SHORT-TERM OUTCOMES OF CHEMORADIOTHERAPY USING ACCELERATED HYPOFRACTIONATION FOR THE TREATMENT OF CANCER OF THE OROPHARYNGEAL MUCOSA

Objectives. The purpose of this study was to assess the tolerance and efficacy of accelerated hypofractionated chemoradiotherapy for oropharyngeal cancer. Material and methods. The study included 54 patients with morphologically confirmed primary stage II–IV oropharyngeal cancer. All the patients received neoadjuvant polychemotherapy with the PF regimen followed by radiation therapy alone. Radiation was delivered in daily 2.4 Gy fractions five days per week to high-risk areas up to a total dose of 62.4 Gy and to low-risk areas up to a total dose of 45.6–48 Gy. Results. A response to neoadjuvant chemotherapy was noted in 75.9 % of cases. Stable disease was seen in 24.1 % of patients. After accelerated hypofractionated radiation therapy, 50 (92.6 %) patients demonstrated tumor response and 4 (7.4 %) demonstrated stable disease. A complete response was achieved in 38 (76.0 %) and partial response was achieved in 12 (24.0 %) patients. The one-year overall survival rate was 83.8 %. Grade III and II oral mucositis was observed in 38 (70.4 %) and 16 (29.6 %) of cases, respectively. Therapy had to be interrupted in 33 (61.1 %) patients. On average, the treatment break lasted 14.2 ± 2.4 days. There was no statistically significant difference in survival rates between the patients treated with or without treatment break (p=0.418). The one-year overall survival rates were 88.9 and 70.0 %, respectively. Conclusion. Evaluation of short-term outcomes and our initial experience with accelerated hypofractionated irradiation at 2.4 Gy per fraction in the treatment of oropharyngeal cancer do not still allow us to draw any firm conclusions on these matters. Further follow-up is needed to make an assessment of long-term treatment outcomes and late toxicities.

1. Chaturvedi A.K., Anderson W.F., Lortet-Tieulent J., Curado M.P., Ferlay J., Franceschi S., Rosenberg P.S., Bray F., Gillison M.L. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013 Dec 20; 31 (36): 4550–9. doi: 10.1200/JCO.2013.50.3870.

2. Gooi Z., Chan J.Y., Fakhry C. The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. Laryngoscope. 2016 Apr; 126 (4): 894–900. doi: 10.1002/lary.25767.

3. Mourad M., Jetmore T., Jategaonkar A.A., Moubayed S., Moshier E., Urken M.L. Epidemiological Trends of Head and Neck Cancer in the United States: A SEER Population Study. J Oral Maxillofac Surg. 2017 Dec; 75 (12): 2562–72. doi: 10.1016/j.joms.2017.05.008.

4. Kaprin A.D., Starinsky V.V., Petrova G.V. The state of oncological assistance to the population of Russia in 2015. Moscow, 2016; 236. [in Russian]

5. National Comprehensive Cancer Network Guidelines. URL: http:// www.nccn.org/professionals/physician_gls/pdf/cns.pdf (дата обращения 01.10.2017).

6. Fowler J.F. Fractionation and glottic carcinoma. Int J Radiat Oncol Biol Phys. 1997 Aug 1; 39 (1): 1–2.

7. Withers H.R., Taylor J.M., Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol. 1988; 27 (2): 131–46.

8. Peters L.J., Withers H.R. Applying radiobiological principles to combined modality treatment of head and neck cancer-the time factor. Int J Radiat Oncol Biol Phys. 1997 Nov 1; 39 (4): 831–6.

9. Shaikh T., Handorf E.A., Murphy C.T., Mehra R., Ridge J.A., Gal-loway T.J. The Impact of Radiation Treatment Time on Survival in Patients with Head and Neck Cancer. Int J Radiat Oncol Biol Phys. 2016 Dec 1; 96 (5): 967–75. doi: 10.1016/j.ijrobp.2016.08.046.

10. Yamazaki H., Nishiyama K., Tanaka E., Koizumi M., Chatani M. Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys. 2006 Jan 1; 64 (1): 77–82. doi: 10.1016/J.IJROBP.2005.06.014

11. Moon S.H., Cho K.H., Chung E.J., Lee C.G., Lee K.C., Chai G.Y., Kang K.M., Lee J.Y., Chung W.K., Park W.Y., Kim J.H. A prospective ran-domized trial comparing hypofractionation with conventional fractionation radiotherapy for T1-2 glottic squamous cell carcinomas: results of a Korean Radiation Oncology Group (KROG-0201) study. Radiother Oncol. 2014 Jan; 110 (1): 98–103. doi: 10.1016/j.radonc.2013.09.016.

12. Bledsoe T.J., Park H.S., Stahl J.M., Yarbrough W.G., Burtness B.A., Decker R.H., Husain Z.A. Hypofractionated Radiotherapy for Patients with Early-Stage Glottic Cancer: Patterns of Care and Survival. J Natl Cancer Inst. 2017 Oct 1; 109 (10). doi: 10.1093/jnci/djx042.

13. Eisbruch A., Harris J., Garden A.S., Chao C.K., Straube W., Harari P.M., Sanguineti G., Jones C.U., Bosch W.R., Ang K.K. Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys. 2010 Apr; 76 (5): 1333–8. doi: 10.1016/j. ijrobp.2009.04.011.

14. Chan A.K., Sanghera P., Choo B.A., McConkey C., Mehanna H., Parmar S., Pracy P., Glaholm J., Hartley A. Hypofractionated accelerated radiotherapy with concurrent carboplatin for locally advanced squamous cell carcinoma of the head and neck. Oncol (R Coll Radiol). 2011 Feb; 23 (1): 34–9. doi: 10.1016/j.clon.2010.07.015.

15. Thomson D.J., Ho K.F., Ashcroft L., Denton K., Betts G., Mais K.L., Garcez K., Yap B.K., Lee L.W., Sykes A.J., Rowbottom C.G., Slevin N.J. Dose intensified hypofractionated intensity-modulated radiotherapy with synchronous cetuximab for intermediate stage head and neck squamous cell carcinoma. Acta Oncol. 2015 Jan; 54 (1): 88–98. doi: 10.3109/0284186X.2014.958528.

16. Spiotto M.T., Koshy M. Impact of fraction size on locally advanced oropharyngeal and nasopharyngeal cancers treated with chemoradiation. Oral Oncol. 2017 May; 68: 27–35. doi: 10.1016/j. oraloncology.2017.03.002.

17. Joiner M.C., Kogel A.J. The linear-quadratic approach to fractionation and calculation of isoeffect relationships. In: Basic Clinical Radiobiology. London: Arnold; 1997. 106–21.

18. Trotti A., Bellm L.A., Epstein J.B., Frame D., Fuchs H.J., Gwede C.K., Komaroff E., Nalysnyk L., Zilberberg M.D. Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol. 2003 Mar; 66 (3): 253–62. doi. org/10.1016/S0167-8140(02)00404-8.

19. Tarnawski R., Fowler J., Skladowski K., Swierniak A., Suwiński R., Maciejewski B., Wygoda A. How fast is repopulation of tumor cells during the treatment gap? Int J Radiat Oncol Biol Phys. 2002 Sep 1; 54 (1): 229–36.

20. Platek M.E., McCloskey S.A., Cruz M., Burke M.S., Reid M.E., Wilding G.E., Rigual N.R., Popat S.R., Loree T.R., Gupta V., Warren G.W., Sullivan M., Hicks W.L.Jr., Singh A.K. Quantification of the effect of treatment duration on local-regional failure after definitive concurrent chemotherapy and intensity-modulated radiation therapy for squamous cell carcinoma of the head and neck. Head Neck. 2013 May; 35 (5): 684–8. doi: 10.1002/hed.23024.

21. González Ferreira J.A., Jaén Olasolo J., Azinovic I., Jeremic B. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: Review of the literature. Rep Pract Oncol Radiother. 2015 Sep-Oct; 20 (5): 328–39. doi: 10.1016/j. rpor.2015.05.010.

22. Roman J., Dissaux G., Gouillou M., Gobel Y., Potard G., Leclere J.C., Conan-Charlet V., Gujral D., Abgral R., Guibourg B., Pradier O., Schick U. Prolonged Overall Treatment Time and Lack of Skin Rash Negatively Impact Overall Survival in Locally Advanced Head and Neck Cancer Patients Treated with Radiotherapy and Concomitant Cetuximab. Target Oncol. 2017 Aug; 12 (4): 505–12. doi: 10.1007/s11523-017-0499-0.