Prognostic factors in stage I/II non-small cell lung cancer

Even in localized stages of non-small cell lung cancer, which are amenable to curative surgery, prognosis has remained disappointing over the last decades. Thus, in these tumor stages, adjuvant therapy strategies are discussed. In the last decade, numerous prognostic factors have been investigated, which might select patients for additional treatment. In this review, the prognostic impact of individual tumor cell dissemination, tumor cell proliferation, apoptosis, several parameters of angiogenesis (microvessel density, VEGF, bFGF, VEGF receptors), p53, bcl-2, ras, p27(Kip1), erbB-2, telomerase as well as the retinoblastoma tumor suppressor gene is analysed. Up to now, none of these factors has gained a sufficient selectivity to serve as an exclusive discriminator for adjuvant therapy. Nevertheless, a combination of several parameters might contribute to characterize patient subgroups with localized non-small cell lung cancer at high risk for distant relapse.     

Surgical approach to non-small cell lung cancer stage I and II

No patient with a potentially curable lung cancer should be denied the opportunity for a curative resection. Solitary pulmonary nodules should be approached as though they were malignant until proven otherwise, either by definitive histologic or extremely convincing circumstantial clinical evidence. Consequently, thoracotomy should be performed, assuming that the patient is physiologically able, if cancer cannot be definitely excluded. The evaluation of patients with synchronous lung nodules is complex owing to the possible causes of the two nodules but should be pursued because of its important effect on therapeutic outcome. The major factor influencing survival is the extent of the tumor at the time of resection. When metastatic lymph nodes are found at the time of surgery, regardless of the location, the survival rate is significantly lower. Lobectomy for patients with stage I disease is usually sufficient treatment, but when the tumor is large (exceeding 4 cm) or centrally located or when hilar lymph nodes are involved, a pneumonectomy must be considered in order to eradicate local disease. Those patients with N1 disease can obtain improved survival when resection is combined with adjuvant radiation and chemotherapy.     

Chemotherapy for stage IV non-small cell lung cancer.

Chemotherapy regimens with consistent activities in NSCLC have been identified. A modest but statistically significant increase in survival has been shown in a single large randomized trial, with three smaller trials showing either similar results or a trend toward an improved survival. However, chemotherapy-related toxicity remains significant and seems exacerbated in patients with a poor performance status at the time of diagnosis. Identification of chemotherapy regimens with higher activity in NSCLC remains a necessity, and the treatment of stage IV patients on clinical trials should be encouraged. Outside the context of a clinical trial, chemotherapy is indicated in selected stage IV patients with good performance status in an attempt to palliate their symptoms and increase their survival.     

168例Ⅰ和Ⅱ期非小细胞肺癌放射治疗疗效观察

目的　探讨Ⅰ和Ⅱ期非小细胞肺癌单纯放射治疗的疗效及预后因素。方法　 16 8例中鳞癌 94例 ,腺癌 19例 ,鳞腺混合癌 3例 ,癌未分型 5 2例。放射治疗采用60 Co或 10MVX射线常规外照射 ,剂量为 4 0～ 76Gy。用Kaplan Meier法和Logrank法分析比较生存率 ,用Cox进行多因素回归分析。结果　放射治疗剂量≥ 6 5Gy组放射治疗结束时X射线片显示治疗有效 (CR +PR)率明显高于 <6 5Gy组 (χ2 =4 .4 2 ,P =0 .0 4 )。中位生存时间 2 2个月 ,总 1、3、5年生存率分别为 6 7.6 %、2 8.0 %、15 .7%。Cox回归模型分析显示放射治疗前患者是否伴有其他内科疾病及卡氏评分是影响患者预后的独立因素。结论　对于放弃手术治疗的早期非小细胞肺癌 ,放射治疗仍是一种有效的治疗手段。经选择的部分病例放射治疗剂量有必要达到 6 5Gy ,从而提高肿瘤局部控制率和患者生存率。     

Ⅰ期非小细胞肺癌的预后因素

Ⅰ期非小细胞肺癌(NSCLC)临床预后因素包括肿瘤大小和患者年龄、手术方式和胸膜浸润情况等.分子生物学预后因素包括肿瘤细胞信号通路中的表皮生长因子及其受体、细胞周期素和凋亡基因Bcl-2、p53的异常表达等,以及肿瘤血管生成中基质金属蛋白酶(MMP)、血管内皮生长因子(VEGF)的异常表达等.因此,需要将Ⅰ期NSCLC临床和分子生物学预后因素两方面综合考虑,才能准确判断预后.     

Radiation therapy for medically inoperable stage I and II non-small cell lung cancer

The published results of primary radiation therapy for early stage NSCLC, indicate that it is a reasonable alternative in patients with medical contraindications or who refuse surgery, resulting in acceptable morbidity, local control, and survival rates. There is no conclusive evidence that EMI is of benefit. Consequently treatment with involved field alone, may be considered when there is no evidence of hilar involvement, or when it is necessary to limit the volume of lung tissue irradiated. Although the data are not conclusive, there is evidence to suggest that the total dose of radiation delivered to the primary should be sufficient to eradicate gross disease (60 Gy or higher). Such does result in high response rates particularly for T1 tumors. There is also an indication that complete responders have better survival than other patients, suggesting that radiotherapeutic strategies to enhance tumor eradication may improve survival.     

Intrapleural BCG in postsurgical stage I non-small cell lung cancer

In a randomized trial comparing intrapleural bacillus Calmette-Guérin (BCG) with placebo in postsurgical stage I non-small cell lung cancer, BCG-treated patients (n = 17) showed a non-significant overall improvement of 5-year and median survival and disease-free interval, but an increased rate of recurrence of cancer compared with control patients (n = 17).     

化疗在不可切除Ⅲ期(N2)非小细胞肺癌中的作用

Ⅲa期(N2)非小细胞肺癌(non-small lung cancer,NSCLC)是一组异质性较大、在多学科治疗中最为复杂、最具争议和挑战性的疾病。该组患者临床疗效不佳,5年生存率仅为15%-23%。     

Radiotherapy for medically inoperable non-small cell lung cancer at clinical stage I and II

We reviewed the records of 36 patients with medically inoperable stage I-II non-small cell lung carcinoma who were treated with radiotherapy. The median dose to the target was 60 Gy with conventional fractionation. Fifteen patients were treated without elective irradiation fields, while the remaining 21 were treated with extended fields including elective mediastinal regional lymph nodes. The overall survival rates at three and five years were 32.3% and 18.8%, the cause-specific survival rates were 40.9% and 27.3%, and the local control rates were 31.7% and 23.8%, respectively. In multivariate analysis the radiation dose had a marginally significant influence on the cause-specific survival, while tumor size had a significant influence on the local control rate. Only one patient had relapse in the regional mediastinal lymph nodes as the only site of metastasis. We conclude that the dose used in the present study is inadequate and recommend that further efforts be made to improve local control by dose escalation within a small target volume.     

Operative results of clinical stage I non-small cell lung cancer

BACKGROUND: Clinical stage (c-stage) I non-small cell lung cancer (NSCLC) is generally indicated for surgery, however, surgical exploration sometimes reveals advanced disease, thus resulting in incomplete resection. PATIENTS AND METHODS: A total of 645 consecutive patients were investigated in which 347 were diagnosed to have c-stage IA in 347 and 298 were diagnosed to have IB disease. All cases underwent operation and were investigated for resectability and the cause of an incomplete resection. RESULTS: The c-Stage IA patients included 16.6% of T3/4 and 10.4% of N2 whereas clinical stage IB patients included 14.4% of T3/4 and 18.8% of N2/3. A complete resection was performed in 594 patients (91%). In 347 c-stage IA patients, the complete resection rates were 93% in adenocarcinomas (235/252), 100% in squamous cell carcinomas (76/76), and 89% in others (17/19). In 298 c-stage IB patients, the complete resection rates were 86% in adenocarcinomas (141/164), 90% in squamous cell carcinomas (90/100), and 94% in others (31/33). The 5-year survival rates of the c-stage IA and IB patients who underwent a complete resection were 66.4 and 48.3%, respectively. However, the same rates were 18.4 and 14.7% for c-stage IA and IB patients who underwent an incomplete resection. The reasons for an incomplete resection in 54 patients were malignant pleurisy in 38 (70.4%), extranodal invasion of mediastinal nodal metastasis in ten (19%), an incomplete bronchial margin in three (5.6%), and ipsilateral pulmonary metastases in two (3.7%), and ipsilateral adrenal metastasis in one (1.3%). In 13% of the c-stage IB adenocarcinomas, pleural metastasis was discovered during thoracotomy. CONCLUSIONS: Pleural dissemination was the most frequent cause of an incomplete resection, and its prevalence was high in c-stage IB adenocarcinomas.     

Chemotherapy for advanced non-small cell lung cancer

Lung cancer is an aggressive disease with poor prognosis after it has advanced. Over the past several years, there has been slow but steady progress in treatment options. Chemotherapy results in a modest improvement in survival, improved quality of life, and decreased pulmonary symptoms. For first-line therapy, platinum-based regimens have generally been the standard of care, with no one regimen clearly superior to the others in terms of overall survival, although there may be differences in response rates, time to progression, toxicities, cost, and schedule. There does not appear to be such a uniform consensus for nonplatinum agents. Triplet regimens are not more effective than doublet regimens and are more toxic and expensive. Chemotherapy should be given for four cycles unless there is unaccepted toxicity or disease progression. Patients with poor PS generally experience increased toxicities and fewer benefits, although this finding needs further investigation to ascertain the appropriate treatment. In second-line setting, docetaxel is the agent that has been extensively studied and approved. Furthermore, molecularly targeted therapy holds a promising future and is discussed in articles elsewhere in this issue. Lung cancer is an aggressive disease with poor prognosis after it has advanced. Over the past several years, there has been slow but steady progress in treatment options. Chemotherapy results in a modest improvement in survival, improved quality of life, and decreased pulmonary symptoms. For first-line therapy, platinum-based regimens have generally been the standard of care, with no one regimen clearly superior to the others in terms of overall survival, although there may be differences in response rates, time to progression, toxicities, cost, and schedule. There does not appear to be such a uniform consensus for nonplatinum agents. Triplet regimens are not more effective than doublet regimens and are more toxic and expensive. Chemotherapy should be given for four cycles unless there is unaccepted toxicity or disease progression. Patients with poor PS generally experience increased toxicities and fewer benefits, although this finding needs further investigation to ascertain the appropriate treatment. In second-line setting, docetaxel is the agent that has been extensively studied and approved. Furthermore, molecularly targeted therapy holds a promising future and is discussed in articles elsewhere in this issue.     

Chemotherapy for advanced non-small cell lung cancer

It is well-known that cisplatin-based chemotherapy can prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). This report reviews the recently published clinical trials of chemotherapy for advanced NSCLC. New agents developed in the 1990s such as paclitaxel, docetaxel, gemcitabine, vinorelbine and irinotecan prolonged the survival of patients with advanced NSCLC by single-agent chemotherapy, and combinations of platinum and one of the new agents were superior to existing platinum-based combinations. Accordingly, the current standard chemotherapy for previously untreated patients with advanced NSCLC is considered to be a two-drug combination consisting of cisplatin and one of the new agents. For elderly patients, single-agent chemotherapy using vinorelbine or gemcitabine is recommended. However, the usefulness of platinum-containing chemotherapy for elderly patients has not yet been throughly evaluated. As salvage chemotherapy for patients previously treated with chemotherapy, the effectiveness of docetaxel is confirmed by two randomized trials. However, since many promising agents including pemetrexed and molecular targeting agents such as gefitinib, erlotinib and bevacizumab have been currently developed, we have to evaluate the usefulness of these agents by well-designed clinical trials.     

A phase II study on stereotactic body radiotherapy for stage I non-small cell lung cancer

Background and purposeThe outcome of stage I non-small cell lung cancer (NSCLC) patients treated with conventional radiotherapy is inferior to that of patients treated surgically. We aimed to evaluate the clinical outcome of stereotactic body radiotherapy (SBRT) in the treatment of stage I NSCLC.Materials and methodsWe performed SBRT for 31 stage I NSCLC patients. Of these, 20 were medically inoperable, and 11 refused surgery. Nineteen tumours were T1-stage masses, and 12 tumours were T2. Median tumour size was 25 mm. SBRT was administered as 45 Gy/3 fractions; however, when the tumour was close to an organ at risk, 60 Gy/8 fractions were used. These doses were prescribed at the centre of the tumours.ResultsThe median duration of observation for all patients was 32 months (range, 4–87 months). In 9 of the 31 cases, local recurrence was observed. The 3-year local control rates of T1 and T2 tumours were 77.9% and 40.0%, respectively. The 3-year overall and cause-specific survival rates were 71.7% and 83.5%, respectively. Although the symptoms improved with medical treatment, 5 patients developed acute pulmonary toxicity ⩾grade 2.ConclusionsSBRT is safe and effective for stage I NSCLC patients. However, a more intensive treatment regimen should be considered for T2 tumours.     

Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.