Radiation Oncology/Prostate/Hypofractionation

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Prostate: Main Page | Prostate Overview | Screening and Prevention | Workup | Natural History | External Beam RT | IMRT | Androgen Suppression Therapy | Brachytherapy | Protons | Prostatectomy | Adjuvant RT after Prostatectomy | Salvage RT | Chemotherapy | Localized prostate cancer | Node Positive | Advanced disease | Recurrence after RT | Cryotherapy | RTOG Prostate Trials | Randomized Evidence


Hypofractionation in Prostate Cancer


Contents

[edit] Randomized

  • Fox Chase -- 76/38 (2 Gy/fx) vs. 70.2/26 (2.7 Gy/fx)
    • Randomized. First 100 men reported. Intermediate-high risk. Neoadjuvant ADH x4 months permitted. Arm 1) conventional 76/38 (@ 2 Gy/fx) vs. Arm 2) hypofractionated 70.2/26 @ 2.7 Gy/fx)
    • 2006 PMID 16242256 -- "Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial." (Pollack A, Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):518-26. Epub 2005 Oct 19.)
      • Toxicity: Slight increase in acute GI toxicity, no difference in GU toxicity
      • Conclusion: Hypofractionation well tolerated acutely
  • Adelaide (Australia)(1996-2003) -- 64/32 (2 Gy/fx) vs. 55/20 (2.75 Gy/fx)
    • Randomized. 217 patients, T1-2N0 PCA. No ADT. Arm 1) conventional 64/32 vs. Arm 2) hypofractionated 55/20.
    • 4-years; 2006 PMID 16965866 -- "Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: updated results of a phase III randomized trial. (Yeoh EE, Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1072-83. Epub 2006 Sep 11.) Median F/U 4 years
      • Outcome: 5-year biochemical/clinical PFS conventional 55% vs. hypofractionated 57% (NS), OS 84% vs 86% (NS)
      • Toxicity: GI urgency worse with hypofractionation, otherwise (NS). GU significantly worse with hypofractionation
      • Conclusion: Hypofractionated schedule equivalent in efficacy, toxicity somewhat worse
  • NCI Canada (1995-1998) -- 66/33 (2 Gy/fx) vs. 52.5/20 (2.62 Gy/fx)
    • Randomized. 936 men, T1-T2, PSA <40, no AST. Technique 3D-CRT, 4F
    • 5-years; 2005 PMID 16135479 -- "Randomized trial comparing two fractionation schedules for patients with localized prostate cancer." (Lukka H, J Clin Oncol. 2005 Sep 1;23(25):6132-8.). Median F/U 5.7 years
      • Outcome: 5-year FFP standard 47% vs. hypofractionated 40% (NS); no difference in post-RT biopsy rate or OS
      • Toxicity: Grade 3 late toxicity 3.2% both arms (NS)
      • Conclusion: Current hypofractionated regimen may be inferior to standard fractionation

[edit] Non-randomized

  • Christie Hospital, UK; 2009 (2002-2003) PMID 19131179 -- "Hypofractionated intensity-modulated radiotherapy for carcinoma of the prostate: analysis of toxicity." (Coote JH, Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1121-7. Epub 2009 Jan 7.)
    • Phase I/II. 60 patients, high risk prostate cancer, T3N0 with any GS and PSA <=50, or T2N0 GS >=7 and PSA 20-50. ADT 6 months. Cohort I 57/19 -> Cohort II 60/20. PTV expansion 0.7 posterior, 1 cm otherwise. IMRT 5 fields.
    • Acute toxicity: No Grade 3-4 GI/GU; Grade 2 GI 15%; Grade 2 GU 10%
    • Late toxicity (2 years): Grade 3 GU 4% (1 patient), no Grade 3 GI; Grade 2 GI 9%, Grade 2 GU 4%. LENT/SOMA general worsening of bowel function
    • Conclusion: Hypfractionated IMRT minimal late toxicity at 2 years
  • Colorado; 2009 PMID 19362783 -- "Toxicity Assessment of Pelvic Intensity-Modulated Radiotherapy with Hypofractionated Simultaneous Integrated Boost to Prostate for Intermediate- and High-Risk Prostate Cancer." (McCammon R, Int J Radiat Oncol Biol Phys. 2009 Apr 11. [Epub ahead of print])
    • Retrospective. 30 patients. Pelvic IMRT 50.4/28 with simultaneous integrated boost 70/28 @ 2.5 Gy/fx. Median F/U 2 years
    • Toxicity: Late Grade 3 in 2/30 patients, Grade 4 in 1/30 patients. Bowel toxicity associated with bowel volume >= 50 Gy
    • Conclusion: Well tolerated
  • Italy Multi-Institutional; 2008 (2004-2006) PMID 18538488 -- "Clinical and Dosimetric Predictors of Acute Toxicity after a 4-Week Hypofractionated External Beam Radiotherapy Regimen for Prostate Cancer: Results from a Multicentric Prospective Trial." (Arcangeli S, Int J Radiat Oncol Biol Phys. 2008 Jun 4. [Epub ahead of print])
    • Phase II. 102 patients, 3 institutions. RT 56/16 @ 3.5 Gy/fx
    • Toxicity: GU Grade 2 39%, Grade 3+ 4%; GI Grade 2 38%, no Grade 3+
    • Conclusion: Acute GU and GI toxicity comparable to other series
  • Montreal; 2008 (2001-2002) PMID 18406883 -- "Combined hypofractionated radiation and hormone therapy for the treatment of intermediate-risk prostate cancer." (Yassa M, Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):58-63.)
    • Phase II. 42 patients, intermediate-risk PCA. RT 57/19 @ 3 Gy/fx. Neoadjuvant/concomitant ADT. Median F/U 3.8 years
    • Outcome: 4-year bPFS 79%
    • Toxicity: Grade 3 8%
    • Conclusion: Hypofractionation with concomitant ADT is well tolerated
  • Princess Margaret; 2007 (2001-2004) PMID 17606331 -- "Phase II Trial of Hypofractionated Image-Guided Intensity-Modulated Radiotherapy for Localized Prostate Adenocarcinoma." (Martin JM, Int J Radiat Oncol Biol Phys. 2007 Nov 15;69(4):1084-9. Epub 2007 Jul 2.)
    • Phase II. 92 patients with T1c-T2c, median PSA 7, GS <=7 (32% low risk, 61% intermediate risk, 7% high risk). RT 60/20 @ 3 Gy/fx. Median F/U 3.2 years
    • Toxicity: Acute G3-4 toxicity in <1%; Late toxicity no G3-4
    • Outcome: 3-year bNED (old ASTRO definition) 76%
    • Conclusion: HFX-RT feasible, low toxicity, bNED comparable to conventional
  • US Multi-Institutional 2005 ASCO Abstract -- "A multi-institutional phase I/II trial of hypofractionated radiation therapy for localized prostate cancer." (Ritter MA, ASCO 2005)
    • Dose escalation. The planned HFX levels I, II and III are 64.7 Gy/ 22 fx @ 2.94 Gy, 58.08 Gy/ 16 fx @ 3.63 Gy, and 51.6 Gy/ 12 fx @ 4.3 Gy. Three increasingly HFX levels were designed per LQ modeling to maintain constant predicted late toxicity relative to 76 Gy in 38 fractions. IMRT is used.
    • Conclusion: First level completed, low level toxicity. Accrual for higher levels ongoing
  • Cleveland Clinic; 2007 (1998-2005) PMID 17544601 -- "Hypofractionated intensity-modulated radiotherapy (70 Gy at 2.5 Gy per fraction) for localized prostate cancer: Cleveland Clinic experience." (Kupelian PA, Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1424-30. Epub 2007 Jun 4.)
    • Retrospective. 770 patients, localized PCA. RT 70/28. Median F/U 3.7 years
    • Outcome: 5-year bPFS 82%; low risk 95%, intermediate risk 85%, high risk 68%
    • Late Toxicity: GI Grade 3+ 1%, GU Grade 3+ 5%
    • Conclusion: Acceptable outcomes and toxicity
  • St. Thomas Hospital; 1991 (UK)(1964-1984) PMID 2069876 -- "Radical external beam radiotherapy for localised carcinoma of the prostate using a hypofractionation technique." (Collins CD, Clin Oncol (R Coll Radiol). 1991 May;3(3):127-32.)
    • Retrospective. 232 patients, clinically localized PCA. RT 36/6
    • Conclusion: Comparable results to other series, early and late morbidity acceptable

[edit] SBRT

[edit] Clinical

  • Seoul; 2007 (2002-2005) ASTRO Abstract -- "Stereotactic Radiation Therapy of Localized Prostate Cancer Using Cyberknife" (Choi C, Int J Radiat Oncol Biol Phys. 2007 69(3):S375, Abstract 2307)
    • Retrospective. 44 patients, 10 low risk, 9 intermediate risk, 25 high risk. RT 32-36/4. Median F/U 13 months
    • Outcome: 3-year bPFS 78%, OS 100%
    • Conclusion: Cyberknife feasible
  • Stanford; 2006 (2003-2006) ASTRO Abstract -- "Hypofractionated Stereotactic Radiotherapy for Prostate Cancer: Early Results" (Hara W, Int J Radiat Oncol Biol Phys. 2008 66(3):S324, Abstract 2206)
    • Prospective. 26 patients with low-risk PCA. RT 36.25/5 over 5 days using CyberKnife
    • Outcome: 18-month PSA 0.22, bounce in 23%
    • Toxicity: Late GU Grade 2 4%, late rectal Grade 2 0%; no Grade 3-4
    • Conclusion: Acute sequelae for SBRT acceptable; early PSA results promising
  • Virginia Mason; 2007 (2000-2004) PMID 17336216 -- "Stereotactic hypofractionated accurate radiotherapy of the prostate (SHARP), 33.5 Gy in five fractions for localized disease: first clinical trial results." (Madsen BL, Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1099-105.)
    • Phase I/II. 40 patients, localized PCA. SBRT 33.5/5 in 5 days. Median F/U 3.4 years
    • Outcome: Actuarial 4-year bPFS (ASTRO) 70%, (nadir+2) 90%
    • Toxicity: Late G1-2 toxicity GU 45%, GI 37%; no Grade 3-4 toxicity; impotence 23%
    • Conclusion: SBRT feasible, with minimal toxicity

[edit] Dosimetry

  • San Diego CyberKnife Center; 2008 PMID 18374232 -- "Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations." (Fuller DB, Int J Radiat Oncol Biol Phys. 2008 Apr 1;70(5):1588-97.)
    • Dosimetry. 10 patients treated with CyberKnife. Used HDR protocol 38/4
    • Comparison: CK had comparable PTV, less V125 and V150, lower urethral dose, lower bladder Dmax but slower dose fall-off, similar rectal doses, and sharper dose fall-off
    • Outcome: 4-month PSA decreased 86%
    • Toxicity: acute toxicity mainly GU, IPSS median increase 10 points, return to baseline by 8 weeks, minimal GI toxicity
    • Conclusion: It is possible to construct and deliver Cyberknife plans that closely recapitulate HDR dosimetry
  • Stanford; 2007 PMID 17472885 -- "Investigation of linac-based image-guided hypofractionated prostate radiotherapy." (Pawlicki T, Med Dosim. 2007 Summer;32(2):71-9.)
    • Comparison of Varian Trilogy and CyberKnife
  • Virginia Mason; 2003 PMID 14630263 -- "Intrafractional stability of the prostate using a stereotactic radiotherapy technique." (Madsen BL, Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1285-91.)
    • Retrospective. 47 patients, each with 3 fiducial markers. 227 RT fractions reviewed. Also ragiographs at 6 min intervals
    • Outcome: sup/inf 2.0 mm, ant/post 1.9 mm, right/left 1.4 mm. Radiographs 0-6 min 1.5 mm greatest, >6 min 0.9 mm greatest
    • Conclusion: Average intrafractional movement 2.0 mm or less. Most movement early, and recommend settling-in period before treatment

[edit] Review

  • Stanford; 2007 PMID 17641522 -- "Prostate cancer therapy with stereotactic body radiation therapy." (Pawlicki T, Front Radiat Ther Oncol. 2007;40:395-406.)
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