EP-1940: Hippocampal avoidance whole brain radiotherapy: a comparison of contouring and planning techniques

PURPOSE Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [ P = .049] and 16.4% v 33.3% [ P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue ( P = .04), less difficulty with remembering things ( P = .01), and less difficulty with speaking ( P = .049) and using imputed data, less interference of neurologic symptoms in daily activities ( P = .008) and fewer cognitive symptoms ( P = .01). CONCLUSION HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

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Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

Neuro-Oncology ◽

10.1093/neuonc/noaa193 ◽

2020 ◽

Author(s):

Wen-Chi Yang ◽

Ya-Fang Chen ◽

Chi-Cheng Yang ◽

Pei-Fang Wu ◽

Hsing-Min Chan ◽

...

Keyword(s):

Brain Metastases ◽

Phase Ii ◽

Whole Brain Radiotherapy ◽

Neurocognitive Function ◽

Mean Difference ◽

Whole Brain ◽

Delayed Recall ◽

Brain Radiotherapy ◽

Hippocampal Avoidance

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.

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On the Estimation of the Location of the Hippocampus in the Context of Hippocampal Avoidance Whole Brain Radiotherapy Treatment Planning

Technology in Cancer Research & Treatment ◽

10.1177/153303460900800604 ◽

2009 ◽

Vol 8 (6) ◽

pp. 425-432 ◽

Cited By ~ 9

Author(s):

Edward T. Bender ◽

Minesh P. Mehta ◽

Wolfgang A. Tomé

Keyword(s):

Treatment Planning ◽

Whole Brain Radiotherapy ◽

Radiotherapy Treatment Planning ◽

Whole Brain ◽

Brain Radiotherapy ◽

Hippocampal Avoidance ◽

Radiotherapy Treatment

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Analyzing Planning Techniques for Whole Brain Radiotherapy

International Journal of Medical Physics Clinical Engineering and Radiation Oncology ◽

10.4236/ijmpcero.2020.91001 ◽

2020 ◽

Vol 09 (01) ◽

pp. 1-13

Author(s):

Soai Dang Quoc ◽

Quang Bui Vinh ◽

Cuong Bui Xuan ◽

Toan Hoang Van ◽

Truong Vu

Keyword(s):

Whole Brain Radiotherapy ◽

Planning Techniques ◽

Whole Brain ◽

Brain Radiotherapy

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SU-E-T-581: Planning Evaluation of Step-And-Shoot IMRT, RapidArc and Helical TomoTherapy for Hippocampal-Avoidance Whole Brain Radiotherapy (HA-WBRT)

Medical Physics ◽

10.1118/1.4735670 ◽

2012 ◽

Vol 39 (6Part19) ◽

pp. 3839-3839

Author(s):

J Evans ◽

Q Chen ◽

E Wuthrick ◽

M Weldon ◽

Y Rong

Keyword(s):

Helical Tomotherapy ◽

Whole Brain Radiotherapy ◽

Whole Brain ◽

Brain Radiotherapy ◽

Hippocampal Avoidance ◽

Step And Shoot

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RADI-26. DOSIMETRIC EVALUATION OF 6 MV VERSUS 10 MV PHOTONS FOR HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIOTHERAPY

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.118 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i26-i27

Author(s):

Diana Julie ◽

Sean Mahase ◽

Diana No ◽

Khaled Salah ◽

Jonathan Knisely

Keyword(s):

Volumetric Modulated Arc Therapy ◽

Whole Brain Radiotherapy ◽

Target Volume ◽

Brain Parenchyma ◽

Whole Brain ◽

Brain Radiotherapy ◽

Hippocampal Avoidance ◽

Signed Rank ◽

Dose Homogeneity ◽

Dose Constraints

Abstract OBJECTIVE: Whole brain radiotherapy (WBRT) causes neurocognitive decline. Hippocampal avoidance WBRT (HA-WBRT) reduces hippocampal irradiation, potentially mitigating neurocognitive sequelae. We compared hippocampal and brain dosimetry with HA-WBRT with 6 megavoltage (MV) versus 10 MV photon energies. METHODS: Twenty consecutive patients treated with WBRT were retrospectively replanned with HA-WBRT techniques using 6 MV and 10 MV photons. Coplanar volumetric modulated arc therapy was employed, with a prescription dose of 3000 cGy in 10 fractions. Planning was done with Eclipse version 13.6 or 15.6. Nine patients were planned with 2.5 mm multileaf collimator leaves, with the remainder planned with 5 mm leaves. The hippocampi were contoured and a HA structure was generated using a uniform 5 mm expansion. A planning target volume (PTV) was defined as the brain parenchyma minus the HA structure. NRG-CC001 dose constraints were used. For each variable, descriptive statistics were calculated. Comparisons were made using two-tailed Wilcoxon signed rank tests or paired t-tests. RESULTS: The minimum hippocampal dose (D100%) was improved with 6 MV plans, 841 cGy compared to 914 cGy with 10 MV (p< 0.005). The maximum hippocampal dose (D0.03cc) was reduced with 6 MV planning, 1614 cGy versus 1676 cGy for 10 MV (p< 0.0001). With 6 MV photons, a greater number of plans met NRG-CC001 constraints without deviations. 6 MV photons improved PTV coverage by the 95% isodose line, 96.6% compared to 95.9% for 10 MV (p=0.021). 6 MV photon plans decreased the volume of PTV receiving ≥105% of the prescription, 84.2% versus 87.9% for 10 MV (p=0.006). The mean dose, hot spots, and cold spots did not differ by photon energy. PTV dose constraints were always met. CONCLUSION: 6 MV photon HA-WBRT plans are dosimetrically superior to 10 MV, reducing hippocampal radiation dose, without compromise in brain coverage and improved target dose homogeneity.

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