Correlation of in vitro drug-sensitivity testing results with response to chemotherapy and survival in extensive-stage small cell lung cancer: a prospective clinical trial

We devised a novel clinical protocol for extensive-stage small cell lung cancer (SCLC), selecting chemotherapy whenever possible on the basis of in vitro drug-sensitivity testing (DST) of individual patients' tumor specimens. Most of the specimens were obtained from metastatic sites during routine staging procedures. Increase of tumor cell number by culture in selective media usually was required before DST could be performed. We used the Weisenthal dye exclusion assay to place the seven drugs in rank order and to select the in vitro best regimen (IVBR), a three-drug combination of proved efficacy in SCLC. After initial staging and specimen acquisition, patients received etoposide and cisplatin (primary therapy) and were restaged after 12 weeks. Patients with partial or no responses and those relapsing after a complete response to primary therapy were switched to the IVBR if DST data were available. If DST data were unavailable, an empiric combination, vincristine-doxorubicin-cyclophosphamide, was administered as secondary therapy. Tumor-containing specimens were collected from 60 of the 80 patients (75%). One or more cell lines were established from 28 patients, and DST data were available from 26 patients (33% of total). Several parameters of in vitro drug sensitivity were significantly associated [two-sided P (P2) less than .05] with clinical response to primary therapy and also with response to the IVBR and were marginally associated with length of survival (.07 less than or equal to P2 less than or equal to .08). Sixteen patients (23%) received their IVBR as secondary therapy, and four of these (25%) attained a complete response, compared with three of 43 (7%) who received an empiric regimen (P2 = .16). We concluded that (a) selection of individualized chemotherapy is labor intensive but feasible in extensive-stage SCLC; (b) DST data are associated with clinical response to primary therapy and to secondary therapy with an IVBR; and (c) further observations will be required if we are to determine whether there is a modest therapeutic benefit to administering the IVBR as a secondary therapy.     

The relative value of conventional staging procedures for developing prognostic models in extensive-stage small-cell lung cancer

Published prognostic models for small-cell lung cancer (SCLC) have either combined limited- and extensive-stage patients or have not included standard anatomic staging information to assess the relative value of the knowledge of specific sites and number of sites of metastases in predicting survival in extensive-stage disease. We studied 136 extensive-stage patients in whom traditional staging procedures were performed and in whom other previously demonstrated significant pretreatment variables were determined. Using the Cox proportional hazards model, when all data were included, three variables were significant: performance status (PS) (P = .0001), number of sites of metastases (P = .0010), and age (P = .0029). A prognostic algorithm was developed using these variables, which divided the patients into three distinct groups. When the anatomic staging data were omitted, the serum albumin (P = .0313) was the only variable in addition to PS (P = .0001) and age (P = .0064) that was significant. An alternative algorithm using these three variables was nearly as predictive as the original. Therefore, in extensive-stage patients, reasonable pretreatment prognostic information can be obtained without using the number or specific sites of metastases as variables once the presence of distant metastases has been demonstrated.     

322例广泛期SCLC不同转移部位的生存分析

目的 探讨广泛期SCLC患者不同转移部位对预后的影响。方法 回顾分析本院2011-2015年间收治的经病理学或细胞学诊断的广泛期SCLC患者322例,其中原发病灶伴远处器官转移246例,原发病灶伴非区域淋巴结转移76例。转移累及单器官261例,累及多器官61例。322例患者绝大多数接受EP、CE方案化疗,187例接受胸部3DRT。采用Kaplan-Meier法计算生存率,Logrank法比较组间生存差异,Cox模型多因素预后分析。结果 全组中位生存期和1、2年OS分别为11.7个月和47.9%、19.5%;转移累及单器官者分别为12.4个月和52.5%、21.9%,转移累及多器官者分别为8.9个月和30.5%、11.2%(P=0.014)。单器官转移中肝转移预后最差,中位生存期仅为8.5个月,非区域淋巴结转移预后最好,中位生存期为14.5个月(P=0.001);除去肝转移以外单器官转移生存差异无统计学意义(P=0.139)。多器官转移中伴肝转移和伴骨转移预后最差(P=0.016、0.006),而有无脑转移对广泛期SCLC多器官转移患者预后影响不大(P=0.995)。单纯肝转移和多器官转移预后无明显差异(P=0.862)。结论 广泛期SCLC患者初诊时单器官转移累及肝脏对预后有影响且预后最差;多器官转移伴肝转移以及伴骨转移预后最差,而有无脑转移对预后影响不大。转移一旦累及肝脏,单器官受累和多器官受累生存无明显差异。     

The Role of Integrated 18F-FDG PET-CT as a Staging Tool for Limited-Stage Small Cell Lung Cancer: A Retrospective Study

Background: The aim of this study was to evaluate whether positron emission tomography-computed tomography (PET-CT) could be used as part of the staging work-up in patients with limited-stage disease (LD) small cell lung cancer (SCLC). Patients and Methods: Between January 2002 and December 2007, a total of 73 patients with presumed LD on CT, who underwent a PET-CT scan, were included in this study. Results: Conventional work-up revealed distant metastases in 12 patients. Out of 61 patients diagnosed as LD SCLC, PET-CT found unexpected distant metastases in 15 (24.6%) patients (LD/extensive-stage disease (ED)) of whom 13 (21.3%) were upstaged as a consequence. In 10 (76.9%) of the 13 upstaged patients, treatment was changed. The median survival of LD/LD SCLC patients who underwent concurrent chemoradiotherapy and chemotherapy only was 21.9 and 17.5 months, respectively. The median survival of LD/ED and ED/ED SCLC patients who received chemotherapy only was 17.4 and 14.1 months, respectively. The median survival of LD/LD SCLC patients who received concurrent chemoradiotherapy was superior to that of LD/ ED and ED/ED patients who received chemotherapy only (p = 0.037 and 0.004, respectively). Conclusion: The addition of PET-CT seems to allow more accurate staging and may thus protect a percentage of SCLC patients from potentially futile and toxic radiotherapy.     

Establishment of tumor cell lines as an independent prognostic factor for survival time in patients with small-cell lung cancer.

We studied tumor samples from 39 patients, who entered our study from January 1989 to May 1990, to assess whether the ability to establish a continually growing tumor cell line from fresh tumor specimens can be associated with decreased survival times in patients with small-cell lung cancer. The tumor samples were used to establish cell lines in culture using a serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). Thirty-three of these specimens were obtained by fiberoptic bronchoscopy from primary sites during routine diagnostic procedures. A total of 11 (28%) cell lines were established: seven (21%) from 33 primary tumors and four (80%) from five peripheral lymph nodes. Survival times of the 11 patients whose tumor cell specimens continually grew in culture at any time during their clinical course were significantly shorter than those of the 28 patients whose tumor cell specimens did not grow in vitro (median survival time of 26 weeks versus 73 weeks; P = .0068). Cox's proportional hazards model, including sex, age, Eastern Cooperative Oncology Group performance status, stage, source of specimen, treatment, and in vitro tumor cell growth in the overall patient group, showed that cell line establishment (P = .0017) and no therapy (P = .0015) were the most important factors indicating poor survival time. For the subgroup of 23 primary tumor patients, the important factors (in decreasing order) that indicated decreased survival times were the establishment of a cell line (P = .0112) and with cyclophosphamide-doxorubicin-vincristine alternating with cisplatin-etoposide, versus cisplatin-vincristine-doxorubicin-etoposide therapy (P = .0463). Our study demonstrates that in vitro tumor cell growth is an adverse predominant prognostic factor in patients with small-cell lung cancer.     

不同转移部位对广泛期小细胞肺癌患者治疗 预后的影响

背景与目的:小细胞肺癌(small cell lung cancer,SCLC)是肺癌中恶性程度最高的病理学类型,易发生远处转移,转移部位及肿瘤负荷对患者的预后有一定预测作用.比较不同远处转移部位及转移器官个数对广泛期SCLC患者预后的影响,以期为临床决策提供参考.方法:收集2014年5月—2019年2月在同济大学附属...     

Examination of bone marrow biopsy specimens and staging of small cell lung cancer

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.     

Prophylactic Cranial Irradiation (PCI) versus Active MRI Surveillance for Small Cell Lung Cancer: The Case for Equipoise

Prophylactic cranial irradiation (PCI) for SCLC offers a consistent reduction in the incidence of brain metastases at the cost of measurable toxicity to neurocognitive function and quality of life, in the setting of characteristic pathologic changes to the brain. The sequelae of PCI have historically been justified by the perception of an overall survival advantage specific to SCLC. This rationale has now been challenged by a randomized trial in extensive-stage SCLC demonstrating equivalent progression-free survival and a trend toward improved overall survival with PCI omission in the context of modern magnetic resonance imaging (MRI) staging and surveillance. In this article, we critically examine the randomized trials of PCI in extensive-stage SCLC and discuss their implications on the historical data supporting PCI for limited-stage SCLC from the pre-MRI era. Further, we review the toxicity of moderate doses of radiation to the entire brain that underlie the growing interest in active MRI surveillance and PCI omission. Finally, the evidence supporting prospective investigation of radiosurgery for limited brain metastases in SCLC is reviewed. Overall, our aim is to provide an evidence-based assessment of the debate over PCI versus active MRI surveillance and to highlight the need for contemporary trials evaluating optimal central nervous system management in SCLC.     

Positron emission tomography in limited-stage small-cell lung cancer: a prospective study.

PURPOSE: To determine how often positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose (FDG-PET) detects extensive-stage small-cell lung cancer (SCLC) in patients considered to have limited-stage disease based on conventional staging procedures, and to determine the impact of PET on treatment planning for presumed limited-stage SCLC. PATIENTS AND METHODS: We prospectively performed pretreatment FDG-PET on 24 patients determined by conventional staging methods to have limited-stage SCLC (defined as disease that could be encompassed within a reasonable radiotherapy portal, excluding bilateral supraclavicular disease). PET images were evaluated for evidence of extensive-stage disease. Tumor-node-metastasis system staging was also assigned for each patient, with and without PET information. RESULTS: FDG-PET demonstrated findings consistent with extensive-stage SCLC in three of 24 patients. FDG-PET correctly upstaged two (8.3%) of 24 patients to extensive-stage disease (95% CI, 1.03% to 27.0%). PET correctly identified tumor in each SCLC mass (primary or nodal) that was suspected on computed tomography (CT) imaging, thus giving a lesion-based sensitivity relative to CT of 100%. PET identified unsuspected regional nodal metastasis in six (25%) of 24 patients, and the radiation therapy plan was significantly altered to include the PET-positive/CT-negative nodes within the high-dose region in each of these patients. Brain PET images in 23 patients disclosed no evidence of brain metastasis. CONCLUSION: FDG-PET has high sensitivity for SCLC and appears to be of value for initial staging and treatment planning of patients with presumed limited-stage disease.     

Elevated serum creatine kinase BB levels in patients with small cell lung cancer

Clinical tumor specimens and cultures of small cell lung cancer (SCLC) produce 10- to 100-fold higher quantities of the BB isoenzyme of creatine kinase (CK-BB) (EC 2.7.3.2) than did other types of lung cancer. Serum CK-BB levels were evaluated in 105 newly diagnosed, previously untreated patients with SCLC. All patients were thoroughly staged, including 42 patients with limited-stage and 63 patients with extensive-stage disease. Serum CK-BB was elevated (greater than 10 ng/ml) in 27 patients (26%) (range, 11 to 522 ng/ml; median, 40 ng/ml). Only 1 of 42 patients with limited disease had an elevated serum CK-BB, while 26 of 63 (41%) of patients with extensive disease did. When patients were subgrouped according to the number of metastatic sites detected in pretreatment staging, a significant association between the presence of an elevated serum CK-BB and the number of metastatic sites was observed (p less than 0.005). No association between the presence of metastatic disease in a specific site and an elevated serum CK-BB could be detected. After adjusting for the number of metastatic sites, survival among patients with a normal pretreatment CK-BB was significantly better than in patients with an elevated CK-BB (p = 0.014). Sequential serum CK-BB determinations in 33 patients revealed an excellent correlation between clinical response to therapy and serum CK-BB levels. Continuous SCLC cell lines established from 13 patients in this study all expressed high levels of CK-BB. These data suggest that serum CK-BB determinations may be of value in estimating the extent of tumor dissemination, assigning prognosis, and monitoring response to therapy in patients with SCLC.     

High pretreatment serum concentration of basic fibroblast growth factor is a predictor of poor prognosis in small cell lung cancer.

Basic fibroblast growth factor (bFGF) is a secreted multifunctional cytokine and a potent stimulator of angiogenesis. We measured bFGF concentrations from serum samples taken from 103 patients with small cell lung cancer at the time of diagnosis. Serum concentration of bFGF (S-bFGF) ranged from undetectable to 54 pg/ml (median, 6 pg/ml). S-bFGF was not associated with age, sex, performance status, or stage. A high pretreatment S-bFGF was associated with poor overall survival. The 1- and 2-year survival rates of the patients within the highest quartile of S-bFGF (>or=17 pg/ml) were only 26% and 11%, respectively, in contrast to the 49% and 20% 1- and 2-year survival rates of those patients with S-bFGF < 17 pg/ml (P = 0.013). The 1- and 2-year survival rates of the patients with extensive-stage disease were 33% and 10%, respectively (P = 0.0091). Interestingly, S-bFGF provided additional prognostic information to the stage because the 1- and 2-year survival rates of patients with extensive-stage disease and a high S-bFGF (>or=17 pg/ml) were as low as 16% and 5%, respectively (P = 0.0026). Similarly, in the multivariate model of survival analysis, patients with both extensive-stage disease and a high S-bFGF (>or=17 pg/ml) were found to have a particularly poor prognosis (relative risk of death, 2.1; 95% confidence interval, 1.2-3.6; P = 0.0057). We conclude that a high S-bFGF at diagnosis is associated with poor outcome in small cell lung cancer, possibly reflecting active angiogenesis and rapid tumor growth, and may complement prognostic information obtained by staging.     

晚期小细胞肺癌和非小细胞肺癌不同转移部位预后意义的比较

  目的  明确不同转移部位对小细胞肺癌（small cell lung cancer,SCLC）和非小细胞肺癌（non-small cell lung cancer,NSCLC）预后影响的差异。  方法  回顾性分析天津医科大学肿瘤医院2012年1月至2017年12月确诊为晚期SCLC 266例和2015年1月至2017年12月确诊为晚期NSCLC 275例,总计541例患者病例资料。主要观察指标为总生存期（overall survival,OS）。  结果  在SCLC中,与多器官转移者相比,单器官转移者的预后更好（P=0.000 4）;在NSCLC中,单器官与多器官转移者之间未见到明显的生存差异（P=0.451）。在SCLC单器官转移者中,脑转移的预后相对最好,骨转移的预后相对较差,肝转移的预后最差,三者的中位生存时间（median survival time,MST）分别为14.5、11.5和10.3个月;在NSCLC单器官转移者中,肺内转移的预后最佳,肝和肾上腺转移者的预后较差,三者的MST分别为未达到、7.6和7.3个月。在SCLC多器官转移者中,有骨（P=0.046）、肝（P=0.019）转移者预后较差;而有无脑（P=0.995）、肺（P=0.847）、肾上腺（P=0.255）转移对患者的预后无显著性影响;在NSCLC多器官转移的患者中,有脑（P=0.054）、肾上腺转移（P=0.006）的患者预后较差;有肺（P=0.008）转移的患者预后较好;而有无骨（P=0.091）、肝（P=0.300）转移对患者的预后无显著性影响。  结论  不同转移部位对SCLC和NSCLC预后的影响存在差异。      

９８例广泛期小细胞肺癌预后多因素分析

目的　探讨影响广泛期小细胞肺癌（ＳＣＬＣ）预后的各种相关因素。方法　回顾性分析９８例广泛期ＳＣＬＣ患者的临床资料并随访,采用Ｃｏｘ模型行多因素分析。结果　９８例患者的１年生存率为４５.３８％,２年生存率１５.１５％,３年生存率８.８４％,中位生存期为１１.２４个月。单因素分析显示,是否有肝转移、起病时乳酸脱氢酶水平、有无接受胸部放疗、有无胸腔积液、化疗周期数、转移是否局限于胸腔、行为状态评分、是否为单发转移灶对患者的生存期有影响;多因素分析显示,是否有肝转移、化疗周期数、起病时乳酸脱氢酶水平、行为状态评分是预测预后的独立因素。结论　无肝转移、化疗周期数＞４、起病时乳酸脱氢酶水平正常、ＰＳ评分０～１均提示广泛期ＳＣＬＣ患者的预后较好。     

Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593--a phase III trial of the Eastern Cooperative Oncology Group.

PURPOSE: To determine the efficacy of topotecan in combination with standard chemotherapy in previously untreated patients with extensive-stage small-cell lung cancer (SCLC), the Eastern Cooperative Oncology Group (ECOG) conducted a phase III trial. PATIENTS AND METHODS: Eligible patients had measurable or assessable disease and an ECOG performance status of 0 to 2; stable brain metastases were allowed. All patients received four cycles of cisplatin and etoposide every 3 weeks (step 1; PE). Patients with stable or responding disease were then randomized to observation or four cycles of topotecan (1.5 mg/m(2)/d for 5 days, every 3 weeks; step 2). A total of 402 eligible patients were registered to step 1, and 223 eligible patients were registered to step 2 (observation, n = 111; topotecan, n = 112). RESULTS: Complete and partial response rates to induction PE were 3% and 32%, respectively. A 7% response rate was observed with topotecan (complete response, 2%; partial response, 5%). The median survival time for all 402 eligible patients was 9.6 months. Progression-free survival (PFS) from date of randomization on step 2 was significantly better with topotecan compared with observation (3.6 months v 2.3 months; P <.001). However, overall survival from date of randomization on step 2 was not significantly different between the observation and topotecan arms (8.9 months v 9.3 months; P =.43). Grade 4 neutropenia and thrombocytopenia occurred in 50% and 3%, respectively, of PE patients in step 1 and 60% and 13% of topotecan patients in step 2. Grade 4/5 infection was observed in 4.6% of PE patients and 1.8% of topotecan patients. Grade 3/4 anemia developed in 22% of patients who received topotecan. No difference in quality of life between topotecan and observation was observed at any assessment time or for any of the subscale scores. CONCLUSION: Four cycles of PE induction therapy followed by four cycles of topotecan improved PFS but failed to improve overall survival or quality of life in extensive-stage SCLC. Four cycles of standard PE remains an appropriate first-line treatment for extensive-stage SCLC patients with good performance status.     

Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P=0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P=0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.     

Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress.

PURPOSE: All cooperative group studies performed in North America for patients with extensive-stage small-cell lung cancer (SCLC) were evaluated to determine the pattern of the clinical trials and the outcome of patients over the past 20 years. PATIENTS AND METHODS: Phase III trials for patients with extensive-stage SCLC were identified through a search of the National Cancer Institute Cancer Therapy Evaluation Program database from 1972 to 1993. Patients with extensive-stage SCLC treated during a similar time interval listed in the Surveillance, Epidemiology, and End Results (SEER) database were also examined. Trends were tested in the number of trials over time, the number and sex of patients entered onto the trials, and the survival time of patients treated over time. RESULTS: Twenty-one phase III trials for patients with extensive-stage SCLC were initiated between 1972 and 1990. The median of the median survival times of patients treated on the control arms of the phase III trials initiated between 1972 and 1981 was 7.0 months; for those patients enrolled onto control arms between 1982 and 1990, the median survival time was 8.9 months (P =.001). Analysis of the SEER database of patients with extensive-stage SCLC over the same time period shows a similar 2-month prolongation in median survival time. CONCLUSION: Analysis of 21 phase III trials initiated in North America and the SEER database from 1972 to 1994 demonstrates that there has been a modest improvement in the survival time of patients with extensive-stage SCLC.     

A phase II study of weekly alternating chemotherapy in extensive-stage small cell lung cancer

Despite the recent development of new chemotherapeutic agents with activity in small cell lung cancer (SCLC), the long-term prognosis of patients with extensive-stage disease remains poor and has not improved in the past 20 years. The present study was designed to evaluate the activity and toxicity of weekly, alternating-regimen chemotherapy in patients with extensive-stage SCLC. Patients with previously untreated extensive-stage SCLC and performance status 0-2 were treated with cyclophosphamide 250 mg/m², etoposide 100 mg/m², and cisplatin 50 mg/m² on day 1; vincristine 1 mg/m² on day 8; and ifosfamide 1.2 gm/m² on days 8 and 9 with the entire treatment repeated every 14 days. Eighteen patients received chemotherapy for a median of 14 weeks (range, 1-35 weeks). Seventeen patients (94%) required dose delays and 16 patients (89%) required at least one dose reduction due to toxicity. Twelve patients (67%) exhibited an objective response (1 complete response, 11 partial response) with a median duration of response of 18 weeks (range, 8-32 weeks). Median survival was 33 weeks (range, 1-57 weeks) with a 1-year survival rate of 22%. Toxicity was primarily hematologic, including grade 3-4 leukopenia (82% of patients) and anemia (53% of patients). Only 2 patients developed grade 3 peripheral neuropathy and none exhibited grade 3-4 renal insufficiency. This regimen of weekly alternating combination chemotherapy resulted in tolerable toxicity as well as response and survival rates comparable to those achieved with standard chemotherapy in patients with extensive-stage SCLC. However, weekly chemotherapy regimens for the treatment of SCLC remain investigational.     

Recent Advances and Future Strategies for Immune-Checkpoint Inhibition in Small-Cell Lung Cancer

Small-cell lung cancer (SCLC) is distinguished from non–small-cell lung cancer by its rapid growth and more frequent metastases. Although patients with SCLC are highly responsive to chemotherapy and radiation therapy, long-term prognosis remains poor, with relapse and disease recurrence occurring in almost all cases. Whereas combination chemotherapies continue to be the standard of care in extensive-stage SCLC, there is value in exploring whether immune-checkpoint inhibition is an effective treatment strategy, given the durable responses in non–small-cell lung cancer. Data from SCLC trials have shown clinical activity and response to cytotoxic T-lymphocyte antigen-4 protein and programmed cell death-1 blockade, suggesting that antibodies targeting these pathways may be effective in improving survival outcome. However, data on clinical activity by programmed cell death-1 ligand expression in SCLC are not widely available. Limited data indicate that programmed cell death-1 ligand expression may not be an ideal biomarker for patient selection. Continued research is necessary to better optimize patient selection and response to therapy.     

小细胞肺癌术后脑转移影响因素及预后分析

目的 分析小细胞肺癌根治术后脑转移的影响因素,探讨术后脑预防照射意义.方法 对本院2000-2009年收治的有完整记录的88例行根治性手术治疗的小细胞肺癌患者资料行回顾性分析,Kaplan-Meier法生存分析,Logistic回归模型分析脑转移发生的影响因素.结果 随访率100％,随访满3年者37例.3例行脑预防照射患者均未发生脑转移;85例未行脑预防照射者脑转移发生率为24％,其中Ⅰ、Ⅱ、Ⅲ期患者3年脑转移发生率分别为4％、26％、29％(x2=7.57,P=0.023).发生脑转移与未发生脑转移患者的中位生存时间分别为18个月和48个月,3年生存率分别为25％和59％(x2=10.63,P=0.001).全组患者单因素及多因素回归分析均显示疗前分期是脑转移的影响因素(x2 =7.57、8.52,P=0.023、0.004),而年龄、性别、肿瘤部位、病理类型、术前化疗、术后放/化疗均不是脑转移的影响因素(x2 =0.03、0.00、0.00、2.58、0.01、1.23、0.84,P=0.869、0.998、0.992、0.109、0.936、0.266、0.361).结论 疗前分期是小细胞肺癌根治术后脑转移的影响因素.Ⅰ期小细胞肺癌脑转移率低、总生存期较长、术后行脑预防照射意义不大,Ⅱ、Ⅲ期患者脑转移率高、发生脑转移后预后差、建议行脑预防照射.