Hypofractionated IMRT for Localized Prostate Cancer

描述(由申请人提供)：有越来越令人信服的证据表明，许多局限性前列腺癌患者的放射治疗结果可以通过向前列腺提供更高的累积辐射剂量来改善。这些剂量递增方案使用了相对较小的1.8-2.0Gy的分割尺寸，基于有证据表明，反应较晚的正常组织，其α/β比较低，相对于大多数肿瘤，其α/β比较高，可以幸免于难。对于前列腺癌，使用这些小部分，需要多达38到45次或更多的治疗才能提供74GY或更高的剂量。 然而，与这些预期相反的是，最近对前列腺癌临床放射反应数据的分析表明，前列腺癌的α/β比率较低，约为1.5GY，而不是大多数肿瘤预期的8GY或更高的典型比率。这个值低于通常归因于高危相邻器官--膀胱和直肠--的值3，可能是因为前列腺癌的增殖率异常低。这意味着前列腺癌有一个不同寻常的机会，可以通过较少但更大比例的放射治疗-换句话说，低分割-来提高放射生物学的治疗比率。有了更好的治疗比例，低分割应该会在不增加晚期毒性的情况下导致更高的肿瘤控制率。 这项应用：1)回顾我们和其他人的工作，为前列腺癌对大剂量放射治疗的相对敏感性提供证据；2)开发和描述一项多机构阶段的L/111临床试验，该试验将在250名患者中检验前列腺减分术既可行又有效的假设，以及3)描述一项附带的相关性研究，该研究检查某些生物标记物的状态与放射治疗后临床结果之间的关系。这项建议结合了四个机构和四组研究人员的努力，他们共同在前列腺癌的放射生物学建模、放射减分割的临床应用和最先进的前列腺癌放射治疗方面拥有全面的经验。 希望这项研究的结果将证明，低分割放射治疗是安全的，至少与积极的、常规分割剂量递增一样有效。如果证明可行，所涉及的治疗分数越少，还将带来显著的经济和资源利用优势，并将减轻与许多当前剂量递增方案中通常需要的38或更多治疗相关的患者负担。

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.