Application of the linear-quadratic model to combined modality radiotherapy

Bodey, Rachel K.; Evans, Philip; Flux, Glenn

doi:10.1016/j.ijrobp.2003.12.031

Cited by 42 publications

(38 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The targeting and excretion kinetics of these agents differ substantially, and as suggested by preclinical and clinical evidence (19,37,38), the dose rate is an important parameter in understanding normal-organ toxicity and tumor response. The BED model has also been used in combination with externalbeam radiotherapy or radionuclide therapy studies (39).…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry

Prideaux¹,

Song²,

Hobbs³

et al. 2007

Journal of Nuclear Medicine

129

111

View full text Add to dashboard Cite

MarylandPhantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ-absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiologic modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. Methods: Three registered SPECT/CT scans were used to generate 3-dimensional images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT scan were provided as input into an EGSnrc-based Monte Carlo calculation: The cumulated activity image was used to define the distribution of decays, and an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a biologically effective dose distribution, which was then used to estimate a single equivalent uniform dose for segmented volumes of interest. Equivalent uniform dose was also calculated from the absorbed dose distribution directly. Results: We validate the method using simple models; compare the dose-volume histogram with a previously analyzed clinical case; and give the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for the tumor were 57.7, 58.5, and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8, and 8.3 Gy, respectively. Conclusion: The analysis demonstrates the impact of radiobiologic modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose nonuniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy.Key Words: dosimetry; radiobiology; 3D-ID; patient-specific dosimetry; treatment planning The tools and methodologies for performing radionuclide dosimetry for therapeutic nuclear medicine applications have evolved over the past 2 decades such that current research focuses on patient-specific 3-dimensional (3D) image or voxel-based approaches (1,2). In this work, we describe an extension of this methodology that incorporates radiobiologic modeling to account for the spatial distribution of absorbed dose and the effect of dose rate on biologic response. The methodology is incorporated into a software package, called 3D-RD, for 3D radiobiologic dosimetry.Patient-specific 3D imaging-based internal dosimetry is a methodology in which the patient's own anatomy and spatial distribution of radioactivity over time are factored into an absorbed dose calculation that provides as o...

show abstract

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry

Prideaux¹,

Song²,

Hobbs³

et al. 2007

Journal of Nuclear Medicine

129

111

View full text Add to dashboard Cite

show abstract

“…This is the usual situation of fractionated external beam radiation therapy (EBRT) where the regimen is based on daily fractions while the sub-lethal damage repair half-time ranges typically between 0.5 and 3 h. 15 In continuous therapy such as radionuclide therapy, the repair process of sublethal damage takes place during the radiation dose delivery and, therefore, a more general formalism is required. Assuming an exponentially decreasing dose-rate and a complete decay of the source, Dale 11 demonstrated that the RE function is given by the following expression: (3) where D is the absorbed dose, μ is the exponential repair rate constant that quantifies the rate of sublethal damage repair, and λ is the effective clearance rate constant given by the sum of the physical decay and the biological clearance rate constants. Note that the standard MIRD notation uses λ for the physical decay rate constant and λ eff for the effective clearance rate constant.…”

Section: Iia Standard Bed Formulationmentioning

confidence: 99%

“…Dose rate considerations have only recently been taken into account in radionuclide therapy dosimetry. [1][2][3][4][5][6][7][8][9][10] Those effects may be examined through the biological effective dose (BED) that relates absorbed dose and dose-rate with radiosensitivity and repair of radiation damage using the standard linear-quadratic (LQ) model. 11,12 The BED represents the dose required for a given biological effect when delivered by infinitely small doses per fraction or at very low dose-rates and is typically used to compare the response implications of total absorbed doses delivered at different dose-rates.…”

Section: Introductionmentioning

confidence: 99%

Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry

et al. 2008

View full text Add to dashboard Cite

In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial activity ratio and the S value ratio between the two. In some a) sebastien.baechler@chuv.ch. scenarios, projected BED based on both the cortex and the medulla is a more appropriate constraint on the administered activity than the BED based on the cortex only. Furthermore, different fractionated regimens were considered to reduce renal toxicity. The MIRD-based BED formalism is expected to be useful for patient-specific adjustments of activity and to facilitate the investigation of dose-toxicity correlations with respect to dose-rate and tissue repair mechanism. NIH Public Access

show abstract

“…The targeting and excretion kinetics of these agents differ substantially, and, as suggested by pre-clinical and clinical evidence (21,(49)(50)(51)(52)(53), the dose-rate is an important parameter in understanding normal organ toxicity and tumor response. The BED model has also been used in combination with external beam radiotherapy/radionuclide therapy studies (54,55).…”

Section: Application To a Patient Studymentioning

confidence: 99%

Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

Sgouros¹

2007

View full text Add to dashboard Cite

Phantom-based and patient-specific imaging-based dosimetry methodologies have traditionally yielded mean organ absorbed doses or spatial dose distributions over tumors and normal organs. In this work, radiobiological modeling is introduced to convert the spatial distribution of absorbed dose into biologically effective dose and equivalent uniform dose parameters. The methodology is illustrated using data from a thyroid cancer patient treated with radioiodine. METHODS: Three registered SPECT/CT scans were used to generate 3-D images of radionuclide kinetics (clearance rate) and cumulated activity. The cumulated activity image and corresponding CT were provided as input into an EGSnrc-based Monte Carlo calculation; the cumulated activity image defined the distribution of decays while an attenuation image derived from CT was used to define the corresponding spatial tissue density and composition distribution. The rate images were used to convert the spatial absorbed dose distribution to a Biologically Effective Dose (BED) distribution which was then used to estimate a single Equivalent Uniform Dose (EUD) for segmented volumes of interest. EUD was also calculated from the absorbed dose distribution directly. RESULTS: Validation using simple models and also comparison of the dose-volume histogram to a previously analyzed clinical case is shown as well as the mean absorbed dose, mean biologically effective dose, and equivalent uniform dose for an illustrative clinical case of a pediatric thyroid cancer patient with diffuse lung metastases. The mean absorbed dose, mean BED and EUD for tumor was 57.7, 58.5 and 25.0 Gy, respectively. Corresponding values for normal lung tissue were 9.5, 9.8 and 8.3 Gy, respectively. CONCLUSION The analysis demonstrates the impact of radiobiological modeling on response prediction. The 57% reduction in the equivalent dose value for the tumor reflects a high level of dose non-uniformity in the tumor and a corresponding reduced likelihood of achieving a tumor response. Such analyses are expected to be useful in treatment planning for radionuclide therapy.

show abstract

Application of the linear-quadratic model to combined modality radiotherapy

Cited by 42 publications

References 43 publications

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry

Three-Dimensional Radiobiologic Dosimetry: Application of Radiobiologic Modeling to Patient-Specific 3-Dimensional Imaging-Based Internal Dosimetry

Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry

Patient-Specific Dosimetry and Radiobiological Modeling of Targeted Radionuclide Therapy Grant - final report

Contact Info

Product

Resources

About