References 42 publications

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

A Dose-Response Model of Local Tumor Control Probability After Stereotactic Radiosurgery for Brain Metastases Resection Cavities

Quality assurance analysis of hippocampal avoidance in a melanoma whole brain radiotherapy randomized trial shows good compliance

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