Advertisement

Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

Published:November 03, 2010DOI:https://doi.org/10.1016/j.ijrobp.2010.02.040

      Purpose

      Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD.

      Methods and Materials

      Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale.

      Results

      The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6–11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1–4.3; p = .04) was more prevalent in the 3D-CRT patients.

      Conclusion

      Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Al-Mamgani A.
        • Heemsbergen W.D.
        • Peeters S.T.
        • et al.
        Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 2008; 72: 980-988
        • Kuban D.A.
        • Tucker S.L.
        • Dong L.
        • 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: 67-74
        • Pollack A.
        • Zagars G.K.
        • Starkschall G.
        • et al.
        Prostate cancer radiation dose response: Results of the M.D. Anderson phase III randomized trial.
        Int J Radiat Oncol Biol Phys. 2002; 53: 1097-1105
        • Zelefsky M.J.
        • Leibel S.A.
        • Gaudin P.B.
        • et al.
        Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer.
        Int J Radiat Oncol Biol Phys. 1998; 41: 491-500
        • Bolla M.
        • Collette L.
        • Blank L.
        • et al.
        Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): A phase III randomised trial.
        Lancet. 2002; 360: 103-106
        • Hanks G.E.
        • Pajak T.F.
        • Porter A.
        • et al.
        Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group protocol 92-02.
        J Clin Oncol. 2003; 21: 3972-3978
        • Horwitz E.M.
        • Bae K.
        • Hanks G.E.
        • et al.
        Ten-year follow-up of Radiation Therapy Oncology Group protocol 92-02: A phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer.
        J Clin Oncol. 2008; 26: 2497-2504
        • Pilepich M.V.
        • Winter K.
        • John M.J.
        • et al.
        Phase III Radiation Therapy Oncology Group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.
        Int J Radiat Oncol Biol Phys. 2001; 50: 1243-1252
        • Feigenberg S.J.
        • Hanlon A.L.
        • Horwitz E.M.
        • et al.
        Long-term androgen deprivation increases grade 2 and higher late morbidity in prostate cancer patients treated with three-dimensional conformal radiation therapy.
        Int J Radiat Oncol Biol Phys. 2005; 62: 397-405
        • Lawton C.A.
        • Bae K.
        • Pilepich M.
        • et al.
        Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: analysis of Radiation Therapy Oncology Group studies 85-31, 86-10, and 92-02.
        Int J Radiat Oncol Biol Phys. 2008; 70: 437-441
        • Lawton C.A.
        • DeSilvio M.
        • Roach III, M.
        • et al.
        An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: Updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions.
        Int J Radiat Oncol Biol Phys. 2007; 69: 646-655
        • Dong L.
        • Antolak J.
        • Salehpour M.
        • et al.
        Patient-specific point dose measurement for IMRT monitor unit verification.
        Int J Radiat Oncol Biol Phys. 2003; 56: 867-877
        • Zelefsky M.J.
        • Chan H.
        • Hunt M.
        • et al.
        Long-term outcome of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer.
        J Urol. 2006; 176: 1415-1419
        • Al-Mamgani A.
        • Heemsbergen W.D.
        • Peeters S.T.
        • et al.
        Role of intensity-modulated radiotherapy in reducing toxicity in dose escalation for localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 2009; 73: 685-691
        • Horwitz E.M.
        • Hanlon A.L.
        • Pinover W.H.
        • et al.
        Defining the optimal radiation dose with three-dimensional conformal radiation therapy for patients with nonmetastatic prostate carcinoma by using recursive partitioning techniques.
        Cancer. 2001; 92: 1281-1287
        • Price R.A.
        • Murphy S.
        • McNeeley S.W.
        • et al.
        A method for increased dose conformity and segment reduction for SMLC delivered IMRT treatment of the prostate.
        Int J Radiat Oncol Biol Phys. 2003; 57: 843-852
        • Monti A.F.
        • Ostinelli A.
        • Frigerio M.
        • et al.
        An ICRU 50 radiotherapy treatment chart.
        Radiother Oncol. 1995; 35: 145-150
        • Jacob R.
        • Hanlon A.L.
        • Horwitz E.M.
        • et al.
        Role of prostate dose escalation in patients with greater than 15% risk of pelvic lymph node involvement.
        Int J Radiat Oncol Biol Phys. 2005; 61: 695-701
        • Pollack A.
        • Hanlon A.L.
        • Horwitz E.M.
        • 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: 518-526
        • Buyyounouski M.K.
        • Hanlon A.L.
        • Horwitz E.M.
        • et al.
        Interval to biochemical failure highly prognostic for distant metastasis and prostate cancer-specific mortality after radiotherapy.
        Int J Radiat Oncol Biol Phys. 2008; 70: 59-66
        • Roach III, M.
        • DeSilvio M.
        • Lawton C.
        • et al.
        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. 2003; 21: 1904-1911
        • Sanguineti G.
        • Marcenaro M.
        • Franzone P.
        • et al.
        Neoadjuvant androgen deprivation and prostate gland shrinkage during conformal radiotherapy.
        Radiother Oncol. 2003; 66: 151-157
        • Schultheiss T.E.
        • Lee W.R.
        • Hunt M.A.
        • et al.
        Late GI and GU complications in the treatment of prostate cancer.
        Int J Radiat Oncol Biol Phys. 1997; 37: 3-11
        • Alcantara P.
        • Schultheiss T.E.
        • Ruth K.
        • et al.
        Dose–volume determinants of late genitourinary toxicity after external beam radiotherapy for prostate cancer.
        Int J Radiat Oncol Biol Phys. 2005; 63 (S294)
        • Zelefsky M.J.
        • Levin E.J.
        • Hunt M.
        • et al.
        Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 2008; 70: 1124-1129

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.