Preoperative induction therapy in non-small cell lung cancer

The clinical significance of preoperative induction therapy for non-small cell lung cancer (NSCLC) is reviewed. As the survival rate in locally advanced NSCLC patients remains poor, preoperative therapy has been attempted in order to improve survival. Whereas some prospective phase II and phase III studies have demonstrated that preoperative cisplatin-based chemotherapy with or without concurrent radiation may improve the prognosis, the efficacy has not been established. Recently, some new chemotherapeutic agents such as paclitaxel and gemcitabine have been introduced, and it has been suggested that preoperative therapy using these new drugs may be more effective. To establish effective preoperative therapy regimens, more sophisticated, prospective, randomized studies in sufficient numbers of homogenous populations such as mediastinoscopy-proven stage IIIA, T1-2N2 patients should be conducted.     

Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer.

BACKGROUND: The impact of short-term preoperative pulmonary rehabilitation on exercise capacity of patients with chronic obstructive pulmonary disease undergoing lobectomy for non-small cell lung cancer is evaluated. METHODS: A prospective observational study was designed. Inclusion criteria consisted of an indication to lung resection because of a clinical stage I or II non-small cell lung cancer and a chronic obstructive disease on preoperative pulmonary function test. In such conditions, maximal oxygen consumption by a cardio-pulmonary exercise test was evaluated; when this resulted as being < or =15 ml/kg/min a pulmonary rehabilitation programme lasting 4 weeks was considered. Twelve patients fulfilled inclusion criteria, completed the preoperative rehabilitation programme and underwent a new functional evaluation prior to surgery. The postoperative record of these patients was collected. RESULTS: On completion of pulmonary rehabilitation, the resting pulmonary function test and diffuse lung capacity of patients was unchanged, whereas the exercise performance was found to have significantly improved; the mean increase in maximal oxygen consumption proved to be at 2.8 ml/kg/min (p<0.01). Eleven patients underwent lobectomy; no postoperative mortality was noted and mean hospital stay was 17 days. Postoperative pulmonary complication was recorded in 8 patients. CONCLUSIONS: Short-term preoperative pulmonary rehabilitation could improve the exercise capacity of patients with chronic obstructive pulmonary disease who are candidates for lung resection for non-small cell lung cancer.     

Preoperative chemotherapy for cStage III-pN0 patients with non-small cell lung cancer

Objectives: Survival benefits with preoperative chemotherapy for non-small cell lung cancer (NSCLC) remain controversial. Preoperative chemotherapy may act on micrometastasis but not lymph node metastasis. To clarify the role of induction chemotherapy for control of micrometastasis, we reviewed and compared 5-year follow-ups of clinical stage III but pathologically-proven node-negative NSCLC patients after complete resection with or without preoperative chemotherapy. Methods: We reviewed 148 consecutive patients who underwent anatomical lung resection and mediastinal nodal dissection for pathologically-proven node-negative NSCLC at our hospital between 1994 and 1999. Fifty-six patients were preoperatively diagnosed as stage III: 26 received platinum-based chemotherapy prior to surgery (PCT group) and 30 underwent surgery without any prior chemotherapy (PRS group). Results: The 5-year survival rate for clinical stage I/II and pathological node-negative patients was 74.9%; for clinical stage III, but for pathological node-negative patients it was 92.3% in the PCT and 63.3% in the PRS groups. The survival benefit of preoperative chemotherapy was significant for clinical stage III patients without node involvement. Conclusion: Preoperative chemotherapy may provide survival benefits for node-negative NSCLC patients.     

Preoperative and adjuvant chemotherapy in locally advanced non-small cell lung cancer

The continued favorable results with surgery in early stage lung cancer have led many investigators to use radiation and chemotherapy to reduce the size of unresectable tumors either before or after definitive surgery. Although earlier results with both radiation and chemotherapy have been poor, the newer cisplatin-containing combination chemotherapy regimens have yielded decreased local recurrence rates when used postoperatively following a complete resection and have produced increased complete resection rates when given preoperatively to patients with locally advanced and unresectable non-small cell lung cancer at diagnosis.     

Preoperative chemotherapy and irradiation for stage III non-small cell lung cancer

Surgical therapy for stage III non-small cell lung cancer (NSCLC) has not resulted in substantial long-term survival. Neoadjuvant treatment programs that could down-stage the tumor and achieve increased long-term survival would be of obvious benefit. We have used preoperative simultaneous chemotherapy and irradiation in 85 patients with clinical stage III non-small cell lung cancer considered candidates for surgical resection. One group of 56 patients was treated with cisplatin, 5-fluorouracil, and simultaneous irradiation for five days every other week for a total of four cycles. After treatment, 39 patients underwent resection, and the operative mortality was 2 (5%) of 39. A second trial was undertaken in which etoposide (VP-16) was added because of its synergism with cisplatin. In this group, 29 patients were considered to have potentially resectable disease, and 23 underwent thoracotomy with 1 operative death (4%). Of the total of 62 patients having thoracotomy, 60 underwent resection (97%). Complications were major, and there were four bronchopleural fistulas. For the 85 patients eligible for surgical intervention in these two groups of patients, the Kaplan-Meier median survival estimate is 40% at 3 years. The median survival of the 62 patients having thoracotomy is 36.6 months. Combination preoperative chemotherapy and irradiation is feasible with acceptable toxicity and operative mortality in patients with clinical stage III non-small cell lung cancer. Prospective randomized studies are suggested for further evaluation of this treatment program.     

Preoperative prognostic factors for pN2 non-small cell lung cancer.

PURPOSE: The prognosis of non-small cell lung cancer (NSCLC) with pathologic mediastinal lymph node involvement (pN2) is poor in general. The majority of previously reported prognostic factors of pN2 disease are not available preoperatively. When we perform preoperative induction chemotherapy, we should undertake therapeutic planning according to preoperative factors. METHODS: We focused on preoperative clinicopathologic factors, and investigated the prognosis in 78 patients with pN2 NSCLC who received complete resection. RESULTS: Age, gender, histologic subtype, tumor location, smoking status and cT status were not related to patients' survival. On the other hand patients with cN0 disease and normal serum carcinoembryonic antigen (CEA) level had a significant favorable survival (p = 0.038 and p = 0.019, respectively). In addition, comorbidity had a significant survival impact (p = 0.031). Despite there being no independent prognostic factors by multivariate analysis, the patients without all of cN1-2 disease, elevated serum CEA level and comorbidity had a significant favorable prognosis (p = 0.008). CONCLUSION: Among the preoperative factors examined, pN2 patients with all cN0 disease, normal serum CEA level and no comorbidities might have a favorable prognosis. Combined use of these might be a useful prognostic determinant, and even in the presence of pN2 disease, patients without these unfavorable 3 factors might have a favorable prognosis when treated with surgery alone.     

Treatment strategy for patients, with locally advanced non-small cell lung cancer

A total of 89 patients with locally advanced lung cancer (pT3-4N0-1) underwent pulmonary resection from April 1994 to April 2003 at our institutions. The overall 5-year survival rate of the 89 patients was 35.5%. No significant difference in the 5-year survival rate was found according to the following variables: histologic type, type of operation, number of resected organs, performance of adjuvant therapy and pulmonary function. In patients with pN1 disease, when patients with nodal metastasis were divided into patients with hilar (# 10) or lobar (# 11 approximately 13) metastasis, the survival rate of lobar metastasis group was superior to those of hilar metastasis group, but not significantly. In patients with pN1 disease, 5 patients were survived for more than 1,000 days. The histology was squamous cell carcinoma in 4 cases. According to the characteristics of pN1 involvement, all cases was involved only a single station.     

Angiogenesis in non-small cell lung cancer

Two processes are necessary for a tumor colony to grow and become invasive: angiogenesis and basement membrane degradation. Angiogenesis is the formation of new blood vessels from the endothelium of existing vasculature, in response to the metabolic demand of the tumor. Assessment of the degree of tumor angiogenesis may improve risk stratification in patients with lung cancer, especially those with early-stage disease. In addition, the strategy of blocking the mechanism of angiogenesis may prove to be an effective therapeutic alternative for patients with nonsmall cell lung cancer. Clinical trials evaluating novel antiangiogenic agents, including antibodies to vascular endothelial growth factor (VEGF) and compounds directed at the tyrosine kinase receptor, are ongoing.     

Postoperative fluorescence bronchoscopic surveillance in non-small cell lung cancer patients

BACKGROUND: Second lung primaries occur at a rate of 1% to 3% per patient-year after complete resections for non-small cell lung carcinoma (NSCLC). Fluorescence bronchoscopy appears to be a sensitive tool for surveillance of the tracheobronchial tree for early neoplasias. METHODS: Patients who were disease-free after complete resection of a NSCLC were entered into a fluorescence bronchoscopy surveillance program. All suspicious lesions were biopsied along with two areas of normal mucosa to serve as negative controls. RESULTS: A total of 73 fluorescence bronchoscopies were performed after conventional bronchoscopy in 51 patients at a median of 13 months postresection. The majority (46 of 51) of patients had stage I or II NSCLC, whereas 10% (5 of 51) had stage IIIA. Three intraepithelial neoplasias and one invasive carcinoma were identified in 3 of 51 patients (6%), all current or former smokers. Of the four lesions identified, three were in the 20 patients with prior squamous cell carcinomas. No intraepithelial neoplasias were identified by white-light bronchoscopy, whereas two of three were detected by fluorescence examination. The one invasive cancer detected was apparent on both white-light and fluorescence bronchoscopic examinations. CONCLUSIONS: Surveillance with fluorescence bronchoscopy identified lesions in 6% of postoperative NSCLC patients thought to be disease-free. Patients with prior squamous cell carcinomas appear to be a population that may warrant future prospective study of postoperative fluorescence bronchoscopic surveillance.     

Pneumonectomy for non-small cell lung cancer

Purpose

To assess the mortality, complications and major morbidity of pneumonectomy for non-small cell lung cancer (NSCLC) and to establish the importance of various prognostic factors.

Methods

We reviewed retrospectively the hospital records of 71 consecutive patients who underwent pneumonectomy for NSCLC between 1992 and 2007 to evaluate the significance of risk factors for an adverse outcome. Patients were divided into two period groups according to the period when they were treated: early (1992–1999; n?=?47) and late (2000–2007; n?=?24).

Results

Both the 30-day and the in-hospital mortality rates were 4.2?% (3/71). Complications developed in 31.3?% (22/71) and overall 5-year survival was 23.1?%. Pathological stage III or more, T3 or more, and N2 or more were risk factors of an adverse outcome. Survival was not significantly influenced by histological type, the side of surgery, or curability. The 5-year survival rates for the early and late periods were 19.6 and 32.9?%, respectively. There were more patients with clinical N2 or 3 disease in the early period than in the late period (66.0 vs. 33.3?%).

Conclusions

Pneumonectomy is associated with acceptable overall morbidity and mortality; however, patients with pathological stage III or more, T3 or more, and N2 or more disease require special consideration. Pneumonectomy should be performed only in selected patients.     

Preoperative chemoradiotherapy and surgery for selected non-small cell lung cancer IIIB subgroups: long-term results.

BACKGROUND: Preoperative chemoradiotherapy is feasible for selected patients with non-small cell lung cancer stage IIIb. The aim of this investigation was to analyze long-term results after this multimodality approach and to identify subgroups with improved long-term prognosis. METHODS: From March 1991 to June 1996, 56 patients were entered. Three cycles of cisplatin (P) (60 mg/m2, days 1 + 7) and etoposide (E) (150 mg/m2, days 3 to 5 qd 22) were followed by one cycle of radiotherapy/chemotherapy (RTx/CTx) (45 Gy, 1.5 Gy bid/3 weeks with P 50 mg/m2 days 2 + 9/E 100 mg/m2 days 4 to 6) followed by repeat mediastinoscopy and surgery. RESULTS: There were 46 men and 10 women (age 34 to 69 years, median 55 years; World Health Organization status 0 to 2, median 1). Twenty-eight had T4, and 32 had proven N3, in detail: T4N0/1, 10; T4N2, 14; T3N3, 9; T4N3, 4; and T1/2N3, 19. Thirty-four (61%) were operated on; 27 (48%) were completely (R0) resected. Survival at 5 years is 26% for all, and 43% for R0 patients. Toxicity included two deaths (one septicemia, one anastomosis insufficiency). CONCLUSIONS: This intensive program proved to be highly effective in unfavorable IIIB subgroups with promising long-term survival for T4 tumors as well as N3 disease.     

非小细胞肺癌1638例治疗及预后探讨

目的 结合2009 TNM分期和患者临床资料分析探讨非小细胞肺痛的预后及其影响因素.方法 回顾性分析2001年1月至2005年1月接受手术的1638例非小细胞肺癌患者的临床资料,并对其预后及影响其预后的临床病理因素进行分析.其中男性1083例,女性555例,平均年龄59.5岁.结果 非小细胞肺癌患者术后总体1年、3年及5年生存率分别为80.0%、52.3%及39.0%.单因素分析显示影响预后的因素为支气管断端是否阳性、手术方式、T分期、N分期、淋巴结清扫个数(0～、10～及＞20个)、淋巴结清扫组数和术后放疗(P＜0.05).Cox回归多因素分析提示,手术方式(P=0.001)、T分期(P=0.000)、N分期(P=0.000)和淋巴结清扫个数(P=0.013)是独立的预后影响因素.结论 非小细胞肺癌总体预后差.手术方式、T分期、N分期及淋巴结清扫个数均是其预后的独立影响因素.

Abstract：

Objective To study the prognosis and prognostic factors of non-small-cell lung carcinoma(NSCLC)according the new TNM stage system.Methods Clinic data of 1638 inpatient cases admitted from January 2001 to January 2005 were retrospectively reviewed.There were 1083 male and 555 female patients in the study and the average age was 59.5 years.All the patients received surgical procedures.Results The overall 1,3,5-year survival rate was 80.0%,52.3%,39.0%.The main prognostic factors were bronchial stump,operation type,T stage,N stage,the number of lymph nodes (LNs)in lymph nodes dissection(1-10,11-20,and＞20),overall N stations(＜4 and ≥4)and postoperative radiotherapy(all P＜0.05).Cox regression suggested that T stage(P = 0.000),N stage (P=0.000),operation type(P=0.001)and LNs(P = 0.013)were independent factors affecting the prognosis.Conclusions The overall survival rate of NSCLC is poor.T stage,N stage,operation type and LNs are independent factors affecting the prognosis.     

老年非小细胞肺癌病人疗效分析

目的 探讨70岁以上老年非小细胞肺癌病人手术、辅助化疗的效果及预后的特点.方法 将70岁以上手术治疗的老年非小细胞肺癌病人按照性别、分期、病理类型、手术方式、是否接受辅助性化疗5个因素与年轻病例进行1:1匹配.用Kaplan-Meier法统计生存率,Log-rank进行差异性检验,用Pearson χ2检验分析手术死亡率及术后短期死亡率在两组人群中的分布差异.结果 共有1304例符合条件并完成匹配,≥70岁者652例,＜70岁者652例.两组总的5年生存率差异无统计学意义(P=0.056),两组之间手术死亡率差异无统计学意义(P=0.265),术后短期死亡率差异有统计学意义(P=0.003),经辅助化疗后两组人群5年生存率大致相等(49.40%对43.89%,P=0.096),两组人群均受益(P=0.049;P=0.000).结论 有手术指征的老年非小细胞肺癌病人应积极手术治疗,术后应行辅助化疗,老年病人经恰当的综合治疗后效果不比年轻者差.     

Management of early stage non-small cell lung cancer in high-risk patients

The preferred treatment of stage I non-small cell lung cancer (NSCLC) is anatomic resection with systematic mediastinal lymph node evaluation. However, 20% of patients with operable lung cancer are not candidates for this type of resection. Recent advancements in radiology-guided technologies have expanded the treatment options for high-risk patients with early-stage NSCLC. There has simultaneously been resurgence in interest and refinement of indications and techniques for sublobar resection in this population. While these treatments appear to have decreased peri-procedural morbidity and mortality, their oncologic efficacy compared to that of lobectomy remains to be determined.     

Preoperative bronchoscopic cancer confirmation does not increase risk of recurrence in stage1A non-small cell lung cancer

Objective

This study was conducted to evaluate the risk of recurrence possibly caused by preoperative bronchoscopic cancer confirmation in stage1A non-small cell lung cancer.

Methods

One hundred and seventy-nine cases of peripheral non-small cell lung cancer (including 151 adenocarcinoma) with no more than 3 cm in their tumor longer diameter were selected. All patients underwent preoperative diagnostic bronchoscopy followed by lobectomy, and were demonstrated to have pathologically free of lymph node involvement and pleural involvement. Radiological and pathological low-grade adenocarcinomas were excluded. Of 179 cases, 95 were confirmed lung cancer by bronchoscope (Group 1) and rest 84 had failed cancer confirmation by bronchoscope before surgery (Group 2). Forty-eight pairs for non-small cell lung cancer and 41 pairs for adenocarcinoma were identified from each group by propensity caliper matching. Kaplan–Meier method and log-rank test were performed on matched groups, and Cox proportional hazard model analysis was performed on whole matched cases.

Results

Log-rank test revealed no significant inferiority of recurrence-free survival of Group 1 in both all-NSCLC and adenocarcinoma subset. Cox proportional hazard model analysis also revealed that the ‘presence of preoperative bronchoscopic cancer confirmation’ dose not increase risk of recurrence in both NSCLC and adenocarcinoma subset.

Conclusions

It is unlikely that preoperative bronchoscopic cancer confirmation would increase recurrence risk in stage1A non-small cell lung cancer; however, a future prospective study with larger cohorts would be warranted to validate the results.