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.     

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.     

Heavy-ion therapy for non-small cell lung cancer

Since carbon beam therapy for non-small cell lung cancer (NSCLC) was initiated in October 1996, seven trials have been conducted; three have already closed and the remaining four are ongoing. The local control rate, cause-specific survival rate, and overall survival rate of 141 patients with clinical stage I NSCLC were 82%, 58%, and 42%, respectively. Radiation pneumonia was rare (2.1%) and not serious. In the phase II clinical study, the local control rate achieved in 50 patients was 100%, with no radiation pneumonia, resulting in a 60% overall survival rate. Carbon beam therapy could be an alternative to surgery, especially for lung cancer patients of advanced age and/or with complications. For locally advanced lung cancer treated with carbon beam therapy, excellent local control comparable to that in stage INSCLC has been demonstrated and offers hopeful prospects for the treatment of lung cancer.     

Sleeve lobectomy for non-small cell lung cancer

Sleeve lobectomy is a procedure in which the involved lobe with part of the main stembronchus is removed. The remaining lobe (s) is reimplanted on the main stembronchus. This procedure is indicated for central tumors of the lung as an alternative to pneumonectomy. It is the aim of this study to describe the technique of sleeve lobectomy and to analyse the early postoperative results and late results (survival-recurrence) after sleeve lobectomy for non-small-cell lung cancer. MATERIAL AND METHODS: Between 1985 and 1999, 77 sleeve lobectomies for bronchogenic carcinoma were performed at the University hospitals Leuven. The most common performed sleeve lobectomy is the right upper lobe sleeve lobectomy (67.5%). In 6 patients a combined sleeve resection of the pulmonary artery was performed. The operative mortality was 3.9%. Two patients developed a broncho-pleural fistula. The five-year survival rate was 45.6%. In 5 patients, an anastomotic suture developed which required a completion pneumonectomy in 2. Thirteen patients developed local tumor recurrence. CONCLUSION: We conclude that sleeve lobectomy can be performed with an acceptable mortality and morbidity. Long term survival rate and recurrence rate are as good as after pneumonectomy. The operative mortality is lower when compared to pneumonectomy, exercise tolerance and quality of life are much better after sleeve lobectomy compared to pneumonectomy. For central tumours we believe that sleeve resection is the procedure of choice.     

Adjuvant chemotherapy for non-small cell lung cancer

The survival after complete resection for non-small cell lung cancer (NSCLC) is unsatisfactory. Until recently, the use of adjuvant therapy after resection for early stage disease has not been proven to improve survival. However, the efficacy of adjuvant therapy has been demonstrated in phase III prospective randomized trials. The appropriate use of adjuvant therapy, including biologic therapy, is currently under investigation.     

Targeted therapy for non-small cell lung cancer

The overall survival for the treatment of lung cancer patients is less than 15%, despite advances in chemotherapy, radiation therapy, and surgery, due to the inability to control metastatic disease. Over the past three decades, the genetics of lung cancer has been progressively delineated. Small molecule drugs or monoclonal antibodies have been developed that target and inactivate specific cancer-related proteins, such as growth factor receptors or their kinases. This article will review the therapeutic implications of molecular changes associated with non-small cell lung cancer and the status of targeted therapies in its treatment.     

Novel targeted therapies for non-small cell lung cancer

Targeted therapies will advance the treatment of NSCLC as we improve our understanding of the underlying biology of NSCLC and enhance our ability to clinically target the optimal therapy to an individual's cancer. Ongoing translational research including tissue arrays, genomic, and proteomic studies will help to identify clinically useful biomarkers that will allow further classification of NSCLC and may allow accurate prediction of response to specific chemotherapeutic regimens. Advances in targeted therapy in NSCLC are already yielding exciting results, and promises to become an increasingly important adjunct to surgical management of NSCLC.     

Heavy ion therapy for non-small cell lung cancer

Carbon beam radiation has well-balanced dual actions on cancer: efficient dose localization and potent biological anticancer effect due to high RBE (Relative Biological Effectiveness). Two phase I/II clinical studies on the carbon beam radiation treatment of inoperable stage I non-small cell lung cancer (NSCLC) were carried out in our institution from October 1996 to February 1999. The dose-limiting toxicity was found to be radiation pneumonia. In the first protocol, 47 patients received 18 fractions of increasing doses from 59.4 GyE by 10% over 6 weeks. The maximum tolerated dose was found to be 95.4 GyE, while the complete tumor control dose was 85.6 GyE. In the second protocol, 34 patients received 9 fractions of in creasing doses from 68.4 GyE by 5% over 3 weeks. The maximum tolerated dose was 79.2 GyE, and the complete tumor control dose was > 68.9 GyE. The 4-year survival rate estimated by the Kaplan-Meier method was 56% for patients receiving the first protocol. Because a higher local control rate was achieved in the second protocol, the 5-year survival rate is estimated to be higher and similar to that achieved after surgery. Another phase II clinical study in patients with stage INSCLC is ongoing. Heavy-particle radiotherapy is a new modality for the treatment of lung cancer which holds promise for the 21st century.     

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.     

Exploratory thoracotomies for unresectable lung cancer

We analysed 55 exploratory thoracotomies undertaken in the Thoracic Surgery Service of the Geneva University Hospital between 1977 and 1987, to determine the preoperative examinations to prevent exploratory thoracotomy, a gesture that brings no benefits at all for the patients. We concluded that the most helpful preoperative examination is the CT-scan.     

非小细胞肺癌淋巴结清扫方式临床研究

目的 比较非小细胞肺癌不同纵隔淋巴结清扫方式间的差异,为规范化开展肺癌淋巴结清扫临床研究提供依据.方法 在202例Ⅰa-Ⅲa期肺癌中进行前瞻性临床对照试验,比较常规清扫(RMLD)和全纵隔骨骼化清扫(SCLD)两种术式,分析手术经过和术后病理分期情况.结果 RMLD 107例,SCLD 95例.两组术前一般情况、临床分期及肺切除方式无明显差异,SCLD组平均扫除淋巴结组数显著高于RMLD组(8.9组对6.2组,P＜0.001),术后总体并发症(14.7%对14.0%,P=0.884)和病死率(2.1%对1.9%,P=0.904)无差异,但SCLD组分别有3例(3.2%)右侧乳糜胸和左侧喉返神经损伤发生.术后病理证实两组组织学类型及分期无明显差异,RNLD和SCLD组pN2分别占27.1%和24.2%(P=0.888),跳跃性纵隔转移率(RMLD 9.3%对SCLD 7.4%,P=0.613)以及纵隔多组转移率(RMLD 15.0%对SCLD 16.8%,P=0.714)亦无明显差异.分析纵隔各组淋巴结转移率发现上叶肺癌下纵隔转移率＜5%,而中、下叶肺癌上、下纵隔转移率均＞10%;cT1病例以及低度恶性肿瘤无一发生纵隔转移.结论 对非小细胞肺癌行常规纵隔清扫可达到与全纵隔骨骼化清扫同样的分期效果,后者手术风险并不高于常规清扫,但应避免右侧乳糜胸和左侧喉返神经损伤的发生;上叶肺癌仅需扫除上纵隔淋巴结而无需常规清扫下纵隔;早早期肺癌以及低度恶性肿瘤没有必要进行常规纵隔清扫.     

Adjuvant chemotherapy for surgically resected non-small cell lung cancer

Despite surgical resection, patients with early-stage (I to IIIA) non-small cell lung cancer (NSCLC) are at considerable risk of recurrence and death from their lung cancer. In recent years, multiple, large, randomized trials assessing the efficacy of adjuvant chemotherapy for resected NSCLC have been reported. Three of 6 trials with 300 or more patients with early-stage NSCLC have demonstrated that adjuvant cisplatin-based chemotherapy can significantly improve 5-year survival in carefully selected patients with resected NSCLC. These benefits have been confirmed in a meta-analysis of modern cisplatin-based adjuvant trials. The most consistent benefit has been reported in patients with resected stage II and IIIA NSCLC. The benefit of adjuvant chemotherapy in patients with resected stage IB NSCLC is less concrete. Herein, we review the results of the major adjuvant chemotherapy trials and their implications for the treatment of patients with completely resected NSCLC. A future challenge will be to identify the subsets of patients who will derive the greatest benefit from adjuvant chemotherapy. Current trials are also underway to define the role of novel targeted therapies, such as inhibitors of the epidermal growth factor receptor and monoclonal antibodies, in adjuvant treatment strategies.     

Incomplete resection for primary non-small cell lung cancer]

A superior outcome is observed for cases of complete resection compared with that of incomplete resection. The reason and the countermeasure of the incomplete resection for lung cancer were analyzed. During 12 years, 274 patients with primary non-small cell lung cancer were surgically treated. Two hundred and forty-eight patients underwent complete resection and 26 incomplete resection. Three-year survival was 62% for patients with complete resection and 17% for patients with incomplete resection. Survival rates were not different between the paroative reduction surgery and the exploratory thoracotomy. Tiny but multiple pleural dissemination or small amount of the malignant pleurfal effusion was not able to detect preoperatively. In these cases, preoperative thoracoscopic observation may useful for avoiding the meaningless thoracotomy. Postoperative radiochemotherapy may improve the prognosis if the therapy is effective. Chemotherapy on the basis of the sensitivity assay is warranted.     

Surgery for intrathoracic recurrence of non-small cell lung cancer

In this study, we defined a solitary lung nodle in the same histology which could be traced its' origin from carcinoma in situ or was found over than two years' follow up as a second primary lung cancer. These cases were excluded. Eighteen cases underwent second surgery for intrathoracic recurrence. Fourteen cases were male and four cases were female. Their ages ranged from 23 to 75 (average 59.6) years. The histology were adenocarcinoma in 9 cases, squamouscarcinoma in 7, adenosquamous carcinoma in 1, large cell carcinoma in 1. The initial surgical procedures were lobectomy in 17, partial resection in 1. The initial stage were I in 13, II in 2, IIIA in 1. Pulmonary recurrence were found in 10, bronchial stump recurrence were found in 4, pulmonary hilus lymph node recurrence were found in 2, mediastinal lymph node recurrence were found in 2, pulmonary stump recurrence was found in 1. The second surgical procedures were completion pneumonectomy in 7, completion lobectomy in 1, lobectomy with segmentectomy in 1, segmentectomy or partial resection in 7, mediastinal dissection in 2. The overall 5-year survival rate of the patients with recurrence after reoperation was 31.8%. An aggressive surgical approach for recurrent lung cancer should be recommended.     

Video-assisted thoracoscopic surgery lobectomy for non-small cell lung cancer

Since 1990s, video-assisted thoracoscopic surgery (VATS) lobectomy has become a standard procedure for early-stage non-small cell lung cancer. However, VATS lobectomies are less common, and no randomized controlled trial of VATS versus conventional open lobectomy for early-stage lung cancer has been performed in Japan. Furthermore, VATS lobectomy procedures are not standardized in Japan, and may vary by institution or by practitioner, which complicates their evaluation. Although VATS procedures (such as pneumonectomy, bronchoplasty, and chest wall resection) have been reportedly performed for patients with advanced disease, whether VATS could be a standard modality for advanced lung cancer is unclear from an oncological perspective. Until recently, VATS lobectomies commonly used three or four ports to conduct systemic lymph node dissection; however, VATS lobectomies with reduced port have been recently reported. This article reviews current trends in VATS lobectomy procedures.