The ELDORADO study: A phase II randomised study of concurrent weekly docetaxel, IMRT, and ltadt in patients with high-risk prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5048-5048
Author(s):  
Derek Wilke ◽  
Lori Wood ◽  
Heather Walker ◽  
David Bell ◽  
Ricardo A. Rendon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Treatment Intensification ◽  
Double Blind ◽  
Randomised Study ◽  
High Risk Prostate Cancer ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Grade 3 ◽  
Dose Reductions

5048 Background: Treatment intensification is warranted for ‘high risk’ prostate cancer. Docetaxel (DO) and radiotherapy (IMRT) may cause dose-limiting GI or GU toxicity. Treating the whole pelvis last (WP-L) versus the whole pelvic lymphatics first (WP-F) could reduce the number of dose delays or omissions of DO. Methods: We performed a double-blind, randomized trial, in patients with ‘high risk’ non-metastatic prostate cancer who had any one of the following: 1) ≥ T2c TNM category, 2) Gleason score ≥ 8, or PSA > 20 and < 50 µg/L, OR have a greater than 50% risk of recurrence after radical prostatectomy (RP), as predicted by the Kattan nomogram, with no evidence of metastatic disease. Patients receive long-term androgen deprivation therapy (LTADT), and after 4 months of neoadjuvant ADT, receive IMRT and concurrent DO 20 mg/m2 x 8 weekly infusions. Patients were randomized to receive WP-F followed by a boost to the prostate/prostate bed, or to have WP-L. The primary outcome was to compare the number of DO dose reductions, delays or omissions due to GI or GU toxicity, between arms. Target sample size was 86 patients (pts). Results: 98 pts were registered, 88 were randomized, 2 withdrew consent, leaving 42 pts randomized to WP-F, and 44 pts to WP-L. The trial was closed to accrual Feb 2, 2012. Twenty-five pts had previous RP (29%). Seven pts (16.6%) allocated to WP-F had chemotherapy dose reductions/delays versus 3 pts (6.8%) allocated to WP-L , which was not statistically significant (p=0.19). Overall 80.2% of pts received all 8 weekly doses of DO and IMRT (WP-F vs. WP-L: 78.6% vs.81.8%, p=0.9). Actuarial overall survival at 4 years is 96 % (WP-F vs. WP-L: 94% vs.97%, p=0.6). Biochemical relapse-free survival at 4 years is 96.7% (WP-F vs. WP-L: 98% vs.97%, p=0.92). Two patients have needed surgical intervention for Grade > 3 GU toxicity. Cumulative treatment-related grade 3 or 4 GI or GU toxicity was 36%. When patients were last seen, only 2/84 (2.3%) patients had ongoing grade 3 GI or GU toxicity at a median follow up of 2.7 years Conclusions: Concurrent use of DO and IMRT is feasible with reasonable toxicity. Sequence inversion does not enhance chemotherapy delivery. Clinical trial information: NCT00452556.

scholarly journals Hypofractionated helical intensity-modulated radiotherapy (75 Gy at 2.5 Gy/fraction) for intermediate- and high-risk prostate cancer: Assessment of toxicity

2011 ◽  
Vol 11 (3) ◽  
pp. 145-154
Author(s):  
Moonkyoo Kong ◽  
Seong Eon Hong ◽  
Jinhyun Choi ◽  
Sung-Goo Chang
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radiation Therapy Oncology Group ◽  
Intensity Modulated Radiotherapy ◽  
Intensity Modulated ◽  
High Risk Prostate Cancer ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Grade 3

AbstractPurpose: To evaluate the toxicity of hypofractionated helical intensity-modulated radiotherapy (IMRT) for men with intermediate- and high-risk prostate cancer.Methods and Materials: A retrospective toxicity analysis was performed in 22 patients treated definitively with hypofractionated helical IMRT. The helical IMRT were designed to deliver 75 Gy in 2.5 Gy/fraction to the prostate gland, 63 Gy in 2.1 Gy/fraction to seminal vesicle, and 54 Gy in 1.8 Gy/fraction to pelvic lymph nodes. No patient received hormonal therapy. Toxicity was graded by the Radiation Therapy Oncology Group (RTOG) scales.Results: All patients tolerated the treatment well without treatment interruption, and there was no Grade 3 or more acute toxicity. With a median follow-up of 24.5 months, there was no Grade 3 or more late toxicity. The late Grade 2 gastrointestinal (GI) and genitourinary (GU) toxicity for total 22 patients were 9.1% and 18.2%, respectively, and the late Grade 1 GI and GU toxicity were 18.2% and 50%, respectively. Late GU toxicity was associated with greater bladder volume irradiated ≥70 Gy. Late GI toxicity did not correlate with any of the dosimetric parameters.Conclusions: This study demonstrate that hypofractionated helical IMRT with high biologic effective dose (BED) is well tolerated with favourable toxicity rate. If longer follow-up periods and larger cohorts confirm the favourable biochemical control rate and our favourable toxicity assessment results, the hypofractionated IMRT (total 75 Gy, 2.5 Gy/fraction) might be implemented in clinical field for treatment of prostate cancer.

scholarly journals Cost and Toxicity Comparisons of Two IMRT Techniques for Prostate Cancer: A Micro-Costing Study and Weighted Propensity Score Analysis Based on a Prospective Study

2022 ◽  
Vol 11 ◽  
Author(s):  
Ingrid Masson ◽  
Martine Bellanger ◽  
Geneviève Perrocheau ◽  
Marc-André Mahé ◽  
David Azria ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Propensity Score Analysis ◽  
Volumetric Modulated Arc Therapy ◽  
Late Toxicity ◽  
Clinical Effectiveness ◽  
High Risk Prostate Cancer ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
The Mean

BackgroundIntensity modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) has become the standard treatment for patients with high-risk prostate cancer. Two techniques of rotational IMRT are commonly used in this indication: Volumetric Modulated Arc Therapy (VMAT) and helical tomotherapy (HT). To the best of our knowledge, no study has compared their related costs and clinical effectiveness and/or toxicity in prostate cancer. We aimed to assess differences in costs and toxicity between VMAT and HT in patients with high-risk prostate cancer with pelvic irradiation.Material and MethodsWe used data from the “RCMI pelvis” prospective multicenter study (NCT01325961) including 155 patients. We used a micro-costing methodology to identify cost differences between VMAT and HT. To assess the effects of the two techniques on total actual costs per patient and on toxicity we used stabilized inverse probability of treatment weighting.ResultsThe mean total cost for HT, €2019 3,069 (95% CI, 2,885–3,285) was significantly higher than the mean cost for VMAT €2019 2,544 (95% CI, 2,443–2,651) (p &lt;.0001). The mean ± SD labor and accelerator cost for HT was €2880 (± 583) and €1978 (± 475) for VMAT, with 81 and 76% for accelerator, respectively. Acute GI and GU toxicity were more frequent in VMAT than in HT (p = .021 and p = .042, respectively). Late toxicity no longer differed between the two groups up to 24 months after completion of treatment.ConclusionUse of VMAT was associated with lower costs for IMRT planning and treatment than HT. Similar stabilized long-term toxicity was reported in both groups after higher acute GI and GU toxicity in VMAT. The estimates provided can benefit future modeling work like cost-effectiveness analysis.

PD63-03 TREATMENT INTENSIFICATION AND OUTCOME IN HIGH-RISK PROSTATE CANCER

2020 ◽  
Vol 203 ◽  
pp. e1293
Author(s):  
Amar Kishan* ◽  
R. Jeffrey Karnes ◽  
Tahmineh Romero ◽  
Giovanni Motterle ◽  
Rahul Tendulkar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Treatment Intensification ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

scholarly journals Conformal radiotherapy plus high dose rate brachytherapy prostate boost in patients with intermediate and high risk prostate cancer: our experience in Asian males

2012 ◽  
Vol 11 (4) ◽  
pp. 257-270
Author(s):  
Mutahir A. Tunio ◽  
Altaf Hashmi ◽  
Amjad Sattar ◽  
Rehan Mohsin ◽  
Shoukat Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
High Dose Rate ◽  
High Dose ◽  
Free Survival ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Post Radiation ◽  
Grade 3 ◽  
3D Crt

AbstractPurpose: Recent studies have shown increased prostate cancer control rates with radiation dose escalation. Herein the experience of dose escalation by high dose rate brachytherapy (HDR-BT) adjunct to the three-dimensional conformal radiation therapy (3D-CRT) for prostate cancer is presented.Patients and methods: During the period between August 2005 and July 2007, patients with intermediate and high risk prostate cancer were treated with 3D-CRT of dose 46Gy ÷ 23 fractions to whole pelvis followed by: Arm A (102 patients): prostate boost with HDR-BT 14 Gy × 2 sessions and Arm B (103 patients): prostate boost via 3D-CRT of dose 26 Gy ÷ 13 fractions. Primary objectives were overall survival (OS), distant metastases free survival (DMFS) and PSA progression free survival (PPFS) rates. Secondary objectives were the toxicity profile and post-radiation histopathological response.Results: At median follow up of 3.5 years, PPFS, DMFS and OS rates were; 97.8% versus 89.0% (p = 0.009), 98.1% versus 93.6% (p = 0.13) and 98.8% versus 91.6% (p = 0.24) in Arm A and Arm B. respectively. Grade 3 or 4 delayed genitourinary toxicities occurred in 2% and 4.8% of patients in Arm A and Arm B, respectively. Delayed grade 3 and 4 gastrointestinal toxicities were seen in 2% and 3.9% of patients in Arm A and Arm B, respectively. The post-radiation prostate biopsies were negative in 14/17(82.3%) and 9/15 (60%) in Arm A and Arm B, respectively.Conclusion: 3D-CRT combined with HDR-BT resulted in better PPFS and lower morbidity than 3DCRT alone for intermediate and high risk prostate cancer.

scholarly journals Proton Therapy of Prostate and Pelvic Lymph Nodes for High Risk Prostate Cancer: Acute Toxicity

2021 ◽  
Vol 8 (2) ◽  
pp. 41-50
Author(s):  
Richard Choo ◽  
David W. Hillman ◽  
Thomas Daniels ◽  
Carlos Vargas ◽  
Jean Claude Rwigema ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Acute Toxicity ◽  
Lymph Nodes ◽  
Seminal Vesicles ◽  
Pelvic Lymph Nodes ◽  
Gu Toxicity ◽  
Risk Prostate Cancer ◽  
Gi Toxicity ◽  
Grade 3

Abstract Purpose To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and pelvic lymph nodes for prostate cancer. Materials and Methods A prospective study (ClinicalTrials.gov: NCT02874014), evaluating moderately hypofractionated IMPT for high-risk or unfavorable intermediate-risk prostate cancer, accrued a target sample size of 56 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 6750 and 4500 centigray radiobiologic equivalent (cGyRBE), respectively, in 25 daily fractions. All received androgen-deprivation therapy. Acute GI and GU toxicities were prospectively assessed from 7 GI and 9 GU categories of the Common Terminology Criteria for Adverse Events (version 4), at baseline, weekly during radiotherapy, and 3-month after radiotherapy. Fisher exact tests were used for comparisons of categorical data. Results Median age was 75 years. Median follow-up was 25 months. Fifty-five patients were available for acute toxicity assessment. Sixty-two percent and 2%, respectively, experienced acute grade 1 and 2 GI toxicity. Grade 2 GI toxicity was proctitis. Sixty-five percent and 35%, respectively, had acute grade 1 and 2 GU toxicity. The 3 most frequent grade 2 GU toxicities were urinary frequency, urgency, and obstructive symptoms. None had acute grade ≥ 3 GI or GU toxicity. The presence of baseline GI and GU symptoms was associated with a greater likelihood of experiencing acute GI and GU toxicity, respectively. Of 45 patients with baseline GU symptoms, 44% experienced acute grade 2 GU toxicity, compared with only 10% among 10 with no baseline GU symptoms (P = 0.07). Although acute grade 1 and 2 GI and GU toxicities were common during radiotherapy, most resolved at 3 months after radiotherapy. Conclusion A moderately hypofractionated IMPT targeting the prostate/seminal vesicles and regional pelvic lymph nodes was well tolerated with no acute grade ≥ 3 GI or GU toxicity. Patients with baseline GU symptoms had a higher rate of acute grade 2 GU toxicity.

Comparison of acute toxicity in patients treated with a 4-field box or IMRT to deliver elective pelvic nodal irradiation for localized high-risk prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 69-69
Author(s):  
Suneil Jain ◽  
Patrick Cheung ◽  
D. Andrew Loblaw ◽  
Gerard Morton ◽  
Cyril Danjoux ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Acute Toxicity ◽  
Urinary Frequency ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Target Volumes ◽  
Common Technique ◽  
Grade 3 ◽  
New Literature

69 Background: To deliver elective pelvic nodal irradiation (EPNI), a 4-field box (4FB) has been a common technique. More recently, there are increasing reports of using IMRT to deliver EPNI. Even though studies show a clear dosimetric benefit to bowel and bladder, there is a lack of good data demonstrating decreased toxicity with the use of IMRT in this setting. Methods: From 2004-2010, 230 patients with localized high risk prostate cancer were enrolled into 3 sequential prospective phase I/II trials of delivering EPNI (45 Gy) along with a concomitant hypofractionated IMRT boost to the prostate (67.5 Gy total) in 25 fractions over 5 weeks time. All patients were to receive 3 years of adjuvant androgen deprivation. During the accrual period, the method used to deliver the EPNI portion of the treatment changed as new literature emerged about target volumes for EPNI. The 3 methods used to deliver EPNI in this large cohort were 1) 4FB, 2) IMRT with 2cm CTV margins around the pelvic vessels as suggested by Shih et al (IMRT-Shih), and 3) IMRT with nodal volumes as suggested by RTOG (IMRT-RTOG). Common Terminology Criteria for Adverse Events v3.0 was used to assess acute toxicity prospectively during treatment and then at 3 months. Results: For EPNI, 94 patients were treated with a 4FB, 53 were treated with IMRT-Shih, and 83 were treated with IMRT-RTOG. There were no acute grade 3 GI toxicities. Patients in the 4FB group had higher rates of acute grade ≥ 2 proctitis compared to the IMRT-Shih and IMRT-RTOG groups (16.0% vs 2.0% vs 2.4%, p=0.0009). The 4FB group also had higher rates of grade ≥ 2 flatulence compared to the 2 other IMRT groups (17.0% vs 7.6% vs 0%, p<0.0001). With regards to acute GU toxicities, patients in the 4FB group had higher rates of grade ≥ 3 urinary frequency compared to the 2 other IMRT groups (5.3% vs 0% vs 0%, p=0.027). Conclusions: In this non-randomized comparison, IMRT resulted in statistically significant decreases in acute proctitis, flatulence, and urinary frequency when compared to a 4FB technique to deliver EPNI in localized high risk prostate cancer. Analysis for possible confounding factors will be performed.

Phase I trial of total androgen blockade, weekly docetaxel, and image-guided intensity-modulated radiotherapy for localized high-risk prostate adenocarcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 96-96
Author(s):  
Stephen J. Ramey ◽  
Ali Reza Golshayan ◽  
Thomas E. Keane ◽  
Andrew S. Kraft ◽  
Uzair Bashir Chaudhary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Intensity Modulated Radiotherapy ◽  
High Dose ◽  
Weekly Docetaxel ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Grade 3

96 Background: High-risk prostate cancer patients have high rates of treatment failure and improved outcomes are needed. Docetaxel has shown efficacy in hormone-resistant prostate cancer and can act as a radiosensitizer. Dose escalation studies with radiation therapy have found improved freedom from failure rates. The addition of androgen deprivation therapy (ADT) improves overall survival. Therefore, this phase I study was designed to find the maximum tolerable dose (MTD) of weekly docetaxel when combined with high-dose image-guided intensity-modulated radiotherapy (IGRT) and ADT in patients with high-risk prostate cancer. Methods: Men with high-risk adenocarcinoma of the prostate (≥T2c, or PSA ≥20ng/ml, or Gleason ≥8) were treated with weekly docetaxel (given at 10-30 mg/m2, increasing by 5 mg/m2until the MTD was reached) concurrently with IGRT of 77.4 Gy in 43 fractions to the prostate and 45 Gy in 25 fractions to the proximal seminal vesicles. ADT consisted of a gonadotropin-releasing hormone agonist (GnRHa) and bicalutamide beginning 2 months before chemoradiation and continuing 2 months concurrently. The GnRHa was then continued for an additional 24 months. Results: 19 patients began combined chemoradiation between April 2006 and December 2010. Median follow-up is 32 months. No dose-limiting toxicities (DLTs) were seen in patients treated with docetaxel doses up to 25 mg/m2. However, at the 30 mg/m2level, 2 of 4 patients experienced DLTs of both grade 3 fatigue and grade 3 upper GI toxicity, indicating the MTD had been exceeded. At last follow-up, 2 patients had died, one from metastatic prostate cancer and the other from heart failure. A second patient demonstrated biochemical failure by the Phoenix criteria at 46 months, giving an actuarial biochemical disease-free survival (bDFS) at 3 years of 94.7%. All patients had ≥grade 2 erectile dysfunction but no other ≥grade 2 long-term toxicities were identified. Conclusions: Weekly docetaxel may be combined with high-dose IGRT and long-term ADT up to a MTD of 25 mg/m2. Long-term side effects with this regimen were minimal, and bDFS rate is encouraging. Clinical trial information: NCT00099086.

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