Table of Contents
Abstract
1. INTRODUCTION
1.A. Definition of relative biological effectiveness
1.B. Rationale for the current clinical use of RBE=1.1
1.C .Advantages and disadvantages of using a constant RBE
1.D. Potential clinical significance of understanding spatial variations in RBE
1.E. Potential reasons for differences in the biological effects between protons and photons
2. PROTON RBE MODELS
2.A. The RBE as parameterized within the linear‐quadraticcell survival model
2.B. Empirical models for the effects of proton LET on α and β
2.C. Empirical models based on experimental microdosimetry
2.D. Mechanism‐inspired models for Proton RBE
2.D.1. Local effect model
2.D.2. Microdosimetric‐kinetic model
2.D.3. Repair‐misrepair‐fixation model
2.E. Clinical implications of biophysical models of proton RBE
3. REVIEW OF PUBLISHED EXPERIMENTS
3.A. Methods
3.B. Clonogenic cell survival as surrogate for the RBE for TCP
3.B.1. RBE as a function of LET
3.B.2. RBE as a function of (α/β) γ
3.B.3 .RBE as a function of dose
3.B.4. Patient variability and RBE as function of genomic heterogeneity
3.B.5. Other biological endpoints related to cell survival
3.B.6. Tumor response in vivo
3.C. Proton RBE related to normal tissue complication probability
3.D. Summary: Assessment of the deviations of RBE from 1.1
4. ASSESS WHETHER THE CURRENT PRACTICE OF A CONSTANT RBE 6;SHOULD BE REVISED
4.A. Should we use an average RBE value different from the current value of 1.1?
4.B. Should we use a constant RBE value, which may differ from tumor to tumor, organ to organ, or patient to patient?
4.C. Is there enough evidence to apply RBE values depending on dose, endpoint, and LET?
4.D. Is there a potential difference in RBE between passively scattered beams and beam scanning?
4.E. What information should be saved in treatment planning systems for outcome analysis?
5. ASSESSMENT OF CLINICAL IMPACT WHEN REVISING CURRENT PRACTICE ON RBE
5.A. Practical considerations when dealing with RBE uncertainties in current practice
5.B. Assess treatment sites for which a revision of current clinical practice would be most significant
5.C. Biological dose in treatment plan optimization
5.D. Impact on dose normalization and clinical physics
6. RECOMMENDATIONS FOR FUTURE EXPERIMENTS
6.A. Uncertainties in measured RBE values: Standardization of dosimetric reporting and experimental parameters
6.B. Novel and mechanistic biology studies to quantify and explain RBE variability
7. SUMMARY AND RECOMMENDATIONS
Abbreviations
References