PMID- 28984517 OWN - NLM STAT- MEDLINE DCOM- 20191010 LR - 20240327 IS - 1933-0693 (Electronic) IS - 0022-3085 (Print) IS - 0022-3085 (Linking) VI - 129 IP - 1 DP - 2018 Jul TI - Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539. PG - 35-47 LID - 2016.11.JNS161170 [pii] LID - 10.3171/2016.11.JNS161170 [doi] AB - OBJECTIVE This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). METHODS NRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I-III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3-year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. RESULTS Fifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09-3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events. CONCLUSIONS This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. Clinical trial registration no.: NCT00895622 (clinicaltrials.gov). FAU - Rogers, Leland AU - Rogers L AD - Department of Radiation Oncology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona. FAU - Zhang, Peixin AU - Zhang P AD - NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania. FAU - Vogelbaum, Michael A AU - Vogelbaum MA AD - Cleveland Clinic Foundation, Cleveland, Ohio. FAU - Perry, Arie AU - Perry A AD - Department of Pathology, University of California, San Francisco, California. FAU - Ashby, Lynn S AU - Ashby LS AD - Department of Radiation Oncology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona. FAU - Modi, Jignesh M AU - Modi JM AD - MidState Medical Center, Hartford HealthCare, Meriden, Connecticut. FAU - Alleman, Anthony M AU - Alleman AM AD - Department of Radiological Science, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. FAU - Galvin, James AU - Galvin J AD - Imaging and Radiation Oncology Core QA Group, Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Brachman, David AU - Brachman D AD - Department of Radiation Oncology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona. FAU - Jenrette, Joseph M AU - Jenrette JM AD - Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina. FAU - De Groot, John AU - De Groot J AD - Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Bovi, Joseph A AU - Bovi JA AD - Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin. FAU - Werner-Wasik, Maria AU - Werner-Wasik M AD - Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina. FAU - Knisely, Jonathan P S AU - Knisely JPS AD - Department of Radiation Medicine, Hofstra North Shore, Manhasset, New York; and. FAU - Mehta, Minesh P AU - Mehta MP AD - Miami Cancer Institute Executive Office, Miami, Florida. LA - eng SI - ClinicalTrials.gov/NCT00895622 GR - U10 CA021661/CA/NCI NIH HHS/United States GR - U10 CA180822/CA/NCI NIH HHS/United States GR - U10 CA180868/CA/NCI NIH HHS/United States GR - UG1 CA189867/CA/NCI NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article DEP - 20171006 PL - United States TA - J Neurosurg JT - Journal of neurosurgery JID - 0253357 SB - IM CIN - J Neurosurg. 2018 Oct;129(4):1104-1105. PMID: 30117772 CIN - J Neurosurg. 2018 Dec 1;129(6):1651-1653. PMID: 30265197 EIN - J Neurosurg. 2018 Dec 1;129(6):1650. PMID: 30485244 MH - Female MH - Humans MH - Male MH - Meningeal Neoplasms/*mortality/*radiotherapy MH - Meningioma/*mortality/*radiotherapy MH - Middle Aged MH - Progression-Free Survival MH - Prospective Studies MH - Risk Assessment MH - Survival Rate MH - Treatment Outcome PMC - PMC5889346 MID - NIHMS919225 OTO - NOTNLM OT - 3DCRT = 3D conformal RT OT - AE = adverse event OT - CGE = cobalt gray equivalent OT - CNED = continual no evidence of disease OT - CTV = clinical tumor volume OT - EBRT = external beam RT OT - EORTC = European Organisation for Research and Treatment of Cancer OT - GTR = gross-total resection OT - GTV = gross tumor volume OT - IMRT = intensity-modulated RT OT - MMSE = Mini-Mental State Examination OT - OAR = organ at risk OT - OS = overall survival OT - PD = progressive disease OT - PFS = progression-free survival OT - PRV = planning risk volume OT - PTV = planning target volume OT - PTVPRV = overlap between the PTV and the particular PRV of concern OT - RT = radiation therapy OT - RTOG = Radiation Therapy Oncology Group OT - SD = stable disease OT - SRS = stereotactic radiosurgery OT - STR = subtotal resection OT - WHO = World Health Organization OT - WHO Grade II (atypical) OT - meningioma OT - oncology OT - radiotherapy EDAT- 2017/10/07 06:00 MHDA- 2019/10/11 06:00 PMCR- 2018/07/02 CRDT- 2017/10/07 06:00 PHST- 2017/10/07 06:00 [pubmed] PHST- 2019/10/11 06:00 [medline] PHST- 2017/10/07 06:00 [entrez] PHST- 2018/07/02 00:00 [pmc-release] AID - 2016.11.JNS161170 [pii] AID - 10.3171/2016.11.JNS161170 [doi] PST - ppublish SO - J Neurosurg. 2018 Jul;129(1):35-47. doi: 10.3171/2016.11.JNS161170. Epub 2017 Oct 6.