Estimation of linear quadratic (LQ) model parameter alpha/beta (α/β) and biologically effective dose (BED) for acute normal tissue reactions in head and neck malignancies

Mirza Athar Ali, Shankar Lal Jakhar, Dharam Pal Punia, MR Bardia, Ajay Sharma, HS Kumar, Sandeep Jain, Neeti Sharma, Vinod Agrawal, Kamlesh Kumar Harsh, Ashok Kumar Kalwar, Muntimadugu Babaiah, Prabhakar Mariappan, N Madhusudhan, Sujana Priya Vuba

Abstract


Purpose: Linear-Quadratic (LQ) model has been widely used for describing radiobiological effectiveness of various fractionation schedules on tumour as well as normal tissues. This study estimates α/β for acute normal tissue reactions using Fe-plot method.

Methods: 50 cases of locally advanced head and neck squamous cell carcinoma (stage III and IV) treated with external beam radiotherapy were included in this study. Patients were randomly distributed into Hyper-fractionation (HF) arm (1.2 Gy/fraction, twice daily, 6 hours apart) and conventional fractionation (CF) arm (2 Gy/fraction, once daily) with 25 cases in each arm. α/β and BED were calculated for acute normal tissue reactions using Fe-plot method.

Results: In our study, the estimated values of α/β for RTOG (Radiation Therapy Oncology Group) grade 1, 2 and 3 skin reactions were 11.2 Gy, 10.1 Gy and 9 Gy respectively. Estimated values of α/β for RTOG grade 1, 2 and 3 mucosal reactions were 9.7 Gy, 8.0 Gy and 9.1 Gy respectively. For Hyper-fractionation arm, calculated BED values for grade 1, 2 and 3 skin reactions were 54.45 Gy11.239, 66.90 Gy10.114 and 73.43Gy9.001 respectively and for grade 1, 2 and 3 mucosal reactions were 33.5 Gy9.797, 57.8 Gy8.011 and 70.8 Gy9.106 respectively. For conventional fractionation arm, calculated BED values for grade 1, 2 and 3 skin reactions were 54.09 Gy11.239, 66.88 Gy10.114 and 73.33 Gy9.001 respectively and for grade 1, 2 and 3 mucosal reactions were 33.52 Gy9.797, 57.68 Gy8.011 and 70.73 Gy9.106 respectively.

Conclusion: LQ model and the concept of BED provide an excellent tool to compare different fractionation schedules in radiotherapy. The estimated values of α/β for acute reacting normal tissues are in good agreement with the available literature.


Keywords


LQ Model, α/β, BED, Fe-plot method.

Full Text:

PDF

References


Coutard H. Principle of x-ray therapy for cancer. Lancet. 1934; 2:1-8.

Douglas BG, Worth AJ. Superfractionation in glioblastoma multiforme-results of a phase II study. Int J Radiat Oncol Biol Phys. 1982; 8(10):1787-94.

Douglas BG. Preliminary results using super-fractionation in the treatment of glioblastoma multiforme. J Can Assoc Radiol. 1977; 28:106-10.

Simpson WJ, Platts ME. Fractionation study in the treatment of glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1976; 1:639–44.

Ellis F. The relationship of biological effect to dose-time-fractionation factors in radiotherapy. W: Ebert M and Howard A. Current Topics in Radiation Research. 1968; 4:357-397.

Kirk J, Gray WM, Watson ER. Cumulative radiation effect. Part 1: Fractionated treatment regimens. Clin Radiol. 1971; 22:145-53.

Orton CG, Ellis F. A simplification in the use of NSD concept in practical radiotherapy. Br J Radiol. 1973; 46(547):529-37.

Barendsen GW. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. Int J Radiat Oncol Biol Phys. 8(11):1981-97.

Perez CA, Brady LW, Halperin EC, et al. Principles and Practice of radiation oncology. 4th Ed. 2004; 1:28-32.

Astrahan M. Some implications of linear-quadratic-linear radiation dose-response with regard to hypofractionation. Medical Physics. 2008; 35(9):4161-4172.

Ellis F. Dose, time and fractionation: A clinical hypothesis. Clinical Radiology. 1969; 20(1):1-7.

Fowler JF. The first James Kirk memorial lecture. What next in fractionated radiotherapy? Br J Cancer Suppl. 1984; 6:285-300.

Williams MW, Denekamp J, Fowler JF. A review of alpha/beta ratios for experimental tumors: implications for clinical studies of altered fractionation. Int J Radiat Oncol Biol Phys. 1985; 11(1):87-96.

Maciejewski B, Preuss-Bayer, Trott KR. The influence of the number of fractions and overall treatment time on the local control of cancer of the larynx. Int J Radiat Oncol Biol Phys. 1983; 9:321.

Douglas BG, Fowler JF. The effect of multiple small doses of x-rays on skin reactions in the mouse and a basic interpretation. Radiat Res. 1976; 66(2):401-26.

Levitt SH, Purdy JA, Perez CA, et al. Technical basis of radiotherapy. 2007; 1:10-11.

Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995; 31(5):1341-6.

Padhani AR, Ollivier L. RECIST criteria: Implications for diagnostic radiologists. Br J Radiol. 2001; 74(887):983-6.

Patrick T, Sussane GA, Elizabeth AE et al. New guidelines to evaluate the response to treatment in solid tumors. Journal of National Cancer Institute. 2000; 92:3.

Saunders MI, Rojas AM. Management of cancer of head and neck – a cocktail with your PORT. N Engl J Med. 2004; 6:350(19):1997-9.

Seiwert TY, Cohen EE. State of the art management of locally advanced head & neck cancers. British J. Cancer. 2005; 92(8):1341-8.

Seiwert TY, Vokes EE. Head and neck cancer. The cancer handbook. 2nd Ed. (Alison.M.R) Chichester, UK, Wiley, in press.

Fowler JF. The linear quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989; 62(740);679-94.

Fowler JF, Denekamp J, Delapeyre C, et al. Skin reactions in mice after multifraction x-irradiation. Int J Radiat Biol Relat Stud Phys Chem Med. 1974; 25(3):213-23.

Douglas BG, Fowler JF. The effect of multiple small doses of x-rays on skin reactions in the mouse and basic interpretation. Radiat Res. 1976; 66(2):401-26.

Joiner MC, Denekamp J, Maughan RL. The use of “top-up” experiments to investigate the effect of very small doses per fraction in mouse skin. Int J Radiat Biol. 1986; 49:565-80.

Bentzen SM, Juul-Christensen J, Overgaard J. Some methodological problems in estimating radiobiological parameters from clinical data: alpha/beta ratios and electron RBE for cutaneous reactions in patients treated with postmastectomy radiotherapy. Acta Oncol. 1988; 27:105-16.

Turesson I, Thames HD. Repair capacity and kinetics of human skin during fractionated radiotherapy: erythema, desquamation and telangiectasia after 3 and 5 years follow up. Radiother Oncol. 1989; 15(2):169-88.

Rezvani M, Alcock CJ, Fowler JF, et al. Normal tissue reactions in the British Institute of Radiology study of 3 fractions per week versus 5 fractions per week in the treatment of carcinoma of the laryngo-pharynx by radiotherapy. Br J Radiol. 1991;64(768):1122-33.

Horiot JC, Le Fur R, N'Guyen T et al. Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol. 1992 ;25(4):231-41.

Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys. 2000 ;48(1):7-16.




DOI: http://dx.doi.org/10.14319/ijcto.44.9

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

------------------------------------------------------------

International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)

© International Journal of Cancer Therapy and Oncology (IJCTO)

To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.

------------------------------------------------------------

Number of visits since October, 2013
AmazingCounters.com