Designing equivalent treatment regimens for prostate radiotherapy based on equivalent uniform dose
Abstract
The purpose of this work was to determine alternative radiotherapy (RT) regimens that are biologically equivalent to clinically proven treatments using different RT modalities or different fractionation schemes. The concept of equivalent uniform dose (EUD) is used with the linear quadratic model to determine equivalent treatment regimens using two representative sets of parameters derived from clinical data: (i) α/β = 3.1 Gy and α = 0.15 Gy−1, and (ii) α/β = 1.5 Gy and α = 0.04 Gy−1. The EUD values for the critical structure (rectum) are also calculated. Representative dose volume histograms were used to account for dose inhomogeneities for different RT modalities. A series of alternative and equivalent fractionation regimens that can be used with different radiotherapy modalities for localized prostate cancer were determined. For example, the alternative regimens, calculated with the α/β ratio of 3.1 Gy, that would be biologically equivalent to external beam RT (EBRT) of 76 Gy (38×2.0 Gy) include: EBRT hypofractionation of 21×3.0 Gy; I-125 implant of 156 Gy; Pd-103 implant of 128 Gy; high dose rate (HDR) brachytherapy of 4×10.5 Gy; I-125 implant of 65 Gy combined with EBRT of 23×2.0 Gy; and HDR brachytherapy of 3×5.9 Gy combined with EBRT of 23×2.0 Gy. Similar data for other parameters are also presented. With caution, the data presented may be useful in designing clinical trials to explore new RT strategies, such as image-guided intensity-modulated RT.
References
1 Hanks GE, Lee WR, Hanlon AL, Hunt M, Kaplan E, Epstein BE, et al. Conformal technique dose escalation for prostate cancer: Improved cancer control with higher doses in patients with pretreatment PSA 10 ngm/ml. Int J Radiat Oncol Biol Phys 1996;35:861–8.
2 Hanks GE, Schultheiss TE, Hanlon AL, Hunt M, Lee WR, Epstein BE, et al. Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study. Int J Radiat Oncol Biol Phys 1997;37:543–50.
3 Hanks GE, Hanlon AL, Schultheiss TE, Pinover WH, Movsas B, Epstein BE, et al. Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions. Int J Radiat Oncol Biol Phys 1998;41:501–10.
4 Pollack A, Zagars GK, Smith LG, Lee JJ, von Eschenbach AC, Antolak JA, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;18:3904–11.
5 Zelefsky MJ, Leibel SA, Kelson S, Fuks Z. Impact of radiation dose on achieving a nadir PSA level after 3-dimensional conformal radiotherapy for patients with localized prostate cancer. Int J Radiat Oncol Biol Phys 1996;36:196
6 Zelefsky MJ, Leibel SA, Gaudin PB, Kutcher GJ, Fleshner NE, Venkatramen ES, et al. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998;41:491–500.
7 Martinez AA, Gustafson G, Gonzalez J, Armour E, Mitchell C, Edmundson G, et al. Dose escalation using comformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer. Int J Radiat Oncol Biol Phys 2002;53:316–27.
8 Martinez AA, Gonzalez J, Spencer W, Gustafson G, Kestin L, Kearney D, et al. Conformal high dose rate brachytherapy improves biochemical control and case specific survival in patients with prostate cancer and poor prognostic factors. J Urol 2003;169:974–9.
9 Dearnaley DP, Hall E, Lawrence D, Huddart RA, Eeles R, Nutting CM, et al. Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects. Br J Cancer 2005;92:488–98.
10 Brabbins D, Martinez AA, Yan D, Lockman D, Wallace M, Gustafson G, et al. A dose-escalation trial with the adaptive radiotherapy process as a delivery system in localized prostate cancer: analysis of chronic toxicity. Int J Radiat Oncol Biol Phys 2005;61:400–8.
11 Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys 1999;43:1095–101.
12 Brenner DJ, Martinez AA, Edmundson G K, Mitchell C, Thames HD, Armour EP. Direct evidence that prostate tumors show high sensitivity to fractionation (low α/β ratio), similar to late-responding normal tissue. Int J Radiat Oncol Biol Phys 2002;52:6–13.
13 Fowler J, Chappell R, Ritter M. Is α/β for prostate cancer really low? Int J Radiat Oncol Biol Phys 2001;50:1021–31.
14 King CR, Fowler JF. A simple analytic derivation suggests that prostate cancer α/β ratio is low. Int J Radiat Oncol Biol Phys 2001;51:213–4.
15 Wang JZ, Guerrero M and Li XA. How low is the α/β ratio for prostate cancer? Int J Radiat Oncol Biol Phys 2003;55:194–203.
16 Wang JZ, Li XA, Yu CX, DiBiase SJ. The low α/β ratio for prostate cancer: What does the clinical outcome of HDR brachytherapy tell us? Int J Radiat Oncol Biol Phys 2003;57:1101–8.
17 Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol 2005;44:265–76.
18 Chappell R, Fowler J, Ritter M. New data on the value of alpha/beta–evidence mounts that it is low. Int J Radiat Oncol Biol Phys 2004;60:1002–3.
19 Nahum AE, Movsas B, Horwitz EM, Stobbe CC, Chapman JD. Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: implications for the alpha/beta ratio. Int J Radiat Oncol Biol Phys 2003;57:391–401.
20 Valdagni R, Italia C, Montanaro P, Lanceni A, Lattuada P, Magnani T, et al. Is the alpha-beta ratio of prostate cancer really low? A prospective, non-randomized trial comparing standard and hyperfractionated conformal radiation therapy. Radiother Oncol 2005;75:74–82.
21 Carlone M, Wilkins D, Nyiri B, Raaphorst P. Comparison of alpha/beta estimates from homogeneous (individual) and heterogeneous (population) tumor control models for early stage prostate cancer. Med Phys 2003;30:2832–48.
22 Brenner DJ. Toward optimal external-beam fractionation for prostate cancer. Int J Radiat Oncol Biol Phys 2000;48:315–6.
23 Fowler JF, Ritter MA, Chappell RJ, Brenner DJ. What hypofractionated protocols should be tested for prostate cancer? Int J Radiat Oncol Biol Phys 2003;56:1093–104.
24 Kupelian PA, Thakkar VV, Khuntia D, Reddy CA, Klein EA, Mahadevan A. Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Long term outcomes. Int J Radiat Oncol Biol Phys 2005;63:1463–8.
25 Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B, et al. Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial. Int J Radiat Oncol Biol Phys 2006;64:518–26.
26 Niemierko A. Reporting and analyzing dose distributions: a concept of equivalent uniform dose. Med Phys 1997;24:103–10.
27 Wang JZ and Li XA. Evaluation of external beam radiotherapy and brachytherapy for localized prostate cancer using equivalent uniform dose. Med Phys 2003;30:34–40.
28 Li XA, Wang JZ, Stewart RD, DiBiase SJ. Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations. Phys Med Biol 2003;48:2753–65.
29 Dale RG. The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol 1985;58:515–28.
30 Brenner DJ, Hall EJ. Conditions for the equivalence of continuous to pulsed low dose rate brachytherapy. Int J Radiat Oncol Biol Phys 1991;20:181–90.
31 Dale RG. Radiobiological assessment of permanent implants using tumor repopulation factors in linear-quadratic model. Br J Radiol 1989;62:241–4.
32 Fowler JF, Ritter MA, Fenwick JD, Chappell RJ. How low is the alpha/beta ratio for prostate cancer? In regard to Wang et al., IJROBP 2003;55:194-203. Int J Radiat Oncol Biol Phys 2003;57:593–5.
33 Wang JZ, Guerrero M, Li XA. Low α/β ratio for prostate cancer: in response to Drs. Fowler et al. Int J Radiat Oncol Biol Phys 2003;57:595–6.
34 Roberts SA, Hendry JH. A realistic closed-form radiobiological model of clinical tumor-control data incorporating intertumor heterogeneity. Int J Radiat Oncol Biol Phys 1998;41:689–99.
35 Lyman JT, Complication probability — as assessed from dose volume histograms. Radiat Res 1985;104:S13–9.
36 Kutcher GJ, Burman C. Calculation probability factors for non-uniform normal tissue irradiation: the effective volume method. Int J Radiat Oncol Biol Phys 1989;16:1623–30.
37 Burman, Kutcher GJ, Emami B, Goitein M. Fitting of normal tissue tolerance data to an analytic function. Int J Radiat Oncol Biol Phys 1991;21:123–35.
38 Brenner D, Armour E, Corry P, Hall E. Sublethal damage repair times for a late-responding tissue relevant to brachytherapy (and external-beam radiotherapy): implications for new brachytherapy protocols. Int J Radiat Oncol Biol Phys 1998;41:135–8.
39 Brenner DJ. Fractionation and late rectal toxicity. Int J Radiat Oncol Biol Phys 2004;60:1013–5.
40 Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109–22.
41 Ling CC, Li WX, Anderson LL. The relative biological effectiveness of I-125 and Pd-103. Int J Radiat Oncol Biol Phys 1995;32:373–8.
