Most Read Articles
Pearl Toh, 08 Jan 2021
Combining the anti-PD-1 antibody sintilimab and a bevacizumab biosimilar significantly improves survival compared with the standard treatment of sorafenib in the first-line setting for patients with advanced, unresectable hepatocellular carcinoma (HCC), according to the ORIENT-32 study presented at ESMO Asia 2020.
Dr Margaret Shi, 15 Jan 2021

Cancer patients at are an increased risk of severe coronavirus disease 2019 (COVID-19) and should be positioned at high priority for vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of age, according to statements issued by the European Society for Medical Oncology (ESMO).

Hippocampal avoidance in WBRT better preserves cognitive function without compromising survival

Christina Lau
20 Apr 2020

Hippocampal avoidance during whole-brain radiotherapy (HA-WBRT), together with memantine, better preserves cognitive function vs WBRT plus memantine in patients with brain metastases, without compromising survival, a multi-institutional phase III trial has shown.

In the NRG Oncology CC001 trial, 518 adult patients (median age, 61.5 years; primary lung cancer, 57.7 percent) with brain metastases outside a 5 mm margin around either hippocampus were randomized to receive HA-WBRT (n=257) or WBRT (n=261), together with memantine. HA-WBRT was delivered using intensity-modulated radiotherapy (IMRT) technique. In both groups, the prescribed WBRT dose was 30 Gy in 10 fractions. [J Clin Oncol 2020;38:1019-1029]

After a median follow-up of 7.9 months for patients who remained alive, the primary analysis showed a significantly lower risk of cognitive failure (defined as decline determined by reliable change index on ≥1 cognitive test) in the HA-WBRT vs WBRT arm (hazard ratio [HR], 0.76; 95 percent confidence interval [CI], 0.60 to 0.98; p=0.03). A significant treatment effect in favour of HA-WBRT plus memantine (HR, 0.74; 95 percent CI, 0.58 to 0.95; p=0.02) was found in the adjusted cause-specific analysis.

The better preservation of cognitive function with HA-WBRT vs WBRT was attributable to lower rates of deterioration in executive function at 4 months (23.3 percent vs 40.4 percent; p=0.01), as well as learning (11.5 percent vs 24.7 percent; p=0.049) and memory (16.4 percent vs 33.3 percent; p=0.02) at 6 months.

Importantly, overall survival (OS) and intracranial progression-free survival (PFS) did not differ significantly between the HA-WBRT and WBRT arms. Median OS was 6.3 months vs 7.6 months (HR, 1.13; 95 percent CI, 0.90 to 1.41; p=0.31), while median intracranial PFS was 5.0 months vs 5.3 months (HR, 1.14; 95 percent CI, 0.93 to 1.41; p=0.21).

Of note, there were fewer HA regional relapses in the HA-WBRT vs WBRT arm (11 vs 16).

No significant difference in grade ≥3 toxicity was reported between the HA-WBRT and WBRT arms.

In terms of symptom burden and quality of life, patients in the HA-WBRT arm experienced fewer cognitive symptoms (p=0.01) and less interference of neurologic symptoms in daily activities (p=0.008) at 6 months than those in the WBRT arm.

At 6 months, patients in the HA-WBRT arm reported less difficulty in remembering things (p=0.01), less difficulty in speaking (p=0.049), and less fatigue (p=0.04) than those in the WBRT arm.

“To our knowledge, this trial provides the first definitive clinical evidence that the hippocampal neuroregenerative niche is important to the pathophysiology of RT-induced cognitive decline,” the investigators wrote. “Our results provide confirmation that conformal avoidance of the hippocampal neuroregenerative stem-cell niche using IMRT during WBRT better preserves cognitive function and [reduces] patient-reported symptoms, with no significant difference observed in toxicity, intracranial PFS or OS.”

In the trial, the benefit of HA-WBRT emerged robustly with ≥4 months of follow-up, the investigators noted. For patients with life spans <4 months, previous trials showed that cognitive decline likely resulted from disease progression or other factors that contributed to shorter survival. [JAMA 2016;316:401-409; J Clin Oncol 2014;32:3810-3816] “Therefore, it seems reasonable to forgo HA during WBRT in patients with expected survival of <4 months,” they suggested.

“With these findings, HA-WBRT plus memantine 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,” they concluded.

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Most Read Articles
Pearl Toh, 08 Jan 2021
Combining the anti-PD-1 antibody sintilimab and a bevacizumab biosimilar significantly improves survival compared with the standard treatment of sorafenib in the first-line setting for patients with advanced, unresectable hepatocellular carcinoma (HCC), according to the ORIENT-32 study presented at ESMO Asia 2020.
Dr Margaret Shi, 15 Jan 2021

Cancer patients at are an increased risk of severe coronavirus disease 2019 (COVID-19) and should be positioned at high priority for vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of age, according to statements issued by the European Society for Medical Oncology (ESMO).