VmP方案和全脑放射序贯治疗小细胞肺癌脑转移

背景与目的:单纯化疗或全脑放射治疗(wholebrainradiotherapy,WBRT)姑息性治疗小细胞肺癌(smallcelllungcancer,SCLC)脑转移,生存期均较短,本研究前瞻性观察比较VmP化疗方案与WBRT的不同序贯方法治疗SCLC脑转移患者的疗效、不良反应和生存期。方法:38例SCLC并脑转移初治患者根据使用床位非随机地分为A、B两组,经四格表精确概率法检验两组无显著差异(P>0.05)。A组(VmP-WBRT)采用先化疗2周期后放疗的治疗方法,B组(WBRT-VmP)采用先放疗后化疗2周期的治疗方法。化疗方案VmP:鬼臼噻吩甙(Teniposide,Vm-26)60mg/m2d1～5,顺铂(cisplatin,DDP)25mg/m2d1～3,4周为一治疗周期;WBRT方案:多灶性脑转移患者2周内放疗3Gy×10次;单灶脑转移患者在WBRT后1周内缩野放疗3Gy×5次。序贯治疗完成后继续化疗2～4周期。结果:两组病人治疗后80%以上的患者神经症状改善,两组脑转移癌、肺原发癌有效率和RECIST总客观有效率分别为68.2%和75.0%(P=0.647),77.3%和75.0%(P=0.871),63.6%和56.3%(P=0.646);肿瘤进展时间(timetoprogressions,TTP)分别为6.0个月(95%CI4.4～7.6)和5.0个月(95%CI3.6～6.4)(P=0.383);中位生存期(mediansurvivaltime,MST)分别为12.0个月(95%CI7.9～16.1)和9.0个月(95%CI5.6～12.4)(P=0.049);1年和2年生存率分     

COAPC方案联合脑部放射治疗非小细胞肺癌脑转移

背景与目的：放射治疗具有治疗脑转移癌的主要手段。而到目前为止化疗与放疗联合治疗脑转移癌的研究较少,本研究旨在观察COAPC方案化疗与脑部放射同时治疗非小细胞肺癌（non-small cell lung cancer,NSCLC)脑转移患者疗效,不良反应及生存率。方法：45例NSCLC脑转移患者接受COAPC方案化疗,环磷酰胺0．3g/m^2第1天静推,长春新碱1．4mg/m^2第1天静推,阿霉素50mg/m^2第1天静推,顺铂20mg/m^2第1－5天静滴,司莫司汀80mg/m2第1天口服,每3－4周为1疗程,脑部放射治疗于化疗第1疗程的第6天开始,每次2Gy,每天1次,每周5天,脑转移灶1－3个者,全脑放疗40Gy后,缩野放疗至总量60Gy,脑转移灶＞3个者,全脑放疗至总量40Gy.结果：治疗后80％患者神经系统症状改善,对脑转移灶的客观有效率为64．4％,对肺原发灶的有效率为40％,治疗的主要不良反应为骨髓抑制(Ⅲ-Ⅳ度占35％）,中位生存期10个月,1年生存率44．1％,5年生存率6．7％,单纯脑转移患者的中位生存期14个月,高于多发远处转移患者的9个月（P＝0．012）。结论：化疗联合脑部放射治疗NSCLC脑转移患者有效率与生存率较高,且患者耐受性较好。     

放化疗同步治疗肺癌脑转移38例临床分析

目的:观察长春瑞滨(NVB)、顺铂(DDP)加用卫萌(Vm-26)联合脑部放射治疗肺癌脑转移患者的疗效、不良反应和生存率。方法:Vm-260·1,静脉滴入,d1~d3;NVB25mg/m2,静脉滴入,d1、d8;DDP20mg/m2,静脉滴入,d1~d3;21d为1个周期,脑部放疗于第1个周期化疗开始后第5天开始,每次DT1·8~2·0Gy,1次/d,每周5次,1~2个病灶者全脑放疗DT40Gy后缩野追加至DT60Gy,≥3个转移灶者给予全颅放疗DT45Gy。结果:治疗后90%患者神经系统症状改善,对脑转移灶的客观有效率为71·1%(27/38),对肺原发灶的有效率为42·1%(16/38),主要不良反应为骨髓抑制和脱发,中位生存期11·01个月,1年生存率39·5%(15/38)。结论:同步放、化疗治疗肺癌脑转移患者有效率和生存率均较高,且患者耐受性好。肿瘤防治杂志,2005,12(19):1502-1504     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响

目的 探索现代诊疗条件下,全脑放疗（WBRT）能否延长小细胞肺癌（SCLC）脑转移患者的生存期。方法 回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例（剂量30 Gy分10次）,无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期（BM‐OS）,采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权（sIPTW）方法对组间变量进行匹配,采用Kaplan‐Meier方法进行生存分析,log‐rank检验进行生存曲线比较。结果 全组患者中位BM‐OS为9.1个月。有无WBRT患者的中位BM‐OS分别为10.6、6.7个月（P=0.003）,应用sIPTW平衡两组影响因素后,两组的BM‐OS差异仍具有统计学意义（P=0.02）。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM‐OS分别为13.0、9.6个月（P=0.007）;广泛期疗中出现脑转移患者127例,有无WBRT的中位BM‐OS分别为8.0、4.1个月（P=0.003）。在50例单纯脑转移患者中,有无WBRT的中位BM‐OS为13.3、10.9个月（P=0.259）;在195例伴有颅外转移的患者中,有无WBRT的中位BM‐OS分别为9.5、5.9个月（P=0.009）。结论 广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

全脑放疗对广泛期小细胞肺癌脑转移的生存影响北大核心CSCD

目的探索现代诊疗条件下,全脑放疗(WBRT)能否延长小细胞肺癌(SCLC)脑转移患者的生存期。方法回顾性分析天津医科大学肿瘤医院2010—2020年245例伴有脑转移的广泛期SCLC患者的病历资料,其中WBRT组168例(剂量30 Gy分10次),无WBRT组77例。所有患者均接受了至少2个周期的化疗,化疗方案均为顺铂或卡铂联合依托泊苷,115例接受了胸部放疗。研究终点为脑转移后生存期(BM-OS),采用卡方检验对分类数据进行比较,采用稳健逆概率处理加权(sIPTW)方法对组间变量进行匹配,采用Kaplan-Meier方法进行生存分析,log-rank检验进行生存曲线比较。结果全组患者中位BM-OS为9.1个月。有无WBRT患者的中位BM-OS分别为10.6、6.7个月(P=0.003),应用sIPTW平衡两组影响因素后,两组的BM-OS差异仍具有统计学意义(P=0.02)。其中,首诊广泛期伴脑转移患者118例,有无WBRT的中位BM-OS分别为13.0、9.6个月(P=0.007);广泛期疗中出现脑转移患者127例,有无WBRT的中位BM-OS分别为8.0、4.1个月(P=0.003)。在50例单纯脑转移患者中,有无WBRT的中位BM-OS为13.3、10.9个月(P=0.259);在195例伴有颅外转移的患者中,有无WBRT的中位BM-OS分别为9.5、5.9个月(P=0.009)。结论广泛期小细胞肺癌脑转移患者行全脑放疗能够为患者带来生存获益。     

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.     

Outcome of Patients with Brain Metastases after Combined Modality Therapy in Small Cell Lung Cancer (SCLC): a Retrospective Study

Abstract

The authors evaluated the role of whole brain radiotherapy (WBRT) on the outcome of brain metastasis and survival in 41 patients with small cell lung cancer (SCLC) treated in their department. In addition to chemotherapy, radiotherapy was given to the primary site in all responder patients. Six patients presented brain metastasis initially and 10 patients after the fourth course of chemotherapy. Brain metastases were symptomatic in 12 of 16 patients with a median time of 5 months (1-14) until symptoms developed. All patients but 2 with brain metastasis received WBRT (30 Gy in 10 fractions) in addition to chemotherapy. The median survival time of patients with brain metastasis was 8.3 months (3.5 to 16) compared to 12 months (4 to 34+) for patients without brain metastasis. In addition, the median survival time for patients with brain metastasis who responded to systemic chemotherapy was better than that of non-responders. The authors found no improvement in survival in patients who received concomitant WBRT after chemotherapy compared to patients who received WBRT after completion of chemotherapy. In conclusion, the role of consolidating cranial irradiation in addition to chemotherapy in SCLC patients is unclear and warrants prospective randomized studies.     

Survival outcomes after whole brain radiotherapy for brain metastases in older adults with newly diagnosed metastatic small cell carcinoma: A national cancer database (NCDB) analysis

BackgroundSmall cell lung cancer (SCLC) is an aggressive malignancy with a tendency to affect older adults and also metastasize to the brain. Older adults tolerate whole brain radiotherapy (WBRT) poorly with marginal survival benefit. We utilized the national cancer database (NCDB) to evaluate the survival outcomes following WBRT in older adults with SCLC and brain metastases.MethodsWe identified 1615 patients ≥75 years old diagnosed with SCLC and brain metastases. Patients were categorized by type of therapy: chemotherapy + WBRT (n = 576), chemotherapy alone (n = 238), WBRT alone (n = 360) and no chemotherapy or WBRT (n = 441). Clinical and demographic characteristics were reported for each treatment cohort with a subsequent multivariable regression analysis for survival.ResultsMedian patient age was 79 years. WBRT median dose was 30 Gy. At time of analysis, 1530 of the cohort had died, yielding a median OS of 2.9 months and 6 month survival of 31% for patients that received chemotherapy. For patients treated without chemotherapy, median OS with WBRT was 1.9 months compared to 1.2 months without (p < .0001). For patients receiving chemotherapy with, and without WBRT, median OS was 5.6 months and 6.4 months, respectively (p = .43). Multivariable cox regression revealed age > 80, extracranial disease, male sex, and rural location as predictors of increased risk of death.ConclusionIn older adult patients with SCLC brain metastasis, WBRT was associated with a modest increase in survival in patients not fit for chemotherapy, and there was no association with increased survival over chemotherapy alone.     

Split-course versus continuous thoracic radiation therapy for limited-stage small-cell lung cancer: final report of a randomized phase III trial

The optimal integration of radiation and chemotherapy for limited-stage small-cell lung cancer (SCLC) remains unclear. This phase III trial was conducted to determine whether chemotherapy plus interdigitating split-course thoracic radiation therapy (RT) improved survival compared with standard-dose continuous thoracic RT. One hundred fourteen patients were randomized to receive 50 Gy thoracic RT delivered in 2.0-Gy fractions given continuously (5 weeks) concurrent with the first 2 cycles of chemotherapy (arm A) or 50 Gy delivered via an interdigitating split course in 2.5-Gy fractions (8 weeks) concurrent with the first 3 cycles of chemotherapy (arm B). During the split-course RT, once-daily radiation was delivered on days 8-17 of each of the first two 21-day cycles and days 8-11 of the third 21-day cycle. All patients received the following chemotherapy: cisplatin/etoposide on cycles 1, 2, and 5 and cyclophosphamide/vincristine/doxorubicin on cycles 3, 4, and 6. Prophylactic cranial irradiation was recommended after a complete response to all therapy. One hundred ten eligible patients were randomized. Grade 3/4 esophagitis was reported in 9% of patients receiving continuous thoracic RT versus 4% of patients receiving split-course RT. Grade 3/4 hematologic toxicity was common in both treatment arms. Complete/partial response was observed in 80% of patients on arm A versus 84% on arm B. Overall survival rates at 5 years were 18% and 17% for arms A and B, respectively. Interdigitating split-course thoracic RT delivered in 2.5-Gy fractions was tolerable in patients with limited-stage SCLC but did not provide a survival advantage.     

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases

Introduction Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. Materials and method We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n=11) and 30 Gy/10 fractions (n=10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. Results Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2–6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0–7 months) without statistically significant differences (Log rank p=0.74). There was one complete response and two partial responses. Conclusions The results suggest that MST was not significantly affected by the total dose/fractionation schedule.     

Phase II study of irinotecan plus cisplatin induction followed by concurrent twice-daily thoracic irradiation with etoposide plus cisplatin chemotherapy for limited-disease small-cell lung cancer.

PURPOSE: Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-na?ve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC). PATIENTS AND METHODS: Between November 2001 and May 2003, 35 chemotherapy-na?ve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (i.v.) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 i.v. on days 43 and 64, and etoposide 100 mg/m2 i.v. on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43. RESULTS: All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT. CONCLUSION: IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.     

Ⅳ期非小细胞肺癌化疗同期胸部三维放疗的前瞻性临床研究(一)——疗效与不良反应

目的 研究Ⅳ期非小细胞肺癌(NSCLC)化疗同期胸内病灶三维放疗的疗效和安全性.方法 2003-2010年共入组201例,可疗效分析182例,安全性分析201例.化疗以铂类为基础二药联合方案,中位周期数为4个.胸内病灶中位计划靶体积剂量为63 Gy.分析患者的生存情况,胃肠道、血液学不良反应,放射性肺炎和食管炎.用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析.结果 201例的随访率为97.5％,随访满＜1、1～2、≥3年者分别为201、170、134例.全组182例中4～5个周期化疗同期三维放疗和同期三维放疗≥63 Gy的1、2、3年生存率以及中位生存期(MST)分别为54％和66％、20％和23％、13％和19％以及14.3个月和16.1个月;相似放化疗强度下单器官和多器官转移的MST分别为13.0个月和8.5个月(x2=10.10,P=0.001);同期放疗≥63 Gy 和＜63 Gy的MST在全组、4～5个周期化疗的分别为14.9个月和8.4个月(x2=20.48,P=0.000)、16.1个月和8.8个月(x2 =11.75,P=0.001),单器官、多器官的分别为16.0个月和9.0个月(x2=10.51,P=0.001)、11.0个月和7.0个月(x2=7.90,P=0.005).多因素分析显示4～5个周期化疗同期放疗≥63 Gy(β=0.243,P=0.019)、治疗后卡氏评分变化(β=1.268,P=0.000)对生存有影响.201例患者的2+3级胃肠反应发生率为45.0％;3+4级白细胞、血小板、血红蛋白不良反应发生率分别为35.0％、18.0％、15.0％;2+3级放射性肺炎和食管炎发生率分别为9.5％和13.4％.结论 Ⅳ期NSCLC化疗同期原发灶高剂量三维放疗可能使生存期延长,不良反应可接受.     

全脑联合三维适形放射治疗30例单病灶脑转移癌的疗效分析

背景与目的:全脑放疗是治疗脑转移癌的主要治疗手段。本文总结全脑联合三维适形放射治疗单病灶脑转移癌的疗效。方法:30例恶性肿瘤单病灶脑转移癌,全脑放疗DT39～45Gy后,以三维适形放疗追加转移病灶DT10～16Gy,常规分割1次/d,5次/w,总剂量DT55Gy。结果:6例CR,21例PR,3例NC,6个月、1年和2年生存率分别为73.3%(22/30)、40%(12/30)、13.3%(4/30),平均生存时间11.9个月。结论:全脑联合三维适形放射治疗单病灶脑转移癌,可以缓解颅脑神经症状,改善生活质量,延长生存期。     

Surgical management of single and multiple brain metastases: results of a retrospective study.

BACKGROUND: Advancement in diagnosis and treatment of various cancer entities led to an increasing incidence of brain metastases in the last decades. Surgical excision of single and multiple brain metastases is one of the central treatment options beside radiotherapy, radiosurgery and chemotherapy. To evaluate the benefit of surgery with/without whole-brain radiation therapy (WBRT) in single brain metastases and the influence of image guidance for brain metastases resection, 104 patients were retrospectively evaluated for post-operative outcome. PATIENTS AND METHODS: Between January 1994 and December 1999 150 patients were surgically treated for brain metastases at the Department of Neurosurgery at the Technical University of Dresden. Outcome could be evaluated in 104 patients with respect to special treatment strategies and survival time (69 patients with single and 35 patients with multiple lesions). RESULTS: Most metastases originated from primary lung and breast tumours. Karnofsky performance score improved on average by 10 after surgery. The extent of the extracerebral tumour burden was the main influence on survival time. Patients' age below 70 years was combined with prolonged survival time (median survival time, MST: 4.5 months vs. 7 months). Patients with solitary cerebral metastasis had a MST of 16 months, whereas patients with singular lesions had a MST of 7 and 4 months, depending on the extent of the extracerebral tumour growth. Additional post-operative WBRT with 30 Gy was combined with an increase in MST in patients with single brain metastasis (surgery + WBRT: MST 13 months; surgery only: MST 8 months). In addition, the rate of recurrent cerebral tumour growth was distinctly higher in the non-WBRT group. Neuronavigation did not significantly improve post-operative survival time. In 80% of patients extracerebral tumour growth limited patients' survival. CONCLUSION: Surgery is an initial treatment option in patients with single and multiple brain metastases especially with large tumours (> 3 cm). Post-operative WBRT seems to prolong survival time in patients with single brain metastasis by decreasing local and distant tumour recurrence. Neuronavigational devices permit a targeted approach. Multiple processes can be extirpated in one session without prolonging the hospitalisation time for the patient. However, neuronavigational devices cannot assure complete tumour resection.     

非小细胞肺癌脑转移患者全脑放疗不同剂量预后分析

目的:分析非小细胞肺癌(NSCLC)脑转移患者不同全脑放疗(WBRT)剂量的预后及影响因素。方法:回顾性分析2013—2015年间于河北医科大学第四医院行WBRT的244例NSCLC脑转移患者。按照不同WBRT剂量(EQD 2Gy)分为30~39 Gy组104例、≥40 Gy组140例。比较两组患者颅内无进...     

Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group.

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m(2) was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P<.001). Time to progression in the brain was longer in the combined-modality group (P=.005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P=.087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.     

局部增量照射无益于全脑照射SCLC脑转移患者生存再提高

目的 探讨局部增量照射(Boost)能否提高WBRT对小细胞肺癌脑转移(SCLC-BM)患者的OS和无颅内进展生存。方法 回顾分析2013—2015年首次诊治SCLC-BM 166例。除外PCI史(16例)或SRT (10例)或单纯局部脑照射(1例),入组142例。利用Kaplan-Meier法计算生存率Logrank法检验和单因素预后分析,Cox模型多因素预后分析。结果 平均年龄59.6岁,女性23%,脑转移灶数目分别为1(35%)、2~3(23%)、≥4(42%),化疗70%。中位OS期9.0个月、无颅内进展生存7.3个月。无照射(53例)、单纯WBRT (33)和WBRT+Boost (56)累计死亡率依次为92%、79%和73%;累计失败(死亡或颅内病灶未控)率为94%、82%和80%;与无照射相比,以上放疗模式对OS有影响(P=0.000、0.000),无颅内进展生存也有影响(P=0.000、0.000)。与单纯WBRT相比,WBRT+Boost对OS无影响(P=0.41、0.51)。结论 WBRT提高SCLC脑转移患者OS和无颅内进展生存,但同期或后续Boost照射无益于再提高生存。     

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。     

Role of radiation therapy in the combined-modality treatment of patients with extensive disease small-cell lung cancer: A randomized study.

PURPOSE: To investigate the efficacy and toxicity of cisplatin/etoposide (PE) chemotherapy (CHT) with or without accelerated hyperfractionated radiation therapy (ACC HFX RT) and concurrent daily carboplatin/etoposide (CE) in patients with extensive-disease small-cell lung cancer. PATIENTS AND METHODS: A total of 210 patients were treated with three cycles of standard PE. Patients with a complete response (CR) at both the local and distant levels (CR/CR) or a partial response (PR) at the local level and CR at the distant level (PR/CR) received either thoracic ACC HFX RT with 54 Gy in 36 fractions over 18 treatment days in combination with CE followed by two cycles of PE (group 1, n = 55) or an additional four cycles of PE (group 2, n = 54). Patients who experienced less response were treated nonrandomly (groups 3, 4, and 5). All patients with a CR at the distant level received prophylactic cranial irradiation. RESULTS: For 206 assessable patients, the median survival time (MST) was 9 months and the 5-year survival rate was 3.4%. Patients in group 1 had significantly better survival rates than those in group 2 (MST, 17 v 11 months; 5-year survival rate, 9.1% v 3.7%, respectively; P =.041). Local control was also better in group 1, but the difference was only marginally not significant (P =.062). There was no difference in distant metastasis-free survival between groups 1 and 2. Acute high-grade toxicity was higher in group 2 than in group 1. CONCLUSION: The addition of ACC HFX RT to the treatment of the most favorable subset of patients led to improved survival over that obtained with CHT alone.     

全身化疗同步或序贯脑放疗治疗非小细胞肺癌脑转移患者的疗效与毒副反应

目的 探讨全身化疗同步脑放疗或序贯脑放疗治疗非小细胞肺癌(NSCLC)脑转移患者的疗效和毒副反应.方法 采用前瞻对照方法,将60例NSCLC脑转移患者分为全身化疗同步脑放疗组(同步组)和全身化疗序贯脑放疗组(序贯组),每组各30例.结果 共59例患者完成治疗,总体客观缓解率(ORR)为22.0%,脑转移灶的ORR为35.6%,中位无进展生存期(PFS)为3个月,中位生存期(MST)为16个月,1年和2年总生存率分别为55.0%和24.4%.同步组和序贯组的总体ORR分别为20.0%和24.1%,脑转移灶的ORR分别为43.3%和27.6%,中位PFS分别为3和4个月,MST分别为16和13个月,差异均无统计学意义(均P>0.05).同步组和序贯组的1年生存率分别为58.5%和52.9%(P=0.365),2年生存率分别为37.2%和18.9%,同步组明显优于序贯组(P=0.011).同步组白细胞减少的发生率低于序贯组,差异有统计学意义(P=0.029);其他毒副反应的发生率差异无统计学意义(P>0.05).结论 全身化疗同步脑放疗治疗NSCLC脑转移可以取得较好疗效,且患者耐受性良好.

Abstract：

Objective To evaluate the efficacy, survival and toxicity in patients with brain metastases from non-small cell lung cancer ( NSCLC), treated with concurrent systemic chemotherapy and whole brain radiation therapy (WBRT) or sequential systemic chemotherapy/WBRT.Methods A total of 60 NSCLC patients with brain metastases were divided into two groups in this prospective clinical study:concurrent systemic chemotherapy and WBRT group (concurrent group ) and sequential systemic chemotherapy/WBRT group (sequential group).Results Of 59 assessable patients, the overall response rate was 22.0%, and the brain response rate was 35.6%;the median progression-free survival time was 3.0 months, and the overall 1- and 2-year survival rates were 55% and 24.4%, respectively, with a median survival time of 16.0 months.The overall response rate was 20.0% in the concurrent group and 24.1% in sequential group (P > 0.05 ).The brain response rates of 43.3% in concurrent group and 27.6% in sequential group were also not significantly different (P > 0.05 ).The median progression-free survival time for the patients in the concurrent group was 3.0 months versus 4.0 months in the sequential group, and the median survival time was 16.0 months versus 13.0 months ( all P >0.05 ).The 1- and 2-year survival rates were 58.5% and 37.2% versus 52.9% and 18.9%, respectively, with a significant difference in the 2-year survival rate between the two groups ( P = 0.011 ).In the sequential group, leukopenia was more frequent during chemotherapy than that in the concurrent group ( P = 0.029).Conclusion Concurrent systemic chemotherapy and WBRT is effective with tolerable adverse events in treating brain metastasis from NSCLC with an encouraging survival, and deserves further large sample and randomized multicenter clinical trials.