Skip to main content

Long-term results of a study using individualized planning target volumes for hypofractionated intensity-modulated radiotherapy boost for prostate cancer

Abstract

Background

This is the final report of a prospective phase I study which evaluated the feasibility, toxicities, and biochemical control in prostate cancer patients treated with a hypofractionated boost utilizing a fiducial marker-based daily image guidance strategy and small patient-specific PTV margins.

Methods

Low- and intermediate-risk prostate cancer patients underwent transperineal ultrasound-guided implantation of three gold fiducial markers and were treated with three-dimensional conformal radiotherapy to 42 Gy (2 Gy/day). During the first nine fractions of treatment, pre- and post-treatment electronic portal imaging was performed to calculate intrafraction prostate motion. Patient-specific PTV margins were derived and a 30 Gy (3 Gy/day) intensity modulated radiotherapy boost was delivered (Total dose = 72 Gy in 31 fractions; EQD2 = 81 Gy, α/β = 1.4).

Results

Thirty-three patients completed treatment and were followed for a median of 7.2 years (range, 1.2 – 9.5). Seven patients (21%) developed Radiation Therapy Oncology Group (RTOG) late grade 2 GI toxicity and 1 patient (3%) developed late grade 2 GU toxicity. No patients developed late grade 3 GI or GU toxicity. To date, nine patients developed PSA relapse according to the Phoenix criteria. The actuarial five, seven and nine year biochemical control (BC) rates were 87% (95% confidence interval: 69–95), 77% (95% confidence interval: 56–89) and 66% (95% confidence interval: 42–82).

Conclusions

Our study demonstrates that the use of prostate fiducial markers in combination with a daily online image guidance protocol permits reduced, patient-specific PTV margins in a hypofractionated treatment scheme. This treatment planning and delivery strategy was well tolerated in the intermediate time frame. The use of very small PTV margins did not result in excessive failures when compared to other radiation regimens of similar radiobiological intensity.

Background

Radiotherapy is a widely accepted treatment option for localized prostate cancer. Technological advances in imaging, treatment planning and delivery techniques have transformed radiotherapy. Randomized trials with dose-escalated radiotherapy (74 – 80 Gy) demonstrate an improvement in biochemical control compared to conventional treatment regimens (64 – 70 Gy) [1-9]. However, dose escalation using 3D-CRT is associated with an increase in late rectal toxicity [10].

Investigators have reported a α/β ratio as low as 1.4 for prostate tumours, which is lower than the surrounding rectum and bladder [11-16]. As such, there has been rising interest in using hypofractionated radiotherapy (higher doses per fraction with fewer fractions) to capitalize on the sensitivity of prostate tumours to high fraction sizes while maintaining similar or lowering rates of late normal tissue toxicity. Furthermore, there is the potential for lower costs and improved patient convenience with a shorter course of treatment [17].

Inter- and intrafraction prostate motion is not negligible [18-20]. The essential elements to safely deliver hypofractionated radiotherapy include the utilization of a daily image-guidance strategy and quantifying the geometric uncertainties associated with the treatment technique to derive the optimal planning target volume (PTV) margins to maximize tumour control while limiting late normal tissue toxicity. For this prospective phase I study, we previously presented the feasibility of a fiducial marker-based daily image guidance strategy to deliver a hypofractionated boost to low and intermediate risk prostate cancer patients. We quantified intrafraction prostate motion, derived patient-specific PTV margins and presented the associated acute toxicities of this treatment technique [21]. In this report, we present the late toxicity and efficacy data.

Methods and materials

Eligibility criteria

From 2002 to 2003, patients with biopsy proven low- and intermediate-risk adenocarcinoma of the prostate were eligible for this study [22]. These included patients with T1-2, Gleason score ≤ 7, and PSA ≤ 20 ng/mL prostate cancer [23]. Patients with evidence of nodal or distant metastases were ineligible. Written consent was obtained from all patients. This project was approved by the Research Ethics Board of the Sunnybrook Health Sciences Centre.

Conventional 3D-CRT planning and treatment delivery

Patients underwent transperineal ultrasound-guided implantation of three gold fiducial markers into the prostate, CT simulation in the supine position with a custom vacuum lock bag for immobilization, and digital fluoroscopic imaging of respiratory-induced prostate motion as previously described [21].

The clinical target volume (CTV) consisted of the prostate and the lowest portion of the seminal vesicles directly posterior to the prostate. There was no attempt to include the seminal vesicles above the most superior slice of the prostate. For the first phase of treatment, a 10-mm PTV margin was added to the CTV in all directions to account intra- and interfraction prostate motion. The rectum was contoured as a single solid organ from the bottom of the ischium to the sigmoid flexure. The bladder was contoured as a single solid organ. A conventional four-field 3D-CRT technique was used to deliver a dose of 42 Gy in 21 fractions (2 Gy/day) to the isocenter without daily image guidance. AP and right lateral digitally reconstructed radiographs were developed to document the location of the fiducial markers relative to the treatment field. During the first nine fractions of treatment, pre- and post-treatment electronic portal imaging was performed to calculate intrafraction prostate motion [21].

Patient-specific PTV margins and intensity modulated radiation (IMRT) boost phase

Using the intrafraction prostate motion data generated from the first phase of treatment, patient-specific PTV margins were generated in the anterior-posterior (AP), superior-inferior (SI) and medial-lateral (ML) directions for the IMRT boost phase [21].

An optimized segmented seven- to nine-field IMRT plan was developed to deliver a dose of 30 Gy in 10 fractions (3 Gy/day) to the patient-specific PTV using inverse planning software (Nomos Corvus). Normal tissue constraints for the IMRT plan were designed to limit the dose to 30% of the rectum and bladder to 60 Gy or less (in equivalent 2-Gy fractions, assuming an α/β value of 2) for the two treatment phases combined. From the two phases combined, the prostate received a total dose of 72 Gy in 31 fractions; an equivalent of 81 Gy in 2 Gy fractions (α/β = 1.4) [13]. These calculations were made using the linear quadratic formula.

Daily image-guidance during the boost phase was achieved by electronic portal imaging in the AP and right lateral direction, and matching the positions of the implanted fiducial markers relative to their initial reference positions on the planning DRR through couch shifts. Only displacements >2 mm were corrected since our own in-house measurements determined the accuracy of the online targeting and correction process to be no less than 2 mm. The IMRT plan incorporated the dose delivered to the prostate and normal tissues from the daily pretreatment imaging.

Toxicity assessment

Time zero was defined as the start of radiotherapy. Late GI and GU toxicity were assessed using the RTOG/EORTC Late Radiation Morbidity Scheme [24] at 6, 12, 18, and 24 months.

Biochemical control

For follow-up, patients had a digital rectal examination and serum PSA performed at 3 and 6 months, and then every 6 months for the first 5 years. Thereafter, follow-up was at the discretion of the attending physician. Biochemical failure was defined using the Phoenix definition (nadir + 2 ng/ml) [25].

Sample size and statistical analysis

At the inception of our study, we estimated the incidence of late grade 2 or greater rectal toxicity between 3% and 14% with our combined 3D-CRT/IMRT treatment technique [26]. Our planned accrual was 30 patients. Time to PSA relapse was defined as the period between the start of radiation treatment and PSA relapse. Patients free from PSA relapse at the end of the study period or by the time they withdrew from the study were censored. The Kaplan-Meier method was used to estimate the PSA relapse-free rate [27]. Statistical analysis was performed in SAS 9.3 (Cary, NC, USA).

Results

At the time of analysis 33 patients had completed treatment and been followed for a median of 7.2 years (range, 1.2 – 9.5). The majority of patients had intermediate-risk disease (79%) and the remainder had low-risk disease (21%) according to the Canadian consensus on prostate cancer risk stratification (ref). Patient characteristics are summarized in Table 1.

Table 1 Patient characteristics (n = 33)

The average PTV margin used during the IMRT hypofractionated boost was 4 mm in the AP direction (range, 2–8 mm), 3 mm in SI direction (range, 2–7 mm), and 3 mm in the RL direction (range, 2–5 mm) [21].

Seven patients (21%) developed late grade 2 GI toxicity and 1 patient (3%) developed late grade 2 GU toxicity. No patients developed late grade 3 GI or GU toxicity after two years of follow-up.

To date, nine patients developed PSA relapse according to the Phoenix criteria. The actuarial five, seven and nine year biochemical control (BC) rates were 87% (95% confidence interval: 69–95), 77% (95% confidence interval: 56–89) and 66% (95% confidence interval: 42–82) (Figure 1).

Figure 1
figure1

Actuarial analysis of biochemical control.

Discussion

We previously showed that the magnitude of intrafraction prostate motion was small (AP 0.72 ± 1.80 mm, SI 0.45 ± 1.27 mm and ML 0.14 ± 0.92 mm), and derived average PTV margins of 4 mm (range 2–8 mm) AP, 3 mm (range 2–7 mm) SI and 3 mm (range 2-5 mm) ML [21]. Since our initial report, additional analyses of prostate fiducial markers with electronic portal images corroborate our findings [28-30]. Kotte et al. [28] showed that margins of at least 2 mm account for intrafraction prostate motion, and Middleton et al. [29] derived PTV margins (AP 3.9 mm, SI 3.2 mm and ML 4.3 mm) that were comparable to ours.

The goal of utilizing a daily-image guidance strategy and reducing the PTV margin is to realize a clinically meaningful difference in treatment toxicity. In the randomized trials of dose escalation the PTV margins used across the studies were heterogeneous, ranging from 5-15 mm. While these studies demonstrated a benefit in biochemical control, there was an increase in late grade 2 or greater GI toxicity (odds ratio of 1.58; 99% CI 1.24–2; p < 0.0001) [31]. In Tables 2 and 3, the PTV margins utilized and the reported late toxicities in the randomized trials of dose escalation [1-9], and contemporary mild hypofractionation [32-36], are summarized alongside the results of the current study for illustrative purposes. Our study was limited by a small sample size and only two years of toxicity follow-up. The variability in the reported toxicities across studies is likely due to differences in the PTV margins, treatment techniques, and dose and fractionation schedules.

Table 2 Summary of randomized trials of dose-escalated external beam radiotherapy
Table 3 Summary of randomized trials of mild hypofractionated radiotherapy

Since Brenner and Hall first reported that prostate cancer may have a low α/β ratio [14], there has been growing interest to use hypofractionated treatment regimens to capitalize on the therapeutic ratio that may exist between the sensitivity of prostate cancer to higher doses of radiation per treatment fraction and reduced normal tissue toxicity. The promise of hypofractionation lies in the potential for improved tumour control and increased patient convenience with a shorter overall treatment time and lower costs compared to a standard course of dose-escalated treatment. To date, data from four contemporary randomized trials comparing hypofractionated to dose-escalated radiotherapy do not demonstrate increased biochemical control with higher biologic equivalent doses to the prostate and equivalent late toxicities [34,36]; or the same biochemical control and less late toxicity with isoeffective doses delivered to the prostate as hypothesized [32,33,37-39] (Table 3).

Based on a α/β ratio of 1.4 [13], we delivered an equivalent dose of 81 Gy in 2 Gy fractions. Our pilot study was small, however, it was reassuring to observe that our BC rate was similar to the MD Anderson (8-year Phoenix 78%) [1]; and higher than the UK (5-year ASTRO 71%) [7,8], French (5-year Phoenix 76%) [9] and Dutch (7-year Phoenix 56%) [3,4] dose-escalation trials. In comparison to the hypofractionated treatment arms of the mild hypofractionation trials (Table 3), our BC rate was also similar to the rates reported by Pollack et al. [36] (5-year Phoenix 86%) and Arcangeli et al. [32,37,38] (5-year Phoenix 85%), and lower than the rate reported by Kuban et al. [34] (5-year Phoenix 96%). While these comparisons look favourable, we recognize the wide confidence intervals in our BC rate due to the small sample size. Furthermore, we have not reached a plateau in our biochemical control curve like those seen with brachytherapy where higher biological doses are given [40,41]. This suggests that further biological dose-escalation is warranted. Our group and others have explored more extreme hypofractionation protocols [42-46]. Recent reports of 135 low- and intermediate-risk patients treated with stereotactic body radiotherapy (SBRT; median follow-up 60 months) showed a 5-year bDFS of 99% for low-risk patients and 93% for intermediate-risk patients. Grade 3 or higher toxicities are reported in approximately 1% of patients with 35–40 Gy delivered with 5-fraction SBRT [43,47]. Thus, the benefits of hypofractionation are being realized with doses of 7–8 Gy per fraction.

Conclusions

Our study demonstrates that the use of prostate fiducial markers in combination with a daily online image guidance protocol permits reduced, patient-specific PTV margins in a hypofractionated treatment scheme. This treatment planning and delivery strategy was well tolerated in the intermediate time frame. The use of very small PTV margins did not result in excessive failures when compared to other radiation regimens of similar radiobiological intensity. We have applied this strategy to our studies of extreme hypofractionation.

Abbreviations

3D-CRT:

Three-dimensional conformal radiotherapy

RTOG:

Radiation Therapy Oncology Group

PTV:

Planning target volume

CTV:

Clinical target volume

IMRT:

Intensity modulated radiotherapy

AP:

Anterior-posterior

SI:

Superior-inferior

ML:

Medial-lateral

References

  1. 1.

    Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70(1):67–74.

    Article  PubMed  Google Scholar 

  2. 2.

    Peeters ST, Heemsbergen WD, van Putten WL, Slot A, Tabak H, Mens JW, et al. Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy to 78 Gy. Int J Radiat Oncol Biol Phys. 2005;61(4):1019–34.

    Article  PubMed  Google Scholar 

  3. 3.

    Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF, 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(13):1990–6.

    Article  PubMed  Google Scholar 

  4. 4.

    Al-Mamgani A, van Putten WL, Heemsbergen WD, van Leenders GJ, Slot A, Dielwart MF, et al. Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;72(4):980–8.

    Article  PubMed  Google Scholar 

  5. 5.

    Zietman AL, DeSilvio ML, Slater JD, Rossi Jr CJ, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294(10):1233–9.

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    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(7):1106–11.

    Article  PubMed Central  PubMed  Google Scholar 

  7. 7.

    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 Oncol. 2007;8(6):475–87.

    Article  PubMed  Google Scholar 

  8. 8.

    Syndikus I, Morgan RC, Sydes MR, Graham JD, Dearnaley DP. Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397). Int J Radiat Oncol Biol Phys. 2010;77(3):773–83.

    Article  PubMed Central  PubMed  Google Scholar 

  9. 9.

    Beckendorf V, Guerif S, Le Prise E, Cosset JM, Bougnoux A, Chauvet B, et al. 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Int J Radiat Oncol Biol Phys. 2011;80(4):1056–63.

    Article  PubMed  Google Scholar 

  10. 10.

    Viani GA, Stefano EJ, Afonso SL. Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials. Int J Radiat Oncol Biol Phys. 2009;74(5):1405–18.

    Article  PubMed  Google Scholar 

  11. 11.

    Brenner DJ, Martinez AA, Edmundson GK, Mitchell C, Thames HD, Armour EP. Direct evidence that prostate tumors show high sensitivity to fractionation (low alpha/beta ratio), similar to late-responding normal tissue. Int J Radiat Oncol Biol Phys. 2002;52(1):6–13.

    Article  PubMed  Google Scholar 

  12. 12.

    Fowler J, Chappell R, Ritter M. Is alpha/beta for prostate tumors really low? Int J Radiat Oncol Biol Phys. 2001;50(4):1021–31.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    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: alpha/beta = 1.4 (0.9-2.2) Gy. Int J Radiat Oncol Biol Phys. 2012;82(1):e17–24.

    Article  PubMed  Google Scholar 

  14. 14.

    Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys. 1999;43(5):1095–101.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Daşu A. Is the alpha/beta value for prostate tumours low enough to be safely used in clinical trials? Clin Oncol (R Coll Radiol). 2007;19(5):289–301.

    Article  Google Scholar 

  16. 16.

    Thames HD, Bentzen SM, Turesson I, Overgaard M, Van den Bogaert W. Time-dose factors in radiotherapy: a review of the human data. Radiol Oncol. 1990;19(3):219–35.

    Article  CAS  Google Scholar 

  17. 17.

    Sethukavalan P, Cheung P, Tang CI, Quon H, Morton G, Nam R, et al. Patient costs associated with external beam radiotherapy treatment for localized prostate cancer: the benefits of hypofractionated over conventionally fractionated radiotherapy. Can J Urol. 2012;19(2):6165–9.

    PubMed  Google Scholar 

  18. 18.

    Aubry JF, Beaulieu L, Girouard LM, Aubin S, Tremblay D, Laverdière J, et al. Measurements of intrafraction motion and interfraction and intrafraction rotation of prostate by three-dimensional analysis of daily portal imaging with radiopaque markers. Int J Radiat Oncol Biol Phys. 2004;60(1):30–9.

    Article  PubMed  Google Scholar 

  19. 19.

    Ghilezan MJ, Jaffray DA, Siewerdsen JH, Van Herk M, Shetty A, Sharpe MB, et al. Prostate gland motion assessed with cine-magnetic resonance imaging (cine-MRI). Int J Radiat Oncol Biol Phys. 2005;62(2):406–17.

    Article  PubMed  Google Scholar 

  20. 20.

    Kupelian P, Willoughby T, Mahadevan A, Djemil T, Weinstein G, Jani S, et al. Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy. Int J Radiat Oncol Biol Phys. 2007;67(4):1088–98.

    Article  PubMed  Google Scholar 

  21. 21.

    Cheung P, Sixel K, Morton G, Loblaw DA, Tirona R, Pang G, et al. Individualized planning target volumes for intrafraction motion during hypofractionated intensity-modulated radiotherapy boost for prostate cancer. Int J Radiat Oncol Biol Phys. 2005;62(2):418–25.

    Article  PubMed  Google Scholar 

  22. 22.

    Lukka H, Warde P, Pickles T, Morton G, Brundage M, Souhami L. Controversies in prostate cancer radiotherapy: consensus development. Can J Urol. 2001;8(4):1314–22.

    CAS  PubMed  Google Scholar 

  23. 23.

    Sobin LH, Fleming ID. TNM Classification of Malignant Tumors, fifth edition (1997). Union Internationale Contre le Cancer and the American Joint Committee on Cancer. Cancer. 1997;80(9):1803–4.

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Roach 3rd M, Hanks G, Thames Jr 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(4):965–74.

    Article  PubMed  Google Scholar 

  26. 26.

    Zelefsky MJ, Fuks Z, Hunt M, Lee HJ, Lombardi D, Ling CC, et al. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol. 2001;166(3):876–81.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Kaplan E, Meier P. Nonparametric estimation from incompete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  28. 28.

    Kotte AN, Hofman P, Lagendijk JJ, van Vulpen M, van der Heide UA. Intrafraction motion of the prostate during external-beam radiation therapy: analysis of 427 patients with implanted fiducial markers. Int J Radiat Oncol Biol Phys. 2007;69(2):419–25.

    Article  PubMed  Google Scholar 

  29. 29.

    Middleton M, See A, Rolfo A, Medwell S, Joon ML, Joon DL, et al. Intraprostatic fiducials for image guidance: Workflow implications in a single linac department. Radiography. 2008;14(4):312–7.

    Article  Google Scholar 

  30. 30.

    Oehler C, Lang S, Dimmerling P, Bolesch C, Kloeck S, Tini A, et al. PTV margin definition in hypofractionated IGRT of localized prostate cancer using cone beam CT and orthogonal image pairs with fiducial markers. Radiat Oncol. 2014;9(1):229.

    Article  PubMed Central  PubMed  Google Scholar 

  31. 31.

    Viani GA, da Silva LG, Stefano EJ. High-dose conformal radiotherapy reduces prostate cancer-specific mortality: results of a meta-analysis. Int J Radiat Oncol Biol Phys. 2012;83(5):e619–25.

    Article  PubMed  Google Scholar 

  32. 32.

    Arcangeli G, Fowler J, Gomellini S, Arcangeli S, Saracino B, Petrongari MG, 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(4):1013–21.

    Article  PubMed  Google Scholar 

  33. 33.

    Dearnaley D, Syndikus I, Sumo G, Bidmead M, Bloomfield D, Clark C, 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(1):43–54.

    Article  PubMed  Google Scholar 

  34. 34.

    Kuban DA, Nogueras-Gonzalez GM, Hamblin L, Lee AK, Choi S, Frank SJ, et al. Preliminary report of a randomized dose escalation trial for prostate cancer using hypofractionation. Int J Radiat Oncol Biol Phys. 2010;78(3):S58–9.

    Article  Google Scholar 

  35. 35.

    Pollack A, Hanlon AL, Horwitz EM, Feigenberg SJ, Konski AA, Movsas B, et al. Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial. Int J Radiat Oncol Biol Phys. 2006;64(2):518–26.

    Article  PubMed Central  PubMed  Google Scholar 

  36. 36.

    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(2):S1.

    Article  Google Scholar 

  37. 37.

    Arcangeli S, Strigari L, Gomellini S, Saracino B, Petrongari MG, Pinnaro P, et al. Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1172–8.

    Article  PubMed  Google Scholar 

  38. 38.

    Arcangeli G, Saracino B, Gomellini S, Petrongari MG, Arcangeli S, Sentinelli S, et al. A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2010;78(1):11–8.

    Article  PubMed  Google Scholar 

  39. 39.

    Hegemann NS, Guckenberger M, Belka C, Ganswindt U, Manapov F, Li M. Hypofractionated radiotherapy for prostate cancer. Radiat Oncol. 2014;9(1):275.

    Article  PubMed Central  PubMed  Google Scholar 

  40. 40.

    Taira AV, Merrick GS, Galbreath RW, Butler WM, Lief J, Adamovich E, et al. Distant metastases following permanent interstitial brachytherapy for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):e225–32.

    Article  PubMed  Google Scholar 

  41. 41.

    Ghadjar P, Oesch SL, Rentsch CA, Isaak B, Cihoric N, Manser P, et al. Late toxicity and five year outcomes after high-dose-rate brachytherapy as a monotherapy for localized prostate cancer. Radiat Oncol. 2014;9:122.

    Article  PubMed Central  PubMed  Google Scholar 

  42. 42.

    King CR, Brooks JD, Gill H, Presti Jr JC. Long-term outcomes from a prospective trial of stereotactic body radiotherapy for low-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2012;82(2):877–82.

    Article  PubMed  Google Scholar 

  43. 43.

    Loblaw A, Cheung P, D'Alimonte L, Deabreu A, Mamedov A, Zhang L, et al. Prostate stereotactic ablative body radiotherapy using a standard linear accelerator: Toxicity, biochemical, and pathological outcomes. Radiother Oncol. 2013;107(2):153–8.

    Article  PubMed  Google Scholar 

  44. 44.

    Madsen BL, Hsi RA, Pham HT, Fowler JF, Esagui L, Corman J. 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(4):1099–105.

    Article  PubMed  Google Scholar 

  45. 45.

    Ritter M, Forman J, Kupelian P, Lawton C, Petereit D. Hypofractionation for prostate cancer. Cancer J. 2009;15(1):1–6.

    Article  PubMed Central  PubMed  Google Scholar 

  46. 46.

    Tang CI, Loblaw DA, Cheung P, Holden L, Morton G, Basran PS, et al. Phase I/II study of a five-fraction hypofractionated accelerated radiotherapy treatment for low-risk localised prostate cancer: early results of pHART3. Clin Oncol (R Coll Radiol). 2008;20(10):729–37.

    Article  CAS  Google Scholar 

  47. 47.

    Meier R, Cotrutz C, Loiselle C, Sima S, Vermeulen S. Long-term outcomes of stereotactic body radiation therapy for organ-confined prostate cancer. Int J Radiat Oncol Biol Phys. 2012;84(3):S417.

    Article  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge Andrea Deabreu for her hard work and dedication in the collection and maintenance of patient data, and Alex Mamedov for the creation and maintenance of the study database.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Patrick Cheung.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

WC analyzed and interpreted the data, and drafted and critically reviewed the manuscript. AL conceived the study, acquired, analyzed and interpreted the data, and critically reviewed the manuscript. KC completed the statistical analysis and critically reviewed the manuscript. GM acquired the data and critically reviewed the manuscript. RC acquired the data and critically reviewed the manuscript. ES acquired the data and critically reviewed the manuscript. CD acquired the data and critically reviewed the manuscript. J-P P acquired the data and critically reviewed the manuscript. PC conceived the study, acquired, analyzed and interpreted the data, and critically reviewed the manuscript. All authors read and approved the final manuscript.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chu, W., Loblaw, D.A., Chan, K. et al. Long-term results of a study using individualized planning target volumes for hypofractionated intensity-modulated radiotherapy boost for prostate cancer. Radiat Oncol 10, 95 (2015). https://doi.org/10.1186/s13014-015-0400-1

Download citation

Keywords

  • Biochemical outcomes
  • Hypofractionation
  • Image-guided radiotherapy
  • Intensity modulated radiotherapy
  • Prostate cancer
  • Toxicity