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

Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 11/2010; 80(2):437-44. DOI: 10.1016/j.ijrobp.2010.02.040
Source: PubMed


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.
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.
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.
Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

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    • "Studies tend to be retrospective [17]. Long-term QoL after IMRT has received attention in a limited number of prospective studies [18,19] even though adverse effects are known to occur late (over 30 months) [20,21]. "
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    ABSTRACT: Objective To determine late toxicity and quality of life (QoL) in patients with localized prostate cancer after high-dose intensity-modulated radiotherapy (IMRT). Patient and methods This was a prospective study in patients with localized prostate adenocarcinoma who had been treated by IMRT (76 Gy) between February and November 2006. Physicians scored acute and late toxicity using the Common Terminology Criteria for Adverse Events (version 3.0). Patients completed cancer and prostate-specific QoL questionnaires (EORTC QLQ-C30 and QLQ-PR25) before IMRT (baseline) and at 2, 6, 18 and 54 months. Result Data were available for 38 patients (median age, 73 years) (18% low risk; 60% intermediate risk; 32% high risk). The incidence of urinary and gastrointestinal toxicity was respectively: immediately post IMRT: 36.8% and 23.7% (grade 1), 5.3% and 5.3% (grade 2), 2.6% and 0% (grade 3); at 18 months: 23.7% and 10.3% (grade 1), 26.3% and 13.2% (grade 2), 0% and 2.6% (grade 3); at 54 months: 34.2% and 23.7% (grade 1), 5.3% and 15.8% (grade 2), 5.3% and 0% (grade 3). At 54 months, significant worsening was reported by patients for 11/19 QoL items but the worsening was clinically relevant (>10 points) for 7 items only: physical, role as well as social functioning, fatigue, pain, dyspnoea and constipation. There was no significant difference between 54-month and baseline QoL scores for global health, gastrointestinal symptoms, treatment-related symptoms and sexual function. However, there was significant - but clinically non-relevant (<10 points) - worsening of urinary symptom. Conclusion High-dose IMRT to the prostate with accurate patient positioning did not induce any clinically relevant worsening in late urinary and gastrointestinal QoL at 54 months. Impaired physical and role functioning may be related to age and comorbidities.
    Full-text · Article · Mar 2013 · Radiation Oncology
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    • "For carcinoma of the cervix, pelvic IMRT permitted sparing of pelvic bone marrow [3] and was associated with lower toxicity rates and favorable outcomes compared to standard radiation therapy [4]. Additionally, for prostate cancer patients treated with androgen deprivation therapy, IMRT significantly reduced acute and late GI toxicities compared to 3DCRT [5]. For anal canal carcinoma, IMRT appeared comparable to 3DCRT with regard to local control and survival while decreasing dermatologic, GI, and hematological toxicities and associated treatment breaks [6] [7]. "
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    ABSTRACT: Purpose. To compare the acute toxicities of IMRT to 3D-conformal radiation therapy (3DCRT) in the treatment of rectal cancer. Methods and Materials. Eighty-six patients with rectal cancer preoperatively treated with IMRT (n = 30) and 3DCRT (n = 56) were retrospectively reviewed. Rates of acute toxicity between IMRT and 3DCRT were compared for anorexia, dehydration, diarrhea, nausea, vomiting, weight loss, radiation dermatitis, fatigue, pain, urinary frequency, and blood counts. Fisher's exact test and chi-square analysis were applied to detect statistical differences in incidences of toxicity between these two groups of patients. Results. There were fewer hospitalizations and emergency department visits in the group treated with IMRT compared with 3DCRT (P = 0.005) and no treatment breaks with IMRT compared to 20% with 3DCRT (P = 0.0002). Patients treated with IMRT had a significant reduction in grade ≥3 toxicities versus grade ≤2 toxicities (P = 0.016) when compared to 3DCRT. The incidence of grade ≥3 diarrhea was 9% among 3DCRT patients compared to 3% among IMRT patients (P = 0.31). Conclusions. IMRT for rectal cancer can reduce treatment breaks, emergency department visits, hospitalizations, and all grade ≥3 toxicities compared to 3DCRT. Further evaluation and followup is warranted to determine late toxicities and long-term results of IMRT.
    Full-text · Article · Aug 2012 · International Journal of Surgical Oncology
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    • "This topic is controversial. Several authors reported that ADT administration increases late GI toxicity [20,22]. In contrast, other studies have indicated lower GI and GU toxicity rates when ADT was added to EBRT for localized prostate cancer [23,24]. "
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    ABSTRACT: Background Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer. Methods In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2–88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. Results The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2–3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed. Conclusions These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.
    Full-text · Article · Jul 2012 · Radiation Oncology
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