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100 Smoking increases the risk of developing metastatic disease in prostate cancer patients treated with radical radiotherapy
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(cetuximab in this case) to augment survival outcome in a curative cohort of patients treated with radiation alone. This finding suggests that other epithelial cancers treated with dominant radiation approaches may warrant clinical investigation regarding the addition of EGFR inhibitors. Second, the results suggest that cetuximab (and possibly other EGFR inhibitors) warrants clinical evaluation regarding capacity to enhance outcome when added to chemoradiation regimens. Finally, the similar survival gains observed with cetuximab/radiation to those observed with chemoradiation (compared against radiation alone) suggest the potential for cetuximab to substitute for chemotherapy; a concept that warrants systematic clinical evaluation. 98 HOW Can We Use Genomics to Understand Non-targeted effects of Radiotherapy?
C. Mothersi//, C. O'Shea, M. Moriarty, C. Seymour. Medica/ Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ontario; St Luke's /nstitute of Cancer Research, Dublin, ~re~and Radiation-induced bystander effects are the subject of intense investigation in radiation protection. While the effects are produced in cells not directly hit by radiation and not in the radiation field, they clearly have a genetic basis in that different strains of mice, cell lines or human patients express different types of "out-of-field" effects. The effects predominate at low doses and have been discussed mainly in terms of the impact on low-dose risk assessment. Possible therapeutic implications have been alluded to, but not discussed in any detail. The purpose of this presentation is to consider the possible areas where genomics could be applied to bystander biology in areas of major importance or interest in radiotherapy. These include consideration of radiation-induced bystander effects during the cell cycle, under hypoxic conditions, when fractionated therapy modalities are used, or when combined radio-chemotherapy is given. Also discussed are individual variations in toxicity of bystander factors and normal tissue "collateral" damage. The importance of considering the tumor in the context of the organ, and even the organism that supports it, is also discussed. Direct clinical radiotherapy studies that consider bystander effects are not in the public domain at the time of writing, although a clinical study is being analysed by this group at present. Many in vitro studies are available that are relevant; some preliminary animal data have also been published. Because radiation-induced bystander effects appear to challenge many of the central assumptions that underlie radiotherapy practice, it is important to consider what unexplored treatment avenues might result from a consideration of these effects. The final part of this presentation is devoted to this point. 99 Acute Genitourinary (GU) Toxicity in Prostate Cancer Patients Treated with External Beam Radiotherapy (EBRT) is Due to the Dose to the Urethra.
M. Schwartz 7, S. Pater, R. Corns2, I. Lavoie2, J. Ske//7, B. Bahoric I, L. Souhami ~. ~McGi// University Department of Radiation Onco/ogy, Montrea/, Quebec; 2McGill University Department of Medical Physics, Montreal, Quebec Objectives: To analyze the dose to the urethra and bladder in relation to acute GU toxicity. Methods: Following CT simulation with a urethrogram, sixteen patients each had three plans generated: i) the original plan that each patient was treated with, ii) a plan from a reduced field technique, and iii) a plan from an anterior urethral block technique. The reduced field and anterior urethral block
CARO 2004
techniques were designed to decrease the dose to the urethra outside of the planning target volume (urethral dose) while maintaining the dose to the PTV. The doses to the urethra, bladder, and urethral volume from the original plan were correlated to acute GU toxicities, and a logistic fit model was generated. Results: The rates of grade 1, 2, and 3 acute GU toxicity were 13.0%, 62.5%, and 13.0%, respectively. The urethral dose significantly correlated with acute GU toxicity (p = 0.0056), but the doses to the bladder and urethral volume did not. The difference of the urethral dose between the anterior urethral block vs. original plan was 14.3% (p < 0.0001) and the reduced field vs. original 10% (p < 0.0001). There were no differences between the three plans in regards to the dose to the PTV, rectum or bladder. Using our predictive model, a dose decrease from 44 to 38.6 Gy using an anterior urethral block would decrease the risk of acute GU grade 3 toxicity by 50%. Conclusions: The dose to the bladder does not correlate with acute GU toxicity. We found a significant correlation with the dose to the urethra and acute GU toxicity, showing that the urethral dose is the limiting factor for acute effects. By using the reduced field or anterior urethral block techniques, the dose to the urethra can be easily decreased without compromising coverage to the PTV. 100 Smoking Increases the Risk of Developing Metastatic Disease in Prostate Cancer Patients Treated with Radical Radiotherapy.
J. Pantarotto', S. Dahrouge 1, L. Eapen ~, Y. Mac2, A.M. Ugnat2, L. Xiez, V. Gallant 1, S. Malone 7. 1The Ottawa Hospital, University of Ottawa, Ottawa, Ontario; 2Centre for Chronic Disease Prevention and Control, Health Canada, Ottawa, Ontario Background: Population-based studies have suggested that smoking is related to an increased risk of developing fatal disease. We evaluated the impact of smoking on long-term outcome in a cohort of men treated at one institution with a uniform radical radiotherapy protocol. Methods: The study is a retrospective cohort review of 313 cT1-T4 NO M0 patients. Treatment consisted of a curative course of external beam radiotherapy (6600 cGy/33) with 44% treated with short course. Results: Median age at treatment was 69. Clinical stage on presentation was 43% T1-T2a, 35% T2b-c, and 22% T3-T4. Gleason scores of < 6 observed in 69%, 7 in 18% and > 8 in 13%. Median PSA was 10.5 ng/mL. 54% of the population were former smokers and 17% were current smokers. Tobacco history was not correlated with stage, Gleason score or pretreatment PSA. Median follow-up was 5.8 years. Smoking was associated with an elevated risk of metastatic failure in the univariate analysis. This association was maintained in the multivariate analysis for former smokers (HR = 2.8, p = 0.11) and for current smokers (HR = 5.7, p = 0.015) when compared to non-smokers. A history of smoking (former and current) was associated with reduced disease-specific survival (HR = 2.20) but this was not statistically significant (p = 0.17). Conclusions: Smoking is associated with an increased risk of developing metastatic disease and may impact on disease specific survival in prostate cancer patients treated with curative radiotherapy.
(cetuximab in this case) to augment survival outcome in a curative cohort of patients treated with radiation alone. This finding suggests that other epithelial cancers treated with dominant radiation approaches may warrant clinical investigation regarding the addition of EGFR inhibitors. Second, the results suggest that cetuximab (and possibly other EGFR inhibitors) warrants clinical evaluation regarding capacity to enhance outcome when added to chemoradiation regimens. Finally, the similar survival gains observed with cetuximab/radiation to those observed with chemoradiation (compared against radiation alone) suggest the potential for cetuximab to substitute for chemotherapy; a concept that warrants systematic clinical evaluation. 98 HOW Can We Use Genomics to Understand Non-targeted effects of Radiotherapy?
C. Mothersi//, C. O'Shea, M. Moriarty, C. Seymour. Medica/ Physics and Applied Radiation Sciences Unit, McMaster University, Hamilton, Ontario; St Luke's /nstitute of Cancer Research, Dublin, ~re~and Radiation-induced bystander effects are the subject of intense investigation in radiation protection. While the effects are produced in cells not directly hit by radiation and not in the radiation field, they clearly have a genetic basis in that different strains of mice, cell lines or human patients express different types of "out-of-field" effects. The effects predominate at low doses and have been discussed mainly in terms of the impact on low-dose risk assessment. Possible therapeutic implications have been alluded to, but not discussed in any detail. The purpose of this presentation is to consider the possible areas where genomics could be applied to bystander biology in areas of major importance or interest in radiotherapy. These include consideration of radiation-induced bystander effects during the cell cycle, under hypoxic conditions, when fractionated therapy modalities are used, or when combined radio-chemotherapy is given. Also discussed are individual variations in toxicity of bystander factors and normal tissue "collateral" damage. The importance of considering the tumor in the context of the organ, and even the organism that supports it, is also discussed. Direct clinical radiotherapy studies that consider bystander effects are not in the public domain at the time of writing, although a clinical study is being analysed by this group at present. Many in vitro studies are available that are relevant; some preliminary animal data have also been published. Because radiation-induced bystander effects appear to challenge many of the central assumptions that underlie radiotherapy practice, it is important to consider what unexplored treatment avenues might result from a consideration of these effects. The final part of this presentation is devoted to this point. 99 Acute Genitourinary (GU) Toxicity in Prostate Cancer Patients Treated with External Beam Radiotherapy (EBRT) is Due to the Dose to the Urethra.
M. Schwartz 7, S. Pater, R. Corns2, I. Lavoie2, J. Ske//7, B. Bahoric I, L. Souhami ~. ~McGi// University Department of Radiation Onco/ogy, Montrea/, Quebec; 2McGill University Department of Medical Physics, Montreal, Quebec Objectives: To analyze the dose to the urethra and bladder in relation to acute GU toxicity. Methods: Following CT simulation with a urethrogram, sixteen patients each had three plans generated: i) the original plan that each patient was treated with, ii) a plan from a reduced field technique, and iii) a plan from an anterior urethral block technique. The reduced field and anterior urethral block
CARO 2004
techniques were designed to decrease the dose to the urethra outside of the planning target volume (urethral dose) while maintaining the dose to the PTV. The doses to the urethra, bladder, and urethral volume from the original plan were correlated to acute GU toxicities, and a logistic fit model was generated. Results: The rates of grade 1, 2, and 3 acute GU toxicity were 13.0%, 62.5%, and 13.0%, respectively. The urethral dose significantly correlated with acute GU toxicity (p = 0.0056), but the doses to the bladder and urethral volume did not. The difference of the urethral dose between the anterior urethral block vs. original plan was 14.3% (p < 0.0001) and the reduced field vs. original 10% (p < 0.0001). There were no differences between the three plans in regards to the dose to the PTV, rectum or bladder. Using our predictive model, a dose decrease from 44 to 38.6 Gy using an anterior urethral block would decrease the risk of acute GU grade 3 toxicity by 50%. Conclusions: The dose to the bladder does not correlate with acute GU toxicity. We found a significant correlation with the dose to the urethra and acute GU toxicity, showing that the urethral dose is the limiting factor for acute effects. By using the reduced field or anterior urethral block techniques, the dose to the urethra can be easily decreased without compromising coverage to the PTV. 100 Smoking Increases the Risk of Developing Metastatic Disease in Prostate Cancer Patients Treated with Radical Radiotherapy.
J. Pantarotto', S. Dahrouge 1, L. Eapen ~, Y. Mac2, A.M. Ugnat2, L. Xiez, V. Gallant 1, S. Malone 7. 1The Ottawa Hospital, University of Ottawa, Ottawa, Ontario; 2Centre for Chronic Disease Prevention and Control, Health Canada, Ottawa, Ontario Background: Population-based studies have suggested that smoking is related to an increased risk of developing fatal disease. We evaluated the impact of smoking on long-term outcome in a cohort of men treated at one institution with a uniform radical radiotherapy protocol. Methods: The study is a retrospective cohort review of 313 cT1-T4 NO M0 patients. Treatment consisted of a curative course of external beam radiotherapy (6600 cGy/33) with 44% treated with short course. Results: Median age at treatment was 69. Clinical stage on presentation was 43% T1-T2a, 35% T2b-c, and 22% T3-T4. Gleason scores of < 6 observed in 69%, 7 in 18% and > 8 in 13%. Median PSA was 10.5 ng/mL. 54% of the population were former smokers and 17% were current smokers. Tobacco history was not correlated with stage, Gleason score or pretreatment PSA. Median follow-up was 5.8 years. Smoking was associated with an elevated risk of metastatic failure in the univariate analysis. This association was maintained in the multivariate analysis for former smokers (HR = 2.8, p = 0.11) and for current smokers (HR = 5.7, p = 0.015) when compared to non-smokers. A history of smoking (former and current) was associated with reduced disease-specific survival (HR = 2.20) but this was not statistically significant (p = 0.17). Conclusions: Smoking is associated with an increased risk of developing metastatic disease and may impact on disease specific survival in prostate cancer patients treated with curative radiotherapy.