Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

Ping Jiang, Katja Krockenberger, Reinhard Vonthein, Jane Tereszczuk, Arne Schreiber, Sebastian Liebau, Stefan Huttenlocher, Detlef Imhoff, Panagiotis Balermpas, Christian Keller, Kathrin Dellas, Rene Baumann, Claus Rödel, Guido Hildebrandt, Klaus-Peter Jünemann, Alex S Merseburger, Alan Katz, Andreas Ziegler, Oliver Blanck, Jürgen Dunst, Ping Jiang, Katja Krockenberger, Reinhard Vonthein, Jane Tereszczuk, Arne Schreiber, Sebastian Liebau, Stefan Huttenlocher, Detlef Imhoff, Panagiotis Balermpas, Christian Keller, Kathrin Dellas, Rene Baumann, Claus Rödel, Guido Hildebrandt, Klaus-Peter Jünemann, Alex S Merseburger, Alan Katz, Andreas Ziegler, Oliver Blanck, Jürgen Dunst

Abstract

Background: For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.

Methods/design: This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3-5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.

Discussion: The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.

Study status: The study is ongoing and currently recruiting patients.

Trial registration: Registration number: NCT02635256 ( clinicaltrials.gov ). Registered 8 December 2015.

Keywords: Clinical trial; CyberKnife; Extreme hypo-fractionation; Localized prostate cancer; Robotic Radiosurgery; Stereotactic body radiation therapy.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the BfS (reference number Z5–22463/2–2013-031) and by the independent ethics committee of the University of Luebeck (reference number 13–052).

Consent for publication

Not applicable.

Competing interests

The study is partly financed by the Dr.-Rurainski-Stiftung (Ettlingen, Germany) and the Saphir Medical Engineering Group GmbH (Guestrow, Germany).

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

    1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–1403. doi: 10.1016/j.ejca.2012.12.027.
    1. Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol. 1974;111:58–64. doi: 10.1016/S0022-5347(17)59889-4.
    1. Gleason DF. Tannenbaum M, ed. Urologic Pathology: The Prostate; 1977. Histologic grading and clinical staging of prostatic carcinoma; pp. 171–197.
    1. Partin AW, Kattan MW, Subong EN, et al. Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update. JAMA. 1997;277:1445–1451. doi: 10.1001/jama.1997.03540420041027.
    1. Partin AW, Mangold LA, Lamm DM, et al. Contemporary update of prostate cancer staging nomograms (Partin tables) for the new millennium. Urology. 2001;58:843–848. doi: 10.1016/S0090-4295(01)01441-8.
    1. Ischia JJ, Pang CY, Tay YK, et al. Active surveillance for prostate cancer: an Australian experience. BJU Int. 2012;109:40–43. doi: 10.1111/j.1464-410X.2012.11045.x.
    1. Chodak GW, Thisted RA, Gerber GS, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med. 1994;330:242–248. doi: 10.1056/NEJM199401273300403.
    1. Waaler G, Stenwig AE. Prognosis of localised prostatic cancer managed by “watch and wait” policy. Br J Urol. 1993;72:214–219. doi: 10.1111/j.1464-410X.1993.tb00690.x.
    1. Wilt TJ, Brawer MK, Jones KM, et al. Prostate cancer intervention versus observation trial (PIVOT) study group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367:203–213. doi: 10.1056/NEJMoa1113162.
    1. Bill-Axelson A, Holmberg L, Ruutu M, et al. Scandinavian prostate cancer group study no. 4. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005;352:1977–1984. doi: 10.1056/NEJMoa043739.
    1. Holmberg L, Bill-Axelson A, Helgesen F, et al. Scandinavian prostatic cancer group study number 4. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002;347(11):781–789. doi: 10.1056/NEJMoa012794.
    1. Alibhai SM, Leach M, Tomlinson G, et al. 30-day mortality and major complications after radical prostatectomy: influence of age and comorbidity. J Natl Cancer Inst. 2005;97:1525–1532. doi: 10.1093/jnci/dji313.
    1. Bishoff JT, Motley G, Optenberg SA, et al. Incidence of fecal and urinary incontinence following radical perineal and retropubic prostatectomy in a national population. J Urol. 1998;160:454–458. doi: 10.1016/S0022-5347(01)62924-0.
    1. Catalona WJ, Basler JW. Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol. 1993;150:905–907. doi: 10.1016/S0022-5347(17)35645-8.
    1. Dearnaley DP, Khoo VS, Norman AR, et al. Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. Lancet. 1999;353:267–272. doi: 10.1016/S0140-6736(98)05180-0.
    1. Nieder AM, Porter MP, Soloway MS. Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study. J Urol. 2008;180:2005–2009. doi: 10.1016/j.juro.2008.07.038.
    1. Sanda MG, Dunn RL, Michalski J, et al. Quality of life and satisfaction with outcome among prostate cancer survivors. N Engl J Med. 2008;358:1250–1261. doi: 10.1056/NEJMoa074311.
    1. Resnick MJ, Koyama T, Fan KH, et al. Long-term functional outcomes after treatment for localized prostate cancer. N Engl J Med. 2013;368:436–445. doi: 10.1056/NEJMoa1209978.
    1. Hamdy FC, Donovan JL, Lane JA, et al; ProtecT Study Group. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375(15):1415-1424.
    1. Alicikus ZA, Yamada Y, Zhang Z, et al. Ten-year outcomes of high-dose, intensity-modulated radiotherapy for localized prostate cancer. Cancer. 2011;17(7):1429–1437. doi: 10.1002/cncr.25467.
    1. Zelefsky MJ, Kollmeier M, Cox B, et al. Improved clinical outcomes with high-dose image guided radiotherapy compared with non-IGRT for the treatment of clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(1):125–129. doi: 10.1016/j.ijrobp.2011.11.047.
    1. Michalski J, Winter K, Roach M, et al. 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;83(3):363–370. doi: 10.1016/j.ijrobp.2011.12.070.
    1. Jacobs BL, Zhang Y, Skolarus TA, et al. Comparative effectiveness of external-beam radiation approaches for prostate cancer. Eur Urol. 2014;65(1):162–168. doi: 10.1016/j.eururo.2012.06.055.
    1. Peeters ST, Heemsbergen WD, Koper PC, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006;24:1990–1996. doi: 10.1200/JCO.2005.05.2530.
    1. Pollack A, Zagars GK, Starkschall G, et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys. 2002;53:1097–1105. doi: 10.1016/S0360-3016(02)02829-8.
    1. Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol. 2005;44(3):265–276. doi: 10.1080/02841860410002824.
    1. Arcangeli G, Fowler J, Gomellini S, et al. Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys. 2011;79:1013–1021. doi: 10.1016/j.ijrobp.2009.12.045.
    1. Miralbell R, Roberts SA, Zubizarreta E, et al. Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 (0.9-2.2) Gy. Int J Radiat Oncol Biol Phys. 2012;82(1):17–24. doi: 10.1016/j.ijrobp.2010.10.075.
    1. Dasu A, Toma-Dasu I. Prostate alpha/beta revisited - an analysis of clinical results from 14168 patients. Acta Oncol. 2012;51(8):963–974. doi: 10.3109/0284186X.2012.719635.
    1. Dearnaley D, Syndikus I, Sumo G, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. Lancet Oncol. 2012;13:43–54. doi: 10.1016/S1470-2045(11)70293-5.
    1. Lee WR, Dignam JJ, Amin MB, et al. Randomized phase III noninferiority study comparing two radiotherapy fractionation schedules in patients with low-risk prostate cancer. J Clin Oncol. 2016;34(20):2325–2332. doi: 10.1200/JCO.2016.67.0448.
    1. Höcht S, Aebersold DM, Albrecht C, et al. Hypofractionated radiotherapy for localized prostate cancer. Strahlenther Onkol. 2017;193(1):1–12. doi: 10.1007/s00066-016-1041-5.
    1. King C. Stereotactic body radiotherapy for prostate cancer: current results of a phase II trial. Front Radiat Ther Oncol. 2011;43:428–437. doi: 10.1159/000322507.
    1. King CR, Brooks JD, Gill H, et al. Stereotactic body radiotherapy for localized prostate cancer: interim results of a prospective phase II clinical trial. Int J Radiat Oncol Biol Phys. 2009;73:1043–1048. doi: 10.1016/j.ijrobp.2008.05.059.
    1. King CR, Brooks JD, Gill H, et al. Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82:877–882. doi: 10.1016/j.ijrobp.2010.11.054.
    1. Lee YH, Son SH, Yoon SC, et al. Stereotactic body radiotherapy for prostate cancer: a preliminary report. Asia Pac J Clin Oncol. 2012;10(2):46–53. doi: 10.1111/j.1743-7563.2012.01589.x.
    1. Townsend NC, Huth BJ, Ding W, et al. Acute toxicity after cyberknife-delivered hypofractionated radiotherapy for treatment of prostate cancer. Am J Clin Oncol. 2011;34:6–10. doi: 10.1097/COC.0b013e3181c4c7c4.
    1. McBride SM, Wong DS, Dombrowski JJ, et al. Hypofractionated stereotactic body radiotherapy in low-risk prostate adenocarcinoma: preliminary results of a multi- institutional phase 1 feasibility trial. Cancer. 2012;118:3681–3690. doi: 10.1002/cncr.26699.
    1. Oermann EK, Suy S, Hanscom HN, et al. Low incidence of new biochemical and clinical hypogonadism following hypofractionated stereotactic body radiation therapy (SBRT) monotherapy for low- to intermediate-risk prostate cancer. J Hematol Oncol. 2011;4:12. doi: 10.1186/1756-8722-4-12.
    1. Hannoun-Levi JM, Benezery K, Bondiau PY, et al. Robotic radiotherapy for prostate cancer with CyberKnife. Cancer Radiother. 2007;11:476–482. doi: 10.1016/j.canrad.2007.07.005.
    1. Madsen BL, Hsi RA, Pham HT, et al. Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results. Int J Radiat Oncol Biol Phys. 2007;67:1099–1105. doi: 10.1016/j.ijrobp.2006.10.050.
    1. Fuller DB, Naitoh J, Lee C, et al. Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. Int J Radiat Oncol Biol Phys. 2008;70:1588–1597. doi: 10.1016/j.ijrobp.2007.11.067.
    1. Freeman DE, King CR. Stereotactic body radiotherapy for low-risk prostate cancer: five-year outcomes. Radiat Oncol. 2011;6:3. doi: 10.1186/1748-717X-6-3.
    1. Katz AJ. CyberKnife radiosurgery for prostate cancer. Technol Cancer Res Treat. 2010;9(5):463–472. doi: 10.1177/153303461000900504.
    1. Katz AJ, Santoro M, Ashley R, et al. Stereotactic body radiation therapy for low- and low-intermediate-risk prostate cancer: is there a dose effect? Front Oncol. 2011;1:49. doi: 10.3389/fonc.2011.00049.
    1. Xie Y, Djajaputra D, King CR, et al. Intrafractional motion of the prostate during hypofractionated radiotherapy. Int J Radiat Oncol Biol Phys. 2008:236–46.
    1. Lei S, Piel N, Oermann EK, et al. Six-dimensional correction of intra-fractional prostate motion with CyberKnife stereotactic body radiation therapy. Front Oncol. 2011;1:48. doi: 10.3389/fonc.2011.00048.
    1. Marino C, Villaggi E, Maggi G, et al. A feasibility dosimetric study on prostate cancer: are we ready for a multicenter clinical trial on SBRT? Strahlenther Onkol. 2015;191(7):573–481. doi: 10.1007/s00066-015-0822-6.
    1. Rucinska M, Kieszkowska-Grudny A, Nawrocki S. SHARP hypofractionated stereotactic radiotherapy is well tolerated in prostate cancer: toxicity and quality of life assessment. Strahlenther Onkol. 2016;192(7):449–457. doi: 10.1007/s00066-016-0971-2.
    1. Rudat V, Nour A, Hammoud M, et al. Image-guided intensity-modulated radiotherapy of prostate cancer: analysis of interfractional errors and acute toxicity. Strahlenther Onkol. 2016;192(2):109–117. doi: 10.1007/s00066-015-0919-y.
    1. Hoffmans-Holtzer NA, Hoffmans D, Dahele M, et al. Roll and pitch set-up errors during volumetric modulated arc delivery: can adapting gantry and collimator angles compensate? Strahlenther Onkol. 2015;191(3):272–280. doi: 10.1007/s00066-014-0766-2.
    1. Widmark A, Gunnlaugsson A, Beckman L, et al. Extreme Hypofractionation versus conventionally fractionated radiotherapy for intermediate risk prostate cancer: early toxicity results from the Scandinavian randomized phase III trial “HYPO-RT-PC”. Int J Radiat Oncol Biol Phys. 2016;96(5):938–939. doi: 10.1016/j.ijrobp.2016.09.049.
    1. Timmerman RD. An overview of hypofractionation and introduction to this issue of seminars in radiation oncology. Semin Radiat Oncol. 2008;18(4):215–222. doi: 10.1016/j.semradonc.2008.04.001.
    1. Grimm J, LaCouture T, Croce R, et al. Dose tolerance limits and dose volume histogram evaluation for stereotactic body radiotherapy. J Appl Clin Med Phys. 2011;12(2):3368. doi: 10.1120/jacmp.v12i2.3368.
    1. Michalski JM, Gay H, Jackson A, et al. Radiation dose-volume effects in radiation-induced rectal injury. Int J Radiat Oncol Biol Phys. 2010;76:123–129. doi: 10.1016/j.ijrobp.2009.03.078.
    1. Viswanathan AN, Yorke ED, Marks LB, et al. Radiation dose-volume effects of the urinary bladder. Int J Radiat Oncol Biol Phys. 2010;76:116–122. doi: 10.1016/j.ijrobp.2009.02.090.
    1. Repka MC, Guleria S, Cyr RA, et al. Acute urinary morbidity following stereotactic body radiation therapy for prostate cancer with prophylactic alpha-adrenergic antagonist and urethral dose reduction. Front Oncol. 2016;6:122. doi: 10.3389/fonc.2016.00122.

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