Surgical treatment of primary lung cancer with synchronous brain metastases

OBJECTIVES: The role of surgical resection for brain metastases from non-small cell lung cancer is evolving. Although resection of primary lung cancer and metachronous brain metastases is superior to other treatment modalities in prolonging survival and disease-free interval, resection of the primary non-small cell lung cancer and synchronous brain metastases is controversial. METHODS: From January 1975 to December 1997, 220 patients underwent surgical treatment for brain metastases from non-small cell lung cancer at our institution. Twenty-eight (12.7%) of these patients underwent surgical resection of synchronous brain metastases and the primary non-small cell lung cancer. RESULTS: The group comprised 18 men and 10 women. Median age was 57 years (range 35-71 years). Twenty-two (78.6%) patients had neurologic symptoms. Craniotomy was performed first in all 28 patients. Median time between craniotomy and thoracotomy was 14 days (range 4-840 days). Pneumonectomy was performed in 4 patients, bilobectomy in 4, lobectomy in 18, and wedge excision in 2. Postoperative complications developed in 6 (21.4%) patients. Cell type was adenocarcinoma in 11 patients, squamous cell carcinoma in 9, and large cell carcinoma in 8. After pulmonary resection, 17 patients had no evidence of lymph node metastases (N0), 5 had hilar metastases (N1), and 6 had mediastinal metastases (N2). Twenty-four (85.7%) patients received postoperative adjuvant therapy. Follow-up was complete in all patients for a median of 24 months (range 2-104 months). Median survival was 24 months (range 2-104). Survival at 1, 2, and 5 years was 64.3%, 54.0%, and 21.4%, respectively. The presence of thoracic lymph node metastases (N1 or N2) significantly affected 5-year survival (P =.001). CONCLUSION: Although the overall survival for patients who have brain metastases from non-small cell lung cancer is poor, surgical resection may prove beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

电视胸腔镜肺段切除术治疗早期非小细胞肺癌的研究进展

2010年美国国家综合癌症网(NCCN)非小细胞肺癌临床实践指南指出,对于多数非小细胞肺癌患者,解剖性肺切除为首选,而且电视胸腔镜手术是一个可以接受的合理选择。我们通过对早期肺癌的治疗手段、早期肺癌肺段切除的现状和预后、早期肺癌肺段切除对肺功能的保护、肺段切除的一般操作流程及肺段切除解剖难题的文献综述,总结胸腔镜肺段切除术治疗早期非小细胞肺癌的可行性和可靠性。     

Symposium on the diagnosis and treatment of common cancers. 1. Lung cancer--1983

The frequency of lung cancer, common in both men and women, seems to be increasing rapidly, particularly in women. The main causative factor appears to be cigarette smoking. Diagnosis and staging have not changed notably in the last few years, although the advent of computerized tomography and gallium scanning have been of some help in identifying mediastinal tumours, which are unresectable. Further refinements in these techniques may allow us to avoid mediastinoscopy but, at present, this is still usually necessary before operation for lung cancer. Operation is the major form of therapy for non-small cell cancer when this is medically and technically possible. Adjuvant therapy in the treatment of this type of lung cancer has so far been of little help. Radiotherapy as primary treatment, although occasionally curative, should be used only if patients refuse operation or clearly have medical contraindications for thoracotomy. Radiotherapy is very useful for palliation. Chemotherapy is of little value in treating advanced, non-small cell lung cancer, although responses can be seen in up to 40% of patients. This does not translate into important, long-term survival, but responders do survive longer than non-responders. Patients with small cell lung cancer should be treated with combination chemotherapy, with or without thoracic irradiation and with or without cranial irradiation. The latter two modalities have not yet been proved to prolong survival, but may reduce the morbidity. Immunotherapy has not been shown to benefit those with non-small cell lung cancer. Thymosin was beneficial in one controlled trial in patients with small cell lung cancer, but this must be confirmed. In the future, many new approaches will be necessary to control or eradicate this steadily increasing cause of cancer death.     

Evidence-based practice guideline for unresectable advanced lung cancer in 2003

Recently evidence-based practice guideline for lung cancer in 2003 has been published. Recommendations for the treatment of unresectable non-small cell and small cell lung cancer are described here. Cisplatin-based chemotherapy combined with thoracic radiotherapy is recommended for the treatment for unresectable stage III non-small cell lung cancer. New chemotherapy agents, including paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan have been incorporated into combination regimens with carboplatin or cisplatin have become the standard therapy for advanced/metastatic NSCLC. Docetaxel is recommended as second-line therapy for patients with locally advanced or metastatic NSCLC who have progressed on first-line therapy. Etopside and cisplatin concurrently combined with twice-daily thoracic radiotherapy (TRT) is the standard care of limited -disease small cell lung cancer (SCLC). Recent randomized controlled trial demonstrated that irinotecan and cisplatin is superior to etoposide and cisplatin, a standard treatment of extensive-disease SCLC. This practice guideline should be updated periodically.     

Five-year tumor-free survival after aggressive trimodality therapy for T3N0M1b non-small cell lung cancer with synchronous solitary brain metastasis

Several recent studies have demonstrated that some patients might benefit from aggressive therapy for thoracic stage I lung cancer and synchronous solitary brain metastasis. However, the indication for the patients with advanced T-stage is still unclear. We herein present a patient with synchronous solitary brain metastasis from non-small cell lung cancer who survived without recurrence for 5 years following surgery after chemotherapy, even though the primary tumor was T3N0 thoracic stage II. Aggressive treatment for both the primary site and brain metastasis may therefore be an effective treatment for locally advanced non-small cell lung cancer patients with synchronous solitary brain metastasis.     

Relevance of an intensive postoperative follow-up after surgery for non-small cell lung cancer

BACKGROUND: Although a minimal follow-up with periodic clinic visits and chest radiographs is usually recommended after complete operation for non-small cell lung cancer, the ideal follow-up has not been defined yet. Objectives of this prospective study were to determine the feasibility of an intensive surveillance program and to analyze its influence on patient survival. METHODS: Follow-up consisted of physical examination and chest roentgenogram every 3 months and fiberoptic bronchoscopy and thoracic computed tomographic scan with sections of the liver and adrenal glands every 6 months. Influence of patient and recurrence characteristics on survival from recurrence was successively analyzed using the log-rank test and a Cox model adjusted for treatment. RESULTS: Among the 192 eligible patients, recurrence developed in 136 patients (71%) and was asymptomatic in 36 patients (26%). In 35 patients, recurrence was asymptomatic and detected by a scheduled procedure: thoracic computed tomographic scan in 10 (28%) patients and fiberoptic bronchoscopy in 10. Fifteen patients (43%) had a thoracic recurrence treated with curative intent. From the date of recurrence, 3-year survival was 13% in all patients and 31% in asymptomatic patients whose recurrence was detected by a scheduled procedure. Asymptomatic recurrences (p < 0.001), female sex (p < 0.001), performance status 2 or less (p = 0.01), and age 61 years or younger (p = 0.01) were shown to be significantly favorable prognostic factors. CONCLUSIONS: This intensive follow-up is feasible and may improve survival by detecting recurrences after surgery for non-small cell lung cancer at an asymptomatic stage.     

Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer

BACKGROUND: Management of solitary adrenal metastasis from non-small cell lung cancer is still debated. Although classically considered incurable, various reports with small numbers of patients have shown that surgical treatment might improve long-term survival. The aim of this study was to review our experience and to identify factors that could affect survival. METHODS: From January 1989 through April 2003, 23 patients underwent complete resection of an isolated adrenal metastasis after surgical treatment of non-small cell lung cancer. There were 19 men and 4 women, with a mean age of 54 +/- 10 years. The diagnosis of adrenal metastasis was synchronous with the diagnosis of non-small cell lung cancer in 6 patients and metachronous in 17 patients. The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5-60.1 months). RESULTS: The overall 5-year survival was 23.3%. Univariate and multivariate analysis demonstrated that a disease-free interval of greater than 6 months was an independent and significant predictor of increased survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of the operation. The 5-year survival was 38% after resection of an isolated adrenal metastasis that occurred more than 6 months after lung resection. Adjuvant therapy and pathologic staging of non-small cell lung cancer did not affect survival. CONCLUSIONS: Surgical resection of metachronous isolated adrenal metastasis with a disease-free interval of greater than 6 months can provide long-term survival in patients previously undergoing complete resection of the primary non-small cell lung cancer.     

空洞型非小细胞肺癌的预后分析

目的 探讨空洞型非小细胞肺癌的临床病理特征对预后的影响.方法 回顾性分析手术治疗的空洞型非小细胞肺癌42例,用Kaplan-Meier法统计生存率,Log-rank进行差异性检验,分析临床病理学特征与预后的关系.将空洞型非小细胞肺癌病人按照性别、年龄、病理类型、淋巴结转移、TNM分期、是否接受术后辅助化疗6个因素与无空洞形成的非小细胞肺癌病例进行1∶2匹配,比较空洞组和无空洞组预后有无差异.结果 42例空洞型非小细胞肺癌的1、3、5年生存率分别为76.%、28.6%和14.7%.单因素分析显示空洞直径和有无胸内淋巴结转移明显影响预后.空洞组和无空洞组总的5年生存率差异无统计学意义(P=0.075).两组中的女性(P=0.040)、年龄小于60岁(P=0.032)、淋巴结转移N0组(P=0.046)、TNM分期Ⅰ期(P=0.048)的5年生存率无空洞组均高于空洞组,差别有统计学意义.结论 空洞直径和胸内淋巴结转移情况是影响空洞型非小细胞肺癌预后的重要因素.癌性空洞影响年龄小于60岁、淋巴结转移阴性和TNM分期Ⅰ期的非小细胞肺癌病人的预后,但是否影响女性非小细胞肺癌病人的预后有待研究.     

Arterial invasion predicts early mortality in stage I non-small cell lung cancer

Background

A retrospective study was performed to evaluate the association between arterial invasion and survival in patients with stage I non-small cell lung cancer.

Methods

One hundred patients were identified who had undergone complete anatomic resection as definitive treatment for stage I non-small cell lung cancer. The tumors were reviewed for the presence or absence of arterial invasion. Five-year survival data were obtained for all patients.

Results

The 100 patients had an overall 5-year survival of 61%. There were 64 stage IA patients with a 62% 5-year survival and 36 stage IB patients with a 58% 5-year survival. The 39 patients identified with arterial invasion had a 38% 5-year survival compared with a 73% 5-year survival in the 61 patients without arterial invasion (p < 0.001), with an unadjusted hazard ratio of 3.5 (p < 0.001). Multivariate analysis by stage IA versus IB and by size greater or less than 2 cm demonstrated hazard ratios of 3.5 and 4.0, respectively (p < 0.001). This difference was independent of demographic characteristics, tumor type, or grade. Subgroup analysis revealed a hazard ratio of 5.8 in patients with stage IA non-small cell lung cancer (p < 0.001) and 19.8 in patients with tumors ≤ 2 cm (p = 0.006).

Conclusions

Arterial invasion is present in a substantial percentage of patients with stage I non-small cell lung cancer and is adversely associated with survival.     

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.     

T4 lung tumors with infiltration of the thoracic aorta: is an operation reasonable?

BACKGROUND: Only anecdotal reports about the results of combined resection of T4 lung tumors infiltrating the thoracic aorta exist. METHODS: Seven patients (mean age, 57.5 years; range, 43 to 78 years) underwent a resection of the infiltrated segment of the thoracic aorta together with a left pneumonectomy (n = 6) or left upper lobectomy (n = 1). Five tumors were primary non-small cell lung carcinomas (T4N2 in 3 patients, T4N1 in 2), one was a metastasis of breast cancer, and one was rhabdomyosarcoma. RESULTS: No patient died perioperatively. The 2 patients with rhabdomyosarcoma and metastasis of breast cancer died 2 and 7 months postoperatively. Of the 5 patients with bronchial carcinoma, 3 died after 17, 26, and 27 months as a result of distant metastasis. Two patients are alive after 14 and 50 months without evidence of disease recurrence. One-year, 2-year, and 4-year survival rates for patients with bronchial carcinoma were 100%, 75%, and 25%, respectively. CONCLUSIONS: Combined resection of the lung and thoracic aorta can be performed with low morbidity and mortality when offered to highly selected patients. Adequate local control of tumor can be achieved for N1 and single-level N2 non-small cell lung carcinomas, but not for tumors with other histologies.     

Prognostic impact of thrombocytosis in resectable non-small cell lung cancer

Relationship between thrombocytosis and poor prognosis has been reported in lung cancer. However, the majority of previous studies included many advanced stage and small cell lung cancer patients. Few studies focused on resectable non-small cell lung cancer patients. In the present study, therefore, consecutive 240 non-small cell lung cancer patients who received surgical resection were reviewed retrospectively, and investigated the survival impact of preoperative platelet count. In our results, the frequency of preoperative thrombocytosis was only 5.83% (14/240). The 5-year survival of patients with and without thrombocytosis was 28.87% and 63.73%, respectively. Both univariate and multivariate analyses indicated the independent prognostic impact of thrombocytosis. The present study is the first evaluation of prognostic effect of thrombocytosis in patients with resectable non-small cell lung cancer. Preoperative platelet count was a prognostic factor for resectable non-small cell lung cancer patients.     

Prognosis in lung cancer: physicians' opinions compared with outcome and a predictive model.

BACKGROUND: Although the study of prognostic factors in small cell lung cancer has reached the stage where they are used to guide treatment, fewer data are available for non-small cell lung cancer. Although correct management decisions in non-small cell lung cancer depend upon a prognostic assessment by the supervising doctor, there has never been any measurement of the accuracy of physicians' assessments. METHODS: A group of consecutive patients with non-small cell lung cancer was studied and the predictions of their physicians as to how long they would survive (in months) was compared with their actual survival. A prognostic index was also developed using features recorded at the patients' initial presentation. RESULTS: Two hundred and seven consecutive patients diagnosed and managed as non-small cell lung cancer, who did not receive curative treatment for their condition, were studied. Of the 196 patients whose date of death was known, physicians correctly predicted, to within one month, the survival of only 19 patients (10%). However, almost 59% of patients (115/196) had their survival predicted to within three months and 71% (139/196) to within four months of their actual survival. Using Cox's regression model, the sex of the patient, the activity score, the presence of malaise, hoarseness and distant metastases at presentation, and lymphocyte count, serum albumin, sodium and alkaline phosphatase levels were all identified as useful prognostic factors. Three groups of patients, distinct in terms of their survival, were identified by the use of these items. When the prediction of survival made by the physician was included as a prognostic factor in the original model, it was shown to differentiate further between the group with a poor prognosis and the other two groups in terms of survival. CONCLUSIONS: Physicians were highly specific in identifying patients who would live less than three months. However, they had a tendency to overestimate survival in these patients, failing to identify almost half the patients who actually died within this time. Both the physicians and the prognostic factor model gave similar performances in that they were more successful in identifying patients who had a short time to survive than those who had a moderate or good prognosis. Physicians appear to use information not identified in the prognostic factor analysis to reach their conclusions.     

Surgical treatment for primary non-small cell lung cancer with synchronous brain metastases

The brain is one of the most common sites of metastasis from lung cancer. The strategies of treatment for non-small cell lung cancer patient with synchronous brain metastases (stage IV) is controversial. We evaluate retrospectively the effectiveness of surgical treatment for these patients. Forty patients were divided into 3 groups on the basis of surgical treatment, group A of patients received both lung and brain resection, group B of patients received lung resection plus gamma knife therapy, group C of patients received brain resection. Median survival from the date of diagnosis of brain metastasis was as follows: group A 331 days, group B 151 days and group C 92 days. Univariate analysis revealed that adenocarcinoma histology and serum LDH significantly affected survival. Multivariate analysis found that only adeocarcinoma histology also affected the survival. It is concluded that surgical treatment may acceptable in selected group of non-small cell lung cancer patients with synchronous brain metastases.     

The role of external radiation and brachytherapy in unresectable non-small cell lung cancer

The role of radiation therapy in the management of non-small cell lung cancer is rapidly changing. Preoperative radiation, with the exception of the superior sulcus tumor, has not been found to benefit patients. The issue of postoperative radiation in completely resected patients with non-small cell lung cancer remains controversial. Current postoperative trials suggest, however, that postoperative radiation in these patients prevents local recurrence and, in combination with chemotherapy, prolongs survival. Primary radiation therapy in inoperable non-small cell lung cancer is associated with a small but definite cure rate. Better definition of treatment volume, proper selection of dose-time, state-of-art treatment planning, and, whenever possible, intraoperative radiation have improved local control rates and decreased severe complications.     

Stage III non-small cell lung cancer and metachronous brain metastases

OBJECTIVES: This study was undertaken to identify management strategies that maximize survival of patients with stage III non-small cell lung cancer and metachronous brain metastases and to determine whether any apparent improved survival was due to treatment or simply to patient selection. METHODS: Treatment evaluations of both primary non-small cell lung cancer and brain metastases were performed in 91 patients. Optimal treatment was identified by multivariable analysis. Propensity scoring and multivariable analysis were used to separate treatment benefit from patient selection. RESULTS: Risk-unadjusted median, 12-, and 24-month survivals were 5.2 months, 22%, and 10%, respectively. Younger age (P =.006), good performance status (P =.003), stage IIIA (P =.001), lung resection (P =.02), no other systemic metastases at time of diagnosis of brain metastases (P =.02), and either metastasectomy (P <.001) or stereotactic radiosurgery (P <.001) predicted best survival. However, metastasectomy or stereotactic radiosurgery was more common after lung resection (P =.02) and in patients with good performance status (P =.006), no other systemic metastases at time of diagnosis of brain metastases (P =.01), and fewer brain metastases (P <.001), suggesting that the patients with the best risk profile were selected for aggressive therapy of both lung primary and brain metastases. Despite this selection, analysis of propensity-matched patients demonstrated the benefit of lung resection and metastasectomy or stereotactic radiosurgery (P <.001). CONCLUSIONS: Younger patients with resected stage IIIA non-small cell lung cancer who have isolated metachronous brain metastases and good performance status do best when treated with metastasectomy or stereotactic radiosurgery. This survival benefit is a brain treatment effect, not the result of selecting the best patients for aggressive therapy.     

Survival in primary lung cancer potentially cured by operation: influence of tumor stage and clinical characteristics

BACKGROUND: Surgical resection is currently standard treatment in early stage lung cancer. The aim of the present study was to identify stage-related factors and patient characteristics influencing survival after complete resection. METHODS: We identified 395 patients with non-small cell lung cancer who had undergone potentially radical operation during 1987 to 1999 at one thoracic surgery institution in central Sweden. Factors independently related to survival were identified in a multivariate analysis. Survival was analyzed in low-, medium-, and high-risk groups based on a risk score calculated from relative hazards for identified risk factors. RESULTS: Overall 5-year survival among the 395 patients was 51%. The strongest factor predicting prognosis was positive lymph nodes at operation. Higher age, earlier period for operation, impaired lung function, current smoking, and major operative complication were all related to poorer prognosis. Patients with tumor stage Ia had a 5-year survival of 69%, compared to 73% in patients in the low-risk group. CONCLUSIONS: Tumor stage is the best prognostic indicator after radical operation. Inclusion of other tumor- and patient-related variables did not add prognostic information of clinical relevance beyond that provided by tumor stage alone.     

Analysis of T1N0M0 nonsmall cell lung cancer undergoing surgical resection without mediastinal lymph node dissection

Eleven patients of T1N0M0 non-small cell lung cancer underwent relatively non-curative surgical resection without mediastinal lymph node dissection (the undissected group). The 5 year survival rate of this group was 70.7% and no significant difference in survival was found between the undissected group and the patients of T1N0M0 non-small cell lung cancer undergoing absolutely curative surgical resection (the dissected group). No patient died of pneumonia in the undissected group, while 4 aged patients in the dissected group died of pneumonia. This may suggest that mediastinal lymph node dissection is also injurious in distant period after surgery, especially in the aged patient. So "simple lobectomy" without mediastinal lymph node dissection may be considered as an elective procedure in the poor risk patient such as the aged, who has an early staged non-small cell lung cancer.     

The effects of preoperative chemotherapy on the resectability of non-small cell lung carcinoma with mediastinal lymph node metastases (N2 M0)

We have defined "clinical N2" disease in non-small cell lung cancer to mean the presence of enlarged metastatic mediastinal nodes evident on plain chest roentgenograms or widening of the carina at bronchoscopy. Forty-one patients with non-small cell carcinoma of the lung and clinical N2 M0 disease presumed operable received 2 to 3 cycles of high-dose cisplatin with vindesine (or vinblastine sulfate) with or without mitomycin-C. Following chemotherapy, 30 patients (73%) had a major radiographic response. Of these patients, 28 had thoracotomy, and 21 (75%) of them had complete resection of the disease, 8 of whom had total sterilization of the tumor proven histologically. An additional 4 patients had limited microscopic foci of residual tumor either in lung or lymph nodes. Survival at 3 years from diagnosis was 34% for all patients, 40% for those who completed the combined treatment (chemotherapy and surgery), and 54% for those who had complete resection with a median follow-up of 44 months and a median survival not yet attained.