The effectiveness and side effects of conformal external beam radiotherapy combined with high-dose-rate brachytherapy boost compared to conformal external beam radiotherapy alone in patients with prostate cancer

Radiation Oncology

Rafał Suwiński¹  Aleksander Zajusz¹  Elżbieta Nowicka¹  Katarzyna Behrendt¹  Monika Giglok¹  Marzena Gawkowska-Suwińska¹  Grzegorz Plewicki¹  Marek Fijałkowski¹  Brygida Białas¹  Leszek Miszczyk¹  Beata Smolska-Ciszewska¹ 

[1] Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Ul. Wybrzeże Armii Krajowej 15, Gliwice 44-100, Poland

关键词: Radiotherapy;    Prostate cancer;    High-dose-rate;    Brachytherapy;   

Others  :  1139651
DOI  :  10.1186/s13014-015-0366-z

 received in 2014-11-20, accepted in 2015-02-20,  发布年份 2015

【 摘 要 】

Background

Clinical data that compare external-beam radiotherapy (EBRT) combined with high-dose-rate brachytherapy (HDR-BT) boost versus EBRT alone are scarce. The analysis of published studies suggest that biochemical relapse-free survival in combined EBRT and HDR-BT may be superior compared to EBRT alone. We retrospectively examined the effectiveness and tolerance of both schemes in a single center study.

Methods

Between March 2003 and December 2004, 229 patients were treated for localized T1-T2N0M0 prostate cancer. Median age was 66 years (range, 49 – 83 years). PSA level ranged from 0.34 to 64 ng/ml (median 12.3 ng/ml) and Gleason score ranged from 2 to 10. The analysis included 99 patients who underwent EBRT with HDR-BT (group A) and 130 patients who were treated with EBRT alone (group B).

Results

Median follow-up was 6 years. Biochemical relapses occurred in 34% vs. 22% (p = 0.002), local recurrences in 17% vs. 5% (p = 0.002), and distant metastases in 11% vs. 6% (p = 0.179) of patients in groups A and B, respectively. Five-year biochemical relapse-free survival was 67% vs. 81% (p = 0.005), local recurrence-free survival 95% vs. 99% (p = 0.002), metastases-free survival 95% vs. 94% (p = 0.302) for groups A and B, respectively. Five-year overall survival was 85% in both groups (p = 0.596). Grade 2/3 late GI complications appeared in 9.2% and 24.8% (p = 0.003), respectively. Grade 2/3 late GU symptoms occurred in 12% in both groups.

Conclusions

Although because of the retrospective character of the study and nonrandomized selection of fractionation schedule the present conclusions had limitations EBRT alone appeared more effective than EBRT combined with HDR-BT. It was likely the result of the less frequent use of androgen deprivation therapy (ADT) for combined scheme group, too low dose in a single BT fraction or inadequate assumptions regarding fractionation sensitivity of prostate cancer.

【 授权许可】

   
2015 Smolska-Ciszewska et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Kupelian PA, Potters L, Khuntia D, Ciezki JP, Reddy CA, Reuther AM et al.. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1–T2 prostate cancer. Int J Radiat Oncol Biol Phys. 2004; 58:25-33.
• [2]Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J et al.. Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int. 2012; 109 Suppl 1:22-9.
• [3]Miralbell R, Roberts SA, Zubizarreta E, Hendry JH. 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:e17-24.
• [4]Dasu A. Is the alpha/beta value for prostate tumours low enough to be safely used in clinical trials? Clin Oncol. 2007; 19:289-301.
• [5]Pollack A, Walker G, Buyyounouski M, Horwitz E, Price R, Feigenberg S et al.. Five year results of a randomized external beam radiotherapy hypofractionation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2011; 81 Suppl 1:S1.
• [6]Kuban DA, Noguaras-Gonzalez GM, Hamblin L, Lee AK, Choi S, Frank SJ et al.. Preliminaary report of a randomized dose escalation trial for prostate cancer using hypofractionation. Int J Radiat Oncol Biol Phys. 2010; 78 Suppl 1:S58-9.
• [7]King CR, Freeman D, Kaplan I, Fuller D, Bolzicco G, Collins S et al.. Stereotactic body radiotherapy for localized prostate cancer: pooled analysis from a multi-institutional consortium of prospective phase II trials. Radiat Oncol. 2013; 109:217-21.
• [8]Prada PJ, Gonzales H, Fernandez J, Jiménez I, Iglesias A, Romo I. Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience. BJU Int. 2011; 7:1-7.
• [9]Hoskin PJ, Colombo A, Henry A, Niehoff P, Paulsen Hellebust T, Siebert FA et al.. GEC/ESTRO recommendations on high dose rate afterloading brachytherapy for localised prostate cancer: an update. Radiother Oncol. 2013; 107:325-32.
• [10]Hoskin PJ, Motohashi K, Bownes P, Bryant L, Ostler P. High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: initial results of a randomised phase three trial. Radiother Oncol. 2007; 84:114-20.
• [11]Hoskin PJ, Rojas AM, Bownes PJ, Lowe GJ, Ostler PJ, Bryant L. Randomised trial of external beam radiotherapy alone Or combined with high-dose-rate brachytherapy boost for localised prostate cancer. Radiother Oncol. 2012; 103:217-22.
• [12]Guix B, Bartina J, Tello J, Henriquez I, Quinzaños L, Lacorte T et al.. Dose escalation with high-dose 3D-conformal radiotherapy (HD-3D-CRT) or low-dose 3D-conformal radiotherapy plus HDR brachytherapy (LD-3D-CRT + HDR-B) for intermediate- or high-risk prostate cancer: higher PSA control with lower toxicity [abstract]. Urology. 2011; 78 Suppl:S23.
• [13]Guix B, Bartina J, Tello J, Solé J, Quinzaños L, Lacorte T et al.. Treatment of intermediate- or high-risk prostate cancer by dose escalation with high-dose 3D-conformal radiotherapy (HD-3D-CRT) or low-dose 3D-conformal radiotherapy plus HDR brachytherapy (LD-3D-CRT + HDR-B) for: early results of a prospective comparative trial [abstract]. Int J Radiat Oncol Biol Phys. 2010; 78 Suppl 1:S78.
• [14]Zwahlen DR, Andrianopoulos N, Matheson B, Duchesne GM, Millar JL. High-dose-rate brachytherapy with conformal external beam radiotherapy in the treatment of prostate cancer. Brachytherapy. 2010; 9:27-35.
• [15]Sathya JR, Davis IR, Julian JA, Guo Q, Daya D, Dayes IS et al.. Randomized trial comparing iridium implant plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. JCO. 2005; 23:1192-9.
• [16]Kestin LL, Martinez AA, Stromberg JS, Edmundson GK, Gustafson GS, Brabbins DS et al.. Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer. J Clin Oncol. 2000; 18:2869-80.
• [17]Pieters BR, de Back DZ, Koning CC, Zwinderman AH. Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic reviev. Radiother Oncol. 2009; 93:168-73.
• [18]Cancer staging AJCC. 7th ed. Springer, New York; 2010.
• [19]D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA et al.. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998; 280:969-74.
• [20]Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Oncology Group (RTOG) and European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995; 31:1341-6.
• [21]Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH et al.. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO phoenix consensus conference. Int J Radiat Oncol Biol Phys. 2006; 65:965-74.
• [22]Fijałkowski M, Białas B, Maciejewski B, Bystrzycka J, Ślusarek K. Three-dimensional (3d) real-time conformal brachytherapy – a novel solution for prosatae cancer treatment. Part II. A feasibility clinical pilot study. Nowotwory, journal of. Oncology. 2005; 55:115-21.
• [23]Kal HB, Van Gellekom MPR. How low is the α/β ratio for prostate cancer? Int J Radiat Oncol Biol Phys. 2003; 57:1116-21.
• [24]Nickers P, Hermesse J, Daneufbourg JM, Vanbelle S, Lartigau E. Which α/β ratio and half-time of repair are useful for predicting outcomes in prostate cancer? Radiather Oncol. 2010; 97:462-6.
• [25]Shaffer R, Pickles T, Lee R, Moiseenko V. Deriving prostate alpha-beta ratio using carefully matched groups, long follow-Up and the phoenix definition of biochemical failure. Int J Radiat Oncol Biol Phys. 2011; 79:1029-36.
• [26]Nahum AE, Movsas B, Horwitz EM, Stobbe CC, Chapman JD. Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: Implications for the a/b ratio. Int J Radiat Oncol Biol Phys. 2003; 57:391-401.
• [27]Roberts SA, Miralbell R, Zubizarreta EH, Fowler JF, Hendry JH. A modelled comparison of prostate cancer control rates after high-dose-rate brachytherapy (3145 multicentre patients) combined with, or in contrast to, external-beam radiotherapy. Radiather Oncol. 2014; 111:114-9.
• [28]Agoston P, Major T, Frohlich G, Szabó Z, Lövey J, Fodor J et al.. Moderate dose escalation with single-fraction high-dose rate brachytherapy boost for clinically localized intermediate- and high-risk prostate cancer: 5-year outcome of the first 100 consecutively treated patients. Brachytherapy. 2011; 10:376-84.
• [29]Boladeras A, Santorsa L, Gutierrez C, Martinez E, Pera J, Pino F et al.. External beam radiotherapy plus single-fraction high dose rate brachytherapy in the treatment of locally advanced prostate cancer. Radiather Oncol. 2014; 112:227-32.
• [30]Dearnaley DP, Sydes MR, Graham JD, Aird EG, Bottomley D, Cowan RA et al.. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet Oncology. 2007; 8:475-87.
• [31]Zietman AL, Bae K, Slater JD, Shipley WU, Efstathiou JA, Coen JJ et al.. 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; 28:1106-11.