Clinical and Dosimetric Predictors of Toxicity for Treatment of Localized Prostate Cancer Using Moderately Hypofractionated Radiotherapy

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PURPOSE: Moderately hypofractionated radiotherapy (MHRT) is a commonly used treatment modality for localized prostate cancer (LPC). In this setting, dosimetric correlations to acute and late toxicities remain poorly defined.

METHODS: Patients with LPC treated with MHRT between September 2008 and April 2018 were retrospectively identified. We excluded those with < 12 months follow up, elective nodal coverage, or additional boost. All patients received either 70Gy/28 fractions or 60Gy/20 fractions. Demographics, clinical outcomes, and toxicity data were obtained. Acute and late (≥3 months following MHRT completion) gastrointestinal (GI) and genitourinary (GU) toxicities were determined per CTCAE 5.0. Univariate and multivariate analyses were performed for acute and late grade 2+ GI/GU toxicity via logistic regression and log rank testing for demographic and dosimetric variables.

RESULTS: A total of 436 patients with LPC were treated with MHRT. Mean age was 64 years (IQR 60-68), median pre-treatment PSA was 8.7 (IQR 5.7-12.2), and T stages included T1a/2a (357), T2b/2c (58), and T3 (21). Acute grade 3 GU and GI toxicities were observed in 16(3.7%) and 3(0.7%) patients respectively, with no acute grade 4 toxicity events. Late grade 3 GU and GI toxicities were observed in 17(3.9%) and 4(0.9%) patients respectively, with two late grade 4 GI (0.05%) events. On multivariate analysis, acute grade 2+ GU toxicity was associated with pre-treatment PSA (odds ratio [OR] 1.02 95% confidence interval [CI] 1.01-1.04, P = 0.011) and pre-radiotherapy AUA SS (OR 1.06 95%CI: 1.03-1.09, P < 0.001); late grade 2+ GU toxicity was associated with pre-treatment AUA (hazard ratio [HR] 1.04 95%CI: 1.02-1.06, P < 0.001), lack of pre-treatment urinary meds (HR 0.65, 95%CI: 0.46-0.92, P = 0.049), and ADT use (HR 1.45, 95%CI: 1.03-2.03, P = 0.034); acute grade 2+ GI toxicity did demonstrate significant correlation; late grade 2+ GI toxicity was associated with ethnicity (Black vs White, HR 0.50, 95% CI: 0.25-0.99, P = 0.008) and pre-treatment PSA (HR 1.02, 95%CI: 1.00- 1.03, P = 0.024).

CONCLUSION: LPC patients completing MHRT experienced low rates of grade 3+ acute and late GU/GI toxicities. No dosimetric variables demonstrated significance on multivariate analysis of acute or late GU/ GI grade 2+ toxicity. Late grade 2+ GU toxicity was associated with ADT use, while late grade 2+ GI toxicity was associated with ethnicity and pre-treatment PSA.

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PURPOSE: Moderately hypofractionated radiotherapy (MHRT) is a commonly used treatment modality for localized prostate cancer (LPC). In this setting, dosimetric correlations to acute and late toxicities remain poorly defined.

METHODS: Patients with LPC treated with MHRT between September 2008 and April 2018 were retrospectively identified. We excluded those with < 12 months follow up, elective nodal coverage, or additional boost. All patients received either 70Gy/28 fractions or 60Gy/20 fractions. Demographics, clinical outcomes, and toxicity data were obtained. Acute and late (≥3 months following MHRT completion) gastrointestinal (GI) and genitourinary (GU) toxicities were determined per CTCAE 5.0. Univariate and multivariate analyses were performed for acute and late grade 2+ GI/GU toxicity via logistic regression and log rank testing for demographic and dosimetric variables.

RESULTS: A total of 436 patients with LPC were treated with MHRT. Mean age was 64 years (IQR 60-68), median pre-treatment PSA was 8.7 (IQR 5.7-12.2), and T stages included T1a/2a (357), T2b/2c (58), and T3 (21). Acute grade 3 GU and GI toxicities were observed in 16(3.7%) and 3(0.7%) patients respectively, with no acute grade 4 toxicity events. Late grade 3 GU and GI toxicities were observed in 17(3.9%) and 4(0.9%) patients respectively, with two late grade 4 GI (0.05%) events. On multivariate analysis, acute grade 2+ GU toxicity was associated with pre-treatment PSA (odds ratio [OR] 1.02 95% confidence interval [CI] 1.01-1.04, P = 0.011) and pre-radiotherapy AUA SS (OR 1.06 95%CI: 1.03-1.09, P < 0.001); late grade 2+ GU toxicity was associated with pre-treatment AUA (hazard ratio [HR] 1.04 95%CI: 1.02-1.06, P < 0.001), lack of pre-treatment urinary meds (HR 0.65, 95%CI: 0.46-0.92, P = 0.049), and ADT use (HR 1.45, 95%CI: 1.03-2.03, P = 0.034); acute grade 2+ GI toxicity did demonstrate significant correlation; late grade 2+ GI toxicity was associated with ethnicity (Black vs White, HR 0.50, 95% CI: 0.25-0.99, P = 0.008) and pre-treatment PSA (HR 1.02, 95%CI: 1.00- 1.03, P = 0.024).

CONCLUSION: LPC patients completing MHRT experienced low rates of grade 3+ acute and late GU/GI toxicities. No dosimetric variables demonstrated significance on multivariate analysis of acute or late GU/ GI grade 2+ toxicity. Late grade 2+ GU toxicity was associated with ADT use, while late grade 2+ GI toxicity was associated with ethnicity and pre-treatment PSA.

PURPOSE: Moderately hypofractionated radiotherapy (MHRT) is a commonly used treatment modality for localized prostate cancer (LPC). In this setting, dosimetric correlations to acute and late toxicities remain poorly defined.

METHODS: Patients with LPC treated with MHRT between September 2008 and April 2018 were retrospectively identified. We excluded those with < 12 months follow up, elective nodal coverage, or additional boost. All patients received either 70Gy/28 fractions or 60Gy/20 fractions. Demographics, clinical outcomes, and toxicity data were obtained. Acute and late (≥3 months following MHRT completion) gastrointestinal (GI) and genitourinary (GU) toxicities were determined per CTCAE 5.0. Univariate and multivariate analyses were performed for acute and late grade 2+ GI/GU toxicity via logistic regression and log rank testing for demographic and dosimetric variables.

RESULTS: A total of 436 patients with LPC were treated with MHRT. Mean age was 64 years (IQR 60-68), median pre-treatment PSA was 8.7 (IQR 5.7-12.2), and T stages included T1a/2a (357), T2b/2c (58), and T3 (21). Acute grade 3 GU and GI toxicities were observed in 16(3.7%) and 3(0.7%) patients respectively, with no acute grade 4 toxicity events. Late grade 3 GU and GI toxicities were observed in 17(3.9%) and 4(0.9%) patients respectively, with two late grade 4 GI (0.05%) events. On multivariate analysis, acute grade 2+ GU toxicity was associated with pre-treatment PSA (odds ratio [OR] 1.02 95% confidence interval [CI] 1.01-1.04, P = 0.011) and pre-radiotherapy AUA SS (OR 1.06 95%CI: 1.03-1.09, P < 0.001); late grade 2+ GU toxicity was associated with pre-treatment AUA (hazard ratio [HR] 1.04 95%CI: 1.02-1.06, P < 0.001), lack of pre-treatment urinary meds (HR 0.65, 95%CI: 0.46-0.92, P = 0.049), and ADT use (HR 1.45, 95%CI: 1.03-2.03, P = 0.034); acute grade 2+ GI toxicity did demonstrate significant correlation; late grade 2+ GI toxicity was associated with ethnicity (Black vs White, HR 0.50, 95% CI: 0.25-0.99, P = 0.008) and pre-treatment PSA (HR 1.02, 95%CI: 1.00- 1.03, P = 0.024).

CONCLUSION: LPC patients completing MHRT experienced low rates of grade 3+ acute and late GU/GI toxicities. No dosimetric variables demonstrated significance on multivariate analysis of acute or late GU/ GI grade 2+ toxicity. Late grade 2+ GU toxicity was associated with ADT use, while late grade 2+ GI toxicity was associated with ethnicity and pre-treatment PSA.

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