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

Peeters, Stéphanie; Heemsbergen, Wilma D.; Koper, P.; Putten, Wim L.J. van; Slot, Annerie; Dielwart, Michel F.H.; Bonfrèr, Johannes M.G.; Incrocci, Luca; Lebesque, Joos V.

doi:10.1200/jco.2005.05.2530

Cited by 879 publications

(487 citation statements)

References 35 publications

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“…The additional strengths of the present study include higher radiation doses and longer follow-up. Dose-escalated RT has been shown to improve FFBF through better local control (20)(21)(22). This benefit with higher doses might allow differences in local control related to secondary factors, such as the NTDR, to be more apparent.…”

Section: Discussionmentioning

confidence: 99%

Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

D’Ambrosio

Horwitz

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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Purpose-The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer.Methods and Materials-Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model. Results-The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR ≥33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR ≥33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined.Conclusions-A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of ≥33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

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Section: Discussionmentioning

confidence: 99%

Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

D’Ambrosio

Horwitz

et al. 2008

International Journal of Radiation Oncology*Biology*Physics

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“…There are now three published PSA-era Phase III prostate cancer radiation dose escalation series (8,28,29). All have shown an improvement in freedom from biochemical failure with higher radiation doses.…”

Section: Discussionmentioning

confidence: 99%

Radiation dose and late failures in prostate cancer

Morgan

Hanlon

Horwitz

et al. 2007

International Journal of Radiation Oncology*Biology*Physics

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Purpose-To quantify the impact of radiotherapy (RT) dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with RT alone.Methods and Materials-A total of 667 men with clinically localized intermediate and high risk prostate cancer treated with 3D-conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and biochemical failure (BF), using ASTRO and Phoenix (Nadir+2) definitions, were determined. Median follow-up was 77 months.Results-Multivariate analysis showed that increasing RT dose was independently associated with decreased ASTRO BF (P<.0001), Nadir+2 BF (P=.001), and DM (P=.006). The preponderance (85%) of ASTRO BF occurred at ≤4 years after RT, while Nadir+2 BF was more evenly spread over years 1-10, with 55% BF in ≤4 years. RT dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74 Gy group. In patients receiving ≥74 Gy, there was a reduction in the risk of DM in both the early and late waves, although the late wave appears reduced to a greater degree.Conclusions-The ASTRO definition of BF systematically underestimates late BF due to backdating. RT dose escalation diminished and delayed BF; the delay suggests that there may still be local persistence in some patients. For DM, higher RT dose reduced both the early and late waves, suggesting that persistence of local disease contributes to both.

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“…Multiple randomized clinical trials have demonstrated a dose escalation benefit for prostate radiotherapy (1)(2)(3)(4)(5). Recent data suggests both inter-and intra-fraction prostate motion is not negligible (6)(7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

A Practical Method of Adaptive Radiotherapy for Prostate Cancer using Real-time Electromagnetic Tracking

Olsen¹,

Noel²,

Baker³

et al. 2009

International Journal of Radiation Oncology*Biology*Physics

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Purpose/Objectives-We have created an automated process utilizing real-time tracking data to evaluate adequacy of PTV margins in prostate cancer, allowing for a process of adaptive radiotherapy with minimal physician workload. We present an analysis of PTV adequacy and a proposed adaptive process.Materials/Methods-Tracking data was analyzed for 15 patients who underwent SMLC IMRT with uniform 5mm PTV margins for prostate cancer utilizing the Calypso® Localization System. Additional plans were generated with 0 and 3 mm margins. A custom software application utilizing the planned dose distribution and structure location from CT simulation was developed to evaluate the dosimetric impact to the target due to motion. The dose delivered to the prostate was calculated for the initial 3, 5, and 10 fractions, and for the entire treatment. Treatment was accepted as adequate if minimum delivered prostate dose (D min ) was at least 98% of the planned D min . Conclusions-Our adaptive process successfully utilized real-time tracking data to predict the need for PTV modifications, without the added burden of physician contouring and image analysis. Our methods are applicable to other utilizations of real-time tracking, including hypofractionated treatment. Results-For

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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

Abstract: This multicenter randomized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy.

Cited by 879 publications

References 35 publications

Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

Does Treatment Duration Affect Outcome After Radiotherapy for Prostate Cancer?

Radiation dose and late failures in prostate cancer

A Practical Method of Adaptive Radiotherapy for Prostate Cancer using Real-time Electromagnetic Tracking

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