Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams

Buchsbaum, Jeffrey C.; McDonald, Mark W.; Johnstone, Peter A.S.; Hoene, Ted A.; Mendonca, Marc S.; Cheng, Chee Wei; Das, Indra J.; McMullen, Kevin P.; Wolanski, M.

doi:10.1186/1748-717x-9-2

Cited by 27 publications

(14 citation statements)

References 18 publications

(16 reference statements)

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“…In addition, it has been suspected that elevated RBE values for low a/b tumors, such as prostate, could impact the interpretation of ongoing clinical trials comparing proton and photon treatments [18]. As far as toxicities are concerned, concerns have been raised that the elevated LET at the end of range of protons beams leads to incidents of necrosis in ependymoma patients where beams typically range out in the brainstem [13,19,20].…”

Section: Introductionmentioning

confidence: 99%

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Paganetti

2017

Acta Oncologica

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Background: Proton therapy uses a constant relative biological effectiveness (RBE) of 1.1. The use of variable RBE values has been suggested but is currently not feasible due to uncertainties. The impact of variable RBE has solely been studied using dosimetric indices. This work elucidates the impact of RBE variations on tumor control and normal tissue complication probabilities (TCP/NTCP). Methods: Models to estimate TCP and NTCP were used in combination with an empirical proton RBE model. Variations in outcome as a function of linear-quadratic model parameters for cellular radiosensitivity were determined for TCP in prostate and ependymoma. In addition, NTCP analysis was done for brainstem necrosis. Results: Considering a variable proton RBE as a dose-modifying factor for prescription doses and dose constraints is misleading, as TCP/NTCP do not simply scale with RBE. The dependency of RBE on a/b cannot be interpreted independent of TCP/NTCP because variations in radiosensitivity affect both photon and proton treatments. Assuming interpatient variability in radiosensitivity results in lower TCP for patients with low a/b. In proton therapy, the magnitude of TCP variations is reduced due to an RBE increase as a/b decreases. The TCP in proton therapy is less affected by interpatient variability in a/b. On the other hand, patients with a lower a/b would have a lower complication probability, which is counteracted by an increase in RBE as a/b decreases. Toxicities in proton therapy would be more affected by a/b variations compared to photon therapy. Conclusions: Assessment of variable RBE in proton therapy should be based on TCP and NTCP. Potential interpatient variability in radiosensitivity causes a smaller variance in TCP but a larger variance in NTCP for proton patients. The relative TCP as a function of a/b was found to be higher than the RBE, whereas the relative NTCP was lower than a calculated RBE.

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Section: Introductionmentioning

confidence: 99%

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Paganetti

2017

Acta Oncologica

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“…It may also explain the reported higher than expected rates of brainstem necrosis . Methods to mitigate the ‘sting in the tail’ include not having an organ at risk at the beam exit and the routine use of range modulation in the planning process …”

Section: Resultsmentioning

confidence: 99%

Defining the role of proton therapy in the optimal management of paediatric patients in Australia and New Zealand

Dwyer

2015

J Med Imag Rad Onc

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Introduction: Optimal management of paediatric patients with tumours may include radiation therapy. Proton therapy, in theory, should achieve superior outcomes. For children referred overseas, multiple factors are taken into consideration. Aim and Methods: The purpose of this article is to provide context to current decision making. The MEDLINE, EMBASE and PubMed databases were searched for relevant literature. Results and Discussion: The delivery of proton therapy is in evolution. Tissue homogeneity, movement and anatomical changes all present a greater challenge for proton therapy compared with photon therapy. Many dosimetry studies are relying on historical data for cost-benefit analyses that do not accurately reflect contemporary photon therapy. The low dose regions generally do not create significant toxicity, whereas moderate dose regions can be reduced by different techniques such as stereotactic radiotherapy and brachytherapy. Neuro-cognitive and neuro-endocrine toxicities are associated with the greatest health cost, so the greatest gain is for tumours within or abutting the central nervous system. Proton therapy does not eliminate the risk of second malignancy. Conclusions:The benefits of proton therapy must be weighed against not just the estimated impact of low and moderate radiation doses on the developing child but the disruptions to the child, and family life. Relative contraindications to proton therapy include when the relevant late toxicities relate to the high radiation dose region, when the tumour volumes encompass whole body sections and when the target is imprecise. Children with base of skull tumours or an inherited risk of cancer (e.g. those with p53 or Rb1 genes) should be considered for proton therapy.

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“…Uncertainties in distal RBE enhancement may also be clinically relevant in 2field plans, particularly if one of the fields terminates in a critical structure. In these cases, uncertainties of distal RBE enhancement could be mitigated by applying ''range modulation'' to the beam that terminates in a critical structure to vary the terminal range of the beam over 2 positions [13]. While each beam is preferentially selected to provide the shortest path to the target, in certain circumstances it may be preferable to orient a beam through a slightly longer path in order to terminate the beam in bone or other noncritical structures.…”

Section: Discussionmentioning

confidence: 99%

Quantifying Proton Fields for Midline Brain Tumors: A Benefit/Cost Analysis of Planning Objectives

Estabrook¹,

Hoene²,

Carlin³

et al. 2016

International Journal of Particle Therapy

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Purpose: We sought to quantify the optimum number of beams by using a midline sagittal arrangement for midline brain tumors when considering the competing demands of a high degree of target conformation and maximizing reduction of nontarget brain dose. The volume of nontarget brain tissue receiving between 5 and 20 Gy (V5-V20) was selected to measure ''low-dose bath'' to normal brain. Materials and Methods: An exploratory model was developed with 6 midline brain targets created by using spheres of 1-, 3-, and 5-cm diameters located in superficial and deep locations. For each, five 3-dimensional proton treatment plans with uniform beam scanning were generated by using 1 to 5 fields. Dose-volume histograms were analyzed to calculate conformation number and V5-V20. A benefit/cost analysis was performed to determine the marginal gain in conformation number and the marginal cost of V5-V20 for the addition of each field and hypothesize the optimum number of treatment fields. We tested our hypothesis by re-planning 10 actual patient tumors with the same technique to compare the averages of these 50 plans to our model. Results: Our model and validation cohort demonstrated the largest marginal benefit in target conformation and the lowest marginal cost in normal brain V5-V20 with the addition of a second proton field. The addition of a third field resulted in a relative marginal benefit in target conformation of just 3.9% but a relative marginal cost in V5-V20 of 78.7%. Normal brain absolute V5-V20 increased in a nearly linear fashion with each additional field. Conclusions: When treating midline brain lesions with 3-dimensional proton therapy in an array of midline sagittal beams, our model suggests the most appropriate number of fields is 2. There was little marginal benefit in target conformation and increasing cost of normal brain dose when increasing the number of fields beyond this.

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Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams

Cited by 27 publications

References 18 publications

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Relating the proton relative biological effectiveness to tumor control and normal tissue complication probabilities assuming interpatient variability in α/β

Defining the role of proton therapy in the optimal management of paediatric patients in Australia and New Zealand

Quantifying Proton Fields for Midline Brain Tumors: A Benefit/Cost Analysis of Planning Objectives

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