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Randomized Controlled Trial
. 2023 Nov 1;117(3):571-580.
doi: 10.1016/j.ijrobp.2023.04.030. Epub 2023 May 6.

Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001

Vinai Gondi  1 , Snehal Deshmukh  2 , Paul D Brown  3 , Jeffrey S Wefel  4 , Terri S Armstrong  5 , Wolfgang A Tome  6 , Mark R Gilbert  4 , Andre Konski  7 , Clifford G Robinson  8 , Joseph A Bovi  9 , Tammie L S Benzinger  8 , David Roberge  10 , Vijayananda Kundapur  11 , Isaac Kaufman  12 , Sunjay Shah  13 , Kenneth Y Usuki  14 , Andrew M Baschnagel  15 , Minesh P Mehta  16 , Lisa A Kachnic  17
Affiliations
Randomized Controlled Trial

Sustained Preservation of Cognition and Prevention of Patient-Reported Symptoms With Hippocampal Avoidance During Whole-Brain Radiation Therapy for Brain Metastases: Final Results of NRG Oncology CC001

Vinai Gondi et al. Int J Radiat Oncol Biol Phys. .

Erratum in

Abstract

Purpose: Initial report of NRG Oncology CC001, a phase 3 trial of whole-brain radiation therapy plus memantine (WBRT + memantine) with or without hippocampal avoidance (HA), demonstrated neuroprotective effects of HA with a median follow-up of fewer than 8 months. Herein, we report the final results with complete cognition, patient-reported outcomes, and longer-term follow-up exceeding 1 year.

Methods and materials: Adult patients with brain metastases were randomized to HA-WBRT + memantine or WBRT + memantine. The primary endpoint was time to cognitive function failure, defined as decline using the reliable change index on the Hopkins Verbal Learning Test-Revised (HVLT-R), Controlled Oral Word Association, or the Trail Making Tests (TMT) A and B. Patient-reported symptom burden was assessed using the MD Anderson Symptom Inventory with Brain Tumor Module and EQ-5D-5L.

Results: Between July 2015 and March 2018, 518 patients were randomized. The median follow-up for living patients was 12.1 months. The addition of HA to WBRT + memantine prevented cognitive failure (adjusted hazard ratio, 0.74, P = .016) and was associated with less deterioration in TMT-B at 4 months (P = .012) and HVLT-R recognition at 4 (P = .055) and 6 months (P = .011). Longitudinal modeling of imputed data showed better preservation of all HVLT-R domains (P < .005). Patients who received HA-WBRT + Memantine reported less symptom burden at 6 (P < .001 using imputed data) and 12 months (P = .026 using complete-case data; P < .001 using imputed data), less symptom interference at 6 (P = .003 using complete-case data; P = .0016 using imputed data) and 12 months (P = .0027 using complete-case data; P = .0014 using imputed data), and fewer cognitive symptoms over time (P = .043 using imputed data). Treatment arms did not differ significantly in overall survival, intracranial progression-free survival, or toxicity.

Conclusions: With median follow-up exceeding 1 year, HA during WBRT + memantine for brain metastases leads to sustained preservation of cognitive function and continued prevention of patient-reported neurologic symptoms, symptom interference, and cognitive symptoms with no difference in survival or toxicity.

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Figures

Figure 1.
Figure 1.
CONSORT diagram. HA=Hippocampal Avoidance; WBRT=Whole Brain Radiation Therapy; HVLT-R=Hopkins Verbal Learning Test-Revised.
Figure 2
Figure 2
Time to cognitive failure. WBRT, whole-brain radiotherapy; HA-WBRT, hippocampal avoidant whole-brain radiotherapy.
Figure 3
Figure 3
Hopkins Verbal Learning Test-Revised (HVLT-R) (A) Total Recall, (B) Delayed Recall and (C) Recognition. Higher score indicates better performance. WBRT, whole-brain radiotherapy; HA-WBRT, hippocampal avoidant whole-brain radiotherapy.
Figure 4
Figure 4
Cognitive Factor from M.D. Anderson Symptom Inventory (MDASI) with Brain Tumor module. Higher score indicates more symptoms. WBRT, whole-brain radiotherapy; HA-WBRT, hippocampal avoidant whole-brain radiotherapy.
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References

    1. Brown PD, Jaeckle K, Ballman KV, et al. Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: A randomized clinical trial. JAMA 2016;316:401–409. - PMC - PubMed
    1. Monje ML, Mizumatsu S, Fike JR, et al. Irradiation induces neural precursor-cell dysfunction. Nat Med 2002;8:955–962. - PubMed
    1. Gondi V, Hermann BP, Mehta MP, et al. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 2013;85:348–354. - PubMed
    1. Gondi V, Tolakanahalli R, Mehta MP, et al. Hippocampal-sparing whole-brain radiotherapy: A “how-to” technique using helical tomotherapy and linear accelerator-based intensity-modulated radiotherapy. International Journal of Radiation Oncology, Biology, Physics 2010;78:1244–1252. - PMC - PubMed
    1. Gondi V, Tome WA Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol 2010;97:370–376. - PMC - PubMed

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