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Title: Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

Abstract

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HRmore » 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.« less

Authors:
 [1];  [2];  [3]; ;  [4];  [5];  [6];  [7];  [8];  [9];  [1];  [10];  [4]
  1. Hospital Universitario de la Princesa, Madrid (Spain)
  2. Hospital Son Espases, Palma de Mallorca (Spain)
  3. Hospital Universitari Vall d'Hebron, Barcelona (Spain)
  4. Hospital General Universitario Gregorio Marañón, Madrid (Spain)
  5. Hospital Universitario 12 de Octubre, Madrid (Spain)
  6. Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca (Spain)
  7. Hospital Plató, Barcelona (Spain)
  8. Hospital Clinic, Barcelona (Spain)
  9. Institut Català d'Oncologia, Barcelona (Spain)
  10. Hospital Do Meixoeiro, Vigo (Spain)
Publication Date:
OSTI Identifier:
22645650
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 96; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANDROGENS; DISEASE INCIDENCE; GY RANGE 10-100; MULTIVARIATE ANALYSIS; MYOCARDIAL INFARCTION; NEOPLASMS; PROSTATE; RADIATION DOSES; RADIOTHERAPY; RECTUM; TOXICITY

Citation Formats

Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org, Guerrero, Araceli, Maldonado, Xavier, Álvarez, Ana, González-San Segundo, Carmen, Cabeza Rodriguez, Maria Angeles, Macías, Victor, Pedro Olive, Agustí, Casas, Francesc, Boladeras, Ana, Martín de Vidales, Carmen, Vázquez de la Torre, Maria Luisa, and Calvo, Felipe A. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.06.2445.
Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org, Guerrero, Araceli, Maldonado, Xavier, Álvarez, Ana, González-San Segundo, Carmen, Cabeza Rodriguez, Maria Angeles, Macías, Victor, Pedro Olive, Agustí, Casas, Francesc, Boladeras, Ana, Martín de Vidales, Carmen, Vázquez de la Torre, Maria Luisa, & Calvo, Felipe A. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial. United States. doi:10.1016/J.IJROBP.2016.06.2445.
Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org, Guerrero, Araceli, Maldonado, Xavier, Álvarez, Ana, González-San Segundo, Carmen, Cabeza Rodriguez, Maria Angeles, Macías, Victor, Pedro Olive, Agustí, Casas, Francesc, Boladeras, Ana, Martín de Vidales, Carmen, Vázquez de la Torre, Maria Luisa, and Calvo, Felipe A. Sat . "Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial". United States. doi:10.1016/J.IJROBP.2016.06.2445.
@article{osti_22645650,
title = {Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial},
author = {Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org and Guerrero, Araceli and Maldonado, Xavier and Álvarez, Ana and González-San Segundo, Carmen and Cabeza Rodriguez, Maria Angeles and Macías, Victor and Pedro Olive, Agustí and Casas, Francesc and Boladeras, Ana and Martín de Vidales, Carmen and Vázquez de la Torre, Maria Luisa and Calvo, Felipe A.},
abstractNote = {Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.},
doi = {10.1016/J.IJROBP.2016.06.2445},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 96,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}