Hippocampal Avoidance During Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer: Randomized Phase II/III Trial NRG-CC003
Abstract
PURPOSE Hippocampal avoidance (HA) during therapeutic whole-brain radiotherapy reduces the risk of neurocognitive function (NCF) toxicity in patients with brain metastasis. This trial hypothesized that HA during prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) leads to noninferior intracranial relapse (ICR) and reduction in NCF toxicity. METHODS This randomized phase II/III trial enrolled patients with SCLC, no brain metastases, and response to chemotherapy. The primary end points were 12-month ICR (noninferiority design, randomized phase II) and 6-month Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall (DR) failure (phase III). Secondary end points were failure in any NCF test, health-related quality of life (HRQOL), overall survival (OS), and toxicity. RESULTS From December 2015 to June 2022, 393 patients were randomly assigned. The median age was 64 years. Stage and memantine usage were balanced. The median follow-up was 17.0 months (all patients) and 30.8 months (alive patients). HA-PCI had noninferior 12-month ICR rate (PCI 14.8% v HA-PCI 14.7%, P < .0001). Six-month HVLT-R DR deterioration was not significantly different (PCI 30.0% v HA-PCI 25.5%, P = .28). Addition of HA to PCI reduced the risk of failure in any NCF test (adjusted hazard ratio [HR], 0.78; 95% CI [0.61 to 0.99]; P = .039). Addition of HA to PCI was not associated with longitudinal change in any HRQOL domain. There were no differences in OS (adjusted HR, 0.88 [95% CI, 0.67 to 1.14]; P = .33) or grade ≥3 toxicity (PCI 31.4% v HA-PCI 30.7%, P = .88). CONCLUSION Although the study did not meet its primary end point of DR preservation, HA during PCI reduces the risk of overall neurocognitive toxicity with noninferior ICR risk and similar survival.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (31)
Vinai Gondi
Andrew B. Lassman, MD, MS, Division of Neuro-Oncology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, Herbert Irving Comprehensive Cancer Center, New York, NY, NewYork-Presbyterian, New York, NY; Mei-Yin C. Polley, PhD, NRG Oncology Statistics and Data Management Center, Chicago, IL, Department of Public Health Sciences, University of Chicago, Chicago, IL; Fabio M. Iwamoto, MD, Division of Neuro-Oncology, Department of Neurology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY,Herbert Irving Comprehensive Cancer Center, New York, NY, NewYork-Presbyterian, New York, NY; Vinai Gondi, MD, Department of Radiation Oncology, Northwestern Medicine Cancer Center Warrenville and Proton Center, Warrenville, IL; Erik P. Sulman, MD, PhD, Department of Radiation Oncology, Duke University School of Medicine, Durham, NC, Duke Cancer Institute, Durham, NC; Jedd D. Wolchok, MD, PhD, Meyer Cancer Center and Department of Medicine, Weill Cor...
Stephanie L. Pugh
NRG Oncology, Philadelphia, PA
Minesh P. Mehta
Jeffrey S. Wefel
University of Texas MD Anderson Cancer Center, Houston, TX
Wolfgang A. Tomé
Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY
Alexander Y. Sun
University Health Network-Princess Margaret Hospital, Toronto, Canada
John Grecula
Ohio State University Comprehensive Cancer Center, Columbus, OH
Kristin J. Redmond
The Johns Hopkins University School of Medicine, Baltimore, MD
Shannon Fogh
UCSF Medical Center-Parnassus, San Francisco, CA
Laurie Gaspar
University of Colorado, Denver, CO
Andre Konski
Chester County Hospital, West Chester, PA
Joseph Bovi
ThedaCare Regional Hospital, Appleton, WI
Clifford G. Robinson
Siteman Cancer Center at Washington University, Saint Louis, MO
Benjamin Corn
Shaare Zedek Medical Center, Jerusalem, Israel
Gregory M. Videtic
Cleveland Clinic Foundation, Cleveland, OH
Benjamin H. Lok
Harold A. Yoon
Heartland NCORP, Decatur, IL
John H. Heinzerling
Atrium Health/Levine Cancer Institute/Wake Forest University School of Medicine, Charlotte, NC
Albert S. DeNittis
Lankenau Medical Center, Wynnewood, PA
Ronald C. McGarry
University of Kentucky, Lexington, KY
Kiran Devisetty
Karmanos Cancer Institute/Wayne State University, Detroit, MI
Vijayananda Kundapur
Saskatoon Cancer Centre, Saskatoon, Canada
Abraham J. Wu
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY
Edward C. McCarron
MedStar Franklin Square Medical Center/Weinberg Cancer Institute, Baltimore, MD
Isabelle Thibault
CHU de Quebec-Université Laval, Quebec, Canada
Edmund L. Simon
Georgia NCI Community Oncology Research Program, Cumming, GA
Andrew M. Baschnagel
University of Wisconsin Carbone Cancer Center, Madison, WI
Samir Narayan
Michigan Cancer Research Consortium NCORP, Ypsilanti, MI
Jondavid Pollock
West Virginia University Healthcare, Wheeling, WV
Rebecca Paulus
NRG Oncology Statistics and Data Management Center, Philadelphia, PA
Lisa A. Kachnic