Abstract
Purpose
To evaluate long-term outcome after dose-escalated, moderately hypofractionated radiotherapy for prostate cancer.
Methods
Since 2005, 150 consecutive patients were treated with primary radiotherapy for localized prostate cancer. Intensity modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) technique was practiced in all patients and doses of 73.9 Gy (n = 41) and 76.2 Gy (n = 109) were delivered in 32 and 33 fractions, respectively. The pelvic lymph nodes were treated in 41 high-risk patients. Treatment was delivered using cone-beam CT based image-guided radiotherapy (IGRT). Toxicity was assessed prospectively using CTCAE 3.0; biochemical failure was defined according to the Phoenix definition of nadir + 2 ng/ml.
Results
Median follow-up of living patients was 50 months. Gastrointestinal (GI) toxicity was mild with > 80 % of the patients free from any GI toxicity during follow-up and no time trend to increased rates or to higher grade of GI toxicity. Two patients suffered from late grade 3 GI toxicity. Acute genitourinary (GU) toxicity grade 1–2 was observed in 85 % of the patients; most patients recovered quickly within 6 weeks after treatment. The rate of GU toxicity grade ≥ 2 was < 10 % at 6–12 month but increased continuously to 22.4 % at 60 months; grade 3 GU toxicity remained below 5 % during follow-up. The 5-year freedom from biochemical failure (FFBF) was 82 % for all patients and 88, 80, and 78 % for low-, intermediate-, and high-risk disease.
Conclusion
Favorable FFBF with simultaneously low rates of toxicity was observed after moderately hypofractionated radiotherapy with 2 Gy-equivalent doses ≥ 80 Gy. Conformal IMRT planning and accurate IGRT treatment delivery may have contributed to these results.
Zusammenfassung
Ziel
Untersucht wurden die Langzeitergebnisse nach dosisintensivierter Strahlentherapie in moderater Hypofraktionierung beim lokal begrenzten Prostatakarzinom.
Methodik
Untersucht wurden 150 konsekutive Patienten, die seit 2005 unter Verwendung von IMRT-Bestrahlungsplanung und simultan integrierter Boost-(SIB-)Technik mit 73,9 Gy (n = 41) bzw. 76,2 Gy (n = 109) in 32 bzw. 33 Fraktionen behandelt wurden. Das pelvine Lymphabflussgebiet wurde bei 41 Hochrisikopatienten behandelt. Die Bestrahlungsapplikation erfolgte nach Cone-beam-CT-geführter Strahlentherapie (IGRT). Die Toxizität wurde prospektiv mittels CTCAE 3.0 erfasst. Ein biochemisches Rezidiv wurde gemäß Phoenix-Definition als Nadir + 2 ng/ml definiert.
Ergebnisse
Die mediane Nachbeobachtungszeit lebender Patienten betrug 50 Monate. Die gastrointestinale (GI-)Toxizität war gering: > 80 % der Patienten waren während der gesamten Nachsorgezeit frei von jeglicher GI-Toxizität. Lediglich 2 Patienten erlitten eine späte GI-Toxizität vom Grad 3. Akute urogenitale (GU-)Toxizität vom Grad 1–2 trat bei 85 % der Patienten während der Behandlungsserie auf, bildete sich aber innerhalb von 6 Wochen zurück. Nach 6–12 Monaten litten < 10 % der Patienten an einer GU-Toxizität vom Grad ≥ 2; dieser Anteil stieg kontinuierlich auf 22,4 % nach 60 Monaten. Die Rate an GU-Toxizität vom Grad 3 war nie > 5 %. Die biochemische Kontrolle betrug 82 % nach 5 Jahren und jeweils 88, 80 und 78 % für Patienten mit niedrigem, intermediärem und hohem Risiko.
Schlussfolgerung
Nach Behandlung mit 2 Gy äquivalenten Bestrahlungsdosen ≥ 80 Gy wurde eine vielversprechende biochemische Kontrolle bei niedriger Toxizität beobachtet. Konsequente Anwendung von konformaler IMRT-Bestrahlungsplanung und IGRT zur Bestrahlungsapplikation könnte zu diesen vielversprechenden Ergebnissen beigetragen haben.
Similar content being viewed by others
References
Alongi F, Fogliata A, Navarria P et al (2012) Moderate hypofractionation and simultaneous integrated boost with volumetric modulated arc therapy (RapidArc) for prostate cancer. Report of feasibility and acute toxicity. Strahlenther Onkol 188:990–996
D’Amico AV, Whittington R, Malkowicz SB et al (1998) Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. Jama 280:969–974
Guckenberger M, Ok S, Polat B et al (2010) Toxicity after intensity-modulated, image-guided radiotherapy for prostate cancer. Strahlenther Onkol 186:535–543
Shih HA, Harisinghani M, Zietman AL et al (2005) Mapping of nodal disease in locally advanced prostate cancer: rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy. Int J Radiat Oncol Biol Phys 63:1262–1269
Roach M 3rd, Marquez C, Yuo HS et al (1994) Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 28:33–37
Guckenberger M, Baier K, Richter A et al (2008) Does Intensity Modulated Radiation Therapy (IMRT) prevent additional toxicity of treating the pelvic lymph nodes compared to treatment of the prostate only? Radiat Oncol 3:3
Guckenberger M, Meyer J, Wilbert J et al (2007) Precision of image-guided radiotherapy (IGRT) in six degrees of freedom and limitations in clinical practice. Strahlenther Onkol 183:307–313
Polat B, Guenther I, Wilbert J et al (2008) Intra-fractional uncertainties in image-guided intensity-modulated radiotherapy (IMRT) of prostate cancer. Strahlenther Onkol 184:668–673
Boer HC de, Os MJ van, Jansen PP, Heijmen BJ (2005) Application of the No Action Level (NAL) protocol to correct for prostate motion based on electronic portal imaging of implanted markers. Int J Radiat Oncol Biol Phys 61:969–983
Al-Mamgani A, Heemsbergen WD, Levendag PC, Lebesque JV (2010) Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial. Radiother Oncol 96:13–18
Dearnaley DP, Sydes MR, Graham JD et al (2007) Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. The lancet oncology 8:475–487
Roach M 3rd, DeSilvio M, Lawton C et al (2003) Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol 21:1904–1911
Pommier P, Chabaud S, Lagrange JL et al (2007) Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Preliminary results of GETUG-01. J Clin Oncol 25:5366–5373
Ganswindt U, Schilling D, Muller AC et al (2011) Distribution of prostate sentinel nodes: a SPECT-derived anatomic atlas. Int J Radiat Oncol Biol Phys 79:1364–1372
Miralbell R, Roberts SA, Zubizarreta E, Hendry JH (2012) Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: alpha/beta = 1.4 (0.9–2.2) Gy. Int J Radiat Oncol Biol Phys 82:e17–e24
Kupelian PA, Willoughby TR, Reddy CA et al (2007) Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Cleveland Clinic Experience. Int J Radiat Oncol Biol Phys 68:1424–1430
Arcangeli S, Strigari L, Gomellini S et al (2012) Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys 84:1172–1178
Thomson D, Merrick S, Swindell R et al (2012) Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and late toxicity. Prostate Cancer 2012:450246
Zelefsky MJ, Kollmeier M, Cox B et al (2012) 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 84(1):125–129
Boda-Heggemann J, Lohr F, Wenz F (2011) kV cone-beam CT-based IGRT: a clinical review. Strahlenther Onkol 187:284–291
Al-Mamgani A, Heemsbergen WD, Peeters ST, Lebesque JV (2009) Role of intensity-modulated radiotherapy in reducing toxicity in dose escalation for localized prostate cancer. Int J Radiat Oncol Biol Phys 73:685–691
Sheets NC, Goldin GH, Meyer AM et al (2012) Intensity-modulated radiation therapy, proton therapy, or conformal radiation therapy and morbidity and disease control in localized prostate cancer. Jama 307:1611–1620
Engels B, Soete G, Verellen D, Storme G (2009) Conformal arc radiotherapy for prostate cancer: increased biochemical failure in patients with distended rectum on the planning computed tomogram despite image guidance by implanted markers. Int J Radiat Oncol Biol Phys 74:388–391
Compliance with ethical guidelines
Conflict of interest. M. Guckenberger, I. Lawrenz, and M. Flentjehere state that there are no conflicts of interest.
All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current, revised form). Informed consent was obtained from all patients included in studies.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Guckenberger, M., Lawrenz, I. & Flentje, M. Moderately hypofractionated radiotherapy for localized prostate cancer. Strahlenther Onkol 190, 48–53 (2014). https://doi.org/10.1007/s00066-013-0443-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-013-0443-x