Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer

PURPOSE: The aim of this study was to determine the risk factors for late gastrointestinal (GI) morbidity after hypofractionated carbon ion radiotherapy (C-ion RT) for prostate cancer. METHODS AND MATERIALS: Between April 2000 and November 2003, a Phase II clinical trial of C-ion RT with a total dose of 66 GyE in 20 fractions was performed on 175 patients with prostate cancer, and the correlations of clinical and dosimetric parameters with the incidence of late GI toxicity in 172 patients who survived for more than 18 months were investigated. RESULTS: Although no Grade 3-4 late morbidities of the rectum were observed, Grade 1 and 2 morbidities developed in 23 (13%) and 4 (2%) patients, respectively. Dose-volume histogram analysis revealed that the percentage of rectal volume receiving 50% of the prescribed dose (V50) was significantly higher in patients with rectal toxicity than without toxicity (13.2 +/- 5.6% with toxicity; 11.4 +/- 4.0% without toxicity, p = 0.046). Multivariate analysis demonstrated that the use of anticoagulation therapy (p = 0.010) and rectal V50 (p = 0.012) were significant risk factors for the occurrence of Grade 1-2 late GI toxicity. CONCLUSIONS: Although C-ion RT with hypofractionation yielded favorable results regarding late GI complication, dosimetric parameter was a very important factor in the occurrence of rectal bleeding after C-ion RT as well as photon beam RT. Our results provide useful information for physicians applying charged particle RT in the treatment of prostate cancer.     

Predictors for chronic urinary toxicity after the treatment of prostate cancer with adaptive three-dimensional conformal radiotherapy: dose-volume analysis of a phase II dose-escalation study

PURPOSE: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. METHODS AND MATERIALS: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. RESULTS: The 3-year rates of Grade > or =2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planning target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving > or =30 Gy (V30) and > or =82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade > or =2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade > or =2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade > or =2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade > or =2 and Grade 3 chronic urinary toxicity. CONCLUSIONS: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm(3) and the V82 to <7 cm(3) when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.     

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

PURPOSE: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. RESULTS: Anal dosimetric variables were associated with RTOG/EORTC Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D(mean). Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus. CONCLUSION: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.     

Dose-volume comparison of proton therapy and intensity-modulated radiotherapy for prostate cancer

PURPOSE: The contrast in dose distribution between proton radiotherapy (RT) and intensity-modulated RT (IMRT) is unclear, particularly in regard to critical structures such as the rectum and bladder. METHODS AND MATERIALS: Between August and November 2006, the first 10 consecutive patients treated in our Phase II low-risk prostate proton protocol (University of Florida Proton Therapy Institute protocol 0001) were reviewed. The double-scatter proton beam plans used in treatment were analyzed for various dosimetric endpoints. For all plans, each beam dose distribution, angle, smearing, and aperture margin were optimized. IMRT plans were created for all patients and simultaneously analyzed. The IMRT plans were optimized through multiple volume objectives, beam weighting, and individual leaf movement. The patients were treated to 78 Gray-equivalents (GE) in 2-GE fractions with a biologically equivalent dose of 1.1. RESULTS: All rectal and rectal wall volumes treated to 10-80 GE (percentage of volume receiving 10-80 GE [V(10)-V(80)]) were significantly lower with proton therapy (p < 0.05). The rectal V(50) was reduced from 31.3% +/- 4.1% with IMRT to 14.6% +/- 3.0% with proton therapy for a relative improvement of 53.4% and an absolute benefit of 16.7% (p < 0.001). The mean rectal dose decreased 59% with proton therapy (p < 0.001). For the bladder and bladder wall, proton therapy produced significantly smaller volumes treated to doses of 10-35 GE (p < 0.05) with a nonsignificant advantage demonstrated for the volume receiving < or =60 GE. The bladder V(30) was reduced with proton therapy for a relative improvement of 35.3% and an absolute benefit of 15.1% (p = 0.02). The mean bladder dose decreased 35% with proton therapy (p = 0.002). CONCLUSION: Compared with IMRT, proton therapy reduced the dose to the dose-limiting normal structures while maintaining excellent planning target volume coverage.     

Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

PURPOSE: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. METHODS AND MATERIALS: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). RESULTS: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 +/- 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50IC (volume irradiated > or =50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50IC > or =0.127 mL and those with V50IC <0.127 mL were 71.4 +/- 8.5% and 11.5 +/- 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 +/- 10.4% and 28.4 +/- 8.0%, respectively. CONCLUSION: Dose-volume histogram analysis with computed tomography indicated that V50IC and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.     

Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer

PURPOSE: To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer. METHODS AND MATERIALS: From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared. RESULTS: The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test). CONCLUSION: The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.     

前列腺癌患者雄激素剥夺治疗后的代谢营养问题

前列腺癌是男性最常见的恶性肿瘤之一，雄激素剥夺治疗是前列腺癌一线治疗方案。长时间雄激素剥夺治疗前列腺癌患者持续处于雄激素低下状态会出现一系列代谢和营养问题，比如肥胖、糖尿病、脂肪代谢异常、代谢综合征、心血管疾病风险增加等，严重影响患者生活质量、肿瘤序列治疗的进行和预后。但相关针对性研究较少，本文对长时间雄激素剥夺治疗前列腺癌患者的代谢和营养问题，就肥胖、糖尿病、血脂异常以及代谢综合征几个方面，进行深入讨论并对相关研究进行展望。     

前列腺癌碳离子治疗直肠剂量体积直方图预测模型

目的 基于日本经验建立局部效应模型(LEM)下前列腺癌碳离子治疗直肠剂量体积直方图(DVH)预测模型,为临床降低直肠不良反应发生率提供参考。方法 收集局限期前列腺癌患者计划CT图像 76例,采用微剂量动力模型(MKM)进行治疗计划;然后,基于与MKM计划相同的射野,采用LEM重新计算生物剂量获得LEM计划,并在LEM计划中提取直肠几何特征及DVH参数。采用线性回归法对其中 61例计划信息进行建模,余 15例计划用于验证。结果 61例患者计划靶体积沿左右方向外扩1cm后与直肠交叠部分体积同直肠体积比值可作为预测直肠DVH的特征参数。15例患者预测DVH同LEM计划DVH的拟合度优(R²=0.964),基于预测DVH进一步预测直肠不良反应与基于LEM计划DVH预测直肠不良反应的结果一致。结论 线性回归方法可建立较为准确的前列腺癌碳离子治疗直肠DVH预测模型,可能为临床降低直肠不良反应发生率提供一定参考,还有待于临床大样本数据进一步验证。     

晚期前列腺癌患者间歇性内分泌治疗的疗效观察

背景与目的：间歇性内分泌治疗是晚期前列腺癌患者的一种新的治疗策略,但该方法的运用仍然存在一定争议。该研究旨在探讨晚期前列腺癌患者行间歇性内分泌治疗的疗效,并对影响疗效的因素进行分析。方法：选取2009年7月—2015年5月间在我院治疗的晚期前列腺癌患者,均先进行6个月的内分泌治疗,然后评估内分泌治疗的疗效,采用随机数表法将对内分泌治疗敏感的患者分为持续治疗组和间歇治疗组,观察两组患者的疗效、患者的生活质量评分及不良反应等指标,并分析影响间歇治疗组患者预后的相关因素。结果：共收治晚期前列腺癌患者128例,经前期内分泌治疗后有96例前列腺特异性抗原(prostate-specific antigen,PSA)明显下降,其中43例患者接受间歇性内分泌治疗,53例患者接受持续性内分泌治疗。间歇组患者治疗间歇期的KPS评分为82.6±7.4,明显高于持续组患者治疗期间的KPS评分(69.8±8.7),两者之间差异有统计学意义(P<0.05)。间歇组患者治疗相关的不良反应发生率、发展成为非激素依赖性的比例均明显低于持续治疗组,差异有统计学意义(P<0.05)。间歇组5年生存率为72.1%,高于持续组的63%,但两者比较差异无统计学意义(P＞0.05)。前期内分泌治疗后的PSA水平及患者治疗前的Gleason评分是患者预后的重要影响因素。间歇组随访13~70个月,患者接受1～4个循环的治疗。随着治疗时间的延长,参与治疗的例数越来越少,两次治疗的间隔也越来越短。结论：间歇性内分泌治疗是一种有效的治疗晚期前列腺癌的方法,疗效满意,安全可靠,能有效改善患者的生活质量,且能使患者的经济负担明显减轻。     

A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.