Application of Constant vs. Variable Relative Biological Effectiveness in Treatment Planning of Intensity-Modulated Proton Therapy (original) (raw)
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(Radio)Biological Optimization of External-Beam Radiotherapy
2012
Biological optimization" (BIOP) means planning treatments using (radio)biological criteria and models, that is, tumour control probability and normal-tissue complication probability. Four different levels of BIOP are identified: Level I is "isotoxic" individualization of prescription dose D presc at fixed fraction number. D presc is varied to keep the NTCP of the organ at risk constant. Significant improvements in local control are expected for non-small-cell lung tumours. Level II involves the determination of an individualized isotoxic combination of D presc and fractionation scheme. This approach is appropriate for "parallel" OARs (lung, parotids). Examples are given using our BioSuite software. Hypofractionated SABR for early-stage NSCLC is effectively Level-II BIOP. Level-III BIOP uses radiobiological functions as part of the inverse planning of IMRT, for example, maximizing TCP whilst not exceeding a given NTCP. This results in non-uniform target doses. The NTCP model parameters (reflecting tissue "architecture") drive the optimizer to emphasize different regions of the DVH, for example, penalising high doses for quasi-serial OARs such as rectum. Level-IV BIOP adds functional imaging information, for example, hypoxia or clonogen location, to Level III; examples are given of our prostate "dose painting" protocol, BioProp. The limitations of and uncertainties inherent in the radiobiological models are emphasized.
Physical and biological aspects of modern radiation therapy planning
Nowotwory, 2003
Over the last 20 years radiation oncology has been exposed to exciting biological and technical developments that have a potential to significantly improve the outcomes of cancer treatment. These developments present new opportunities but also create new challenges for the practitioners of radiation oncology. New tools, methods and techniques are required to fully utilize these developments to create, evaluate and optimize the process of radiation treatment. Here a number of tools for planning modern radiation therapy are presented and discussed. In particular, the need for biological considerations in the treatment planning process is emphasized and a concept of Equivalent Uniform Dose (EUD) based on modeling of cell survival and tissue architecture is described. Examples of IMRT dose distributions for a head and neck cancer developed using purely dosimetric (that is, dose and dose-volume) considerations and using EUD-based considerations are shown. Nowoczesna radioterapia - wp∏yw ...
Relative biological effectiveness (RBE) values for proton beam therapy
International Journal of Radiation Oncology*Biology*Physics, 2002
Purpose: Clinical proton beam therapy has been based on the use of a generic relative biological effectiveness (RBE) of 1.0 or 1.1, since the available evidence has been interpreted as indicating that the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBEs. As substantial clinical experience and additional experimental determinations of RBE have accumulated and the number of proton radiation therapy centers is projected to increase, it is appropriate to reassess the rationale for the continued use of a generic RBE and for that RBE to be 1.0-1.1. Methods and Materials: Results of experimental determinations of RBE of in vitro and in vivo systems are examined, and then several of the considerations critical to a decision to move from a generic to tissue-, dose/fraction-, and LET-specific RBE values are assessed. The impact of an error in the value assigned to RBE on normal tissue complication probability (NTCP) is discussed. The incidence of major morbidity in protontreated patients at Massachusetts General Hospital (MGH) for malignant tumors of the skull base and of the prostate is reviewed. This is followed by an analysis of the magnitude of the experimental effort to exclude an error in RBE of >10% using in vivo systems. Results: The published RBE values, using colony formation as the measure of cell survival, from in vitro studies indicate a substantial spread between the diverse cell lines. The average value at mid SOBP (Spread Out Bragg Peak) over all dose levels is Ϸ1.2, ranging from 0.9 to 2.1. The average RBE value at mid SOBP in vivo is Ϸ1.1, ranging from 0.7 to 1.6. Overall, both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. There is agreement that there is a measurable increase in RBE over the terminal few millimeters of the SOBP, which results in an extension of the bioeffective range of the beam in the range of 1-2 mm. There is no published report to indicate that the RBE of 1.1 is low. However, a substantial proportion of patients treated at Ϸ2 cobalt Gray equivalent (CGE)/fraction 5 or more years ago were treated by a combination of both proton and photon beams. Were the RBE to be erroneously underestimated by Ϸ10%, the increase in complication frequency would be quite serious were the complication incidence for the reference treatment >3% and the slope of the dose response curves steep, e.g., a ␥ 50 Ϸ 4. To exclude >1.2 as the correct RBE for a specific condition or tissue at the 95% confidence limit would require relatively large and multiple assays. Conclusions: At present, there is too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, proton energy, etc. The experimental in vivo and clinical data indicate that continued employment of a generic RBE value and for that value to be 1.1 is reasonable. However, there is a local "hot region" over the terminal few millimeters of the SOBP and an extension of the biologically effective range. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in laboratory animal systems, especially as a function of dose/fraction in the range of 1-4 Gy.
Optimized radiation therapy based on radiobiological objectives
Seminars in Radiation Oncology, 1999
In the broad field of radiation therapy optimization, both simple and complex problems have their origins in the interaction of the radiation beams with the biological structures of normal and malignant tissues of the human body. Therefore, it is no great surprise that many treatment optimization problems are best handled by the use of well-designed radiobiological models. The classic way of quantifying dose-response relations for tumors and normal tissues as well as their crosscorrelation with each other and their dependence on the underlying genetic and molecular biology of the cell are first briefly reviewed. Radiobiological objective functions, such as the probability of achieving complicationfree cure and its expectation value under influence of stochastic processes during the course of treatment, are defined and shown to solve many of the problems of radiation therapy planning. Finally, it is shown through the use of these quantifiers that, simply by introducing biologically optimal intensity modulated dose delivery, the treatment outcome can be improved by about 20% or more in cases with a complex spread of the disease. Once radiobiological optimal plans have been developed, they can be approximated by ordinary physical planning, but the biological objective functions are still needed to have a figure of merit for the quality of the treatment.
International Journal of Radiation Oncology*Biology*Physics, 2000
Purpose: The dose distributions of intensity-modulated radiotherapy (IMRT) treatment plans can be shown to be significantly superior in terms of higher conformality if designed to simultaneously deliver high dose to the primary disease and lower dose to the subclinical disease or electively treated regions. We use the term "simultaneous integrated boost" (SIB) to define such a treatment. The purpose of this paper is to develop suitable fractionation strategies based on radiobiological principles for clinical trials and routine use of IMRT of head and neck (HN) cancers. The fractionation strategies are intended to allow escalation of tumor dose while adequately sparing normal tissues outside the target volume and considering the tolerances of normal tissues embedded within the primary target volume. Methods and Materials: IMRT fractionation regimens are specified in terms of "normalized total dose" (NTD), i.e., the biologically equivalent dose given in 2 Gy/fx. A linear-quadratic isoeffect formula is applied to convert NTDs into "nominal" prescription doses. Nominal prescription doses for a high dose to the primary disease, an intermediate dose to regional microscopic disease, and lower dose to electively treated nodes are used for optimizing IMRT plans. The resulting nominal dose distributions are converted back into NTD distributions for the evaluation of treatment plans. Similar calculations for critical normal tissues are also performed. Methods developed were applied for the intercomparison of several HN treatment regimens, including conventional regimens used currently and in the past, as well as SIB strategies. This was accomplished by comparing the biologically equivalent NTD values for the gross tumor and regional disease, and bone, muscle, and mucosa embedded in the gross tumor volume. Results: (1) A schematic HN example was used to demonstrate that dose distributions for SIB IMRT are more conformal compared to dose distributions when IMRT is divided into a large-field phase and a boost phase. Both were shown to be significantly superior compared to dose distributions obtained using conventional beams for the large-field phase followed by IMRT for the boost phase. (2) The relationship between NTD and nominal dose for HN tumors was found to be quite sensitive to the choice of tumor clonogen doubling time but relatively insensitive to other parameters. (3) For late effect normal tissues embedded in the tumor volume and assumed to receive the same dose as the tumor, the biologically equivalent NTD for the SIB IMRT may be significantly higher. (4) Normal tissues outside the target volume receive lower dose due to the higher conformality of the IMRT plans. The biologically equivalent NTDs are even lower due to the lower dose per fraction in the SIB strategy. Conclusions: IMRT dose distributions are most conformal when designed to be delivered as SIB. Using isoeffect radiobiological relationships and published HN data, fractionation strategies can be designed in which the nominal dose levels to the primary, regional disease and electively treated volumes are appropriately adjusted, each receiving different dose/fx. Normal tissues outside the treated volumes are at reduced risk in such strategies since they receive lower total dose as well as lower dose/fx. However, the late effect toxicities of tissues embedded within the primary target volume and assumed to receive the same dose as the primary may pose a problem. The efficacy and safety of the proposed fractionation strategies will need to be evaluated with careful clinical trials.
Development of Radiation Therapy Optimization
Acta Oncologica, 2000
The principal radiobiological problems in the treatment of advanced tumors and the solution of many of them by radiobiologically optimized intensity-modulated radiation therapy are presented. Considerable improvements of the treatment outcome using radiobiologically optimized intensity-modulated treatments are achieved by: (a) increasing the tumor dose and dose per fraction; (b) keeping constant or even reducing slightly the dose and dose per fraction to organs at risk; (c) reducing the overall treatment time and the number of treatment fractions. The merits of the new radiation modalities and advanced intensity-modulated treatment techniques are compared in terms of equipment costs per patient cured. It is predicted that the new development of radiobiologically optimized intensity-modulated radiation therapy will rapidly become an important clinical tool, increasing the efficiency of the collaboration between radiation physicists, radiation biologists and radiation oncologists. Not only does it allow the optimal treatment of every patient, but it also promotes an efficient feedback of treatment outcome and complication data to improve the accuracy of known dose response relations to further augment future treatment results. Equipment costs may go up during a transition period until efficient interfaces between new diagnostic equipment, treatment-planning systems and intensity-modulated treatment units are fully developed. From then onwards the cost of high quality biologically optimized intensity-modulated treatments will decrease and so will the treatment time and personnel requirements, at the same time as the treatment quality is greatly improved particularly for more advanced tumors.
PLOS ONE, 2018
In particle radiotherapy, range uncertainty is an important issue that needs to be overcome. Because high-dose conformality can be achieved using a particle beam, a small uncertainty can affect tumor control or cause normal-tissue complications. From this perspective, the treatment planning system (TPS) must be accurate. However, there is a well-known inaccuracy regarding dose computation in heterogeneous media. This means that verifying the uncertainty level is one of the prerequisites for TPS commissioning. We evaluated the range accuracy of the dose computation algorithm implemented in a commercial TPS, and Monte Carlo (MC) simulation against measurement using a CT calibration phantom. A treatment plan was produced for eight different materials plugged into a phantom, and two-dimensional doses were measured using a chamber array. The measurement setup and beam delivery were simulated by MC code. For an infinite solid water phantom, the gamma passing rate between the measurement and TPS was 97.7%, and that between the measurement and MC was 96.5%. However, gamma passing rates between the measurement and TPS were 49.4% for the lung and 67.8% for bone, and between the measurement and MC were 85.6% for the lung and 100.0% for bone tissue. For adipose, breast, brain, liver, and bone mineral, the gamma passing rates computed by TPS were 91.7%, 90.6%, 81.7%, 85.6%, and 85.6%, respectively. The gamma passing rates for MC for adipose, breast, brain, liver, and bone mineral were 100.0%, 97.2%, 95.0%, 98.9%, and 97.8%, respectively. In conclusion, the described procedure successfully evaluated the allowable range uncertainty for TPS commissioning. The TPS dose calculation is inefficient in heterogeneous media with large differences in density, such as lung or bone tissue. Therefore, the limitations of TPS in heterogeneous media should be understood and applied in clinical practice.
Optimization of radiotherapy fractionation schedules based on radiobiological functions
The British Journal of Radiology, 2017
Objective: To present a method for optimizing radiotherapy fractionation schedules using radiobiological tools and taking into account the patient´s dose-volume histograms (DVH). Methods: This method uses a figure of merit based on the uncomplicated tumour control probability (P +) and the generalized equivalent uniform dose (gEUD). A set of doses per fraction is selected in order to find the dose per fraction and the total dose, thus maximizing the figure of merit and leading to a biologically effective dose that is similar to the prescribed schedule. Results: As a clinical example, a fractionation schedule for a prostate treatment plan is optimized and presented herein. From a prescription schedule of 70 Gy/35 × 2 Gy, the resulting optimal schema, using a figure of merit which only takes into account P + , is 54.4 Gy/16 × 3.4 Gy. If the gEUD is included in that figure of merit, the result is 65 Gy/26 × 2.5 Gy. Alternative schedules, which include tumour control probability (TCP) and the normal tissue complication probability (NTCP) values are likewise shown. This allows us to compare different schedules instead of solely finding the optimal value, as other possible clinical factors must be taken into account to make the best decision for treatment. Conclusion: The treatment schedule can be optimized for each patient through radiobiological analysis. The optimization process shown below offers physicians alternative schedules that meet the objectives of the prescribed radiotherapy. Advances in knowledge: This article provides a simple, radiobiological-function-based method to take advantage of a patient's dose-volume histograms in order to better select the most suitable treatment schedule.