Subgroup analysis of patients with localized prostate cancer treated within the Dutch-randomized dose escalation trial

Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Radiotherapy and Oncology (Impact Factor: 4.36). 03/2010; 96(1):13-8. DOI: 10.1016/j.radonc.2010.02.022
Source: PubMed


To investigate the effect of dose escalation within prognostic risk groups in prostate cancer.
Between 1997 and 2003, 664 patients with localized prostate cancer were randomly assigned to receive 68- or 78-Gy of radiotherapy. Two prognostic models were examined: a risk group model (low-, intermediate-, and high-risk) and PSA-level groupings. High-risk patients with hormonal therapy (HT) were analyzed separately. Outcome variable was freedom from failure (FFF) (clinical failure or PSA nadir+2 microg/L).
In relation to the advantage of high-dose radiotherapy, intermediate-risk patients benefited most from dose escalation. However no significant heterogeneity could be demonstrated between the risk groups. For two types of PSA-level groupings: PSA<10 and > or = 10 microg/L, and <8, 8-18 and >8 microg/L, the test for heterogeneity was significant (p=0.03 and 0.05, respectively). Patients with PSA 8-18 microg/L (n=297, HR=0.59) derived the greatest benefit from dose escalation. No heterogeneity could be demonstrated for high-risk patients with and without HT.
Intermediate-risk group derived the greatest benefit for dose escalation. However, from this trial no indication was found to exclude low-risk or high-risk patients from high-dose radiotherapy. Patients could be selected for high-dose radiotherapy based on PSA-level groupings: for patients with a PSA<8 microg/L high-dose radiotherapy is probably not indicated, but should be confirmed in other randomized studies.

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Available from: Wilma D Heemsbergen, Mar 14, 2014
    • "Over the last ten years several dose escalation trials have been conducted for PCa. Based on these results, prescribed doses (D pres ) around 78 Gy are now common practice in EBRT and higher doses are known to be related to unacceptable toxicity risks [6] [7] [8] [9]. On the other hand local recurrences tend to occur at the site of primary tumor [10] [11]. "
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    ABSTRACT: Background and purpose: Advancements in imaging and dose delivery enable boosting of the dominant intraprostatic lesions (DIL), while maintaining organs-at-risk (OAR) tolerances. This study aimed to assess the feasibility of DIL boosting for volumetric modulated arc therapy (VMAT), intensity modulated proton therapy (IMPT) and high dose rate brachytherapy (HDR-BT). Material and methods: DILs were defined on multiparametric magnetic resonance imaging and fused with planning CT for twelve patients. VMAT, IMPT and HDR-BT plans were created for each patient with an EQD2α/β DIL aimed at 111.6Gy, PTVinitialDpres was 80.9Gy (EBRT) with CTV D90%=81.9Gy (HDR-BT). Hard dose constraints were applied for OARs. Results: Higher boost doses were achieved with IMPT compared to VMAT, keeping major OAR doses at similar levels. Patient averaged EQD2α/β D50% to DIL were 110.7, 114.2 and 150.1Gy(IsoE) for VMAT, IMPT and HDR-BT, respectively. Respective rectal wall Dmean were 30.5±5.0, 16.7±3.6, 9.5±2.5Gy(IsoE) and bladder wall Dmean were 21.0±5.5, 15.6±4.3 and 6.3±2.2Gy(IsoE). Conclusions: DIL boosting was found to be feasible with all investigated techniques. Although OAR doses were higher than for standard treatment approach, the risk levels were reasonably low. HDR-BT was superior to VMAT and IMPT, both in terms of OAR sparing and DIL boosting.
    No preview · Article · Sep 2015 · Radiotherapy and Oncology
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    • "One must however be careful using PSA cutoffs when poorly differentiated tumors are involved since in these cases PSA is a poor indicator for tumor load. Some studies also reported suboptimal effects of dose-escalation for relatively high PSA levels, including reports from this trial [12] [18]. At the current update, we found again an optimal result for BCF and CF within the 8–18 lg/L subgroup (n = 297) with (borderline for CF) significant heterogeneity. "
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    ABSTRACT: Nowadays, advanced irradiation techniques make it possible to escalate safely the dose in prostate cancer. We studied the effect of a higher dose on tumor control in a randomized trial with a median follow-up of 110months. Patients with T1b-T4N0 prostate cancer (n=664) were randomized between 78Gy and 68Gy. Primary endpoint was biochemical and/or clinical failure (BCF) according to the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines (3 consecutive rises), and to Phoenix (nadir plus 2μg/L). Secondary endpoints were clinical failure (CF), local failure (LF), prostate cancer death (PCD), and overall survival (OS). Explorative subgroup analyses were performed. BCF rate (HR=0.8; 20% less events) and LF rate (HR=0.5; 50% less events) were significantly lower in the 78Gy arm (p<0.05). CF, PCD and OS were similar in both arms. A significant heterogeneity of treatment effect was found for PSA cutoffs between 7 and 10μg/L. We observed significantly less BCF and LF in the high-dose arm. This suggests improvement of the therapeutic ratio. However, we observed similar rates of CF and PCD at the current update. More follow-up is needed to investigate which patients benefit in terms of prolonged OS.
    Full-text · Article · Nov 2013 · Radiotherapy and Oncology
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    • "Patient quality of life (QoL) following primary treatment of localized prostate cancer is, to a large extent, influenced by adverse changes in bowel, urinary, and sexual function . While local dose escalation has been shown to significantly improve outcomes of radiotherapy of local and locally advanced prostate cancer [1] [2], rectal toxicity [3] limits the extent of acceptable escalation [4]. A number of technical developments aim to reduce rectal radiation dose [5] [6] [7] [8], some of which rely on tissue separation between the dorsal prostate and ventral rectal wall [9] [10] [11] [12] [13]. "
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    ABSTRACT: Purpose: To evaluate dose reduction caused by the implantation of an interstitial inflatable and biodegradable balloon device aiming to achieve lower rectal doses with virtual 3D conformal external beam radiation treatment. Materials and methods: An inflatable balloon device was placed, interstitially and under transrectal ultrasound guidance, into the rectal-prostate interspace prior treatment initiation of 26 patients with localized prostate cancer, who elected to be treated with radiotherapy (3D CRT or IMRT). The pre- and post-implant CT imaging data of twenty two patients were collected (44 images) for the purpose of the 3D conformal virtual planning presented herein. Results: The dorsal prostate-ventral rectal wall separation resulted in an average reduction of the rectal V70% by 55.3% (± 16.8%), V80% by 64.0% (± 17.7%), V90% by 72.0% (± 17.1%), and V100% by 82.3% (± 24.1%). In parallel, rectal D2 ml and D0.1 ml were reduced by 15.8% (± 11.4%) and 3.9% (± 6.4%), respectively. Conclusions: Insertion of the biodegradable balloon into the prostate-rectum interspace is similar to other published invasive procedures. In this virtual dose distribution analysis, the balloon insertion resulted in a remarkable reduction of rectal volume exposed to high radiation doses. This effect has the potential to keep the rectal dose lower especially when higher than usual prostate dose escalation protocols or hypo-fractionated regimes are used. Further prospective clinical investigations on larger cohorts and more conformal radiation techniques will be necessary to define the clinical advantage of the biodegradable interstitial tissue separation device.
    Full-text · Article · Feb 2013 · Radiotherapy and Oncology
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