Dataset Information

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

ABSTRACT:

Background

Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs.

Methods

A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment-related, physician-defined Radiation Therapy Oncology Group gastrointestinal (GI) and genitourinary (GU) toxicity. Covariates identified on univariate analysis for toxicity and disease control were examined on multivariable analysis. All statistical tests were 2-sided, and a P less than .05 was considered statistically significant.

Results

A total of 155 of 587 men (26.4%) had 1 or more MAs, most commonly to penicillin (n?=?71), sulfa (n?=?35), and aspirin or nonsteroidal antiinflammatory drugs (n?=?28). On univariate analysis, men with MAs had superior 10-y FFBF (71.5% vs 63.5%, P = .02) and higher incidence of late GI grade 2 or higher (G2+; 20.6% vs 13.2%, P = .04) and grade 3 or higher (G3+; 7.5% vs 3.9%, P = .08) as well as late GU G2+ (42.5% vs 33.2%, P = .04) and G3+ (7.5% vs 3.0%, P = .02) toxicity than men without MAs. On multivariable analysis, MA history remained a statistically significant predictor of FFBF (hazard ratio [HR] = 0.64, 95% confidence interval [CI] = 0.43 to 0.93, P = .02), late G2+ GI (HR = 1.76, 95% CI = 1.06 to 2.90, P=.03), and G3+ GU (HR = 2.69, 95% CI = 1.16 to 6.27, P = .02) toxicity after controlling for corresponding covariates in each model.

Conclusions

Men with MAs had improved FFBF and increased treatment-related toxicity following radiotherapy for prostate cancer. MA history could be a relevant consideration in the management of men with localized prostate cancer.

SUBMITTER: Turchan WT

PROVIDER: S-EPMC7771007 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

Turchan William Tyler WT Gutiontov Stanley I SI Spiotto Michael T MT Liauw Stanley L SL

JNCI cancer spectrum 20200911 6

<h4>Background</h4>Given similarities in the mediators of medication allergy (MA) and tissue response to radiotherapy, we assessed whether outcomes following prostate radiotherapy differ in patients with MAs.<h4>Methods</h4>A total 587 men with known MA history and nonmetastatic prostate cancer underwent radiotherapy from 1989 to 2006. Clinicopathologic and treatment variables were analyzed for association with freedom from biochemical failure (FFBF) and late treatment-related, physician-defined ...[more]

PMID: 33409456

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Project description:BackgroundA total of 10%-20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies.MethodsWe conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10-8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided.ResultsMeta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10-10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10-10), and rs11122573 with hematuria (Pmeta = 1.8 × 10-8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10-6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts.ConclusionsThis study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile.

Project description:OBJECTIVES:To report on initial patient characteristics, treatment practices, toxicity, and early biochemical disease-free survival (bDFS) of localized prostate cancer treated with stereotactic body radiotherapy (SBRT) and enrolled in the RSSearch(®) Patient Registry. METHODS: A retrospective analysis was conducted on patients with clinically localized prostate cancer enrolled in RSSearch(®) from June 2006 - January 2015. Patients were classified as low-risk (PSA ? 10 ng/ml, T1c-T2a, Gleason score ? 6), intermediate-risk (PSA 10.1 - 20 ng/ml, T2b-T2c, or Gleason 7), or high-risk (PSA > 20 ng/ml, T3 or Gleason ? 8). Toxicity was reported using Common Toxicity Criteria for Adverse Events, version 3. Biochemical failure was assessed using the Phoenix definition (nadir + 2 ng/ml). The Kaplan-Meier analysis was used to calculate bDFS and association of patient and tumor characteristics with the use of SBRT. RESULTS: Four hundred thirty-seven patients (189 low, 215 intermediate, and 33 high-risk) at a median of 69 years (range: 48-88) received SBRT at 17 centers. Seventy-eight percent of patients received 36.25 Gy/5 fractions, 13% received 37 Gy/5 fractions, 6% received 35 Gy/5 fractions, 3% received 38 Gy/4 fractions, and 5% received a boost dose of 19.5-29 Gy following external beam radiation therapy. Median follow-up was 20 months (range: 1-64 months). Genitourinary (GU) and gastrointestinal (GI) toxicities were minimal, with no acute or late Grade 3+ GU or GI toxicity. Late Grade 1 and 2 urinary frequency was 25% and 8%. Late Grade 1 and 2 proctitis was 3% and 2%. Median PSA decreased from 5.8 ng/ml (range: 0.3-43) to 0.88, 0.4, and 0.3 ng/ml at one, two, and three years. Two-year bDFS for all patients was 96.1%. Two-year bDFS was 99.0%, 94.5%, and 89.8% for low, intermediate, and high-risk patients (p < 0.0001). Two-year bDFS was 99.2%, 93.2%, and 90.4% for Gleason ? 6, Gleason 7, and Gleason ? 8 (p < 0.0001). Two-year bDFS was 96.4%, 97.2%, and 62.5% for PSA ? 10 ng/ml, PSA 10.1 - 20 ng/ml, and PSA > 20 ng/ml (p < 0.0001). Clinical T Stage was not significantly associated with bDFS. CONCLUSIONS: Early disease outcomes of SBRT for the treatment of clinically localized prostate cancer from a multicenter patient registry compare favorably with reports from single institutions. Acute and late GU and GI toxicities were minimal, and PSA response to SBRT was highly encouraging. Continued accrual and follow-up will be necessary to confirm long-term results.

Dataset Information

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

Background

Methods

Results

Conclusions

Publications

Prostate Cancer Radiotherapy: Increased Biochemical Control and Late Toxicity in Men With Medication Allergies.

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