Hypofractionated IMRT for Localized Prostate Cancer

大分割 IMRT 治疗局限性前列腺癌

• 批准号: 7251482
• 负责人: Mark A Ritter
• 金额: $ 22.28万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-24 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7251482
• 关键词: Arts; Biological Markers; Bladder; Clinical; Clinical Trials; Correlative Study; Data; Dose; Economics; Fractionation; Institution; Intensity-Modulated Radiotherapy; Lead; Localized; Malignant neoplasm of prostate; Measures; Modeling; Normal tissue morphology; Organ; Outcome; Outcome Study; Patients; Phase; Prostate; Prostatic Neoplasms; Radiation; Radiation therapy; Rate; Rectum; Relative (related person); Research Personnel; Resources; Risk; Standards of Weights and Measures; Testing; Therapeutic; Toxic effect; Treatment Protocols; Work; base; clinical application; cost effective; expectation; experience; improved; response; size; tumor

DESCRIPTION (provided by applicant): There is increasingly convincing evidence that radiotherapy outcomes for many patients with localized prostate cancer can be improved by delivering higher cumulative radiation doses to the prostate. These dose escalation regimens employ relatively small fraction sizes of 1.8-2.0 Gy, based upon evidence that late responding normal tissues, with their lower alpha/beta ratios, are spared relative to most tumors with their higher alpha/beta ratios. For prostate tumors, as many as 38 to 45 or more treatments have been required to deliver escalated doses of 74 Gy or higher using these small fraction sizes. Contrary to these expectations, however, recent analyses of clinical prostate cancer radioresponse data have indicated a low alpha/beta ratio for prostate cancer on the order of 1.5 Gy, not the typical ratio of 8 Gy or higher expected for most tumors. This value is lower than the value of 3 typically ascribed to the adjacent organs at risk, bladder and rectum, probably because prostate tumors have unusually low proliferation rates. What is implied is an unusual opportunity in prostate cancer to improve the therapeutic ratio radiobiologically by treating with fewer but larger fractions of radiation - in other words, with hypofractionation. With a better therapeutic ratio, hypofractionation should lead to higher rates of tumor control without increase in late toxicity. This application: 1) reviews the work of ourselves and others providing evidence for the high relative sensitivity of prostate tumors to large radiation fraction sizes; 2) develops and describes a multi-institutional phase l/ll clinical trial that will test in 250 patients the hypotheses that prostate hypofractionation is both feasible and efficacious and 3) describes an accompanying correlative study that examines the relationship between the status of certain biomarkers and clinical outcome after radiation hypofractionation. This proposal combines the efforts of four institutions and four sets of investigators who collectively have comprehensive experience with the radiobiological modeling, the clinical application of radiation hypofractionation and state-of-the-art prostate cancer radiotherapy for prostate cancer. It is hoped that outcomes from this study will demonstrate that hypofractionated radiotherapy is safe and is at least as efficacious as aggressive, conventional-fraction-size dose escalation. If proven feasible, the fewer treatment fractions involved would also result in significant economic and resource utilization advantages and would reduce the patient burden associated with the 38 or more treatments typically required in many current, dose escalation regimens.

描述（由申请人提供）：越来越令人信服的证据表明，可以通过将较高的累积辐射剂量向前列腺提供较高的累积辐射剂量来改善许多局部前列腺癌患者的放射治疗结果。这些剂量升级方案采用相对较小的分数1.8-2.0 Gy，基于证据表明，较晚的正常组织及其α/β比率较低的正常组织相对于大多数肿瘤而保留了较高的α/beta比率。对于前列腺肿瘤，使用这些小分数需要多达38至45次或更多治疗才能递送74 Gy或更高的剂量。 然而，与这些预期相反，最近对临床前列腺癌辐射数据数据的分析表明，前列腺癌的α/β比率低1.5 Gy，而不是大多数肿瘤的典型比率为8 Gy或更高。该值低于通常归因于处于危险，膀胱和直肠的相邻器官3的值，这可能是因为前列腺肿瘤的增殖率异常较低。暗示的是前列腺癌中不寻常的机会，可以通过更少但较大的辐射分数来改善放射性生物学的治疗比率 - 换句话说，换句话说。在更好的治疗比率下，低分性应导致更高的肿瘤控制发生率，而不会增加毒性。 该应用：1）回顾我们自己和其他人的工作，为前列腺肿瘤对大辐射分数的高度敏感性提供了证据； 2）开发并描述了一项多机构的L/LL临床试验，该试验将在250名患者中测试前列腺下级化值既是可行且有效的假设，3）描述了一项随附的相关性研究，该研究检查了某些生物标志物和临床结果的状态之间的关系。该提案结合了四个机构和四组研究人员的努力，这些机构在放射生物学建模，放射性低分化的临床应用以及先前的前列腺癌放射治疗中统一具有全面的经验。 希望这项研究的结果能够证明降压放射疗法是安全的，并且至少具有侵略性的，常规的摘要剂量升级。如果可行的话，涉及的治疗部分越少，也将带来显着的经济和资源利用优势，并减轻与许多当前剂量升级方案中通常需要的38或更多治疗相关的患者负担。