Deparment of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany.
BMC Cancer. 2012 Apr 3;12:137. doi: 10.1186/1471-2407-12-137.
Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.
In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.
With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.
NCT01528683.
直肠癌患者的治疗标准取决于初始分期，包括手术切除、放疗和化疗。对于 II 期和 III 期肿瘤，除手术外，还应进行放化疗，优先采用术前放化疗或短程低分割放疗。手术方法的进步，特别是直肠系膜全切除术（TME）的建立与复杂的放疗和化疗相结合，已将局部复发率降低至仅百分之几。然而，由于直肠癌的高发病率，仍有大量患者出现复发性直肠癌，因此需要有效的治疗。
碳离子具有物理和生物学优势。由于其剂量分布倒置和布拉格峰内的高局部剂量沉积，可以精确应用剂量并保护正常组织。此外，与光子相比，碳离子提供了相对生物学效应（RBE）的增加，根据细胞系和分析的终点，RBE 可以计算在 2 到 5 之间。
日本对以前未接受放疗的复发性直肠癌患者的治疗数据表明，碳离子治疗的局部控制率优于手术。因此，当使用常规光子进行剂量应用受到限制时，也应评估这种治疗方案对放疗后复发的疗效。此外，这些患者可能受益于碳离子的增强生物学疗效。
在当前的 I/II 期 PANDORA-01 研究中，将在 I 期部分确定复发性直肠癌碳离子放疗的推荐剂量，在研究的 II 期部分评估可行性和无进展生存期。在 I 期部分，将应用 12×3 GyE 至 18×3 GyE 的递增剂量。I 期部分的主要终点是毒性，II 期部分的主要终点是无进展生存期。
常规光子照射治疗复发性直肠癌受到限制，临床效果仅为中等。由于碳离子束的物理和生物学特性，预计可以获得更好的结果。然而，作为再放疗，在这种临床情况下适用的最佳剂量仍需确定。这将与疗效一起在本 I/II 期试验中进行评估。
NCT01528683。
