Intensity-modulated radiation therapy from 70Gy to 80Gy in prostate cancer: six- year outcomes and predictors of late toxicity

Abstract

ObjectiveTo report grade ≥2 overall late rectal and urinary toxicities in patients (pts) with prostate cancer treated by intensity-modulated radiotherapy (IMRT) at 3 dose-levels. Identify predictors of radiation toxicity and report biochemical progression free survival (bPFS).MethodsA total of 277 pts were treated with 70Gy (10.8%), 74Gy (63.9%) and 80 Gy (25.3%) using IMRT without pelvic irradiation were analyzed. Short or long-course androgen deprivation therapy (ADT) was allowed in 46.1% of pts. The toxicity was described using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scale. Cox regression models addressed demographics, disease and dosimetry characteristics as potential predictors of late grade ≥2 toxicity after adjusting for other modifying factors.ResultsThe median follow-up was 77 months (range 15; 150). There was no grade ≥4 toxicity. The 5-year cumulative rate of grade ≥2 late rectal and urinary toxicities was 6.3% (95% CI = 3.8%; 10.3%) and 25.3% (95% CI = 19.8%; 31.8%) respectively. In multivariate analysis, only the dose (80Gy vs 74 and 70Gy) was found to increase the risk of rectal toxicity (HR = 2.96 [1.07; 8.20]). For pts receiving 74 Gy, International Prostate Symptom Score (IPSS) at baseline ≥8 (HR = 2.40 [1.08; 5.35]) and dose ≥73Gy delivered in more than 2% of bladder (D2%) were found to be predictors of bladder toxicity (HR = 3.29 [1.36; 7.98]). The 5–year biochemical relapse free survival was 81.0% [74.5%; 86.0%] in the entire population, 97.5% [83.5%; 99.6%] in the low risk group, 84.9% [76.7%; 90.3%] in the intermediate risk group and 66.4% [51.8%; 77.4%] in the high-risk group. D’Amico low (HR = 0.09 [0.01; 0.69]) and intermediate risk groups (HR = 0.50 [0.28; 0.88]) as well as PSA nadir ≥0.2 ng/ml (HR = 1.79 [1.01; 3.21]) were predictive of biochemical relapse.ConclusionsThe rate of late rectal toxicity increased with higher doses, while Dmax ≥74Gy, D2% ≥ 73Gy for bladder wall and baseline IPSS ≥8 increased late urinary toxicity.

Prognosis of nasopharyngeal carcinoma with insufficient radical dose to the primary site in the intensity‐modulated radiotherapy era

“…8 Recently, Hao Peng et al reported that the rate of CR and PR after three cycles of IC regimen of TPF were 11.3% and 79.6%, respectively, in a phase III clinical trial. 24,25 Therefore, it is necessary to investigate whether reduced-dose radiotherapy is feasible for NPC and how to reduce radiation dose. However, it was not possible to assess tumor response because these patients were not examined with MRI after IC in our study.…”

Understanding Urinary Toxicity after Radiotherapy for Prostate Cancer: First Steps Forward

“…An organ with such an architecture is highly sensitive to small volumes receiving high doses. In the particular case of the urinary bladder, reducing the volume that receives more than 75-78 Gy or more than 8-12 Gy per week (5,9,11,12,15,26,27,34,(53)(54)(55) may significantly decrease the risk of acute and/or late urinary toxicity. Table II reports some details of trials highlighting the relationship between acute/late urinary toxicity and bladder doses/prescription dose (with prescription dose being a surrogate for dose to small bladder volumes).…”

“…A first essential risk factor for urinary toxicity, consistently described by different trials, is the baseline urinary functionality (8,13,15,44,77,78), with patients having an already impaired functionality being at higher risk of experiencing severe acute and late urinary toxicity. For this reason, an evaluation of the baseline situation should be mandatory before treatment planning, also considering the possibility of stricter dose limits for some patients.…”

“…Other patient-related characteristics have been emphasized as being associated with an increased risk of worsening of acute and late symptoms: previous transurethral resection of the prostate (8,11,16,26,44,60) as well as smoking (30,(79)(80)(81)(82), age (13,30,34,44,53,62,78), vascular comorbidities and use of cardiovascular drugs (34,62,78), diabetes (15,62,78,79), and use of antihypertensive medication (30,34). These last patient-related characteristics are indirect markers of possible damage to the microcirculation leading to impairment of tissue oxygenation, a key step in the repair of radiation-induced tissue damage.…”

“…The International Prostate Symptoms Score (IPSS (28)) thus became widely used to score obstructive symptoms and generate an overall assessment of urinary functionality (15,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42). Urinary incontinence can be prospectively assessed by the International Consultation on Incontinence Modular Questionnaire Short Form (ICIQ-SF (43)), which also includes the patient's perception of the impact of incontinence on quality of life (14,44).…”