Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Paganetti, Harald

doi:10.14338/ijpt-18-00011.1

Cited by 59 publications

(51 citation statements)

References 87 publications

(91 reference statements)

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“…31 For example, our model does not take into consideration potential RBE variations with dose or different endpoints of interest such as tumor control or normal tissue complication probability. 41 However, our MCDB model approximates previously published models derived from fits to in vitro cell survival data (Fig 1). 31 Increasing evidence suggests that biologic range extension can have important clinical consequences.…”

Section: Discussionsupporting

confidence: 72%

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy

Mutter

Jethwa

Tseung

et al. 2020

Practical Radiation Oncology

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The relative biologic effectiveness (RBE) rises with increasing linear energy transfer toward the end of proton tracks. Presently, there is no consensus on how RBE heterogeneity should be accounted for in breast cancer proton therapy treatment planning. Our purpose was to determine the dosimetric consequences of incorporating a brachial plexus (BP) biologic dose constraint and to describe other clinical implications of biologic planning. Methods and Materials: We instituted a biologic dose constraint for the BP in the context of MC1631, a randomized trial of conventional versus hypofractionated postmastectomy intensity modulated proton therapy (IMPT). IMPT plans of 13 patients treated before the implementation of the biologic dose constraint (cohort A) were compared with IMPT plans of 38 patients treated on MC1631 after its implementation (cohort B) using (1) a commercially available Eclipse treatment planning system (RBE Z 1.1); (2) an in-house graphic processor unit-based Monte Carlo physical dose simulation (RBE Z 1.1); and (3) an in-house Monte Carlo biologic dose (MCBD) simulation that assumes a linear relationship between RBE and dose-averaged linear energy transfer (product of RBE and physical dose Z biologic dose). Results: Before implementation of a BP biologic dose constraint, the Eclipse mean BP D0.01 cm 3 was 107%, and the MCBD estimate was 128% (ie, 64 Gy [RBE Z biologic dose] in 25 fractions for a 50-Gy [RBE Z 1.1] prescription), compared with 100.0% and 116.0%, respectively, after the implementation of the constraint. Implementation of the BP biologic dose constraint did not significantly affect clinical target volume coverage. MCBD plans predicted greater internal mammary node coverage and higher heart dose than Eclipse plans.

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Section: Discussionsupporting

confidence: 72%

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy

Mutter

Jethwa

Tseung

et al. 2020

Practical Radiation Oncology

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“…Gensheimer et al [39] analyzed an overshoot of the proton beam visible in MR images; this overshoot effect might be attributable to an increased RBE at the distal edge [37]. But it remains to be elucidated how the apparent discrepancy between in-vitro and clinical results can be resolved, and the debate about whether variable RBE values larger than 1.1 need to be used in treatment planning is still ongoing [40][41] [43] [44]. Additional in-vivo experiments to determine tolerance doses of late responding tissues, e.g.…”

Section: Specific Aspects For Protonsmentioning

confidence: 99%

State-of-the-Art and Future Prospects of Ion Beam Therapy: Physical and Radiobiological Aspects

Scholz

2020

IEEE Trans. Radiat. Plasma Med. Sci.

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The number of facilities offering radiotherapy with protons or heavier ions is continuously increasing; worldwide, more than 160000 patients have been treated with protons, and more than 25000 with heavier ions. Despite this substantial clinical experience, there is still a need for further developments and improvements which are specific to the properties of particle beams. This contribution briefly summarizes the main physical and radiobiological properties of ion beams which make them favorable for application in tumor therapy. In addition, major challenges that are currently addressed in different research areas are reviewed. These comprise the fields of biophysical modelling, treatment planning, mitigation of target motion and novel approaches based on particular spatio-temporal beam delivery techniques.

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“…Despite the limited impact on tumor control, these variations could have a significant impact on toxicity and might contribute to unusual CNS (central nervous system) radiological and clinical abnormalities following PT [11]. Consequently, several reports have stressed the importance of Monte Carlo calculation models, LET cartography, and individual sensitivity with regard to dose escalation and more active treatment of radioresistant cases [12]. Beyond calculation and simulation tools, experimental studies must be performed to accurately compare the bioeffectiveness of protons and other beams and between various types of proton beams, such as scattered beams and the more recent scanned beams.…”

Section: Proton Therapy In Tumor Controlmentioning

confidence: 99%

Hadrontherapy Interactions in Molecular and Cellular Biology

Thariat

Valable

Laurent

et al. 2019

IJMS

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The resistance of cancer cells to radiotherapy is a major issue in the curative treatment of cancer patients. This resistance can be intrinsic or acquired after irradiation and has various definitions, depending on the endpoint that is chosen in assessing the response to radiation. This phenomenon might be strengthened by the radiosensitivity of surrounding healthy tissues. Sensitive organs near the tumor that is to be treated can be affected by direct irradiation or experience nontargeted reactions, leading to early or late effects that disrupt the quality of life of patients. For several decades, new modalities of irradiation that involve accelerated particles have been available, such as proton therapy and carbon therapy, raising the possibility of specifically targeting the tumor volume. The goal of this review is to examine the up-to-date radiobiological and clinical aspects of hadrontherapy, a discipline that is maturing, with promising applications. We first describe the physical and biological advantages of particles and their application in cancer treatment. The contribution of the microenvironment and surrounding healthy tissues to tumor radioresistance is then discussed, in relation to imaging and accurate visualization of potentially resistant hypoxic areas using dedicated markers, to identify patients and tumors that could benefit from hadrontherapy over conventional irradiation. Finally, we consider combined treatment strategies to improve the particle therapy of radioresistant cancers.

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Proton Relative Biological Effectiveness – Uncertainties and Opportunities

Cited by 59 publications

References 87 publications

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy

Incorporation of Biologic Response Variance Modeling Into the Clinic: Limiting Risk of Brachial Plexopathy and Other Late Effects of Breast Cancer Proton Beam Therapy

State-of-the-Art and Future Prospects of Ion Beam Therapy: Physical and Radiobiological Aspects

Hadrontherapy Interactions in Molecular and Cellular Biology

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