原发中枢神经系统淋巴瘤(PCNSL): 关注放射治疗的作用 Dr. Rico Liu Consultant, Department of Clinical Oncology, Queen Mary Hospital Honorary Clinical Associate Professor, Department of Clinical Oncology, The University of Hong Kong Deputy Hospital Chief Executive, Queen Mary Hospital BTG 2013 Feb 2013

讨论重点 照射的生物学效应 并非每个人都适合放疗，那么何人适合？何时候适合呢？ 新技术的意义

照射的生物学效应 凋亡 外部放疗 高能X线 光子- 伽玛射线-来源于射线活性衰减，如Colbert 高能粒子 电子 光子 近距放射治疗 系统性放射治疗

治疗性照射的生物学效应

正常组织耐受 Milano et al., Semin Radiat Oncol. 17 (2007): 131-140

治疗提高生存 中位生存(月) 未治疗 ~2 单用全脑照射治疗(WBRT) ~12 WBRT后序贯化疗 ~ 48 Henry JM et al. Cancer 34: 1293, 1974 Nelson DF et al. IJROBP Volume 23, Issue 1, 1992, Pages 9–17 Ferreri AJ et al. Ann Oncol. 2000 Aug;11(8):927-37

PCNSL：单用放疗 RTOG 8315 WBRT的II期研究40Gy +额外20Gy N = 41 中位总体生存时间12.2个月 额外剂量的获益受到质疑：在额外增加剂量的照射野，疾病仍常复发；生存并未优于以往未增加剂量的治疗 眼部受累：双眼36Gy(或利妥昔单抗加上高剂量MTX) Nelson DF et al. IJROBP Volume 23, Issue 1, 1992, Pages 9–17

PCNSL：化疗联合放疗 CR 58%, PR 36% (总体反应率94%) 总体生存时间：37个月 15% ( 12例)发生严重的迟发神经毒性 12例中8例死亡(5例年龄>60岁，3例年龄<60岁)

老年患者迟发神经毒性更为严重 Omuro AM et al. Arch Neurol. 2005 Oct;62(10):1595-600

G-PCNSL-SG-1 试验

尚无足够证据放弃WBRT 试验的不足之处 统计强度低 违背方案率高 失访率高 在神经毒性统计中样本量小

针对CR患者减低放疗剂量

WBRT- 准备

PCNSL的治疗 Flow chart of therapeutic management of PCNSL in everyday practice. (1) Mostly marginal zone B-cell lymphoma, small lymphocytic lymphoma, and lymphoplasmacytic lymphoma. (2) Mostly intravascular large B-cell lymphoma and neurolymphomatosis. (3) Conclusion from the IELSG no. 20 trial.40 (4) Several regimens are available (Table 3). (5) A higher amount of available evidence suggests WBRT. The discussion with selected patients about the pros and cons of the use of consolidation WBRT or HDC/ASCT is recommended. (6) Available literature suggesting that some elderly patients in CR after primary chemotherapy could be watchful waited without OS impairment is constituted by a few small retrospective series. However, to delay WBRT until relapse is an acceptable strategy considering the increased risk of disabling neurotoxicity in these patients. (7) Radiation field and dose should be chosen on the bases of response to primary chemotherapy. WBRT dose reduction to 23-30 Gy in patients in CR after chemotherapy is recommended. DLBCL indicates diffuse large B-cell lymphoma; HD-MTX, high-dose methotrexate; ara-C, cytarabine; WBRT, whole-brain radiotherapy; CR, complete remission; PR, partial response; SD, stable disease; PD, progressive disease; and HDC/ASCT, high-dose chemotherapy supported by autologous stem cell transplantation. 放疗的作用 Ferreri A J M Blood 2011;118:510-522

新技术的意义 Neuro Oncol (August 2009) 11 (4): 423-429

总结 PCNSL罕见 化疗+/- 放疗可以获得最佳生存结果 迟发神经毒性常见，并且可以致残、致死 减低迟发神经毒性的发生危险 在<60岁的患者减低强化剂量 在>60岁的患者暂缓WBRT 对不适于化疗的患者放疗仍是有效的治疗方法

谢谢