Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer.
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DOI：
10.1186/s12885-016-2075-x
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发表时间：
2016-02-05
期刊：
影响因子：
3.8
通讯作者：
Grizzle WE
中科院分区：
文献类型：
--
作者：
Demark-Wahnefried W;Nix JW;Hunter GR;Rais-Bahrami S;Desmond RA;Chacko B;Morrow CD;Azrad M;Frugé AD;Tsuruta Y;Ptacek T;Tully SA;Segal R;Grizzle WE
肥胖与超过15种恶性肿瘤（包括前列腺癌）的肿瘤侵袭性和疾病特异性死亡率相关。临床前研究表明，通过限制热量摄入和增加体力活动来减轻体重可能会抑制激素、能量感应和炎症因子，这些因素会推动肿瘤的进展；然而，确切的机制尚未确定，人体实验也很有限。我们在40名选择前列腺切除术的超重或肥胖的新诊断前列腺癌患者中进行了一项随机对照试验，以探讨术前减肥干预的可行性，通过热量限制和身体活动促进体重减轻约1公斤/周−1，并评估对肿瘤生物学和循环生物标志物的影响。可行性指标（应计性、保留性、依从性和安全性）是主要终点。探索目的是针对干预对肿瘤增殖（Ki-67）和其他肿瘤标志物（活化的caspase-3、胰岛素和雄激素受体、VEGF、TNFβ、NFκB和4E-BP1）、循环生物标志物（PSA、胰岛素、葡萄糖、VEGF、TNFβ、瘦素、SHBG和睾酮）、淋巴细胞相应因子基因表达和中性粒细胞细胞生物能量学的影响，以及对肠道微生物组的影响。同意的患者以1:1的比例随机分为两组：1)通过健康的、基于指南的饮食和锻炼方案减肥；或者2)等候名单控制。虽然生物测试目前正在进行中，但本文详细介绍了我们的方法和可行性结果。101例（入组率39.6%）均达到预期目标。其他结果包括保留率85%，良好的依从性（95%），无严重不良事件报告。受试者与非受试者在年龄、种族或体重方面没有显著差异。不参加的最常见原因是“太忙”（30%）、医疗排除（21%）和“距离”（16%）。手术前试验为研究饮食和运动干预对肿瘤组织的直接影响，以及其他可行和安全的宿主因素提供了一种方法，尽管需要修改，以便在较短的时间内进行试验，并通过远程医学为基础的方法。术前试验对于阐明生活方式干预对介导癌变的特定机制的影响以及随后可作为治疗靶点的影响至关重要。NCT01886677
Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. We conducted a randomized controlled trial among 40 overweight or obese, newly-diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week−1 via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention’s effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFβ, NFκB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFβ, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines-based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. The accrual target was met after screening 101 cases (enrollment rate: 39.6 %). Other outcomes included a retention rate of 85 %, excellent adherence (95 %), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non-enrollees. The most common reasons for non-participation were “too busy” (30 %), medical exclusions (21 %), and “distance” (16 %). Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. NCT01886677