DOSE-ESCALATED EXTERNAL BEAM RADIOTHERAPY DURING HORMONO-RADIOTHERAPY FOR PROSTATE CANCER

Introduction. The introduction of modern technologies of conformal external beam radiotherapy (EBRT) into clinical practice for the treatment of prostate cancer requires proper quality assurance measures as well as a careful analysis of both the efficacy and toxicity data of treatments. The purpose of this study was to inves- tigate tolerance and the immediate efficacy of conformal dose-escalated EBRT during hormono-radiotherapy for prostate cancer. material and methods. The study involved 156 prostate cancer patients treated with EBRT. Among them, 30 patients received a total dose of 70 Gy, and in 126 patients the total dose was esca- lated to 72-76 Gy (median total dose - 74.0 Gy). Fifty-nine patients received intensity modulated radiation therapy. Results. The prescribed course of treatment was completed in all the patients with prostate cancer. Acute radiation-induced bladder reactions (RTOG) were observed in 50 (32.1 %) patients, of whom 48 (30.8 %) experienced grade I reactions, and 2 (1.3 %) experienced grade II reactions. Eighteen (11.5 %) patients had radiation-induced rectum reactions, not above grade I. The development of grade II dysuric phenomena necessitated treatment interruption only in two patients. Of 9 (5.8 %) patients who had late bladder complica- tions (RTOG/EORTC), 8 (5.1 %) patients developed grade I complications, and one (0.6 %) patient developed grade II complications. Of 11 (7.1 %) patients who had rectum complications, 8 (5.1 %) patients developed grade I complications, and 3 (1.9 %) patients developed grade II complications. No patients experienced the increase in toxicity of treatment during dose escalation up to a total dose exceeding 70 Gy. During the follow-up period, only one patient developed recurrent disease. Conclusion. The results of our study suggest acceptable levels of toxicity following a continuous course of dose-escalated EBRT given in conjunction with hormono-radiotherapy to prostate cancer patients. Further studies are needed to investigate the impact of dose escalation on long-term outcomes as well as the rate and grade of late complications.

1. The state of cancer care in Russia in 2014 / Ed. by A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. M., 2015. 236 p. [in Russian]

2. Beckendorf V., Guerif S., Le Prise E., Cosset J.M., Bougnoux A., Chauvet B., Salem N., Chapet O., Bourdain S., Bachaud J.M., Maingon P., Hannoun-Levi J.M., Malissard L., Simon J.M., Pommier P., Hay M., Dubray B., Lagrange J.L., Luporsi E., Bey P. 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial // Int. J. Radiat. Oncol. Biol. Phys. 2011. Vol. 80 (4). P. 1056–1063. doi: 10.1016/j.ijrobp.2010.03.049.

3. Budaus L., Bolla M., Bossi A., Cozzarini C., Crook J., Widmark A., Wiegel T. Functional outcomes and complications following radiation therapy for prostate cancer: a critical analysis of the literature // Eur. Urol. 2012. Vol. 61. P. 112–127. doi: 10.1016/j.eururo.2011.09.027.

4. Chennupati S.K., Pelizzari C.A., Kunnavakkam R., Liauw S.L. Late toxicity and quality of life after definitive treatment of prostate cancer: redefining optimal rectal sparing constraints for intensity-modulated radiation therapy // Cancer Med. 2014. Vol. 3 (4). P. 954–961. doi: 10.1002/cam4.261.

5. Creak A., Hall E., Horwich A., Eeles R., Khoo V., Huddart R., Parker C., Griffin C., Bidmead M., Warrington J., Dearnaley D. Randomized pilot study of dose escalation using conformal radiotherapy in prostate cancer: long-term follow-up // Br. J. Cancer. 2013. Vol. 109 (3). P. 651–657. doi: 10.1038/bjc.2013.394.

6. Dearnaley D.P., Jovic G., Syndikus I., Khoo V., Cowan R.A., Graham J.D., Aird E.G., Bottomley D., Huddart R.A., Jose C.C. Matthews J.H.L., Millar J.L., Murphy C., Russell J.M., Scrase C.D., Parmar M.K.B., Sydes M.R. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial // Lancet Oncol. 2014. Vol. 15 (4). P. 464–473. doi: 10.1016/S1470-2045(14)70040-3.

7. Fuentes-Raspall R., Inoriza J.M., Rosello-Serrano A., Aunon-Sanz C., Garcia-Martin P., Oliu-Isern G. Late rectal and bladder toxicity following radiation therapy for prostate cancer: Predictive factors and treatment results // Rep. Pract. Oncol. Radiother. 2013. Vol. 18 (5). P. 298–303. doi: 10.1016/j.rpor.2013.05.006.

8. Heemsbergen W.D, Al-Mamgani A., Slot A. Dielwart M.F., Lebesque J.V. Long-term results of the Dutch randomized prostate cancer trial: impact of dose-escalation on local, biochemical, clinical failure, and survival // Radiother. Oncol. 2014. Vol. 110 (1). P. 104–109. doi: 10.1016/j. radonc.2013.09.026.

9. Horwich A., Hugosson J., Reijke T., Wiegel T., Fizazi K., Kataja V. & Panel Members. Prostate cancer: ESMO Consensus Conference Guidelines 2012 // Ann. Oncol. 2013. Vol. 24 (5). P. 1141–1162. doi: 10.1093//annonc/mds 624.

10. Jacobs B.L., Zhang Y., Skolarus T.A., Wei J.T., Montie J.E., Miller D.C., ollenbeck B.K. Comparative effectiveness of external beam radiation approaches for prostate cancer // Eur. Urol. 2014. Vol. 65 (1). P. 162–168. doi: 10.1016/j.eururo.2012.06.055.

11. Kuban D.A., Tucker S.L., Dong L., Starkschall G., Huang E.H., Cheung M.R., Lee A.K., Pollack A. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer // Int. J. Radiat. Oncol. Biol. Phys. 2008. Vol. 70 (1). P. 67–74.

12. Liauw S.L., Stadler W.M., Correa D., Weichselbaum R.R., Jani A.B. Dose-escalated radiotherapy for high-risk prostate camcer: outcomes in modern era with short-term androgen deprivation therapy // Int. J. Radiat. Oncol. Biol. phys. 2010. Vol. 77 (1). P. 125–130. doi: 10.1016/j.ijrobp.2009.04.074.

13. Matzinger O., Duclos F., van den Bergh A., Carrie C., Villa S., Kitsios P., Poortmans P., Sundar S., Steen-Banasik E.M., Gulyban A., Collette L., Bolla M. Acute toxicity of curative radiotherapy for intermediate-and high-risk localized prostate cancer in the EORTC trial 22991 // Eur. J. Cancer. 2009. Vol. 45 (16). P. 2825–2834. doi: 10.1016/j.ejca.2009.07.009.

14. Michalski J.M., Bae K., Roach M., Marcoe A.M., Sandler H.M., Ryu J., Parliament M.B., Straube W., Valicenti R.K., Cox J.D. Long-term toxicity following 3D conformal radiation therapy for prostate cancer from the RTOG 9406 phase I/II dose escalation study // Int. J. Radiat. Oncol. Biol. Phys. 2010. Vol. 76 (1). P. 14–22. doi: 10.1016/j.ijrobp.2009.01.062.

15. Michalski J., Winter K., Roach M., Markoe A., Sandler H.M., Ryu J., Parliament M., Purdy J.A., Valicenti R.K., Cox J.D. Clinical outcome of patients treated with 3D conformal radiation therapy 3D-CRT for prostate cancer on RTOG 9406 // Int. J. Radiat. Oncol. Biol. Phys. 2012. Vol. 83 (3). P. 363–370. doi: 10.1016/j.ijrobp.2011.12.070.

16. Spratt D.E., Pei X., Yamada J., Kollmeier M.A., Cox B., Zelefsky M.J. Long-term survival and toxicity in patients treated with high-dose intensity modulated radiation therapy for localized prostate cancer // Int. J. Radiat. Oncol. Biol. Phys. 2013. Vol. 85 (3). P. 686–692. doi: 10.1016/j.ijrobp.2012.05.023.

17. Sveistrup J., Rosenschold P.M., Deasy J.O., Oh J.H., Pommer T., Petersen P.M., Engelholm S.A. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance //Radiat. Oncol. 2014. Vol. 9. P. 44. doi: 10.1186/1748-717X-9-44.

18. Vora S.A., Wong W.W., Schild S.E., Ezzell G.A., Andrews P.E., Ferrigni R.G., Swanson S.K. Outcome and toxicity for patients treated with intensity modulated radiation therapy for localized prostate cancer // J. Urol. 2013. Vol. 190 (2). P. 521–526. doi: 10.1016/j.juro.2013.02.012.

19. Wilcox S.W., Aherne N.J., Benjamin L.C., Wu B., Silva T.C., McLachlan C.S., McKay M.J., Last A.J., Shakespeare T.P. Long-term outcomes from dose-escalated image-guided intensity-modulated radiotherapy with androgen deprivation: encouraging results for intermediateand high-risk prostate cancer // Onco. Targets Ther. 2014. Vol. 30 (7). P. 1519–1523. doi.org/10.2147/OTT. S65238.

20. Wortel R.C., Incrocci L., Pos F.J., Lebesque J.V., Witte M.G., van der Heide U.A., van Herk M., Heemsbergen W.D. Acute toxicity after image-guided intensity modulated radiation therapy compared to 3D conformal radiation therapy in prostate cancer patients // Int. J. Radiat. Oncol. Biol. Phys. 2015. Vol. 91 (4). P. 737–744. doi: 10.1016/j. ijrobp.2014.12.017.

21. Zelefsky M.J., Levin E.J., Hunt M., Yamada Y. Shippy A.M., Jackson A., Amols H.I. Incidence of late rectal and urinary toxicities after threedimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer // Int. J. Radiat. Oncol. Biol. Phys. 2008. Vol. 70 (4). P. 1124–1129. doi: 10.1016/j.ijrobp.2007.11.044.

22. Zietman A.L., Bae K., Slater J.D., Shipley W.U., Efstathiou J.A. Coen J.J., Bush D.A., Lunt M., Spiegel D.Y., Skowronski R., Jabola B.R., Rossi C.J. Randomized trial comparing conventional-dose with high-dose conformal radiation therapy in early-stage adenocarcinoma of the prostate: long-term results from Proton Radiation Oncology Group/American College of Radiology 95-09 // J. Clin. Oncol. 2010. Vol. 28 (7). P. 1106–1111. doi: 10.1200/JCO.2009.25.8475.

23.