Safety of Purified Isoflavones in Men With Clinically Localized Prostate Cancer

Our purpose was to evaluate the safety of 80 mg of purified isoflavones administered to men with early stage prostate cancer. A total of 53 men with clinically localized prostate cancer, Gleason score of 6 or below, were supplemented with 80 mg purified isoflavones or placebo for 12 wk administered in 2 divided doses of 40 mg to provide a continuous dose of isoflavones. Compliance, changes in plasma isoflavones, and clinical toxicity were analyzed at baseline, 4, and 12 wk. A total of 50 subjects completed the 12-wk intervention. A continuous, divided-dose administration of 80 mg/day of purified isoflavones at amounts that exceeded normal American dietary intakes significantly increased (P < 0.001) plasma isoflavones in the isoflavone-treated group compared to placebo and produced no clinical toxicity. With the current evidence on the cancer preventive properties of isoflavones, these results are significant and offer promise for these phytochemicals to be developed as potent agents to prevent cancer progression.     

分析前列腺癌三维适形放疗的预后因素

目的 分析前列腺癌三维适形放疗的疗效及预后因素。方法 对37例前列腺癌患者进行三维适形放疗,24例三维适形放疗前接受双侧睾丸切除,4例行放疗去势。20例同时服用艾去适内分泌化疗药物9~12个月。采用三维适形放疗技术照射前列腺靶区,5次/周,2Gy/次。肿瘤中位剂量72Gy(60~76Gy)。用Longrank进行单因素,Cox进行多因素分析。结果 中位随访27个月(6~107个月),随访率为95%。3、5a生存率分别为80%、70%。单因素分析显示年龄、治疗前PSA(前列腺特异抗原)水平、有无区域淋巴结转移、是否合并远处转移、靶区照射剂量及是否采用综合治疗对生存期有影响。多因素分析显示治疗前PSA水平、靶区照射剂量及是否采取综合治疗3个因素影响预后。结论 前列腺癌三维适形放疗安全有效,治疗前PSA水平、靶区照射剂量及是否采取综合治疗是预后的影响因素。     

头颈肿瘤放射治疗后口干症的临床分析

目的：探讨放射治疗头颈肿瘤后产生口干症的影响因素。方法：对2005年8月～2006年1月收治的头颈肿瘤82例，在放疗期间每周末询问患者的口干情况，根据结果分析口干症的严重程度及影响。结果：当患者所接受放射剂量逐增时，口干症的发生率有非常显著的差异（x^2=26．24，P〈0．001）；年龄低于40岁组口干症的发生率与40岁以上组比较无明显差异（x^2=0.026，P〉0．05）。结论：头颈肿瘤放射治疗后可以发生口干症，与患者所受放射总剂量有关：而当患者接受高剂量照射时，患者年龄对口干症的发生率影响不大。放疗期间应尽可能降低或延迟口干症的发生．保证放疗质量。     

Impact of Soy Isoflavones on the Epigenome in Cancer Prevention

Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.     

Effects of Soy Protein Isolate Consumption on Prostate Cancer Biomarkers in Men With HGPIN,ASAP, and Low-Grade Prostate Cancer

Fifty-eight men at high risk of prostate cancer or with low-grade prostate cancer were randomly assigned to consume 1 of 3 protein isolates containing 40 g protein: 1) soy protein (SPI+, 107 mg isoflavones/d); 2) alcohol-washed soy protein (SPI–, <6 mg isoflavones/d); or 3) milk protein (MPI). Proliferating cell nuclear antigen (PCNA), epidermal growth factor receptor, B-cell non-Hodgkin lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) were assessed in baseline and ending prostate biopsy cores. Serum collected at 0, 3, and 6 mo was analyzed for total and free prostate specific antigen (PSA). Consumption of SPI+ did not alter any of the prostate cancer tumor markers. Bax expression decreased from baseline in the SPI– group, resulting in lower Bax expression than the MPI group. PCNA expression also decreased from baseline in the SPI– group, but this was not different from the other 2 groups. PSA did not differ among the groups at 3 or 6 mo. Interestingly, a lower rate of prostate cancer developed in the soy groups compared to the milk group (P = 0.01). These data suggest that 6-mo SPI+ consumption does not alter prostate tissue biomarkers, SPI– consumption exerts mixed effects, and less prostate cancer is detected after 6 mo of soy consumption regardless of isoflavone content.     

Chemoprevention of Rat Prostate Carcinogenesis by Soy Isoflavones and by Bowman-Birk Inhibitor

Epidemiology studies suggest that soy consumption confers protection against human prostate cancer. To identify the soy component(s) that may be responsible for this chemopreventive activity, studies were conducted to determine the influence of a soy isoflavone mixture (PTI G-2535; 45% genistein, 22% daidzein, 2% glycitein) and a soy-derived protease inhibitor (Bowman-Birk Inhibitor Concentrate; BBIC) on prostate carcinogenesis in rats. Prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate and testosterone propionate, followed by a single intravenous injection of N-methyl-N-nitrosourea (MNU) and chronic androgen stimulation. In separate studies, PTI G-2535 and BBIC were administered continuously at 0 (control), 200, or 2000 mg/kg diet, beginning 1 wk post-MNU. PTI G-2535 and BBIC both conferred modest, but statistically significant and dose-related protection against carcinogenesis in the dorsolateral + anterior prostate. These data demonstrate that both the isoflavone and protein (protease inhibitor) components of soy can inhibit prostate carcinogenesis in the rat. However, the modest individual activities of soy isoflavones and BBIC suggest that while both components may contribute to the chemopreventive activity of soy, combination administration (or exposure to whole soy) may be more effective in prostate cancer prevention than is administration of either component alone.     

A Combination of Tomato and Soy Products for Men With Recurring Prostate Cancer and Rising Prostate Specific Antigen

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (± 15 mg) and mean soy intake for Group B was 39 g (± 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 ± 0.09 μ mol/l to 1.21 ± 0.10 μ mol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 ± 5.7 μ mol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.     

Relationship of Dietary Protein and Soy Isoflavones to Serum IGF-1 and IGF Binding Proteins in the Prostate Cancer Lifestyle Trial

High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.     

A Phase II Trial of a Soy Beverage for Subjects Without Clinical Disease With Rising Prostate-Specific Antigen After Radical Radiation for Prostate Cancer

Our objective was to evaluate the tolerability and effect of a daily soy beverage in prostate cancer patients with biochemical failure after radiotherapy. Patients with rising prostate-specific antigen (PSA) after radical radiation for prostate cancer were instructed to consume 500 ml of soy beverage daily for 6 mo. Tolerability of the soy beverage and compliance were assessed. PSA doubling times before and after the consumption of soy were compared. Thirty-four subjects were enrolled; 5 withdrew before 1 mo of soy for reasons unrelated to soy consumption. All remaining 29 subjects were included in the analysis. Mean consumption of the assigned soy beverage was 93%. Mild gastrointestinal upset (38%) not affecting soy consumption was the commonest side effect. PSA showed a declining trend in 4 patients (13.8%), and there was a > 100% prolongation of PSA doubling time in 8 patients (27.6%). However, PSA doubling time also showed a 50% or more shortening in 5 patients (17.2%). In our cohort of North American subjects, 6 mo of a daily soy beverage was well tolerated and was associated with a declining trend or more than 2 times prolongation of PSA doubling time in 41% of subjects. Confirmatory studies are warranted.     

异黄酮对前列腺癌细胞的激素受体基因表达的影响

[目的] 通过大豆异黄酮的活性物质染料木黄酮和大豆苷元抑制前列腺癌PG-3和LNCaP细胞增殖和对激素基因表达的影响，探讨大豆异黄酮治疗和预防前列腺癌的可能机制。[方法] 0、10、20、40、60、80和160μmol／L剂量组的染料木黄酮和大豆苷元处理前列腺癌细胞，细胞存活率用MTT方法检测，α雌激素受体(ERα)、β雌激素受体(ERβ)、雄激素受体(AR)和血管上皮生长因子(VEGF)等基因的mRNA表达用RT-PCR进行检测。[结果] 染料木黄酮和大豆苷元对PC-3、LNCaP细胞具有明显的抑制生长作用，在160μmol／L的浓度时，染料木黄酮、大豆苷元作用72h后，PC-3细胞的存活率分别为12．28％和44．88％，LNCaP细胞的存活率分别为25．48％和43．14％，其抑制效应具有时间和剂量依赖性，同时发现对．PC-3细胞的VEGF、ERα和ERβ基因表达下调，AR基因处理前后没有检测到；对LNCaP细胞的VEGF和AR基因表达下调，ERα和ERβ的表达并无影响。[结论] 大豆异黄酮能抑制前列腺癌细胞的增殖效应，存在时间和剂量效应关系，雌激素受体基因可能直接在大豆苷元抑制PC-3细胞的增殖中参与作用，而染料木黄酮抑制PC-3细胞和染料木黄酮及大豆苷元抑制LNCaP细胞可能主要是通过Akt通路影响VEGF和AR等基因而实现。     

晚期前列腺癌的内分泌治疗

近年来由于前列腺癌 (Ｐｃａ)发病率逐年上升以及内分泌治疗的进展 ,人们对晚期Ｐｃａ越来越重视。本院自 1988年至 1998年 4月采用内分泌疗法治疗 14例 ,疗效满意 ,现报告如下。1　临床资料1·1　一般资料　 14例中 ,年龄 5 7～ 76岁 ,平均 6 5 6岁 ,病史 3个月至 4年。所有病例都有不同程度的排尿困难。合并尿频、肉眼血尿、下腹部包块各 4例 ;胸水或腹水 3例 ;进行性消瘦 5例。经Ｂ超及ＣＴ诊断 ,所有病例肿瘤已侵犯到前列腺包膜外。其中累及膀胱、直肠各 2例 ;合并膀胱或淋巴结转移 6例 ;骨盆、肋骨转移各 3例 ;肝、肺、股骨及腰椎转移…     

宫颈癌术后调强放疗与普通放疗对骨盆的影响

目的分析比较调强放疗(Intensity-modulated Radiation Therapy,IMRT)与普通放疗(radiation therapy,RT)在宫颈癌术后治疗对骨盆正常组织的影响。方法收集2010年1月~2015年12月在医院行手术治疗后接受IMRT的109名宫颈癌患者临床资料,与既往在医院接受RT的109名宫颈癌术后患者临床资料进行对比,回顾分析治疗前和治疗后的CT扫描结果,比较IMRT与RT对骨盆的影响。结果 IMRT组中,4例出现骨折(随访中位时间26.0个月),RT组出现18例骨盆并发症,其中12例骨折,2例股骨头坏死,4例骨髓炎(随访中位时间31.0个月),两组数据具有统计学差异(P=0.01)。结论 IMRT出现骨盆并发症的风险明显小于RT。     

Cost-Effectiveness of Providing the Depression Care for People With Cancer Program to Patients With Prostate Cancer in the United States

ObjectivesThe Depression Care for People with Cancer program (DCPC) is a cost-effective depression care model for UK patients with cancer. However, DCPC’s cost-effectiveness in the United States is unknown, particularly for patients with prostate cancer in the United States. This study evaluates the health and economic impact of providing DCPC to patients with prostate cancer.MethodsDCPC was compared with usual care in a mathematical model that simulates depression and its outcomes in a hypothetical cohort of US patients with prostate cancer. DCPC was modeled as a sequential combination of universal depression screening, post-screening evaluations, and first-line combination therapy. Primary outcomes were lifetime direct costs of depression care, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Secondary outcomes included life expectancy, number of depression-free months and lifetime depressive episodes, duration of depressive episodes, cumulative incidence of depression, lifetime depression diagnoses/misdiagnoses, and the cumulative incidence of maintenance therapy for depression. Sensitivity analyses were used to examine uncertainty.ResultsIn the base case, DCPC dominated usual care by offering 0.11 more QALYs for $2500 less per patient (from averted misdiagnoses). DCPC also offered 5 extra depression-free months, shorter depressive episodes, and a lower chance of maintenance therapy. DCPC’s trade-offs were a higher cumulative incidence of depression and more lifetime depressive episodes. Life expectancy was identical under usual care and DCPC. Sensitivity analyses indicate that DCPC was almost always preferable to usual care.ConclusionCompared with usual care, DCPC may offer more value to US patients with prostate cancer. DCPC should be considered for inclusion in prostate cancer survivorship care guidelines.     

Cost-Effectiveness Analysis of Treating Patients With NTRK-Positive Cancer With the Histology-Independent Therapy Entrectinib

ObjectivesThis study tackles several challenges of evaluating histology-independent treatments using entrectinib as an example. Histology-independent treatments are provided based on genetic marker(s) of tumors, regardless of the tumor type. We evaluated the lifetime cost-effectiveness of testing all patients for NTRK fusions and treating the positive cases with entrectinib compared with no testing and standard of care (SoC) for all patients.MethodsThe health economic model consisted of a decision tree reflecting the NTRK testing phase followed by a microsimulation model reflecting treatment with either entrectinib or SoC. Efficacy of entrectinib was based on data from basket trials, whereas historical data from NTRK-negative patients were corrected for the prognostic value of NTRK fusions to model SoC.Results“Testing” (testing for NTRK fusions, with subsequent entrectinib treatment in NTRK-positive patients and SoC in NTRK-negative patients) had higher per-patient quality-adjusted life-years (QALYs) and costs than “No testing” (SoC for all patients), with a difference of 0.0043 and €732, respectively. This corresponded to an incremental cost-effectiveness ratio (ICER) of €169 957/QALY and, using a cost-effectiveness threshold of €80 000/QALY, an incremental net monetary benefit of ?€388. When excluding the costs of genetic testing for NTRK fusions, the ICER was reduced to €36 290/QALY and the incremental net monetary benefit increased to €188.ConclusionsWhen treatment requires the identification of a genetic marker, the associated costs and effects need to be accounted for. Because of the low prevalence of NTRK fusions, the number needed-to-test to identify patients eligible for entrectinib is large. Excluding the testing phase reduces the ICER substantially.     

A Phase II Randomized,Placebo-Controlled Clinical Trial of Purified Isoflavones in Modulating Steroid Hormones in Men Diagnosed With Localized Prostate Cancer

Our purpose was to evaluate the safety and effectiveness of purified isoflavones in producing an increase in plasma isoflavones and a corresponding change in serum sex hormone binding globulin (SHBG) and steroid hormone levels in men diagnosed with early stage prostate cancer. In this Phase II randomized, double-blinded, placebo-controlled trial, 53 prostate cancer patients with a Gleason score of 6 or below were supplemented with 80 mg purified isoflavones or placebo for 12 weeks. Changes in plasma isoflavones, serum steroid hormones, and safety markers were analyzed from baseline to 12 wk. A total of 50 subjects completed the study. Although significant increases in plasma isoflavones (P < 0.001) was observed with no clinical toxicity, the corresponding modulation of serum SHBG, total estradiol, and testosterone in the isoflavone-treated group compared to men receiving placebo was nonsignificant. Increasing plasma isoflavones failed to produce a corresponding modulation of serum steroid hormone levels in men with localized prostate cancer. The study establishes the need to explore other potential mechanisms by which prolonged and consistent purified isoflavone consumption may modulate prostate cancer risk.     

Systematic Review of the Cost Effectiveness of Radiation Therapy for Prostate Cancer from 2003 to 2013

Background

Prostate cancer remains a prevalent diagnosis with a spectrum of treatment choices that offer similar oncologic outcomes but differing side effect profiles and associated costs. As the technology for prostate radiation therapy has advanced, its associated costs have escalated, thus making cost-effectiveness analyses critical to assess the value of competing treatment options, including watchful waiting, surgery, brachytherapy, intensity-modulated radiation therapy (IMRT), 3D-conformal radiation therapy (3D-CRT), proton beam therapy (PBT), and stereotactic body radiation therapy (SBRT).

Objective

The aim of this systematic review was to identify articles that performed a cost-effectiveness analysis on different radiation treatment options for localized prostate cancer, summarize their findings, and highlight the main drivers of cost effectiveness.

Methods

A literature search was performed on two databases, PubMed and the Cost-Effectiveness Analysis Registry (https://research.tufts-nemc.org/cear4), using search terms that included ‘prostate’, ‘cost effectiveness prostate radiation’ and ‘cost analysis comparative effectiveness prostate radiation’. Studies were included in this review if the cost data were from 2002 or later, and outcomes reported both cost and effectiveness, preferably including a cost–utility analysis with the outcome of an incremental cost-effectiveness ratio with quality-adjusted life-year (QALY) as the effectiveness measure.

Results

There were 14 articles between 2003 and 2013 that discussed cost effectiveness of prostate radiotherapy in men over the age of 65. All but four of the papers were from the US; the others were from Canada and the UK. The majority of the papers used Markov decision analysis and estimated cost from a payer’s perspective, usually from Medicare reimbursement data. Assumptions for the model and utilities to calculate QALYs were estimated using published literature at the time of the analysis. Each analysis had a sensitivity analysis to compensate for the uncertainty of the model inputs. The main drivers of cost effectiveness were the cost of the radiation treatment and the differential QALYs accrued because of different treatment-related morbidities. Brachytherapy was consistently found to be more cost effective when compared with surgery and other radiation treatment options. IMRT was cost effective when compared with 3D-CRT. PBT was not found to be cost effective in any of the analyses, mostly due to the high costs of PBT. SBRT was the newest technology that was analyzed, and it was also found to be cost effective compared with IMRT and PBT.

Conclusions

Cost-effectiveness research of prostate radiation treatments allows patients, providers, and payers to better understand the true value of each treatment choice. Due to the variation in each of these analyses (e.g., costing, and disease and complication assumptions, etc.), it is difficult to generalize the results. One must be careful in drawing conclusions from these studies and extrapolating to individual patients, particularly with the clear utility dependence seen in the majority of these studies.     

Role of Isoflavones in the Hypocholesterolemic Effect of Soy

Epidemiologic data suggest an inverse relationship between the consumption of soy isoflavones and cardiovascular disease risk. The aims of this review are to determine if isoflavones play a role in the hypocholesterolemic effect of soy and whether the studies realized with that scope were adequately designed. In humans, most studies have been performed in postmenopausal women. The results are inconsistent, however; some studies show a decrease in total cholesterol and low-density lipoprotein concentrations, and an increase in high-density lipoprotein levels, and other investigations fail to show any beneficial effect of soy isoflavones on lipid profiles. In most studies, beneficial effects could not be attributed with certainty to soy isoflavones. If these components have any health-protecting effect in humans, it is small in comparison with the effect of soy protein itself. There are currently not enough data to recommend the consumption of isoflavone supplements to lower plasma cholesterol levels.     

An Occupational Therapy Program for Patients With Swallowing Dysfunction Following Cancer Treatment

Eating, the intimate activity of daily living, carries with it many emotional, social and physical implications. Medical treatment of patients with cancers of the head and neck is frequently radical and almost certainly impacts on the patient's ability to eat. This paper outlines an occupational therapy program for patients with swallowing dysfunction following treatment for cancers of the head and neck. Discussed in this paper are the medical treatments particular to cancer treatment that directly affect swallowing function, along with evaluation and treatment by the occupational therapist. The paper concludes with a case study.