Clinical radiobiology of head and neck cancer: the hypothesis of stem cell activation
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To estimate and reduce uncertainties of a self-consistent set of radiobiological parameters based on the outcome of head and neck cancer (HNC) patients treated with radiotherapy (RT).
Published studies comparing at least two RT schedules for HNC patients were selected. The method used to estimate the radiobiological parameters consists of three sequential steps that allow a significant reduction of uncertainties: the first, in which the intrinsic (α) and the repair (β) radio-sensitivities were estimated together with the doubling time (T d) by an analytical/graphical method; the second, in which the kick-off time for accelerated proliferation (T k) was estimated applying the hypothesis of activation for sub-populations of stem cells during the RT; the third, in which the number of clonogens (N) was obtained by the Tumor Control Probability (TCP) model. Independent clinical data were used to validate results.
The best estimate and the 95 % confidence intervals (95 % CIs) were: α = 0.24 Gy−1 (0.23–0.26), β = 0.023 Gy−2 (0.021–0.025), α/β = 10.6 Gy (8.4–12.6), T d = 3.5 days (3.1–3.9), T k = 19.2 days (15.1–23.3), N = 7 × 107 (4 × 107–1 × 108). From these data, the dose required to offset repopulation occurring in 1 day (D prolif) and starting after T k was also estimated as 0.69 Gy/day (0.52–0.86).
The estimation of all the radiobiological parameters of HNC was obtained based on the hypothesis of activation for specifically tumorigenic sub-populations of stem cells. The similarity of results to those from other studies strengthens such a hypothesis that could be very useful for the predictivity of the TCP model and to design new treatment strategies for HNC.
KeywordsRadio-sensitivity Fractionation Stem cells Tumor control probability
Conflict of interest
The authors declare no competing interests.
- 2.Million RR, Cassisi NJ, Mancuso AA. Oral cavity. In: Million RR, Cassisi NJ, editors. Management of head and neck cancer: a multidisciplinary approach. 2nd ed. Philadelphia: J.B. Lippincott; 1994. p. 321–400.Google Scholar
- 3.Fowler JF. Is there an optimum overall time for head and neck radiotherapy? A review, with new modeling. Clin Oncol. 2007;19:8–22.Google Scholar
- 4.Fu KK, Pajak TF, Trotti A, Jones CU, Spencer SA, Phillips TL, 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: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000;48:7–16.PubMedGoogle Scholar
- 5.Marcial VA, Pajak TF, Chang C, Tupchong L, Stetz J. Hyperfractionated photon radiation therapy in the treatment of advanced squamous cell carcinoma of the oral cavity, pharynx, larynx, and sinuses, using radiation therapy as the only planned modality: preliminary report by the Radiation Therapy Oncology Group (RTOG). Int J Radiat Oncol Biol Phys. 1987;13:41–7.PubMedGoogle Scholar
- 6.Cox JD, Pajak TF, Marcial VA, Hanks GE, Mohiuddin M, Fu KK, et al. Dose-response for local control with hyperfractionated radiation therapy in advanced carcinomas of the upper aero digestive tracts: preliminary reportof Radiation Therapy Oncology Group protocol 83-13. Int J Radiat Oncol Biol Phys. 1990;18:515–21.PubMedGoogle Scholar
- 8.Pedicini P, Nappi A, Strigari L, Jereczek-Fossa BA, Alterio D, Cremonesi M, et al. Correlation between EGFr expression and accelerated proliferation during radiotherapy of head and neck squamous cell carcinoma. Radiat Oncol. 2012;24:143.Google Scholar
- 11.Pedicini P. In regard to Pedicini et al. Int J Radiat Oncol Biol. 2013;87(5):858.Google Scholar
- 12.Efron B. Censored data and the bootstrap. J Am Stat Assoc. 1981;76:312–9.Google Scholar
- 14.Awwad HK, Lotayef M, Shouman T, Begg AC, Wilson G, Bentzen SM, et al. Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation. Br J Cancer. 2002;86:517–23.PubMedCentralPubMedGoogle Scholar
- 15.Chung CH, Zhang Q, Hammond EM, Trotti AM 3rd, Wang H, Spencer S, et al. Integrating epidermal growth factor receptor assay with clinical parameters improves risk classification for relapse and survival in head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2011;81:331–8.PubMedCentralPubMedGoogle Scholar
- 16.Pinto LH, Canary PC, Araújo CM, Bacelar SC, Souhami L. Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 1980;21:557–62.Google Scholar
- 18.Jackson SM, Weir LM, Hay JH, Tsang VH, Durham JS. A randomized trial of accelerated versus conventional radiotherapy in head and neck cancer. Int J Radiat Oncol Biol Phys. 1997;43:39–46.Google Scholar
- 19.Horiot JC, Bontemps P, van den Bogaert W, Le Fur R, van den Weijngaert D, Bolla M, et al. Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomized trial. Radiother Oncol. 1997;44:111–21.PubMedGoogle Scholar
- 20.Katori H, Tsukuda M, Watai K. Comparison of hyperfractionation and conventional fractionation radiotherapy with concurrent docetaxel, cisplatin and 5-Xuorouracil (TPF) chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cancer Chemother Pharmacol. 2007;60:399–406.PubMedGoogle Scholar
- 22.Bentzen SM, Atasoy BM, Daley FM, Dische S, Richman PI, Saunders MI, et al. Epidermal growth factor receptor expression in pretreatment biopsies from head and neck squamous cell carcinoma as a predictive factor for a benefit from accelerated radiation therapy in a randomized controlled trial. J Clin Oncol. 2005;23:5560–7.PubMedGoogle Scholar
- 26.Steel GG. Growth kinetics of tumours. Oxford: Clarendon-Press; 1977.Google Scholar