Long-Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer

Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York, United States
The Journal of Urology (Impact Factor: 4.47). 10/2006; 176(4 Pt 1):1415-9. DOI: 10.1016/j.juro.2006.06.002
Source: PubMed


We report on the long-term results and late toxicity outcomes of high dose intensity modulated radiation therapy for patients with clinically localized prostate cancer.
Between 1996 and 2000 a total of 561 patients with clinically localized prostate cancer were treated with intensity modulated radiation therapy. All patients were treated to a dose of 81 Gy prescribed to the planning target volume. Prostate specific antigen relapse was defined according to the American Society for Therapeutic Radiology and Oncology consensus and Houston definitions (absolute nadir plus 2 ng/ml dated at the call). Median followup was 7 years (range 5 to 9).
The 8-year actuarial PSA relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the American Society for Therapeutic Radiology and Oncology definition were 85%, 76% and 72%, respectively (p <0.025). The 8-year actuarial prostate specific antigen relapse-free survival rates for patients in favorable, intermediate and unfavorable risk groups according to the Houston definition were 89%, 78% and 67%, respectively (p = 0.0004). The 8-year actuarial likelihood of grade 2 rectal bleeding was 1.6%. Three patients (0.1%) experienced grade 3 rectal toxicity requiring either 1 or more transfusions or a laser cauterization procedure. No grade 4 rectal complications have been observed. The 8-year likelihood of late grade 2 and 3 (urethral strictures) urinary toxicities were 9% and 3%, respectively. Among patients who were potent before intensity modulated radiation therapy, erectile dysfunction developed in 49%. The cause specific survival outcomes for favorable, intermediate and unfavorable risk cases were 100%, 96% and 84%, respectively.
These long-term results confirm our previous observations regarding the safety of high dose intensity modulated radiation therapy for clinically localized prostate cancer. Despite the application of high radiation doses, the incidence of rectal bleeding at 8 years was less than 2%. Despite the increased conformality of the dose distribution associated with intensity modulated radiation therapy, excellent long-term tumor control outcomes were achieved.

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    • "SBRT may possibly have an advantage over IMRT as well. Zelefsky et al. published a series on IMRT with similar length of follow up (18). With 8-year median follow up, only 89 and 78% of low- and intermediate-risk patients were biochemically controlled, respectively, which is inferior to our results for SBRT. "
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    ABSTRACT: Objectives: Stereotactic body radiation therapy (SBRT) takes advantage of the prostate's low α/β ratio to deliver a large radiation dose in few fractions. Initial studies on small groups of low-risk patients support SBRT's potential for clinical efficacy while limiting treatment-related morbidity and maintained quality of life. This prospective study expands upon prior studies to further evaluate SBRT efficacy for a large patient population with organ confined, low- and intermediate-risk prostate cancer patients. Methods: Four hundred seventy-seven patients with prostate cancer received CyberKnife SBRT. The median age was 68.6 years and the median PSA was 5.3 ng/mL. Three hundred twenty-four patients were low-risk (PSA <10 ng/mL and Gleason <7), 153 were intermediate-risk (PSA 10-20 ng/mL or Gleason = 7). Androgen deprivation therapy was administered to 51 patients for up to 6 months. One hundred fifty-four patients received 35 Gy delivered in five daily fractions; the remaining patients received a total dose of 36.25 Gy in five daily fractions. Biochemical failure was assessed using the phoenix criterion. Results: Median follow-up was 72 months. The median PSA at 7 years was 0.11 ng/mL. Biochemical failures occurred for 11 low-risk patients (2 locally), 14 intermediate-risk patients (3 locally). The actuarial 7-year freedom from biochemical failure was 95.6 and 89.6% for low- and intermediate-risk groups, respectively (p < 0.012). Among patients with intermediate-risk disease, those considered to have low intermediate-risk (Gleason 6 with PSA >10, or Gleason 3 + 4 with PSA <10; n = 106) had a significantly higher bDFS than patients with high intermediate-risk (Gleason 3 + 4 with PSA 10-20 or Gleason 4 + 3; n = 47), with bDFS of 93.5 vs. 79.3%, respectively. For the low-risk and low intermediate-risk groups, there was no difference in median PSA nadir or biochemical disease control between doses of 35 and 36.25 Gy. Conclusion: CyberKnife SBRT produces excellent biochemical control rates. Median PSA levels compare favorably with other radiation modalities and strongly suggest durability of response. These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for low- and intermediate-risk patients.
    Frontiers in Oncology 09/2014; 4:240. DOI:10.3389/fonc.2014.00240
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    • "The utilization of dose-escalated (DE) radiotherapy for the primary treatment of clinically localized prostate cancer has become increasingly prevalent since the demonstration of improved outcomes with doses above 70 Gy.1,2 Intensity-modulated radiotherapy (IMRT) with image guidance has been widely accepted as a valuable technique of dose-escalation, with favorable long-term biochemical control and excellent mature toxicity profiles.3,4 The addition of androgen deprivation therapy (ADT) to conventional radiotherapy doses has also been shown to improve the outcomes of patients with localized prostate cancer.5–8 "
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    ABSTRACT: Purpose Dose-escalated (DE) radiotherapy in the setting of localized prostate cancer has been shown to improve biochemical disease-free survival (bDFS) in several studies. In the same group of patients, androgen deprivation therapy (ADT) has been shown to confer a survival benefit when combined with radiotherapy doses of up to 70 Gy; however, there is currently little long-term data on patients who have received high-dose intensity-modulated radiotherapy (IMRT) with ADT. We report the long-term outcomes in a large cohort of patients treated with the combination of DE image-guided IMRT (IG-IMRT) and ADT. Methods and materials Patients with localized prostate cancer were identified from a centralized database across an integrated cancer center. All patients received DE IG-IMRT, combined with ADT, and had a minimum follow up of 12 months post-radiotherapy. All relapse and toxicity data were collected prospectively. Actuarial bDFS, metastasis-free survival, prostate cancer-specific survival, and multivariate analyses were calculated using the SPSS v20.0 statistical package. Results Seven hundred and eighty-two eligible patients were identified with a median follow up of 46 months. Overall, 4.3% of patients relapsed, 2.0% developed distant metastases, and 0.6% died from metastatic prostate cancer. At 5-years, bDFS was 88%, metastasis-free survival was 95%, and prostate cancer-specific survival was 98%. Five-year grade 2 genitourinary and gastrointestinal toxicity was 2.1% and 3.4%, respectively. No grade 3 or 4 late toxicities were reported. Pretreatment prostate specific antigen (P=0.001) and Gleason score (P=0.03) were significant in predicting biochemical failure on multivariate analysis. Conclusion There is a high probability of tumor control with DE IG-IMRT combined with androgen deprivation, and this is a technique with a low probability of significant late toxicity. Our long term results corroborate the safety and efficacy of treating with IG-IMRT to high doses and compares favorably with published series for the treatment of prostate cancer.
    OncoTargets and Therapy 08/2014; 7:1519-23. DOI:10.2147/OTT.S65238 · 2.31 Impact Factor
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    • "Furthermore, androgen signaling involved in development and homeostasis of the prostate, and cancer initiation and progression correlated with activation of androgen receptor [17] [18]. Treatments of prostate cancer involved surgery, external beam therapy, hormone therapy, small molecular drug and cryosurgery [19] [20] [21] [22] [23] [24]. Currently, natural plant extracts or human tissues active ingredients are widely used for the treatment of cancer, and further isolated effective substances in the extract [25] [26]. "
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    ABSTRACT: Background/Aim: The Jamaican "Guinea Hen Weed" (Petiveria alliacea L.) plant has been traditionally used in folklore medicine to treat a variety of diseases including cancer. In the present study we investigated on the therapeutic feasibility of dibenzyl trisulfide (DTS) (isolated from the Jamaican Guinea Hen Weed) as a potent small-molecule kinase inhibitor to treat cancer. We investigated the inhibitory effects of DTS against a large panel of kinases using a well-established competitive binding assay. Cell proliferation data were obtained using the WST-1 colorimetric assay. DTS inhibited the activity of the C-terminal kinase domain of RSK1 (80% compared to control) with a Kd of 1.3 μM. Anti-proliferative effects of DTS were observed in small lung, pancreatic, breast, and prostate cancer cells with IC50 values ranging from 0.34-0.84 μM. We have identified DTS as a highly selective and isoform-specific RSK1 kinase inhibitor with broad cancer therapeutic potential.
    Anticancer research 04/2014; 34(4):1637-41. · 1.83 Impact Factor
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