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Title: Radiation dose and late failures in prostate cancer

Abstract

Purpose: To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone. Methods: The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months. Results: Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at {<=}4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in {<=}4 years. Radiation 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, a reduction occurred in the risk of DM in the early and late waves, although the latemore » wave appeared reduced to a greater degree. Conclusion: The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.« less

Authors:
 [1];  [2];  [1];  [1];  [3];  [4]
  1. Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States)
  2. Department of Public Health, Temple University, Philadelphia, PA (United States)
  3. Department of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States)
  4. Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States). E-mail: alan.pollack@fccc.edu
Publication Date:
OSTI Identifier:
20944765
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2006.10.023; PII: S0360-3016(06)03360-8; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, 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; CARCINOMAS; FAILURES; HEALTH HAZARDS; METASTASES; MULTIVARIATE ANALYSIS; PATIENTS; PROSTATE; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Morgan, Peter B., Hanlon, Alexandra L., Horwitz, Eric M., Buyyounouski, Mark K., Uzzo, Robert G., and Pollack, Alan. Radiation dose and late failures in prostate cancer. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.10.023.
Morgan, Peter B., Hanlon, Alexandra L., Horwitz, Eric M., Buyyounouski, Mark K., Uzzo, Robert G., & Pollack, Alan. Radiation dose and late failures in prostate cancer. United States. doi:10.1016/j.ijrobp.2006.10.023.
Morgan, Peter B., Hanlon, Alexandra L., Horwitz, Eric M., Buyyounouski, Mark K., Uzzo, Robert G., and Pollack, Alan. Thu . "Radiation dose and late failures in prostate cancer". United States. doi:10.1016/j.ijrobp.2006.10.023.
@article{osti_20944765,
title = {Radiation dose and late failures in prostate cancer},
author = {Morgan, Peter B. and Hanlon, Alexandra L. and Horwitz, Eric M. and Buyyounouski, Mark K. and Uzzo, Robert G. and Pollack, Alan},
abstractNote = {Purpose: To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone. Methods: The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months. Results: Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at {<=}4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in {<=}4 years. Radiation 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, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree. Conclusion: The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.},
doi = {10.1016/j.ijrobp.2006.10.023},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 67,
place = {United States},
year = {Thu Mar 15 00:00:00 EDT 2007},
month = {Thu Mar 15 00:00:00 EDT 2007}
}
  • A retrospective analysis of the incidence of radiation proctitis was performed in 154 patients with carcinoma of the prostate treated with external radiotherapy assisted by CT-scan planning from 1983 to 1985. An attempt was made to assess a dose-response relationship for proctitis. Multivariate Cox regression analysis showed that previous bowel disease or surgery, anterior rectal dose, and average rectal dose contributed to a higher risk of proctitis. The anterior rectal dose was the most important indicator. No statistically significant correlation was found for the posterior rectal dose. The actuarial 2-year incidence of moderate or severe proctitis was 22% for anteriormore » rectal doses less than 70 Gy and 20% for anterior rectal doses between 70 and 75 Gy, but increased to 60% when the dose was more than 75 Gy. A dose effect relation was evident, with a sharp dose-response gradient around 75 Gy at the anterior rectal wall.« less
  • 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 andmore » 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.« less
  • We seek to identify dosimetric and anatomic indicators of late rectal toxicity in prostate cancer patients treated with intensity modulated radiation therapy (IMRT). Data from 49 patients sampled from 698 patients treated for clinically localized prostate cancer at the Memorial Sloan-Kettering Cancer Center with IMRT to a dose of 81 Gy were analyzed. The end point of the study was late Grade 2 or worse rectal toxicity within 30 months of treatment. Dosimetric analysis was performed on the rectum surface in three dimensions and on two-dimensional dose maps obtained by flattening the rectum surface using a conformal mapping procedure. Severalmore » parameters including the percentage and absolute surface area of the rectum irradiated, mean dose as a function of location on the rectum, planning target volume (PTV) size and rectum size were analyzed for correlation to toxicity. Significance was set at p<0.05 for a two-sided t-test. Correlation between absolute areas irradiated and toxicity was observed on both the rectum surface and flattened rectum. Patients with toxicity also received a significantly higher mean dose to the superior 25% of the rectum surface and 15% of the flattened rectum. PTV volume, PTV height, rectum surface area and average cross-sectional area were significantly larger in patients with toxicity. The conformal mapping procedure has potential utility for evaluating dose to the rectum and risk of toxicity. Late rectal toxicity was related to the irradiation of the upper part of the rectum and also to the absolute area irradiated, PTV size, and rectum size on the planning computed tomography (CT) scan.« less
  • Purpose: Several randomized trials have shown a benefit of dose escalation to 78 to 79 Gy for men treated with external radiation for localized prostate cancer. Single-institution data suggest a benefit with even higher doses. American College of Radiology 03-12 is a Phase II trial testing the safety and efficacy of 82 GyE (Gray equivalent) delivered with conformal proton radiation. Methods and Materials: From 2003-2006, 85 men with localized prostate cancer were accrued to American College of Radiology 03-12. Eighty-four were eligible for analysis. They were treated with conformal proton radiation alone to a total dose of 82 GyE. Themore » study was designed to test whether the rate of 18-month Grade 3+ late toxicity was greater than 10%. Results: The median follow-up was 31.6 months. Regarding treatment-related acute toxicity, there were 39 Grade 1 cases (46%), 19 Grade 2 cases (23%) and 2 Grade 3 cases (2%). Regarding genitourinary/gastrointestinal toxicity, there were 42 Grade 1 cases (50%), 12 Grade 2 cases (14%) and 1 Grade 3 case (1%). Regarding late toxicity, there were 28 Grade 1 cases (33%), 22 Grade 2 cases (26%), 6 Grade 3 cases (7%), and 1 Grade 4 case (1%). The late genitourinary/gastrointestinal rates were the same. The estimated rate of Grade 3+ late toxicity at 18 months was 6.08%. Conclusions: Although not free of late toxicity, 82 GyE at 2 GyE per fraction delivered with conformal proton radiation did not exceed the late morbidity target tested in this trial. There was sufficient morbidity, however, that this may be the maximal dose that can be delivered safely with this technique and fractionation.« less
  • Purpose: We compared acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients treated with three different high-dose radiation techniques. Methods and Materials: A total of 1,903 patients with localized prostate cancer were treated with definitive RT at William Beaumont Hospital from 1992 to 2006: 22% with brachytherapy alone (BT), 55% with image-guided external beam (EB-IGRT), and 23% external beam with high-dose-rate brachytherapy boost (EBRT+HDR). Median dose with BT was 120 Gy for LDR and 38 Gy for HDR (9.5 Gy Multiplication-Sign 4). Median dose with EB-IGRT was 75.6 Gy (PTV) to prostate with or without seminalmore » vesicles. For EBRT+HDR, the pelvis was treated to 46 Gy with an additional 19 Gy (9.5 Gy Multiplication-Sign 2) delivered via HDR. GI and GU toxicity was evaluated utilizing the NCI-CTC criteria (v.3.0). Median follow-up was 4.8 years. Results: The incidences of any acute {>=} Grade 2 GI or GU toxicities were 35%, 49%, and 55% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Any late GU toxicities {>=} Grade 2 were present in 22%, 21%, and 28% for BT, EB-IGRT, and EBRT+HDR (p = 0.01), respectively. Patients receiving EBRT+HDR had a higher incidence of urethral stricture and retention, whereas dysuria was most common in patients receiving BT. Any Grade {>=}2 late GI toxicities were 2%, 20%, and 9% for BT, EB-IGRT, and EBRT+HDR (p < 0.001). Differences were most pronounced for rectal bleeding, with 3-year rates of 0.9%, 20%, and 6% (p < 0.001) for BT, EB-IGRT, and EBRT+HDR respectively. Conclusions: Each of the three modern high-dose radiation techniques for localized prostate cancer offers a different toxicity profile. These data can help patients and physicians to make informed decisions regarding radiotherapy for prostate andenocarcinoma.« less