肺癌新TNM分期系统解析及外科治疗策略

 国际肺癌研究协会已公布了新修订的肺癌TNM分期系统。该系统是在完成了全球范围内大量肺癌病例的数据回顾、验证及统计学分析后,向国际抗癌联盟和美国癌症联合委员会提出修改建议并被采纳的。主要修订有：原发肿瘤（T）,将T1分为T1a（≤2 cm）、T1b（＞2 cm,≤3 cm）;将T2分为T2a（＞3 cm,≤5 cm）、T2b（＞5 cm,≤7 cm）,将＞7 cm者定义为T3,原发肿瘤所在肺叶内发现结节定义为T3,同侧非原发肺叶内出现结节定义为T4;区域淋巴结（N）,未行修订;远处转移（M）,恶性胸腔积液和对侧肺内结节定义为M1a,其他肺外远处转移定义为M1b。新分期反映了肺癌工作者对肺癌的新认识并带来了肺癌外科治疗策略的改变。     

TNM因素对非小细胞肺癌治疗效果的影响

目的 探讨肺部原发肿瘤的大小、淋巴结不同区域的转移及有无远处转移对非小细胞肺癌(NSCLC)综合治疗效果的影响.方法 回顾性分析手术治疗的987例NSCLC患者的临床资料,将其中以手术+化、放疗的574例患者与单纯手术治疗的413例患者进行对比分析.结果 全组患者的1、3、5、10年生存率分别为87.7%、57.5%、54.6%和54.5%.其中综合治疗组的1年生存率高于单纯手术组(P<0.01).在T4患者中,手术+放疗组的5年生存率高于单纯手术组(P<0.05).在N0患者中,手术+化疗组、手术+放疗组与单纯手术组比较,1年生存率差异有统计学意义(均P<0.05);在N1患者中,手术+化疗组、手术+放化疗组与单纯手术组比较,1年生存率差异有统计学意义(P<0.01);在N2患者中,手术+化疗组与单纯手术组比较,1年和3年生存率差异均有统计学意义(均P<0.05).结论 对于NSCLC患者,以手术为主的综合治疗疗效优于单纯手术.对T4患者应加强术后局部放疗,对NO和N1患者应辅以适度化、放疗,对N2患者则应强调辅以足够的化疗.     

A training-testing approach to the molecular classification of resected non-small cell lung cancer.

PURPOSE: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance. EXPERIMENTAL DESIGN: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray. RESULTS: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High alpha-actinin-4 expression was identified as highly correlated with poor prognosis. CONCLUSIONS: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.     

Surveillance of resected non-small cell lung cancer

Lung cancer is the most common cancer in the world. 15?% of all patients with lung cancer are diagnosed at an early stage, and surgery is the treatment of choice for them. 40?% of all patients survive more than 5 years after surgery, and most of them die as a result of systemic disease. Half of all recurrences are diagnosed within the first 24 months after curative treatment, and 90?% in the first 5 years. Despite this, it is not standardized who should do the monitoring, what additional tests are needed and how often should they be performed. We present here a review on the various recommendations in clinical guidelines.     

Adjuvant chemotherapy in resected non-small cell lung cancer

There is still a high mortality ratio in completely resected non-small cell lung cancer patients either due to local or, more often, to metastatic recurrence. The NSCLC Collaborative Group Meta-analysis demonstrated a not statistically significant advantage in patients treated with cisplatin-based regimens. Many subsequent trials were unable to demonstrate the real effectiveness of cisplatin-based adjuvant chemotherapy with a significant rate of toxicity. The IALT trial demonstrated little advantage in overall and disease-free survival with acceptable toxicity. A recent meta-analysis of trials including 5716 patients demonstrated the role of cisplatin-based chemotherapy as adjuvant treatment of resected non-small cell lung cancer even if results shoud be carefully examined. At present, adjuvant chemotherapy in non-small cell cancer should not be reserved to experimental trials.     

Surgical staging for non-small cell lung cancer

The treatment of non-small cell lung cancer is stage specific. Aggressive staging is associated with improved stage-specific prognosis. Available methods of surgical staging include scalene node biopsy, mediastinoscopy, anterior mediastinotomy, and thoracoscopy. In this article the various surgical staging methods are described and their respective roles are discussed.     

Adjuvant therapy for resected non-small cell lung cancer

Surgery remains the initial treatment for patients with early-stage non-small cell lung cancer (NSCLC). The frequent occurrence of distant metastases and local regional failure after surgical resection would indicate that additional treatment is necessary. Early trials of adjuvant chemotherapy and postoperative radiation were often plagued by small patient sample size, inadequate surgical staging, and ineffective or antiquated treatment. A 1995 meta-analysis found a nonsignificant reduction in risk of death for postoperative cisplatin-based chemotherapy. This was followed by a new generation of randomized phase III trials some of which have reported a benefit for chemotherapy in the adjuvant setting. Based on the results of these trials, platin-based chemotherapy has become the standard of care for resected stages II and IIIA NSCLC. The role of postoperative radiation therapy remains to be defined. In the future, improvement in survival outcomes from adjuvant treatment is likely to result from the evaluation of novel agents, identification of tumor markers predictive of disease relapse, and definition of factors that determine sensitivity to therapeutic agents. Some of the molecularly targeted agents such as the angiogenesis and epidermal growth factor receptor inhibitors are being incorporated into clinical trials. Gene expression profiles and proteomics are techniques being used to create prediction models to identify patients at risk for disease relapse. Molecular markers such as ERCC1 may determine response to treatment. Increasing the understanding of the molecular makeup of lung cancer will hopefully increase cure rates for patients by maximizing the efficacy of the adjuvant therapy.     

Diagnosing and staging of non-small cell lung cancer

Lung cancer remains the most common cause of death due to neoplasm in the United States. Despite recent efforts, early diagnosis provided through screening studies has not resulted in improved survival. Most lung cancer victims are symptomatic at presentation, and 50% have distant metastases. The diagnosis, often suspected on plain chest radiograph, can usually be confirmed with bronchoscopy or sputum cytology. The most useful routine staging evaluation, in addition to history and physical examination, is computed tomography. The routine use of other staging modalities is not recommended. A new staging system, currently in use throughout North America, western Europe, and Japan, permits accurate estimation of prognosis and assignment to therapeutic groups.     

Current concepts in the staging of non-small cell lung cancer

When evaluating a patient diagnosed with non-small cell lung cancer (NSCLC), staging helps define the extent of disease. The main goals of staging are to assist in determining appropriate treatment options (surgery versus non-surgical) and in predicting prognosis. Based on the recommendation of the American Joint Committee for Cancer (AJCC), a TNM (tumor, node, and metastases) staging system is used for NSCLC. Clinical staging (cTNM) is determined using non-invasive techniques such as clinical assessment and radiologic testing. Pathologic staging (pTNM) is determined using invasive techniques such as bronchoscopy, mediastinoscopy, and video-assisted thoracoscopic surgery, or at the time of thoracotomy. Recently, new staging modalities such as positron emission tomography and intraoperative sentinel node mapping have been used with promising results. In the near future, these techniques, as well as molecular and serum tumor markers, will likely be used to more accurately determine the burden of disease and allow for more appropriate treatment.     

PET scan in the staging of non-small cell lung cancer

Imaging techniques play an essential role in the diagnosis, staging, and follow-up of patients with lung cancer. Positron emission tomography (PET) has become an important innovation in lung cancer imaging. In this report, a comprehensive overview is given of the important number of prospective performance studies, looking at the value of PET in locoregional and distant staging of NSCLC, and at its potential impact on patient management. In the assessment of locoregional lymph node spread, PET has a high negative predictive value in the exclusion of N2 or N3 disease, so that mediastinoscopy can be omitted in most patients with negative mediastinal PET-images. False negative mediastinal PET findings may occur in patients with minimal N2 disease. Because of possible false positive findings in patients with inflammatory nodes or granulomatous disorders, confirmation and lymph node mapping by mediastinoscopy remains mandatory in these situations. In the extrathoracic staging, PET is a useful adjunct to conventional imaging, because it is able to detect unexpected metastatic lesions. An isolated positive finding that determines the possibility for radical treatment requires pathological verification, because of the possibility of a false positive result. PET is also able to exclude malignancy in equivocal lesions, but caution is needed in case of small lesions. There are currently insufficient data to state that PET could replace standard imaging. The use of PET as described in the performance studies, now undergoes further validation in large-scale randomised patient outcome studies. In the meanwhile, a current recommendation for the use of PET in contemporary lung cancer staging is provided.     

Multimodality approach to early-stage non-small cell lung cancer

The results of large randomised studies have clearly demonstrated that adjuvant chemotherapy prolongs overall survival by approximately 5% at 5 years in patients with early-stage non-small cell lung cancer (NSCLC). The benefit appears to be largely confined to patients with stage II/III disease, although approximately 25% of patients with stage I disease are at high risk of relapse within 5 years of surgery and therefore could benefit from adjuvant chemotherapy. There is an urgent need to predict more accurately which patients are likely to relapse after surgery and who, therefore, might benefit from further therapy. Preliminary studies indicate that molecular tumour markers may be able to identify tumours that are more likely to respond to chemotherapy and patients who are more likely to achieve improved survival from those who do not benefit at all from adjuvant chemotherapy. A pivotal study has shown that analysis of tumour gene expression can be used to predict the risk of relapse with greater accuracy than that which is achievable using clinical factors. In the future, pharmacogenomics may be used in this approach to identify patients for adjuvant chemotherapy, thus increasing the efficacy of treatment and reducing the burden of therapy in patients who are unlikely to benefit from further therapy.     

非小细胞肺癌分期技术的应用研究及第七版肺癌分期的解析

肺癌最常用的肿瘤分期系统是TNM分期,国际肺癌研究协会(IASLC)在第13界世界肺癌大会上公布了新修订的第七版肺癌TNM分期.准确的临床分期有赖于从病史、临床检查、影像学检查及侵入性检查等多方面分析,准确的临床分期对于指导治疗具有重要意义,第七版肺癌TNM分期分别从原发病灶、淋巴结转移及远隔脏器转移方面分别作了修订,使之更准确地对应患者预后.     

非小细胞肺癌术后三维适形放疗疗效分析

目的 分析非小细胞肺癌(NSCLC)术后接受三维适形放射治疗(3DCRT)的初步结果.方法 84例NSCLC患者术后接受3DCRT,其中肺叶切除65例(77.4%),全肺切除19例(22.6%);完整的R0切除54例(64.3%),镜下切缘阳性的R1切除15例(17.9%),肉眼残存的R2切除15例(17.9%).术后病理分期为Ⅰ B期1例,ⅡB期7例,ⅢA期52例,ⅢB期24例.全组术后中位放疗剂量为60 Gy(40～70 Gy,2 Gy/次).术后37例患者接受中位3个周期的辅助化疗.中位随访时间为35.5个月.结果 全组患者的3年生存率为58.6%,4年生存率为43.9%.有43例(53.1%)出现复发转移,其中胸内复发8例(9.9%),远处转移38例(46.9%).单因素分析显示,患者性别、年龄、体重下降、肿瘤大小、病理类型和分期与预后无关.接受R1、R2切除的患者预后较差.随访中,有9例(11.1%)患者出现2级以上放射性肺炎.结论 NSCLC患者术后采用3DCRT放疗效果较好,不良反应发生率较低,安全可靠.     

Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study

For the scheduled future revision of the TNM staging system for lung cancer, it is important that the present 1997 version be evaluated in a large population. In 2001, the Japanese Joint Committee of Lung Cancer Registry sent a questionnaire to 320 Japanese institutions regarding the prognosis and clinicopathological profiles of patients who underwent the resection for primary lung neoplasms in 1994. We compiled the data for 7408 patients from 303 institutions (94.7%). Among these, 6644 patients with non-small cell histology were studied in terms of prognosis. The 5-year survival rate of the entire group was 52.6%. The 5-year survival rates by clinical (c-) stage were as follows: 72.1% for IA (n = 2423), 49.9% for IB (n = 1542), 48.7% for IIA (n = 150), 40.6% for IIB (n = 746), 35.8% for IIIA (n = 1270), 28.0% for IIIB (n = 366) and 20.8% for IV (n = 147). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The 5-year survival rates by pathological (p-) stage were as follows: 79.5% for IA (n = 2009), 60.1% for IB (n = 1418), 59.9% for IIA (n = 232), 42.2% for IIB (n = 757), 29.8% for IIIA (n = 1250), 19.3% for IIIB (n = 719) and 20.0% for IV (n = 259). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The survival curves of stages IB and IIA were almost superimposed in both c- and p-settings. These findings indicated that the present stages IB and IIA should be merged into the same stage category. Otherwise, the present TNM staging system seemed to well characterize the stage-specific prognosis in non-small cell lung cancer. The future revision should focus on the subdivision of stages I and II.     

非小细胞肺癌同侧肺内转移术后预后因素分析

目的探讨原发性非小细胞肺癌(NSCLC)同侧肺内转移外科手术的疗效及预后因素.方法对46例经手术病理证实并行完全切除的原发性非小细胞肺癌同侧肺内转移的病例进行回顾性研究,分为与原发肿瘤灶同叶的肺内转移(pm1)22例和不同叶的肺内转移(pm2)24例二组.结果本组病例总的3年生存率为47.8%,中位生存期(MST)为34.3个月,pm1的3年生存率为63.6%,MST为48个月.pm2的3年生存率为33.3%,MST为24个月.pm1和pm2的3年生存率有统计学差异(P=0.0215).并分析了患者的生存率与一些临床病理因素的关系(病理类型、肺转移结节数、淋巴结分期).其中N0的3年生存率为68.8%,与N1～33年生存率为36.7%比较有显著差异(P=0.0175).结论肺内转移灶与原发灶同叶和不同叶、有无淋巴结转移是影响非小细胞肺癌肺内转移术后预后的重要因素.     

Surgical approach to non-small cell lung cancer stage IIIA

Patients with stage IIIa non-small cell carcinoma of the lung who could benefit from surgical treatment include those with tumors that invade chest wall, diaphragm, or mediastinum, as well as patients who present with mediastinal lymph node involvement. As long as surgery remains the most effective mode of treatment in non-small cell lung carcinoma, it is important that it be made available, when indicated, to the greatest number of patients possible. The continuing high incidence of deaths due to distant metastases underscores the need to combine effective chemotherapy and radiotherapy with the surgical treatment.     

三级淋巴结构在非小细胞肺癌中的研究进展

肺癌是世界上死亡率最高的恶性肿瘤,其中以非小细胞肺癌(non-small cell lung cancer,NSCLC)为著.肿瘤微环境是由肿瘤细胞、成纤维细胞、免疫细胞和肿瘤内脉管系统之间的相互作用形成的复杂网络.近年来有研究发现非小细胞肺癌中存在着三级淋巴结构(tertiary lymphoid structures,TLSs),有趣的是,这种三级淋巴结构有着与淋巴结类似的解剖结构.另外,三级淋巴结构中成熟DC/CD8+T细胞计数密度比值与非小细胞肺癌患者预后存在正相关性.本文将对NSCLC中有关TLSs的结构、功能及临床意义作简要概述.