TOPAS-RBE: Relative biological effectiveness of protons

The relative biological effectiveness (RBE) is defined as the ratio of the doses required by two radiations to cause the same level of effect. Thus, the RBE needs to be considered if dose constraints from photon therapy are to be adopted. Proton therapy has been based on the use of a generic RBE of 1.1, which is applied to all treatments independent of dose/fraction, position in the irradiated volume, beam energy or the tissue. Quantitative dependencies of the RBE on various physical and biological properties are disregarded. Elevated RBE values might be expected particularly near the edges of the high-dose volume because doses may be deposited by high-LET particles. Furthermore, the increase in RBE as a function of depth in the patient results in an extension of the bio-effective range of the beam, which is being considered in treatment planning.  Heavy ions have a potential advantage compared to protons when it comes to their therapeutic ratio due to an elevated RBE in the tumor (based on the oxygen enhancement ratio and higher average LET values) compared to the surrounding tissue. However, there are considerable variations in RBE within the irradiated volume that have to be considered in treatment planning and delivery. At present there are still considerable uncertainties in RBE values and their dependencies on dose, LET, and alpha/beta ratio. We are studying the clinical significance of RBE variations for proton therapy treatments and develop methods for biologically optimized treatment planning in proton therapy.  

We have publicly released extensions to score RBE in the TOPAS Monte Carlo simulation software. These are available here.

The group is involved in

  • developing novel biophysical models
  • performing clinical RBE sensitivity studies
  • conducting in-vivo and in-vitro experiments
  • developing biological treatment plan optimization

Key MGH personnel involved

  • Harald Paganetti, PhD (PI)
  • Drosoula Giantsoudi, PhD
  • Tracy Underwood, PHD
  • Clemens Grassberger, PhD
  • Aimee McNamara, PhD
  • Jan Schuemann, PhD
  • David Hall, DPhil
  • Henning Willers, MD
  • Maria Marteinsdottir

Collaborators

  • Leo Gerweck, MGH Radiation Biology
  • Kathy Held, MGH Radiation Biology 
  • Andrzej Niemierko, PhD, MGH Radiation Oncology Biostatistics
  • Saveli Goldberg, MGH Radiation Oncology Biostatistics 
  • Stephen McMahon, Queens University, Belfast, UK

Publications

  1. Underwood T and Paganetti H: Variable Proton Relative Biological Effectiveness: How Do We Move Forward? International Journal of Radiation Oncology, Biology and Physics 2016 96; 59-61
  2. Liu Q; Underwood TSA; Kung J; Wang M; Lu H-M; Paganetti H; Held KD; Hong TS; Efstathiou JA and Willers H: Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation. International Journal of Radiation Oncology, Biology and Physics 2016 96; 78-85
  3. Giantsoudi D; Sethi RV; Yeap BY; Eaton BR; Ebb DH; Caruso PA; Rapalino O; Chen YLE; Adams J; Yock TI; Tarbell NJ; Paganetti H and MacDonald SM: Incidence of CNS Injury for a Cohort of 111 Patients Treated with Proton Therapy for Medulloblastoma; LET and RBE Associations for Areas of Injury. International Journal of Radiation Oncology, Biology and Physics 2016 96; 287-296
  4. Underwood T; Giantsoudi D; Moteabbed M; Zietman A; Efstathiou J; Paganetti H and Lu H-M: Can we advance proton therapy for prostate? Considering alternative beam angles and RBE variations when comparing against IMRT. International Journal of Radiation Oncology, Biology and Physics 2016 96; 454-464
  5. McMahon SJ; Schuemann J; Paganetti H and Prise KM: Mechanistic Modelling of DNA Repair and Cellular Survival Following Radiation-Induced DNA Damage. Nature Scientific Reports 2016 6; 33290
  6. Unkelbach J; Botas P; Giantsoudi D; Gorissen B and Paganetti H: Reoptimization of intensity-modulated proton therapy plans based on linear energy transfer. International Journal of Radiation Oncology, Biology and Physics 2016; in press; online ahead of print
  7. Wouters BG; Skarsgard LD; Gerweck LE; Carabe-Fernandez A; Wong M; Durand RE; Nielson D; Bussiere MR; Wagner M; Biggs P; Paganetti H and Suit HD: Radiobiological Intercomparison of the 160 MeV and 230 MeV Proton Therapy Beams at the Harvard Cyclotron Laboratory and at Massachusetts General Hospital. Radiation Research 2015 183: 147-187
  8. Paganetti H: Relating proton treatments to photon treatments via the relative biological effectiveness (RBE) – Should we revise the current clinical practice? International Journal of Radiation Oncology, Biology and Physics 2015 91: 892-894
  9. Liu Q; Ghosh P; Magpayo N; Testa M; Tang S; Biggs P; Paganetti H; Efstathiou JA; Lu HM; Held KD and Willers H: Lung Cancer Cell Line Screen Links Fanconi Anemia Pathway Defects to Increased Relative Biological Effectiveness of Proton Radiation. International Journal of Radiation Oncology, Biology and Physics 2015 91: 1081-1089 4.       McNamara AL; Schuemann J and Paganetti H: A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data. Physics in Medicine and Biology 2015 60; 8399-8416
  10. Grosse N; Fontana AO; Hug EB; Lomax A; Coray A; Paganetti H; Sartori AA and Pruschy M: Deficiency in Homologous Recombination Renders Mammalian Cells more Sensitive to Proton versus Photon Irradiation. International Journal of Radiation Oncology, Biology, Physics 2014 88: 175-181
  11. Sethi RV; Giantsoudi D; Raiford M; Rappalino O; Caruso P; Yock TI; Tarbell NJ; Paganetti H and MacDonald SM: Patterns of failure following proton therapy in medulloblastoma; LET distributions and RBE associations for relapses. International Journal of Radiation Oncology, Biology, Physics 2014 88: 655-663
  12. Gerweck LE; Huang P; Lu HM; Paganetti H and Zhou Y: Lifetime Increased Cancer Risk in Mice Following Exposure to Clinical Proton Beam-Generated Neutrons. International Journal of Radiation Oncology, Biology, Physics 2014 89: 161-166; Named one of the issue highlights
  13. Paganetti H: Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Physics in Medicine and Biology 2014 59: R419-R472; Listed as one of the highlights of 2014 in Physics in Medicine and Biology
  14. Paganetti H and van Luijk P: Biological considerations when comparing proton therapy with photon therapy. Seminars in Radiation Oncology 2013 23: 77-87; Top 5 most downloaded papers in Seminars in Radiation Oncology in the first half of 2013
  15. Carabe A; España A; Grassberger C and Paganeti H: Clinical consequences of Relative Biological Effectiveness variations in proton radiotherapy of the prostate, brain and liver. Physics in Medicine and Biology 2013 58: 2103-2117
  16. Zeng C; Giantsoudi D; Grassberger C; Goldberg S; Niemierko A; Paganetti H; Efstathiou JA and Trofimov A: Maximizing the biological effect of proton dose delivered with scanned beams. Medical Physics 2013 40: 051708
  17. Giantsoudi D; Grassberger C; Craft D; Niemierko A; Trofimov AV and Paganetti H: Linear energy transfer (LET)-Guided Optimization in intensity modulated proton therapy (IMPT): feasibility study and clinical potential. International Journal of Radiation Oncology, Biology, Physics 2013 87: 216-222
  18. Butterworth KT; McGarry CK; Clasie B; Carabe-Fernadez A; Schuemann J; Depauw N; Tang S; McMahon SJ; Schettino G; O’Sullivan JM; Lu HM; Kooy H; Paganetti H; Hounsell AR; Held KD and Prise KM: Cell survival responses to modulated proton beams delivered by passive scattering and pencil beam scanning. Physics in Medicine and Biology 2012 57: 6671-6680
  19. Carabe A; Moteabbed M; Depauw N; Schuemann J and Paganetti H: Range uncertainty in proton therapy due to variable biological effectiveness. Physics in Medicine and Biology 2012 57: 1159–1172
  20. Grassberger C and Paganetti H: Elevated LET components in clinical proton beams. Physics in Medicine and Biology 2011 56: 6677-6691
  21. Grassberger C; Trofimov A; Lomax A and Paganetti H: Variations in linear energy transfer within clinical proton therapy fields and the potential for biological treatment planning. International Journal of Radiation Oncology, Biology, Physics 2011 80: 1559-1566
  22. Carabe-Fernandez A; Dale RG and Paganetti H: Repair kinetics considerations in particle beam radiotherapy. British Journal of Radiology 2010 84: 546-555
  23. Carabe-Fernandez A; Dale RG; Hopewell JW; Jones B and Paganetti H: Fractionation effects in particle radiotherapy: implications for hypo-fractionation regimes. Physics in Medicine and Biology: 2010 55:5685-5700
  24. Suit H; Delaney T; Goldberg S; Paganetti H; Clasie B; Gerweck L; Niemierko A; Hall E; Flanz J; Hallman J and Trofimov A: Proton vs carbon ion beams in the definitive radiation treatment of cancer patients. Radiotherapy and Oncology: 2010 95, 3-22