非小细胞肺癌纵隔淋巴结转移危险因素分析及术前纵隔镜检查的应用策略

目的 探讨纵隔镜技术评估非小细胞肺癌(NSCLC)术前纵隔淋巴结状态(是否存在转移)的临床应用策略.方法 2000年10月至2007年6月,对临床连续收治的经病理确诊的临床分期为Ⅰ～Ⅲ期的NSCLC患者152例,分别采用CT和纵隔镜技术评估纵隔淋巴结状态.根据纵隔淋巴结最终病理结果,计算CT下纵隔肺门淋巴结阴性NSCLC的纵隔镜检查阳性率和实际纵隔淋巴结转移发生率.以患者性别、年龄、肿瘤部位、病理类型、肿瘤T分期、肿瘤类型(中央型或外周型)、CT下纵隔淋巴结大小和血清癌胚抗原(CEA)水平等作为预测因子,进行纵隔淋巴结转移危险因素的单因素和多因素分析.结果 69例CT下纵隔肺门淋巴结阴性NSCLC,纵隔镜检查阳性8例,阳性率为11.6%;实际纵隔淋巴结转移14例,发生率为20.1%.62例临床Ⅰ期(cT1～2NOMO)NSCLC,纵隔镜检查阳性7例,阳性率为11.3%;实际纵隔淋巴结转移12例,发生率为19.4%.对全部152例NSCLC患者纵隔淋巴结转移危险因素的分析结果显示,病理类型和CT下纵隔淋巴结大小是纵隔淋巴结转移的独立危险因素.对69例CT下纵隔肺门淋巴结阴性NSCLC患者纵隔淋巴结转移危险因素的分析结果显示,病理类型是纵隔淋巴结转移的独立危险因素.结论 对于CT下纵隔淋巴结短径≥1 cm的NSCLC患者,术前必须进行纵隔镜检查;对于腺癌患者,即使是CT下纵隔肺门淋巴结短径<1 cm,术前也应该进行纵隔镜检查.     

Assessment of Updated Commission on Cancer Guidelines for Intraoperative Lymph Node Sampling in Early Stage NSCLC

IntroductionThe American College of Surgeons Commission on Cancer recently updated its sampling recommendations for early stage NSCLC from at least 10 lymph nodes to at least one N1 (hilar) and three N2 (mediastinal) lymph node stations. Nevertheless, intraoperative lymph node sampling minimums remain subject to debate. We sought to evaluate these guidelines in patients with early stage NSCLC.MethodsWe performed a cohort study using a uniquely compiled data set from the Veterans Health Administration. We manually abstracted data from operative notes and pathology reports of patients with clinical stage I NSCLC receiving surgery (2006–2016). Adequacy of lymph node sampling was defined using count-based (≥10 lymph nodes) and station-based (≥three N2 and one N1 nodal stations) minimums. Our primary outcome was recurrence-free survival. Secondary outcomes were overall survival and pathologic upstaging.ResultsThe study included 9749 patients. Count-based and station-based sampling guidelines were achieved in 3302 (33.9%) and 2559 patients (26.3%), respectively, with adherence to either sampling guideline increasing over time from 35.6% (2006) to 49.1% (2016). Adherence to station-based sampling was associated with improved recurrence-free survival (multivariable-adjusted hazard ratio = 0.815, 95% confidence interval: 0.667–0.994, p = 0.04), whereas adherence to count-based sampling was not (adjusted hazard ratio = 0.904, 95% confidence interval: 0.757–1.078, p = 0.26). Adherence to either station-based or count-based guidelines was associated with improved overall survival and higher likelihood of pathologic upstaging.ConclusionsOur study supports station-based sampling minimums (≥three N2 and one N1 nodal stations) for early stage NSCLC; however, the marginal benefit compared with count-based guidelines is minimal. Further efforts to promote widespread adherence to intraoperative lymph node sampling minimums are critical for improving patient outcomes after curative-intent lung cancer resection.     

Ⅲ期N2非小细胞肺癌的外科治疗

目的：探讨Ⅲ期N2非小细胞肺癌（NSCLC）患者外科治疗的疗效及影响预后的因素。方法：回顾性分析1982－1996年手术治疗的266例Ⅲ期N2 NSCLC患者的5年生存率,与同期手术的N0、N1患者做比较,用Cox模型分析病理分型、淋巴结转移数目、淋巴结转移区域、手术方式、T状态、手术性质等对N2的NSCLC患者预后的影响。结果：266例Ⅲ期N2的NSCLC患者的5年生存率为17．3％,明显低于同期N0、N1患者的5年生存率（51．4％和30．4％）,淋巴结转移数目、淋巴结转移区域、T状态、手术性质为影响预后的重要因素。结论：对单区域纵隔淋巴结转移且估计能完全切除的Ⅲ期N2（特别是T1）NSCLC应采取以手术为主的综合治疗。     

Induction chemotherapy with cisplatin, vinorelbine, and mitomycin-C followed by surgery for patients with pathologic N2 non-small-cell lung cancer

PURPOSE: The treatment strategy for patients with non-small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS: Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS: From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36-57.2). CONCLUSION: Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.     

Endoscopic ultrasound guided biopsy versus mediastinoscopy for analysis of paratracheal and subcarinal lymph nodes in lung cancer staging

BACKGROUND: Exact mediastinal evaluation of patients with non-small-cell lung cancer (NSCLC) is mandatory to improve selection of resectable and curable patients for surgery. Mediastinoscopy (MS) and endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) are considered complementary, MS covering the anterior- and EUS-FNA the posterior mediastinum. Both methods can reach the paratracheal- and subcarinal-regions, but little is known about which method is most accurate, when compared in patients having both procedures performed. The aim of this study was to assess and compare the diagnostic value of MS and EUS-FNA with regard to mediastinal malignancy in the paratracheal- and subcarinal-regions. METHODS: Sixty patients considered to be potential candidates for resection of verified or suspected NSCLC underwent MS and EUS-FNA. The EUS-FNA diagnoses were confirmed either by open thoracotomy, MS or clinical follow-up. RESULTS: MS and EUS-FNA were conclusive for paratracheal or subcarinal mediastinal disease in 6 and 24 patients, respectively. Two patients with N2 disease diagnosed by EUS-FNA were upstaged to N3 by MS. The sensitivity for lymph node metastases in the right paratracheal region (2/4R) was 67% for EUS-FNA versus 33% for MS (p=0.69). In the left paratracheal region (2/4L) the sensitivity of EUS-FNA was 80% versus 33% for MS (p=0.06). In the subcarinal region (7) the sensitivity of EUS-FNA was 100% versus 7% for MS (p<0.01). The sensitivity for lymph node metastases in region 2/4L and/or 2/4R and/or 7 was 96% for EUS-FNA versus 24% for MS (p<0.01). CONCLUSION: In our hands EUS-FNA was superior to MS in the examination of paratracheal- and subcarinal-regions of patients considered for resection of lung cancer.     

Occult Nodal Disease in Patients With Non–Small-Cell Lung Cancer Who are Suitable for Stereotactic Ablative Body Radiation

IntroductionStereotactic ablative body radiotherapy is a therapeutic option for patients with peripheral stage I NSCLC in whom surgical resection is considered high risk. Patients receiving SABR do not undergo systematic nodal dissection and any occult nodal metastases will therefore go undetected. Our aim was to determine what proportion of cases this might represent.Materials and MethodsWe retrospectively studied patients who underwent lung resections for presumed stage I NSCLC between 2008 and 2011 at a United Kingdom teaching hospital. We reviewed postoperative pathological lymph node staging and analyzed a subset of these patients in whom SABR would have been be technically possible.ResultsWe reviewed 128 cases of presumed NSCLC preoperatively staged as T1/2a N0 M0. Of 89 cases with peripheral tumor location, 8 patients (8.9%) had nodal involvement at surgical resection.ConclusionOur data show that approximately 1 in 11 patients with peripheral stage I NSCLC will have occult mediastinal/hilar nodal involvement. Although this is a relatively small proportion, routine use of EBUS-TBNA for nodal staging in patients undergoing SABR might identify a greater proportion of patients with nodal disease compared with a strategy of nodal staging directed according to positron emission tomography-computed tomography findings.     

Mediastinal restaging: EUS-FNA offers a new perspective

STUDY OBJECTIVE: We hypothesized that transoesophageal endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has the potential to be a valuable and accurate new diagnostic technique for mediastinal restaging in non-small cell lung cancer (NSCLC) after induction chemotherapy. The current restaging modalities either have a low diagnostic accuracy (computed tomography (CT) scan of the thorax) or they are invasive, can be technically difficult and are therefore not commonly performed (remediastinoscopy). METHODS AND PATIENTS: Nineteen consecutive patients with NSCLC and proven ipsilateral or subcarinal lymph node metastases (N2 disease) who had been treated with induction chemotherapy underwent mediastinal restaging by EUS-FNA. Patients had either a partial response (n=14) or stable disease (n=5) based on sequential CT scans of the thorax. INTERVENTIONS: EUS-FNA was performed in an ambulatory setting with biopsy of mediastinal lymph nodes (LN). No complications occurred. When EUS-FNA restaged the mediastinum as no regional lymph node metastasis (N0), surgical resection of the tumour with lymph node sampling or dissection was performed. RESULTS: The positive predictive value, negative predictive value, sensitivity, specificity and diagnostic accuracy of EUS-FNA in restaging mediastinal LN were 100, 67, 75, 100 and 83%, respectively. CONCLUSIONS AND SIGNIFICANCE: EUS-FNA qualifies as an accurate, safe and minimally invasive diagnostic technique for the restaging of mediastinal lymph nodes after induction therapy in NSCLC. In the future EUS-FNA might play an important role in the mediastinal restaging in NSCLC, particularly to identify the subgroup of down staged patients who benefit most from further surgical treatment.     

非小细胞肺癌纵隔淋巴结转移(N2)的外科治疗选择

目的 探讨有纵隔淋巴结转移（N2）的非小细胞肺癌（NSCLC）的外科治疗选择。方法 回顾性分析总结325例N2 NSCLC的外科治疗效果和经验。结果 全组5年生存率为19．6％,其中根治性切除者高于姑息性切除者,鳞癌高于腺癌,行袖式肺叶切除和全肺切除者高于常规肺叶切除者,纵隔淋巴结转移1～3枚者高于〉3枚者,术后综合治疗者高于单一外科治疗者,上述差异均有统计学意义。所有T3、T4以及M1患者均无5年生存者。结论 对于N2 NSCLC肿瘤为Tl或T2、病理类型为非腺癌以及纵隔转移淋巴结〈4枚者,外科治疗是最好的选择。对于肿瘤为T3的患者,外科治疗可能并非良策,肿瘤的根治性切除以及肺门和纵隔的系统淋巴结清扫,是病变分期和生存率提高的关键所在,术后综合治疗有助于患者的远期生存,尤其适用于有肿瘤残留和（或）纵隔转移淋巴结〉3枚的患者。     

The dutch national clinical audit for lung cancer: A tool to improve clinical practice? An analysis of unforeseen ipsilateral mediastinal lymph node involvement in the Dutch Lung Surgery Audit (DLSA)

Objective

Optimal treatment selection for patients with non-small cell lung cancer (NSCLC) depends on the clinical stage of the disease. Particularly patients with mediastinal lymph node involvement (stage IIIA-N2) should be identified since they generally do not benefit from upfront surgery. Although the standardized preoperative use of PET-CT, EUS/EBUS and/or mediastinoscopy identifies most patients with mediastinal lymph node metastasis, a proportion of these patients is only diagnosed after surgery. The objective of this study was to identify all patients with unforeseen N2 disease after surgical resection for NSCLC in a large nationwide database and to evaluate the preoperative clinical staging process.

两种纵隔淋巴结清扫方式治疗的219例ⅢA期非小细胞肺癌患者生存分析

背景与目的:在可切除的ⅢA期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者手术治疗中,如何正确处理纵隔淋巴结对预后非常关键,目前国内外学者对ⅢA期NSCLC患者纵隔淋巴结的清扫范围有较大争议.本研究目的在于探讨以两种纵隔淋巴结清扫方式对NSCLC患者生存的影响.方法:回顾性分析1999年1月至2004年1月,在新疆医科大学附属肿瘤医院外科行完全性切除术的219例ⅢA期NSCLC患者的临床资料及生存状况,其中109例采用采样式纵隔淋巴结清扫术(mediastinal lymph node sampling,LS),110例采用系统纵隔淋巴结清扫术(systematic mediastinal lymphadenectomy,SML).寿命表法和Kaplan-Meier法比较累积生存率及中位生存时间,Cox多因素生存模型分析影响生存的主要因素.结果:LS组患者术后1、3、5年生存率分别为82%、28%、13%,SML组分别为88%、37%、16%,两组术后中位生存期分别为20.0、23.5个月,有统计学意义(P＜0.05).Cox多因素分析结果表明,病理类型、纵隔淋巴结转移状况、纵隔淋巴结清扫方式是影响ⅢA期NSCLC N1或N2转移患者预后的因素(P＜0.05).结论:对可手术治疗的ⅢA期NSCLC患者行系统性纵隔淋巴结清扫可以提高生存率.     

肺癌纵隔淋巴结合理廓清范围的临床探讨

目的：探讨非小细胞肺癌(NSCLC)纵隔淋巴结转移方式。方法：回顾性研究1989年1月—1999年1月，淋巴结廓清术后病理证实的纵隔淋巴结转移(pN2)137例。分析临床病理因素与pN2的关系．应用Logistic回归分析判定纵隔淋巴结CT扫描阴性时(cN0-1)pN2有意义的预测指标；总结不同位置肺癌纵隔淋巴结转移的方式。结果：NSCLC无论病理类型和临床状态如何，均有纵隔淋巴结转移发生。纵隔淋巴结增大(cN2)和cT2或cT3腺癌患者转移的发生率较高(65．0％，75．0％)。纵隔淋巴结转移多为区域性(80．9％)，跨区域纵隔淋巴结转移多数伴有隆凸下淋巴结受累。结论：对NSCLC应行纵隔淋巴结廓清，尤其对cN2和cT3、cT3腺癌。多数患者单独廓清区域纵隔淋巴结即可达到目的。建议手术中对肺门和隆凸下淋巴结冰冻病理检查，无转移时可不必廓清非区域纵隔淋巴结。     

In vivo identification of sentinel lymph nodes for clinical stage I non-small cell lung cancer for abbreviation of mediastinal lymph node dissection

BACKGROUND: We previously reported that an identification of sentinel lymph node (SN) with a techenetium-99m (99mTc) tin colloid by ex vivo counting, i.e. the radio-activity of dissected lymph nodes, was a reliable method of establishing the first site of nodal metastasis in non-small cell lung cancer [J. Thorac. Cardiovasc. Surg. 124(2002)486]. However, for SN navigation surgery, SN should be identified before lymph node dissection (in vivo) but not after that (ex vivo). In order to reduce mediastinal lymph node dissection for clinical stage I non-small cell lung cancer (NSCLC) by SN navigation surgery, the SN identifications for hilar lymph nodes by ex vivo counting, and for mediastinal lymph nodes by in vivo, were evaluated. METHODS: Intra-operative SN identification using 99mTc tin colloid was conducted on 104 patients with clinical stage I NSCLC who had had major lung resections with mediastinal lymph node dissections. The hilar SNs were identified by ex vivo counting (after lung resection) and the mediastinal SNs were identified by in vivo counting (before lymph node dissection). To evaluate the accuracy of mediastinal SN identification by in vivo counting, it was compared with the data by ex vivo counting. RESULTS: SNs were identified in 84 patients (81%). SNs were identified at the hilum by ex vivo counting in 78 patients (93%) and at the mediastinum by in vivo counting in 40 patients (48%). While 15 patients had lymph node metastases, i.e. N1 in six and N2 in nine, the SNs could be found to have metastases during operation in 13 of the 15 patients (87%). The in vivo counting of the mediastinum missed out the mediastinal SNs identified by ex vivo counting in four of the 84 patients (5%). CONCLUSION: If the hilar SNs identified by ex vivo counting and the mediastinal SNs identified by in vivo counting had no metastases, then mediastinal lymph node dissection could be abbreviated for patients with clinical stage I NSCLC.     

手术前PET-CT对非小细胞肺癌纵隔淋巴结转移的诊断价值

目的探讨术前PET-CT显像对非小细胞肺癌(NSCLC)纵隔淋巴结转移的诊断价值。方法选取2011年10月至2012年8月间进行手术根治或纵隔淋巴结活检的25例NSCLC患者。所有患者术前均行PET-CT检查,并根据手术或纵隔镜结果进行诊断及分期,计算PET-CT对诊断纵隔淋巴结的准确性、灵敏度、特异度、阳性预测值和阴性预测值。结果 25例患者中,纵隔淋巴结阳性率为28.0%。PET-CT对诊断纵隔淋巴结转移的准确性、灵敏度、特异度、阳性和阴性预测值分别为76.0%、57.1%、83.3%、57.1%和83.3%。3例假阴性患者的纵隔最大淋巴结短径分别为1.0、0.9和0.7cm。3例假阳性患者均为炎性增生。结论 PET-CT对NSCLC手术患者纵隔淋巴结转移的诊断灵敏度较低,特异度和阴性预测值较高。因此,PET-CT显示为阳性的纵隔淋巴结,有必要行纵隔镜检查;而阴性者则可不需行纵隔镜检查。     

Outcome following lung resections for pT1 non-small cell lung cancer.

AIMS: To analyse the outcome of patients with pT1 NSCLC treated at our institution by antero-lateral thoracotomy, anatomical lung resections and mediastinal lymph node dissection between 1980 and 2001. METHODS: Follow-up data were obtained retrospectively from 1980 to 1990 and prospectively after 1990. Survival was analysed using the Kaplan-Meier method. RESULTS: Histopathological examinations revealed mediastinal lymph node infiltration in 27.6% (pN1 17.8% and pN2 9.8%). pN2 was classified in 14.1% of adenocarcinomas compared to 6.2% of squamous cell carcinomas. Median overall survival of patients with pT1 carcinomas was 89+16 months (median+standard error). Histopathological N-classification indicates differential prognostic and therapeutic implications in pT1 adeno- and squamous cell carcinomas. CONCLUSIONS: Complete lymph node dissection is required for all patients with T1 NSCLC treated by either open surgery or VATS resection. Histopathological N-classification indicates differential prognostic and therapeutic implications in pT1 adeno- and squamous cell carcinomas.     

Histoculture drug response assay (HDRA) guided induction concurrent chemoradiotherapy for mediastinal node-positive non-small cell lung cancer

To improve the response to chemotherapy for non-small cell lung cancer (NSCLC), effective drugs should be selected for each patient. In 1994 we introduced histoculture drug response assay (HDRA) for NSCLC patients. For clinical N2 patients, biopsy of mediastinal lymph node is performed both for histological diagnosis and for HDRA. Induction concurrent chemoradiotherapy is then performed using HDRA positive chemotherapy agents. We have treated three patients with this strategy. HDRA could be performed using mediastinal lymph node biopsy specimens. Tumor reduction rates of these patients were 80.4%, 85.3%, and 57.1%. Their histological responses were Ef.3, Ef.2, and Ef.1b, respectively. Complete resection was done in all patients. This strategy appeared to be useful in NSCLC patients with mediastinal lymph node metastasis.     

Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer

BACKGROUND: Skip metastasis to mediastinal lymph nodes is a well-known phenomenon in non-small cell lung cancer (NSCLC). Little is reported in the literature about its clinical importance. It is still under discussion whether any prognostic differences exist between resected NSCLC with either skip metastases or continuous mediastinal lymph node metastases (N2). PATIENTS AND METHODS: We analyzed retrospectively the data of 45 patients with a pN2-stage, who underwent resection for NSCLC. Seventeen of these patients (37.8%), showing no metastatic involvement of hilar (N1) lymph nodes, were compared to the remaining 28 patients with infiltration of hilar nodes (N1) as well as N2 nodes. RESULTS: Multivariate analysis showed no statistically significant difference between the skip metastasis and the continuous N2 group regarding sex, age, histology, T- or M-status. The frequency of skip metastasis was higher in patients with a primary tumor in the upper lobe (n = 12, 71%) compared to the lower lobe (n = 5, 29%). This difference was not statistically significant. In patients with a non-continuous lymph node spread, 29 out of 119 resected mediastinal lymph nodes were infiltrated (1.7 per patient, range: 1-10). Compared to 83 metastatic involved lymph nodes out of 198 resected mediastinal nodes (three per patient, range: 1-10) in patients with involvement of N1 and N2 nodes (P = 0.034, Mann-Whitney test). The 5-year survival rate of pN2 patients with skip metastasis was 41% compared to 14% in patients with involvement of N1 and N2 nodes (P = 0.019). CONCLUSIONS: pN2 patients with mediastinal lymph node skip metastasis have a more favorable prognosis compared to pN2 patients with continuous infiltration of the regional lymph nodes. Patients with a continuous lymph node involvement show an increased number of infiltrated mediastinal lymph nodes per patient compared to patients with a non-continuous spread. Skip metastasis is an independent prognostic factor of survival. The presence of skip metastasis seems to be a unique subgroup of pN2 disease in NSCLC.     

Frequency of noncontiguous lymph node involvement in patients with resectable nonsmall cell lung carcinoma.

BACKGROUND: This study was undertaken to investigate the patterns of lymph node spread and the frequency of involvement of noncontiguous lymph node stations in patients with nonsmall cell lung carcinoma who had complete surgical resection. METHODS: All patients who had surgical resection as their sole treatment for nonsmall cell lung carcinoma during the years 1987-1990 were reviewed. All patients were treated similarly. Generally, complete mediastinal lymph node dissection was performed after resection of the primary lesion and N1 lymph nodes. Patients were assessed for patterns of involvement of N1 and N2 lymph node stations. The frequency of noncontiguous involvement of lymph nodes (involvement of N2 lymph nodes without involvement of N1 lymph nodes) was determined. Patient and tumor characteristics were assessed to ascertain whether certain factors were likely to predict this noncontiguous pattern of lymph node spread. RESULTS: During the 4-year period of study, 336 patients with nonsmall cell lung carcinoma were managed with surgical resection alone. Of the 336, 100 had no involvement of lymph nodes, 108 had involvement of N1 lymph nodes only, 76 had involvement of N1 and N2 lymph nodes, and 52 had involvement of N2 lymph nodes only. Therefore, 52 of all 336 patients (15%) and 52 of 236 patients with lymph node involvement (22%) had noncontiguous lymph node spread. A review of the initial patient and tumor characteristics revealed that patients with a suggestion of enlarged mediastinal lymph nodes on preoperative computed tomography scans of the chest (compared with negative findings) and patients with T1 and T2 lesions (compared with T3 and T4) were more likely to have noncontiguous lymph node spread; the odds ratios (with 95% confidence intervals) were 2.18 (1.01-4.71) and 2.82 (1.36-5.84), respectively. CONCLUSIONS: Noncontiguous involvement of thoracic lymph nodes occurred in approximately 15% of patients who had complete surgical resection of nonsmall cell lung carcinoma. This factor suggests that lack of involvement of N1 lymph nodes does not rule out mediastinal involvement and provides important information for complete surgical staging.     

Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial.

PURPOSE: A multicenter, phase II trial investigated the efficacy and toxicity of neoadjuvant docetaxel-cisplatin in locally advanced non-small-cell lung cancer (NSCLC) and examined prognostic factors for patients not benefiting from surgery. PATIENTS AND METHODS: Ninety patients with previously untreated, potentially operable stage IIIA (mediastinoscopically pN2) NSCLC received three cycles of docetaxel 85 mg/m2 day 1 plus cisplatin 40 mg/m2 days 1 and 2, with subsequent surgical resection. RESULTS: Administered dose-intensities were docetaxel 85 mg/m2/3 weeks (range, 53 to 96) and cisplatin 95 mg/m2/3 weeks (range, 0 to 104). The 265 cycles were well tolerated, and the overall response rate was 66% (95% confidence interval [CI], 55% to 75%). Seventy-five patients underwent tumor resection with positive resection margin and involvement of the uppermost mediastinal lymph node in 16% and 35% of patients, respectively (perioperative mortality, 3%; morbidity, 17%). Pathologic complete response occurred in 19% of patients with tumor resection. In patients with tumor resection, downstaging to N0-1 at surgery was prognostic and significantly prolonged event-free survival (EFS) and overall survival (OS; P =.0001). At median follow-up of 32 months, the median EFS and OS were 14.8 months (range, 2.4 to 53.4) and 33 months (range, 2.4 to 53.4), respectively. Local relapse occurred in 27% of patients with tumor resection, with distant metastases in 37%. Multivariate analyses identified mediastinal clearance (hazard ratio, 0.22; P =.0003) and complete resection (hazard ratio, 0.26; P =.0006) as strongly prognostic for increased survival. CONCLUSION: Neoadjuvant docetaxel-cisplatin is effective and tolerable in stage IIIA pN2 NSCLC. Resection is recommended only for patients with mediastinal downstaging after chemotherapy.     

A preoperative alternating chemotherapy and radiotherapy program for patients with stage IIIA (N2) non-small cell lung cancer

The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within an acceptable range. Surgery was not indicated for two patients because of distant metastasis; one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.     

电视胸腔镜与开胸肺癌切除淋巴结清扫的对比研究

目的：探讨电视胸腔镜肺癌切除术淋巴结清扫的彻底性和完全性。方法：50例准备常规开胸切除的肺癌患者先采用电视胸腔镜行肺叶切除＋纵隔淋巴结清扫术,随后再接受同组医师的开胸肺门纵隔淋巴结清扫。对开胸后清扫的淋巴结单独标注、计数后送组织病理学检查。结果：50例胸腔镜肺癌切除淋巴结清扫术后,开胸重新清扫淋巴结数共48枚,每例0枚～3枚,平均0．96枚。病理检查全部未查见癌细胞转移。结论：电视胸腔镜肺癌切除淋巴结清扫是彻底的、完全的。