Improving the Clinical Effectiveness and Understanding of the Biophysical Basis

描述(申请人提供)：癌症治疗的目标是治愈而不发病。放射治疗可能是一种有效的局部癌症治疗方法。挑战是在不使正常组织暴露在过量剂量的情况下，仅向肿瘤提供适当的剂量。与可比的光子场相比，没有超出目标的出射剂量的质子对正常组织的照射较少。可提高治愈率和并发症的治愈率。虽然许多患者已经在许多疾病部位接受了质子治疗，取得了令人印象深刻的临床结果，而且质子实际上已经在一些临床场景中被广泛接受，但进一步的研究可以极大地提高质子的临床有效性和适用性，特别是通过强度调节质子治疗(IMPT)。IMPT是一种强大的工具，有独特的机会通过显着不同的剂量模式来改善这两种结果，即对质子的物理和生物物理方面的理解。这个多机构计划项目的主要目标是研究和完善IMPT，以改善肺癌、肝癌、口咽癌、鼻咽癌和脑癌的随机II期试验和需要脊髓放疗的儿童中枢神经系统肿瘤、腹膜后肉瘤、乳房、不典型和恶性脑膜瘤以及胶质母细胞瘤的非随机L/11期试验的结果。该项目支持NCI改善癌症患者的治疗和持续护理的使命。 假设通过更好地了解质子与组织的相互作用，以及对运动和解剖变化的研究和管理，可以在质子治疗(PT)中实现更高的准确性，以进一步提高靶区覆盖，减少剂量浴，并详细说明和管理治疗反应的生物物理决定因素。提出了四个综合项目：(1)通过随机临床试验评估IMPT和IMRT的疗效；(2)L/11期临床研究的探索性研究，以提高PT的治愈率；(3)评估和了解物理和生物因素对PT结局的影响；以及(4)通过优化利用质子的物理和生物学特性来改善结局。

DESCRIPTION (provided by applicant): The goal of cancer treatment is cure without morbidity. Radiation can be an effective locoregional cancer treatment. The challenge is to deliver the appropriate dose to only the tumor without exposing normal tissues to excessive dose. Protons, with no exit dose beyond the target, irradiate less normal tissue than comparable photon fields. This can improve the therapeutic ratio of cure vs. complication. While many patients have been treated with protons with impressive clinical results in a number of disease sites, and while protons have in fact become widely accepted in some clinical scenarios, further research can greatly enhance the clinical effectiveness and applicability of protons, particularly through intensity-modulated proton therapy (IMPT). IMPT is a powerful tool with unique opportunities to improve both outcomes the understanding of physical and biophysical aspect of protons through its markedly different dose patterns. The primary objective of this multi-institutional program project is to study and refine IMPT to improve outcome in randomized phase II trials for cancers of the lung, liver, oropharynx, nasopharynx and brain; and in non-randomized phase l/ll trials for pediatric CNS tumors needing craniospinal irradiation, retroperitoneal sarcoma, breast, atypical and malignant meningioma, and glioblastoma. This project supports the mission of the NCI to improve the treatment and continuing care of cancer patients. The hypothesis is that through better understanding of the proton interactions with tissues, and study and management of motion and anatomic changes, higher accuracy in proton therapy (PT) can be achieved to further improve target coverage, reduce the dose bath and elaborate and manage biophysical determinants of treatment response. Four integrated projects are proposed: (1) Assessment of the Effectiveness of IMPT vs. IMRT through Randomized Clinical Trials; (2) Exploratory Phase l/ll Clinical Studies to Improve the Therapeutic Ratio of PT; (3) Assessing and Understanding the Impact of Physical and Biological Factors on Outcomes of PT; and (4) Improving Outcomes by Optimally Exploiting Physical and Biological Characteristics of Protons.