局限期小细胞肺癌放射治疗研究进展

摘 要：手术、全身化疗、胸部放疗及预防性脑照射的综合治疗已成为局限期小细胞肺癌的治疗共识。近几十年,药物治疗没有明显突破。在放射治疗方面,放射治疗加入的时机、靶区范围、剂量分割方式以及预防性脑照射等是研究热点问题。全文对局限期小细胞肺癌放疗方面的相关争议及研究进展作一分析。     

小细胞肺癌放射治疗进展

目的 放射治疗是小细胞肺癌治疗的主要方式,其实施过程涉及到小细胞肺癌的诸多环节,总结国内外关于小细胞肺癌放射治疗的研究现状,探讨胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中的价值.方法 应用PubMed、西文生物医学期刊文献数据库、中国知网及万方期刊全文数据库检索系统,以"小细胞肺癌,放疗,全脑预防性照射"为中文关键词,以"small cell lung cancer,radiotherapy,prophylactic cranial irradiation"为英文关键词,联合检索1996-01-2016-12的相关文献.共检索到英文文献377篇,中文文献4篇.纳入标准:(1)小细胞肺癌;(2)放疗;(3)全脑预防性照射.排除标准:(1)非小细胞肺癌;(2)手术;(3)化疗.根据剔除标准剔除中文文献2条,英文文献326条,最后纳入分析37篇文献.结果局限期小细胞肺癌的胸部放疗的分割剂量和模式为45 Gy/30次,超分割放疗或60~70 Gy/30~35次,常规分割放疗.胸部放疗参与的最佳时间为于化疗第1个周期或第2个周期参与.胸部同步放化疗结束以后行全脑预防性照射,放疗期间可给予药物盐酸美金刚以保护神经认知功能或海马保护的调强放射治疗;广泛期小细胞肺癌的胸部放疗的分割剂量和模式为30 Gy/10次或45 Gy/15次.全脑预防性照射存在争议.结论胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中起着非常重要的作用.     

局限期小细胞肺癌放疗现状及研究进展

小细胞肺癌中大约30％～40％属于局限期.大量研究已经证明胸部放疗联合同步化疗可以改善局部控制率及总生存率,是目前局限期小细胞肺癌的标准治疗模式,预防性脑照射也被证实可以改善小细胞肺癌的预后.目前认为放疗应在化疗早期加入,个体化制定合适的放疗靶区,放疗方案推荐超分割方式或常规分割方式.     

局限期小细胞肺癌的放射治疗进展

文章主要对局限期小细胞肺癌放射治疗参与的时机、化疗与放疗联合的方式、放射治疗的剂量和分割方式、照射靶区、预防性脑照射等问题进行探讨，并回顾这些方面的进展。     

局限期小细胞肺癌脑预防照射研究进展

随着放化疗等综合治疗手段的应用,局限期小细胞肺癌的局控率和生存率均有了提高,然而脑转移成为影响有长期生存可能患者生存质量的重要因素。本文综述脑预防照射在局限期小细胞肺癌患者中应用的可行性、结果及可能引起的放疗后期毒性,及脑预防照射的开始时间、分割方式、放疗剂量等方面。     

小细胞肺癌的综合治疗进展

基于铂类的化疗方案联合胸部放疗已成为局限期小细胞肺癌的标准治疗方案,放疗的尽早参与能够提高患者的生存期.对于治疗后达到或接近CR者应行预防性脑照射.广泛期小细胞肺癌化疗仍然是主要治疗方法,而胸部放疗也逐步体现出其在综合治疗中的价值.     

局限期小细胞肺癌的放射治疗

局限期小细胞肺癌治疗的主要进展来自于放射治疗,涉及放射治疗实施过程中的诸多细节,如放射治疗加入的时机,放射治疗的靶区、剂量和分割方式,预防性脑照射及老年患者的放射治疗等。     

放射治疗在小细胞未分化肺癌治疗中的作用

小细胞未分化肺癌(简称SCLC)对放化疗的敏感性与其它类型肺癌不同。通常采用3～4种化疗药物联合应用并加胸部放疗,对局限期病例可提高生存率,广泛期病例可有较好的姑息作用。近年来,国内外很多学者对局限期和广泛期Sclc治疗中胸部照射的作用,预防性全脑照射,大面积照射是否必要进行了探讨,期望能够提高疗效。     

局限期小细胞肺癌胸部放疗剂量分割现状

胸部放疗是局限期小细胞肺癌的重要治疗手段,与之相关的剂量分割存在一定争议。超分割放疗方案(2 次/d)作为前瞻性研究确立的标准方案,由于不良反应的发生和治疗的不便利,在临床实践中常常被其他治疗策略代替。另外在不可手术的淋巴结阴性的Ⅰ期小细胞肺癌中,立体定向消融放疗为部分高龄且预计难以耐受长疗程放疗的患者提供了新的选择。合适的剂量分割方案既可以保证治疗疗效,也能降低放疗相关急性及晚期损伤。本文将对目前局限期小细胞肺癌剂量分割研究现状进行阐述。     

局限期小细胞肺癌胸部放疗及放射损伤的研究现状

目的:总结国内外局限期小细胞肺癌(LSCLC)胸部放疗研究的现状。方法:应用PubMed和CHKD期刊全文数据库检索系统,以"局限期小细胞肺癌、胸部放疗和放射损伤"为关键词,检索1986-01-2008-04相关LSCLC胸部放疗的文献,共检索到英文文献430篇和中文文献187篇。纳入标准:1)LSCLC胸部放疗的疗效评价;2)LSCLC胸部放疗的方法;3)LSCLC胸部放疗与化疗结合的研究;4)LSCLC胸部放疗损伤的研究。根据纳入标准,精选82篇,最后纳入分析29篇。结果:配合胸部放疗可以提高LSCLC生存期,虽然胸部放疗的剂量、照射范围、分割方式、放化疗的顺序和最佳时机的选择等一直存有争议,但多数专家认为胸部放疗更为合理的方式为早期配合化疗(3个周期内)常规的累及野照射,剂量45～55Gy为宜。这几个热点问题也是引起胸部放疗损伤的重要因素。结论:胸部放疗在LSCLC的治疗中占重要地位,应选择适宜的放疗时机、合理的照射靶区和剂量,给予个体化治疗,以最小的放疗损伤获得最佳的治疗效果。     

小细胞肺癌放射治疗新进展——东西方的探索

小细胞肺癌(SCLC)是我国肺癌常见类型之一,90年代后,SCLC的全身治疗方面没有令人兴奋的进展,但是放疗在SCLC中的应用研究取得了部分进展,为SCLC治疗疗效的提高提供了可能,这些进展主要包括广泛期SCLC的胸部放疗及脑预防照射、局限期SCLC胸部放疗剂量及放疗技术的研究、早期SCLC脑预防照射的价值研究等。笔者就其内容在东西方研究的进展加以综述,希望能带给读者一些帮助和借鉴。     

Recent developments in radiotherapy for small-cell lung cancer: a review by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

Small-cell lung cancer (SCLC) accounts for 13% of all lung tumours. The standard treatment in patients with limited-stage disease is radiotherapy combined with chemotherapy. In extensive SCLC, the importance of consolidation thoracic radiotherapy in patients with a good treatment response has become increasingly recognized. In both limited and extensive disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer (NSCLC). Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present study we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway in order to identify future trends.     

广泛期小细胞肺癌放射治疗研究进展

胸部放疗和预防性脑照射在局限期小细胞肺癌治疗中占有重要的地位和作用，使总生存有大幅度提高。本文回顾近几年国内外关于其在广泛期小细胞肺癌治疗中的作用，对其作一综述，以便为临床实际工作提供借鉴和下一步研究提供参考。     

Chemoradiotherapy for lung cancer: current status and perspectives

For many years, thoracic radiotherapy had been regarded as the standard treatment for patients with unresectable locally advanced non-small cell lung cancer. However, meta-analyses show that cisplatin-containing chemoradiotherapy is significantly superior to radiothe-rapy alone in terms of survival. Moreover, concurrent chemoradiotherapy yields a significantly increased response rate and enhanced survival duration when compared with the sequential approach. Cisplatin-based chemotherapy with concurrent thoracic radiotherapy yields a 5-year survival rate of approximately 15% for patients with unresectable locally advanced non-small cell lung cancer. The state-of-the-art treatment for limited-stage small cell lung cancer is considered to be four cycles of combination chemotherapy with cisplatin plus etoposide combined with early concurrent twice-daily thoracic irradiation (45Gy). If patients achieve complete remission, prophylactic cranial irradiation should be administered. A 5-year survival rate of approximately 25% is expected with the state-of-the-art treatment for limited-stage small cell lung cancer. Chemoradiotherapy is considered to be a standard treatment for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer. Several new strategies are currently being investigated to improve the survival of these patients. The incorporation of target-based drugs such as gefitinib is considered to be the most promising strategy for unresectable locally advanced non-small cell lung cancer. The incorporation of irinotecan is also a promising strategy to improve the survival of patients with limited-stage small cell lung cancer. The Japan Clinical Oncology Group is conducting clinical trials to develop new treatment strategies for both unresectable locally advanced non-small cell lung cancer and limited-stage small cell lung cancer.     

Small-cell lung cancer at the millennium: radiotherapy innovations improve survival while new chemotherapy treatments remain unproven

Because of the systemic nature of small-cell lung cancer, one could predict that treatment advances would mainly come from innovations of chemotherapy. Although combination chemotherapy is better than monotherapy, a clearly superior multidrug regimen has not emerged. Investigations of more intensive chemotherapy with increased drug diversity and delivery have not prospered, and advantages of regimens including new agents have not yet been demonstrated in controlled trials. As we enter the new millennium, twenty-five years have passed since the publication of studies describing the combined used of cyclophosphamide, doxorubicin, and vincristine for small-cell lung cancer. It has been almost 20 years since the publication of the combination of etoposide and cisplatin became the widely accepted standard for the treatment of small-cell lung cancer. Today, both treatment regimens continue to be widely used as standard therapy. Ironically, proven advances in this systemic disease have been associated with innovations of local therapy. Data from limited-stage small-cell lung cancer clinical trials published during the 1990s demonstrated that a number of radiotherapy interventions had significant survival benefits. These radiotherapy interventions include addition of thoracic irradiation to chemotherapy, early delivery of thoracic irradiation concurrently with chemotherapy, more intense thoracic irradiation, and prophylactic cranial irradiation. As we await improved systemic therapy in the next millennium, the prognosis for extensive-stage disease remains guarded, and adherence to optimal radiotherapy detail remains crucial for routine management of limited-stage patients.     

Limited small-cell lung cancer: a potentially curable disease

Patients with limited-stage small-cell carcinoma of the lung are treated with combined-modality therapy with the intent to cure. Standard therapy consists of platinum-based combination chemotherapy, thoracic irradiation, and for responders, prophylactic cranial irradiation. Despite this aggressive approach, too few patients achieve 5-year survival. In the past several years, new chemotherapeutic agents, including the taxanes and the topoisomerase I inhibitors, have demonstrated substantial activity against small-cell carcinoma. These agents are now being incorporated into clinical trials for patients with limited-stage disease. The best combination of these agents with platinum-based regimens is yet to be determined, and data supporting increased survival are awaited. Other studies are exploring thoracic radiation issues. Questions remain regarding optimal timing, dose, volume, and fractionation schemes. The most effective combination of thoracic irradiation and the newer chemotherapy agents also remains to be determined. The current approach to limited-stage small-cell carcinoma is reviewed, ongoing trials are described, and future directions are explored.     

Prophylactic cranial irradiation for patients with lung cancer

The central nervous system is a common site of metastasis in patients with small cell lung cancer (SCLC) and non-small-cell lung cancer. Despite advances in combined modality therapy, intracranial relapse continues to be a common site of recurrence and a major cause of morbidity for patients with lung cancer. Prophylactic cranial irradiation (PCI) has proven to be effective in reducing the incidence of brain metastases in patients with lung cancer. Based upon results of a metaanalysis demonstrating a small improvement in overall survival, PCI is now routinely offered to patients with limited-stage SCLC after a complete or near-complete response to initial treatment. However, many questions remain unanswered regarding the optimal dose, fractionation, and toxicity of PCI in patients with limited-stage SCLC. Additionally, the role of PCI in patients with extensive-stage SCLC and locally advanced non-small-cell lung cancer is unclear. Several important collaborative group trials are under way in an attempt to further define the role of PCI in patients with lung cancer.     

Small cell lung cancer: have we made any progress over the last 25 years?

Twenty-five years ago, small cell lung cancer was widely considered to be the next cancer added to the list of "curable cancers." This article attempts to summarize the progress made toward that goal since then. Clinical trials have provided landmarks in the therapy of limited-stage small cell lung cancer (LS-SCLC). These are: (a) the proof that thoracic radiation therapy adds to systemic chemotherapy, (b) the superiority of twice-daily radiation therapy over daily fractionation, and (c) the need for prophylactic central nervous system radiation (prophylactic cranial irradiation). Each of these innovations adds about 5%-10% to the overall survival rate. In extensive-stage disease, irinotecan plus cisplatin may be a possible alternative to the "standard" etoposide-cisplatin chemotherapy doublet, but there has been little progress otherwise. It is imperative that, whenever possible, patients be given the opportunity to participate in future clinical trials so that the survival for these patients can continue to improve.