Schild S E, Vokes E E
Department of Radiation Oncology, Mayo Clinic, Scottsdale
Department of Medicine and Comprehensive Cancer Center, University of Chicago Medicine and Biologic Sciences, Chicago, USA.
Ann Oncol. 2016 Apr;27(4):590-9. doi: 10.1093/annonc/mdv621. Epub 2015 Dec 27.
Lung cancer is the leading cause of cancer deaths, having caused an estimated 1.6 million deaths worldwide in 2012 [Ferlay J, Soerjomataram I, Dikshit R et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359-E386].
Although the majority of patients are not cured with currently available therapies, there have been significant improvements in stage-specific outcomes over time [Videtic G, Vokes E, Turrisi A et al. The survival of patients treated for stage III non-small cell lung cancer in North America has increased during the past 25 years. In The 39th Annual Meeting of the American Society of Clinical Oncology, ASCO 2003, Chicago, IL. Abstract 2557. p. 291]. This review focuses on past progress and ongoing research in the treatment of locally advanced, inoperable nonsmall-cell lung cancer (NSCLC).
In the past, randomized trials revealed advantages to the use of thoracic radiotherapy (TRT) and then, the addition of induction chemotherapy. This was followed by studies that determined concurrent chemoradiotherapy to be superior to sequential therapy. A recent large phase III trial found that the administration of 74 Gy of conventionally fractionated photon-based TRT provided poorer survival than did the standard 60 Gy. However, further research on other methods of applying radiotherapy (hypofractionation, adaptive TRT, proton therapy, and stereotactic TRT boosting) is proceeding and may improve outcomes. The molecular characterization of tumors has provided more effective and less toxic targeted treatments in the stage IV setting and these agents are currently under investigation for earlier stage disease. Similarly, immune-enhancing therapies have shown promise in stage IV disease and are also being tested in the locally advanced setting.
For locally advanced, inoperable NSCLC, standard therapy has evolved from TRT alone to combined modality therapy. We summarize the recent clinical trial experience and outline promising areas of investigation in an era of greater molecular and immunologic understanding of cancer care.
肺癌是癌症死亡的主要原因，2012年全球估计有160万人死于肺癌[费雷J，索约马塔拉姆I，迪克希特R等。全球癌症发病率和死亡率：GLOBOCAN 2012中的来源、方法和主要模式。《国际癌症杂志》2015年；136：E359 - E386]。
尽管大多数患者目前无法通过现有疗法治愈，但随着时间的推移，特定分期的治疗效果有了显著改善[维德蒂克G，沃克斯E，图里西A等。在过去25年中，北美接受III期非小细胞肺癌治疗患者的生存率有所提高。在美国临床肿瘤学会第39届年会上，2003年，伊利诺伊州芝加哥。摘要2557。第291页]。本综述重点关注局部晚期、无法手术的非小细胞肺癌（NSCLC）治疗的既往进展和正在进行的研究。
过去，随机试验显示了胸部放疗（TRT）的优势，随后又显示了加用诱导化疗的优势。接着有研究确定同步放化疗优于序贯治疗。最近一项大型III期试验发现，给予74 Gy的传统分割光子束TRT的患者生存率低于标准的60 Gy。然而，关于其他放疗方法（大分割放疗、自适应TRT、质子治疗和立体定向TRT增强）的进一步研究正在进行，可能会改善治疗效果。肿瘤的分子特征在IV期疾病中提供了更有效且毒性更小的靶向治疗，目前正在对这些药物用于早期疾病进行研究。同样，免疫增强疗法在IV期疾病中显示出前景，也正在局部晚期疾病中进行测试。
对于局部晚期、无法手术的NSCLC，标准治疗已从单纯TRT发展为综合治疗模式。我们总结了最近的临床试验经验，并概述了在对癌症治疗有更深入分子和免疫理解的时代中前景广阔的研究领域。
