小细胞肺癌的治疗现状与进展

小细胞肺癌占肺癌总数的15%～20%,具有增殖快、早期转移等特点。尽管其对放、化疗比较敏感,但中位生存期仍然较短。EP/EC方案依旧是局限期小细胞肺癌的标准一线化疗方案。Irinotecan开始成为广泛期小细胞肺癌的一线用药。早期同步放化疗可提高局限期小细胞肺癌的生存率。根治性手术可延长部分早期小细胞肺癌患者的生存时间。单用imatinib疗效较差,联合其他药物可能会提高疗效。Gefitinib已被证实对小细胞肺癌的治疗无效。Temsirolimus有望成为治疗SCLC新的分子靶向药物。     

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.     

局限期小细胞肺癌的放射治疗

小细胞肺癌 (ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＳＣＬＣ)约占原发性肺癌的 2 0 %。临床上一般将ＳＣＬＣ简单地分为局限期小细胞肺癌 (ｌｉｍｉｔｅｄｓｔａｇｅｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＬＳＣＬＣ)和广泛期小细胞肺癌 (ｅｘｔｅｎｓｉｖｅｓｔａｇｅｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒ,ＥＳＣＬＣ)。ＥＳＣＬＣ的病变范围超出一侧胸腔 ,治疗以化疗为主辅以姑息性放射治疗。ＬＳＣＬＣ的病灶范围较为局限 ,在全身化疗消灭远处微小转移灶的基础之上联合局部放射治疗 ,有可能使部分患者得到长期生存 ,ＬＳＣＬＣ…     

非小细胞肺癌脑转移的治疗进展

肺癌是发病率和死亡率很高的恶性肿瘤,其中非小细胞肺癌约占肺癌的80%,而且在疾病发展过程中易发生脑转移,一旦发生脑转移,严重影响患者的生存质量并危及生命。肺癌脑转移的治疗方法包括外科手术、化疗、全脑放射治疗、立体定向放射治疗、分子靶向治疗和免疫治疗等,治疗手段多种多样,治疗效果有差异,对于不同患者如何选择合理且有效的治疗方案是目前研究的热点之一。本文将对非小细胞肺癌脑转移相关进展进行综述,以期为肺癌脑转移患者选择更合理的临床治疗方案。     

局限期小细胞肺癌放射治疗研究进展

小细胞肺癌（small cell lung cancer,SCLC）是高度恶性肿瘤,生物学特点是倍增时间短、增殖指数高和侵袭能力强。尽管对化放疗高度敏感,但极易耐药和复发,预后很差。确诊时约1/3属于局限期（limited-stage,LS）。LS-SCLC具有潜在治愈的可能,采用以铂类为基础的化疗联合胸部放疗,长期生存率达20%～25%。初治达完全或部分缓解的LS-SCLC患者行预防性脑照射(prophylactic cranial irradiation,PCI)可降低脑转移发生率,改善生活质量。随着SCLC患者生存期延长,局部治疗变得非常重要,如何最大程度地降低局部复发的危险性一直是临床研究热点。本文中我们分析了LS-SCLC放射治疗的研究现状,探索最佳放射剂量、次数、靶区、时机及PCI。     

小细胞肺癌脑转移治疗进展

肺癌是呼吸系统发病率、死亡率最高的恶性肿瘤,小细胞肺癌属于神经内分泌癌,侵袭性强、恶性程度高,易发生脑转移,严重影响患者生活质量及生存期。小细胞肺癌脑转移治疗方式有手术、化疗、放疗、靶向治疗和免疫治疗,治疗措施多,治疗效果差异大。随着各种诊断、治疗措施进展,小细胞肺癌脑转移治疗效果较前明显改善,对不同患者如何选择个体精准有效的临床治疗措施,延长脑转移患者生存时间,提高生活质量,是目前研究的热点之一。     

非小细胞肺癌脑转移的药物治疗进展

肺癌发病率和病死率高,最常见的病理类型为非小细胞肺癌,24%～40%的晚期非小细胞肺癌患者出现脑转移,预后不良。手术治疗以及传统放疗效果并不理想,血脑屏障也阻碍了化疗药物发挥其疗效。近年来,靶向药物及免疫治疗的出现为非小细胞肺癌脑转移患者提供了新的治疗希望,该文就目前非小细胞肺癌脑转移患者的药物治疗方式展开了全面综述,比较各类药物单用及联用的临床疗效,为非小细胞肺癌脑转移患者提供更合理的治疗方案建议。     

小细胞肺癌的治疗现状及进展

小细胞肺癌是一种恶性程度较高的肿瘤,具早期发生远处转移的倾向。因绝大多数患者于确诊时已伴有淋巴结或远处转移且无手术治疗的指征,小细胞肺癌的分期很少采用TNM分期法,而根据病灶范围简单地分为局限期与广泛期。不利的预后因素包括广泛期疾病、LDH值升高、不良的行为状态评分体重下降与男性性别。局限期小细胞肺癌的治疗应采用4—6个周期EP方案[（依托泊苷VP-16）＋顺铂（DDP）]化疗联合同期胸部放射的治疗方案。广泛期疾病以全身化疗为主,方案多采用VP-16联合顺铂或卡铂。即便对于老年或行为状态评分较差的患者,联合化疗仍值得推荐。治疗后肿瘤达完全缓解者应接受预防性全颅放疗,以降低颅脑转移率。     

小细胞肺癌预防性脑照射的远期疗效

目的：探讨预防性全脑照射对局限期小细胞肺癌脑转移率和生存率的影响。方法：51例经化疗加放射治疗后完全缓解的局限期小细胞肺癌病例被随机分为脑照射组（26例）和对照组（25例）。脑照射组在肿瘤完全缓解后11－58d开始常规分割照射，采用双侧野照射，剂量为25．2－3．6Gy。结果：脑照射组脑转移率为3．8％，明显低于对照组的32．0％（χ^2=5.15,P=0.02)。脑照射组1、3、5年生存率分别为84．6％、42．3％、34．6％，对照组分别为72．0％、32．0％、24．0％，两组比较差异无显著性意义（χ^2=2.25,P=0.13)。脑照射组没有出现严重的放射后遗症。结论：预防性全脑照射能减少局限期小细胞肺癌的脑转移，可能有提高其生存率的趋势。     

Neurocognitive function in patients with small cell lung cancer : effect of prophylactic cranial irradiation

BACKGROUND: The use of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer (SCLC) has been tempered by fears of detrimental effects on cognitive function. Neuropsychologic testing was prospectively conducted before and after PCI to evaluate its effects on cognitive function in patients with SCLC. METHODS: Ninety-six patients who completely or partially responded to initial therapy underwent formal neurocognitive testing before PCI. Three patients who had central nervous system metastasis were excluded. Of the remaining patients, 69 received PCI (mean dose, 25 grays [Gy] in 10 fractions). Repeat testing was performed on 37 patients (median follow-up, 23 months; range, 6-120 months). RESULTS: Baseline impairment was defined as > or =1.5 standard deviations below the normative mean. Before undergoing PCI, 47% of patients had evidence of impaired cognitive function. After PCI, univariate analysis revealed significant transient declines in executive function (pre-PCI mean, 15.6 +/- 11.5; post-PCI, 27.1 +/- 17.6 [P = .008]) and language (pre-PCI mean, 33.8 +/- 9.9; post-PCI, 31.0 +/- 9.0 [P = .049]) at early timepoints. Controlling for noncentral nervous system disease progression the deficit in executive function was no longer significant. Moreover, these deficits were not sustained, and significant improvements in language and motor coordination were recorded. On multivariate analysis, no significant differences before and after PCI were found. CONCLUSIONS: Neurocognitive testing demonstrated that a substantial portion of patients with SCLC had impaired brain functioning at baseline. Persistent declines in cognitive function were not observed after cranial irradiation. These data do not favor the omission of PCI on the basis of fears of neurotoxic effects.     

Outcome of small cell lung cancer (SCLC) patients with brain metastases in a routine clinical setting

Background

Small cell lung cancer (SCLC) represents approximately 13 to 18% of all lung cancers. It is the most aggressive among lung cancers, mostly presented at an advanced stage, with median survival rates of 10 to12 months in patients treated with standard chemotherapy and radiotherapy. In approximately 15-20% of patients brain metastases are present already at the time of primary diagnosis; however, it is unclear how much it influences the outcome of disease according the other metastatic localisation. The objective of this analysis was to evaluate the median survival of SCLC patients treated by specific therapy (chemotherapy and/or radiotherapy) with regard to the presence or absence of brain metastases at the time of diagnosis.

Patients and methods

All SCLC patients have been treated in a routine clinical practice and followed up at the University Clinic Golnik in Slovenia. In the retrospective study the medical files from 2002 to 2007 were review. All patients with cytological or histological confirmed disease and eligible for specific oncological treatment were included in the study. They have been treated according to the guidelines valid at the time. Chemotherapy and regular followed-up were carried out at the University Clinic Golnik and radiotherapy at the Institute of Oncology Ljubljana.

Results

We found 251 patients eligible for the study. The median age of them was 65 years, majority were male (67%), smokers or ex-smokers (98%), with performance status 0 to 1 (83%). At the time of diagnosis no metastases were found in 64 patients (25.5%) and metastases outside the brain were presented in 153 (61.0%). Brain metastases, confirmed by a CT scan, were present in 34 patients (13.5%), most of them had also metastases at other localisations. All patients received chemotherapy and all patients with confirmed brain metastases received whole brain irradiation (WBRT). The radiotherapy with radical dose at primary tumour was delivered to 27 patients with limited disease and they got 4–6 cycles of chemotherapy. Median overall survival (OS) of 34 patients with brain metastases was 9 months (95% CI 6–12) while OS of 153 patients with metastases in other locations was 11 months (95% CI 10–12); the difference did not reach the level of significance (p = 0.62). As expected, the OS of patients without metastases at the time of primary diagnosis turned out to be significantly better compared to the survival of patients with either brain or other location metastases at the primary diagnosis (15 months vs 9 and 11 months, respectively, p < 0.001).

Conclusions

In our investigated population, the prognosis of patients with extensive SCLS with brain metastases at the primary diagnosis treated with chemotherapy and WBRT was not significantly worse compared to the prognosis of patients with extensive SCLC and metastases outside the brain. In extensive SCLC brain metastases were not a negative prognostic factor per se if the patients were able to be treated appropriately. However, the survival rates of extensive SCLC with or without brain metastases remained poor and novel treatment approaches are needed. The major strength of this study is that it has been done on a population of patients treated in a routine clinical setting.     

Efficacy and safety of prophylactic cranial irradiation in patients with small cell lung cancer

Background: Prophylactic cranial irradiation (PCI) as part ofthe treament regimen for patients with limited stagesmall cell lung cancer (SCLC) remains controversial. Thepresent study was performed to analyze the efficacyand safety of PCI in patients with limitedstage SCLC who achieved complete remission.Patients and methods: Between 1983 and 1993, thirty-ninepatients with limited stage SCLC who had showncomplete remission after chemotherapy were enrolled prospectively intothe non-randomized study. Eighteen of them received PCI(PCI+), while 21 did not (PCI–). Pretreatment CTor MRI of the brain was performed inall patients. Patients were prospectively evaluated by aneurologist at regular intervals. Results: Three PCI+ patientsand seven PCI– patients developed brain metastases. Thefrequencies of brain metastases were not significantly differentbetween the groups (Fisher's exact test, p =0.207), but brain metastases in PCI+ patients tendedto occur later (log rank, p=0.008).Overall survival was significantly longer in PCI+ patients(log rank, p < 0.001).Early toxicity consisted of headache, nausea, fatigue, concentrationproblems and alopecia. These symptoms and signs weremild and usually reversible within a few months.Late toxicity was studied in patients whose survivalexceeded two years. Seven PCI+ patients survived formore than two years, while no PCI– patientssurvived for more than two years. Memory problemswere seen in six of the seven patients.These problems were non-disabling and, once established, remainedstable for months to years.The most prominent radiologic abnormalities were cortical atrophyand leukoencephalopathy, found in four of the fivepatients who underwent radiologic follow-up examination.Conclusions: This non-randomized study suggests that PCI maybe effective by decreasing the frequency of brainmetastases and by increasing the brain metastasis-free survivaland overall survival, with a minor risk ofclinical and radiologic neurotoxicity.     

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。     

小细胞肺癌治疗的新探索

与其他癌症相同,小细胞肺癌（ＳＣＬＣ）也秉承分期治疗的原则,手术只适用于早期患者,且能实施手术的患者仅占全部患者的５％,因此化疗、放疗仍是ＳＣＬＣ治疗的主要策略。近年来,胸部放疗提高局限期ＳＣＬＣ患者的３年生存率约５％,减少胸部复发风险约２５％,而预防性脑照射（ＰＣＩ）也进一步改善了ＳＣＬＣ的临床预后,新的治疗药物、靶点及策略不断涌现为ＳＣＬＣ的治疗带来了希望。