Acute toxicity of hypofractionated intensity-modulated radiotherapy for prostate cancer.

BACKGROUND Dose-escalated hypofractionated radiotherapy (hfrt) using intensity-modulated radiotherapy (imrt), with inclusion of the pelvic lymph nodes (plns), plus androgen suppression therapy (ast) in high-risk prostate cancer patients should improve patient outcomes, but acute toxicity could limit its feasibility. METHODS Our single-centre phase ii prospective study enrolled 40 high-risk prostate cancer patients. All patients received hfrt using imrt with daily mega-voltage computed tomography imaging guidance, with 95% of planning target volumes (ptv68 and ptv50) receiving 68 Gy and 50 Gy (respectively) in 25 daily fractions. The boost volume was targeted to the involved plns and the prostate (minus the urethra plus 3 mm and minus 3 mm from adjacent rectal wall) and totalled up to 75 Gy in 25 fractions. Acute toxicity scores were recorded weekly during and 3 months after radiotherapy (rt) administration. RESULTS For the 37 patients who completed rt and the 3-month follow-up, median age was 65.5 years (range: 50-76 years). Disease was organ-confined (T1c-T2c) in 23 patients (62.1%), and node-positive in 5 patients (13.5%). All patients received long-term ast. Maximum acute genitourinary (gu) and gastrointestinal (gi) toxicity peaked at grade 2 in 6 of 36 evaluated patients (16.6%) and in 4 of 31 evaluated patients (12.9%) respectively. Diarrhea and urinary frequency were the chief complaints. Dose-volume parameters demonstrated no correlation with toxicity. The ptv treatment objectives were met in 36 of the 37 patients. CONCLUSIONS This hfrt dose-escalation trial in high-risk prostate cancer has demonstrated the feasibility of administering 75 Gy in 25 fractions with minimal acute gi and gu toxicities. Further follow-up will report late toxicities and outcomes.

[1]  C. Ma,et al.  Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial. , 2006, International journal of radiation oncology, biology, physics.

[2]  H. Lukka Prostate cancer: risk categories and role of hormones and radiotherapy. , 2002, The Canadian journal of urology.

[3]  J. Fowler,et al.  Acute and late toxicity in a randomized trial of conventional versus hypofractionated three-dimensional conformal radiotherapy for prostate cancer. , 2011, International journal of radiation oncology, biology, physics.

[4]  Lidia Strigari,et al.  A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer. , 2010, International journal of radiation oncology, biology, physics.

[5]  R. Orecchia,et al.  Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation. , 2011, Urologic oncology.

[6]  R. Stoyanova,et al.  Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer , 2011 .

[7]  Rakesh R. Patel,et al.  Phase I trial of pelvic nodal dose escalation with hypofractionated IMRT for high-risk prostate cancer. , 2012, International journal of radiation oncology, biology, physics.

[8]  David J Brenner,et al.  What hypofractionated protocols should be tested for prostate cancer? , 2002, International journal of radiation oncology, biology, physics.

[9]  Patrick A Kupelian,et al.  Hypofractionated intensity-modulated radiotherapy (70 gy at 2.5 Gy per fraction) for localized prostate cancer: long-term outcomes. , 2005, International journal of radiation oncology, biology, physics.

[10]  R. Holloway,et al.  Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. , 2006, International journal of radiation oncology, biology, physics.

[11]  W. Ghidey,et al.  OC-0052: Late toxicity in the randomized phase III Dutch Hypofractionation Trial for prostate cancer patients (HYPRO) , 2013 .

[12]  Annie Gao,et al.  Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: preliminary safety results from the CHHiP randomised controlled trial. , 2012, The Lancet. Oncology.

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

[14]  L. Zhao,et al.  Proton therapy vs. VMAT for prostate cancer: a treatment planning study , 2014 .

[15]  Michael Lock,et al.  Comparing two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the hypofractionated treatment of high-risk prostate cancer , 2008, Radiation oncology.

[16]  L. Pérez-Romasanta,et al.  Prognostic factors for acute toxicity in prostate cancer patients treated with high-dose hypofractionated radiotherapy , 2013, Clinical and Translational Oncology.

[17]  C. Ménard,et al.  Phase II trial of hypofractionated image-guided intensity-modulated radiotherapy for localized prostate adenocarcinoma. , 2007, International journal of radiation oncology, biology, physics.

[18]  M. Mackenzie,et al.  Acute toxicity in high-risk prostate cancer patients treated with androgen suppression and hypofractionated intensity-modulated radiotherapy. , 2010, International journal of radiation oncology, biology, physics.

[19]  V. De Sanctis,et al.  Hypofractionated radiotherapy with or without IGRT in prostate cancer: preliminary report of acute toxicity. , 2011, Anticancer research.

[20]  M. V. van Herk,et al.  Physical aspects of a real-time tumor-tracking system for gated radiotherapy. , 2000, International journal of radiation oncology, biology, physics.

[21]  A. Kiss,et al.  Hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer: late toxicity. , 2012, International journal of radiation oncology, biology, physics.

[22]  Sunita Ghosh,et al.  Phase 2 Study: Feasibility and Acute Toxicity of Dose-Escalated Hypofractionated Intensity Modulated Radiation Therapy With Concurrent Treatment of Pelvic Lymph Nodes in High-Risk Prostate Cancer Patients , 2013 .

[23]  Shinichi Shimizu,et al.  Reduction in Acute Morbidity Using Hypofractionated Intensity‐Modulated Radiation Therapy Assisted with a Fluoroscopic Real‐Time Tumor‐Tracking System for Prostate Cancer: Preliminary Results of a Phase I/II Study , 2003, Cancer journal.

[24]  Lidia Strigari,et al.  Updated results and patterns of failure in a randomized hypofractionation trial for high-risk prostate cancer. , 2012, International journal of radiation oncology, biology, physics.

[25]  E. Wong,et al.  A Phase II trial of arc-based hypofractionated intensity-modulated radiotherapy in localized prostate cancer. , 2011, International journal of radiation oncology, biology, physics.

[26]  W. J. Morris,et al.  Randomized trial comparing two fractionation schedules for patients with localized prostate cancer. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  B. Kavanagh,et al.  Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer. , 2009, International journal of radiation oncology, biology, physics.

[28]  J. Fowler,et al.  Hypofractionated versus conventionally fractionated radiotherapy for prostate carcinoma: final results of phase III randomized trial. , 2011, International journal of radiation oncology, biology, physics.

[29]  J. Fowler,et al.  Acute toxicity after hypofractionated conformal radiotherapy for localized prostate cancer: nonrandomized contemporary comparison with standard fractionation. , 2008, International journal of radiation oncology, biology, physics.

[30]  K. Haustermans,et al.  Hypofractionated intensity modulated irradiation for localized prostate cancer, results from a phase I/II feasibility study , 2007, Radiation oncology.

[31]  Joos V Lebesque,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. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  Guy Storme,et al.  Phase II study of a four-week hypofractionated external beam radiotherapy regimen for prostate cancer: report on acute toxicity. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[33]  W. Ghidey,et al.  OC-0218 ACUTE TOXICITY OF THE RANDOMIZED PHASE III DUTCH HYPOFRACTIONATION TRIAL (HYPRO) FOR PROSTATE CANCER , 2012 .