The online version of this article (https://doi.org/10.1186/s13014-017-0930-9) contains supplementary material, which is available to authorized users.
Despite mounting evidence for the use of re-irradiation (re-RT) in recurrent high grade glioma, optimal patient selection criteria for re-RT remain unknown. We present a novel scoring system based on radiobiology principles including target independent factors, the likelihood of target control, and the anticipated organ at risk (OAR) toxicity to allow for proper patient selection in the setting of recurrent glioma.
Thirty one patients with recurrent glioma who received re-RT (2008–2016) at NCI – NIH were included in the analysis. A novel scoring system for overall survival (OS) and progression free survival (PFS) was designed to include:1) target independent factors (age, KPS (Karnofsky Performance Status), histology, presence of symptoms), 2) target control, and 3) OAR toxicity risk. Normal tissue complication probability (NTCP) calculations were performed using the Lyman model. Kaplan-Meier analysis was performed for overall survival (OS) and progression free survival (PFS) for comparison amongst variables.
No patient, including those who received dose to OAR above the published tolerance dose, experienced any treatment related grade 3–5 toxicity with a median PFS and OS from re-RT of 4 months (0.5–103) and 6 months (0.7–103) respectively. Based on cumulative maximum doses the average NTCP was 25% (0–99%) for the chiasm, 21% (0–99%) for the right optic nerve, 6% (0–92%) for the left optic nerve, and 59% (0–100%) for the brainstem. The independent factor and target control scores were each statistically significant for OS and the combination of independent factors plus target control was also significant for both OS (p = 0.02) and PFS (p = 0.006). The anticipated toxicity risk score was not statistically significant.
Our scoring system may represent a novel approach to patient selection for re-RT in recurrent high grade glioma. Further validation in larger patient cohorts including compilation of doses to tumor and OAR may help refine this further for inclusion into clinical trials and general practice.
Additional file 1: Table S1. A. maximum Dose and NTCP to OAR based on Maximum Dose values. B. Mean Dose (EUD) and NTCP to OAR based on Mean Dose values. (DOCX 200 kb)13014_2017_930_MOESM1_ESM.docx
Additional file 2: Figure S1. Normal Tissue complication probability (NTCP) (%) vs. A. maximum dose administered to the organ. B. Mean Dose administered to the organ. TheTD65/5 (Maximum Tolerated Dose 50% rate at 5 years at a dose of 65 Gy) curve based on Emami et al. was used to model NTCP using our retrospective data. (DOCX 58 kb)13014_2017_930_MOESM2_ESM.docx
Additional file 3: Figure S2. Comparison with existing scoring systems A. Carson 2007. B. Combs 2013. (DOCX 28 kb)13014_2017_930_MOESM3_ESM.docx
Park JK, Hodges T, Arko L, et al. Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28:3838–43. CrossRef
Minniti G, Armosini V, Salvati M, et al. Fractionated stereotactic reirradiation and concurrent temozolomide in patients with recurrent glioblastoma. J Neuro-Oncol. 2011;103(3):683–91. CrossRef
Grosu AL, Weber WA, Franz M, et al. Reirradiation of recurrent high-grade gliomas using amino acid PET (SPECT)/CT/MRI image fusion to determine gross tumor volume for stereotactic fractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2005;63(2):511–9. 15. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40. Last accessed March 10, 2017
Lyman JT. Complication probability as assessed from dose-volume histograms. Radiat Res. 1985;8(Suppl):S13–9.
IMAIOS SAS Anatomy, IMAIOS SAS. www.imaios.com. Accessed 10 Mar 2017.
2017. www.qarc.org/cog/ACNS0331Atlas.pdf. Accessed Mar 10.
Pyakuryal A, Myint WK, Gopalakrishnan M, et al. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD). Phys Med Biol. 2008;53:23–36. CrossRef
Kukolowicz P. Clinical aspects of normal tissue complication probability. Rep Pract Oncol Radiother. 2004;9:261–7. CrossRef
Stavrev PV, Stavreva NA, Round WH. A study of objective functions for organs with parallel and serial architecture. Australas Phys Eng Sci Med. 1997;20(1):4–10. PubMed
- Re-irradiation for recurrent glioma- the NCI experience in tumor control, OAR toxicity and proposal of a novel prognostic scoring system
Andra Valentina Krauze
Dee Dee Smart
- BioMed Central
Neu im Fachgebiet Onkologie
e.Med Kampagnen-Visual, Mail Icon II