Clinical and Radiologic Outcomes in Adults and Children Treated with Pencil-Beam Scanning Proton Therapy for Low-Grade Glioma.

Shahed N Badiyan,Ralf Schneider,Robert S Malyapa,Francesca Albertini,Anna S M Fredh,Stephan Ulmer,Alessandra Bolsi,Damien C Weber,Dominic Leiser,Frank J Ahlhelm,Beate Timmermann,Gabriele Calaminus,Antony J Lomax,Ulrike Kliebsch

doi:10.14338/ijpt-16-00031.1

Abstract

We assessed clinical and radiologic outcomes in adults and children with low-grade glioma (LGG) of the brain treated with pencil-beam scanning (PBS) proton therapy (PT). Between 1997 and 2014, 28 patients were treated with PBS PT, 20 (71%) of whom were younger than 18 years. Median age at start of PT was 12.3 years (range, 2.2-53.0 years). Nine patients (32%) underwent at least a subtotal resection; 12 (43%) underwent biopsy; and 7 (25%) were diagnosed radiographically. Twelve patients (43%) had grade II and 9 (32%) had grade I gliomas. Eleven patients (39%) received chemotherapy before PT. A median dose of 54 Gy (relative biologic effectiveness) was administered. Radiologic response to PT was determined using the Response Evaluation Criteria in Solid Tumors (RECIST). Eight domains of quality of life (QoL) for 16 pediatric patients were assessed prospectively by patients' parents using the pediatric QoL proxy questionnaire. Progression-free survival and overall survival (OS) were estimated by the Kaplan-Meier method. Median follow-up was 42.1 months for living patients. Ten patients (36%) developed local, clinical failure. Three patients (11%) died, all of tumor progression. Radiographic tumor response by RECIST was evaluable in 11 patients: 9 (82%) with stable disease, 1 (9%) with partial response, and 1 (9%) with complete response to PT. Three-year OS and progression-free survival were 83.4% and 56.0%, respectively. No ≥ grade III acute toxicities were observed. Grade III, late radiation necrosis developed in 1 patient (4%). No appreciable change in pediatric QoL proxy scores in children was noted in any of the 8 domains at any time point. Treatment with PBS PT is effective for LGG, with minimal acute toxicity and, in children, no appreciable decline in QoL. More patients and longer follow-up are needed to determine the long-term efficacy and toxicity of PT for LGG.

Highlights

Low-grade gliomas (LGGs) are a heterogeneous group of tumors that account for up to 60% of all primary brain tumors in children and 10% in adults [1, 2]
Chemotherapy has been shown to improve outcomes in adults with certain subtypes of World Health Organization (WHO) grade II LGGs when given with radiation therapy [3, 7] and is frequently used in children to postpone the use of radiation therapy [8]
One adult patient was diagnosed with a grade II oligodendroglioma of the frontal lobe and underwent a biopsy without resection followed by proton therapy (PT)

Summary

Introduction

Low-grade gliomas (LGGs) are a heterogeneous group of tumors that account for up to 60% of all primary brain tumors in children and 10% in adults [1, 2]. The prognosis of patients with LGG varies depending on tumor grade, histology, tumor genetics, and extent of disease but is typically favorable after treatment in adults, with median overall survival (OS) ranging from 4.5 to 13.3 years [3, 4] and is quite favorable in children, with a 20-year OS of 87% [5]. Because of the favorable prognosis and young age of many patients with LGG, treatment is tailored to provide local tumor control while minimizing long-term toxicities. Maximal safe surgical resection is the first-line therapy and provides valuable histologic confirmation of, and prognostic information about, the disease. Chemotherapy has been shown to improve outcomes in adults with certain subtypes of WHO grade II LGGs when given with radiation therapy [3, 7] and is frequently used in children to postpone the use of radiation therapy [8]

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