5 Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

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THE GEC ESTROHANDBOOKOF BRACHYTHERAPY | Part I: The Basics of Brachytherapy Version 1 - 22/10/2015

5 Radiobiology of LDR, HDR, PDR and VLDR Brachytherapy

Erik Van Limbergen, Michael Joiner, Albert Van der Kogel, Wolfgang Dörr

1. Summary 2. Introduction

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7. Biological effects of dose inhomogeneity 12 8. Volume, anatomical site, and patient-related effects 12 9. Clinical Results: LDR, MDR, HDR and PDR BT 13 10. Practical Applications 16 11. Key messages 17 12. References 18

3. Radiation Effects and Tissue Responses 4. Dose - Time Patterns in BT 5. The four R’s of Radiobiology and the Dose Rate Effect 6. Mathematical modelling of different dose rates and the EQD2 concept

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1. SUMMARY

Brachytherapy (BT) differs from external beam therapy (EBRT) in two main ways: the distribution of the absorbed dose and the time-dose patterns. Dose distribution: Total dose and dose rate in BT decrease dramatically with the distance from the sources. The dose is pre- scribed to a CTV, i.e. an isodose surface often encompassing a volume of ~20 - 200 cm 3 . The GTV receives about >150% of the prescribed dose. Dose rates: for brachytherapy are divided, somewhat arbitrarily, into three ranges: low-dose rate (LDR) < 1 Gy h -1 , medium dose rate (MDR) between 1 and 12 Gy h -1 and high-dose rate (HDR) >12 Gy h -1 . Changing dose rate in the MDR range causes the most pronounced changes in biological effect. In the present report, terms describing dose-time-distributions specific to cervix brachytherapy, including (mean) dose rate, fractionation, pulse, application and overall time are defined. Moreover, biological mechanisms potentially impacting on effectiveness of the treatment, such as repopulation, re-oxygenation and redistribution, are discussed. The large decrease in dose with distance and the large variation in dose rate and fraction size require a common concept and a joint terminology to facilitate biological comparison between the different brachytherapy schedules feasible. The LQ formalism and EQDX: allows comparison of the predicted effects of a particular BT schedule with other BT and external beam schedules, with regard to both tumour control and normal tissue effects. With a set of assumptions, even the additional ef- fect of chemotherapy may be quantified, but with large uncertainties. This formalism can be safely applied within a range of doses per fraction from 0.5 Gy to 6-10 Gy; it might, however, potentially overestimate the effects at higher doses per fraction For all dose rates the calculations of the effects are strongly dependent on the recovery capacity (related to the α/βvalues) and half- times for recovery T 1/2 that are assumed in the modelling. But uncertainties in the estimates of these values need to be considered. This applies to tumours as well as to normal tissues. For photon irradiations an α/β value of 10 Gy and a recovery half-time of 1.5 h for cervix tumour tissue is generally assumed and of 3 Gy and 1.5 h for late effects in the OAR. For more specific and precise calculations, tissue specific recovery parameters should be used where available. The Equieffective Absorbed Dose Concept, EQDX: has been developed for comparing different irradiation protocols and tech- niques. Equieffective doses delivered in X Gy fractions (EQDX) are defined as total doses that - delivered under different condi- tions, which have to be specified in the context, are assumed to produce the same probability of a specific effect (endpoint), as the resultant total dose given in X Gy fractions. For protocols involving only one type of radiation equi-effective doses can be calcu- lated using the LQ formalism; and assumed values of α/β well as the T 1/2 of recovery if required for the EQDX calculations have to be specified by subscripts: EQDX α/β , T 1/2 . Because recovery is often assumed to be complete between fractions, the reference to T 1/2 may be omitted, depending on the details of the dose delivery. Because of historical precedents and clinical experience EQD2 referring to photon doses of 2Gy /fraction is commonly used. For protocols involving different radiations assumed values of β are required for both radiation types and must be specified. The ICRU/GEC-ESTRO report 88 recommends use of the equi-effective formalism, particularly EQD2, in addition to absorbed doses, to report doses for planning aims, prescriptions and doses delivered.