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Dual-timing PSA as a biomarker for patients with salvage intensity modulated radiation therapy for biochemical failure after radical prostatectomy.

ABSTRACT: We investigated the outcomes and the associated clinical-pathological factors in patients with prostate cancer (PCa) undergoing salvage intensity modulated radiation therapy (IMRT) for post-radical-prostatectomy (RP) biochemical failure. We report clinical outcomes of post-RP salvage IMRT, and describe chronic toxicity in these patients.Fifty patients with PCa underwent post-RP salvage IMRT. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Clinical-pathological and toxicity information were collected. The prostate cancer-specific survival (PCSS), disease-free survival (DFS), and biochemical-failure-free survival (BFFS) were calculated. Prognostic factors were analyzed for their association with disease control.The median follow-up time was 74 months. The 5-year PCSS, DFS, and BFFS after salvage IMRT were 95%, 88%, and 60%, respectively. Two patients (4%) experienced late gastrointestinal toxicity ≥ grade 3, and 5 patients (10%) had late genitourinary toxicity ≥ grade 3. On multivariate analysis, post-RP prostate-specific antigen (PSA) nadir ≤0.1 ng/ml (P=0.018) and PSA ≤0.5 ng/ml at salvage IMRT (P=0.016) were independent factors predicting better BFFS. Patients with both post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT had a 5-year BFFS of 83% as compared with 43% in other patients (P=0.001).In conclusion, with hormonal therapy in most PCa patients, the addition of salvage IMRT for post-RP biochemical failure can achieve a good outcome with low toxicity. Patients with a post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT could benefit the most from salvage IMRT.

SUBMITTER: Wang YJ

PROVIDER: S-EPMC5190091 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTo compare long-term outcomes and late toxicity between patients treated with 3-dimensional conformal radiation therapy (3D-CRT) and with dose-escalated intensity modulated radiation therapy (IMRT) as salvage radiation therapy (SRT) after prostatectomy.Methods and materialsA total of 110 patients who had been treated at our institution between 2010 and 2018 with SRT for biochemical recurrence after radical prostatectomy were included. The patients were treated either by 3D-CRT with 64 Gy (59 patients) or by IMRT with 70 Gy (51 patients). The irradiation target was the prostate bed only (106 patients) or the prostate bed and pelvic region (4 patients). Twelve patients (11%) received concurrent androgen deprivation therapy. The differences in clinical outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicity between the 3D-CRT and IMRT groups were retrospectively assessed. Toxicities were recorded using the Common Terminology Criteria for Adverse Events, version 5.0. Prostate-specific antigen (PSA) progression after SRT was defined as an increase in the serum PSA level of 0.2 ng/mL from the PSA nadir after SRT and confirmed by a second PSA measurement that was higher than the first.ResultsThe median follow-up time was 7.8 years for 3D-CRT (range:,0.3-9.2 years) and 3.1 years for IMRT (range, 0.4-7.2 years). There was no significant difference in the 4-year biochemical no-evidence-of-disease (bNED) rate between the 3D-CRT and IMRT groups (43.5% vs 52.1%; P = .20). Toxicity analysis showed no significant difference in late GI or GU toxicities of grade 2 or greater between the 3D-CRT and IMRT groups. The respective 4-year cumulative rates of toxicity in the 3D-CRT and IMRT groups were as follows: grade ≥2 GI toxicity, 8.8% and 4.4% (P = .42); grade ≥2 GU toxicity, 19.1% and 20.3% (P = .93); and grade ≥2 hematuria, 5.3% and 8.0% (P = .67). In the 3D-CRT group, the 8-year cumulative rates of GI toxicity, GU toxicity, and hematuria of grade 2 or greater were 8.8%, 28.4%, and 12.6%, respectively.ConclusionsDose-escalated IMRT showed no improvements in bNED or late toxicity compared with 3D-CRT. In addition, the results suggest that GU toxicity can occur after a long period (even after 6 years), whereas GI toxicity is seldom newly observed after 4 years.

Project description:Purpose:To evaluate 2 published normal tissue complication probability models for radiation-induced hypothyroidism (RHT) on a large cohort of oropharyngeal carcinoma (OPC) patients who were treated with intensity-modulated radiation therapy (IMRT). Methods and Materials:OPC patients treated with retrievable IMRT Digital Imaging and Communications in Medicine (DICOMs) data and available baseline and follow-up thyroid function tests were included. Mean dose (Dmean) to the thyroid gland (TG) and its volume were calculated. The study outcome was clinical HT at least 6 months after radiation therapy, which was defined as grade ?2 HT per Common Terminology Criteria for Adverse Events grading system (symptomatic hypothyroidism that required thyroid replacement therapy). Regression analyses and Wilcoxon rank-sum test were used. Receiver operating characteristic curves and area under the curve for the fitted model were calculated. Results:In the study, 360 OPC patients were included. The median age was 58 years. Most tumors (51%) originated from the base of tongue. IMRT-split field was used in 95%, and median radiation therapy dose was 69.96 Gy. In the study, 233 patients (65%) developed clinical RHT that required thyroid replacement therapy. On multivariate analysis higher Dmean and smaller TG volume maintained the statistically significant association with the risk of clinical RHT (P < .0001). Dmean was significantly higher in patients with clinical RHT versus those without (50 vs 42 Gy, P < .0001). Patients with RHT had smaller TG volume compared with those without (11.8 compared with 12.8 mL, P < .0001). AUC of 0.72 and 0.66 were identified for fitted model versus for the applied Boomsma et al and Cella et al models, respectively. Conclusions:Volume and Dmean of the TG are important predictors of clinical RHT and shall be integrated into normal tissue complication probability models for RHT. Dmean and thyroid volume should be considered during the IMRT plan optimization in OPC patients.

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Dual-timing PSA as a biomarker for patients with salvage intensity modulated radiation therapy for biochemical failure after radical prostatectomy.

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