Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study.

PURPOSE To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. METHODS AND MATERIALS After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. RESULTS All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. CONCLUSIONS Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

[1]  Daniel W. Miller,et al.  Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. , 2005, JAMA.

[2]  C. Ling,et al.  Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. , 1999, International journal of radiation oncology, biology, physics.

[3]  J H Hendry,et al.  Hypofractionation for prostate cancer. , 2001, International journal of radiation oncology, biology, physics.

[4]  George Starkschall,et al.  Prostate cancer radiation dose response: results of the M.D. Anderson phase III randomized trial , 2003 .

[5]  D. Brenner,et al.  Direct evidence that prostate tumors show high sensitivity to fractionation (low α/β ratio), similar to late-responding normal tissue , 2002 .

[6]  H. Sandler,et al.  3D conformal radiation therapy (3DCRT) for high grade prostate cancer: a multi-institutional review. , 2000, International journal of radiation oncology, biology, physics.

[7]  Rick Chappell,et al.  Is α/β for prostate tumors really low? , 2001 .

[8]  Peter Bownes,et al.  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. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[9]  K. Johansson,et al.  Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer. , 2005, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  L. Schour,et al.  High-dose-rate intensity-modulated brachytherapy with external beam radiotherapy for prostate cancer: California endocurietherapy's 10-year results. , 2005, International journal of radiation oncology, biology, physics.

[11]  N. Sadato,et al.  11C-acetate PET imaging of prostate cancer. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[12]  D. Baltas,et al.  3D conformal HDR brachytherapy and external beam irradiation combined with temporary androgen deprivation in the treatment of localized prostate cancer. , 2004, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[13]  K. Tai,et al.  Patterns of toxicity following high-dose-rate brachytherapy boost for prostate cancer: mature prospective phase I/II study results. , 2007, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[15]  T. Hara,et al.  PET imaging of prostate cancer using carbon-11-choline. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[16]  C. Ménard,et al.  Androgen withdrawal in patients reduces prostate cancer hypoxia: implications for disease progression and radiation response. , 2007, Cancer research.

[17]  Yoshiya Yamada,et al.  Long-term results of conformal radiotherapy for prostate cancer: impact of dose escalation on biochemical tumor control and distant metastases-free survival outcomes. , 2008, International journal of radiation oncology, biology, physics.

[18]  J. Pouliot,et al.  Inverse planning for HDR prostate brachytherapy used to boost dominant intraprostatic lesions defined by magnetic resonance spectroscopy imaging. , 2004, International journal of radiation oncology, biology, physics.

[19]  P. Walsh,et al.  Prostate cancer tumor volume: measurement with endorectal MR and MR spectroscopic imaging. , 2002, The Journal of urology.

[20]  Patrick A Kupelian,et al.  Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Cleveland Clinic experience. , 2007, International journal of radiation oncology, biology, physics.

[21]  Qing Guo,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. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  D. Johnston,et al.  Detailed mapping of prostate carcinoma foci , 2000, Cancer.

[23]  P. Rzehak,et al.  Long-term outcome after elective irradiation of the pelvic lymphatics and local dose escalation using high-dose-rate brachytherapy for locally advanced prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[24]  P. Carroll,et al.  Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer. , 1994, International journal of radiation oncology, biology, physics.

[25]  R. Coleman,et al.  Comparison of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for positron emission tomography of androgen dependent and androgen independent prostate cancer. , 2002, The Journal of urology.

[26]  Lei Dong,et al.  Dose-response for biochemical control among high-risk prostate cancer patients after external beam radiotherapy. , 2003, International journal of radiation oncology, biology, physics.

[27]  G E Hanks,et al.  The effect of dose on local control of prostate cancer. , 1988, International journal of radiation oncology, biology, physics.

[28]  P. Lipponen,et al.  Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. , 1994, European journal of cancer.

[29]  F. Vicini,et al.  Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better? , 2001, International journal of radiation oncology, biology, physics.

[30]  T. Pajak,et al.  Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) , 1995, International journal of radiation oncology, biology, physics.

[31]  C. Parker,et al.  Salvage radiotherapy for PSA failure after radical prostatectomy. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[32]  Paul Schellhammer,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. , 2006, International journal of radiation oncology, biology, physics.

[33]  A. Nahum,et al.  Incorporating clinical measurements of hypoxia into tumor local control modeling of prostate cancer: Implications for the α/β ratio , 2003 .

[34]  R. Fraser,et al.  Evidence for efficacy without increased toxicity of hypofractionated radiotherapy for prostate carcinoma: early results of a Phase III randomized trial. , 2003, International journal of radiation oncology, biology, physics.

[35]  David J Brenner,et al.  Hypofractionation for prostate cancer radiotherapy--what are the issues? , 2003, International journal of radiation oncology, biology, physics.

[36]  A. D'Amico,et al.  A clinical method for real-time dosimetric guidance of transperineal 125I prostate implants using interventional magnetic resonance imaging. , 2000, International journal of radiation oncology, biology, physics.