Neoadjuvant chemoradiation in non-small cell lung cancer]

In 2006 preoperative chemoradiation is a major part of the treatment of stage III locally advanced non-small cell lung cancer. Previous studies have clearly demonstrated the feasibility both regarding toxicities and resectability rates of the sequential and concurrent combination of radiation to chemotherapy in a neoadjuvant setting. However, induction chemoradiation has never been randomly compared to exclusive preoperative chemotherapy. Besides, the doses of radiation and the optimal drug combination remain undetermined at the time. Regarding the global therapeutic strategy of stage III non-small cell lung cancer, recently reported phase III trials evaluating the role of surgical resection after induction chemotherapy or chemoradiation, all showed the prognostic importance of the tumoral and mediastinal downstaging to select patients really benefiting from surgery. These developments make of the treatment of locally advanced non-small cell lung cancer a model for multimodal therapeutic strategies combining chemotherapy, radiotherapy and surgery.     

Induction therapy for non-small cell lung cancer]

Induction therapy for non-small cell lung cancer was reviewed. Surgical therapy remains the treatment of choice for resectable non-small cell lung cancer. However, postoperative survival of the patients with locally advanced NSCLC is far from acceptable. Several phase II and phase III trials have been attempted to define whether surgical resection after induction therapy provides better local control and survival than surgery alone. Most studies have reported high response and resectability rates, and long-term follow up of two randomized trials shows that patients having cisplatin-based induction chemotherapy prior to surgical resection were significantly more likely to have better 5-year survival than patients operated without preoperative treatment. However, the results of the randomized trials are still controversial owing to the relatively small and inhomogeneous population used. To identify the future direction of effort in improving the therapy of NSCLC, more sophisticated randomized prospective trials should be conducted.     

Chemotherapy in stage I+II non-small cell lung cancer

Although surgical resection offers the best chance for long-term survival for patients with non-small cell lung cancer (NSCLC), the limited number of resectable patients and the presence of micrometastatic disease is limiting the effectiveness of this modality as sole treatment. Results of randomized trials demonstrated a survival benefit for preoperative (neoadjuvant) cisplatin-based chemotherapy in patients with stage IIIA NSCLC compared to surgery alone. In stage I+II NSCLC preoperative chemotherapy, although still experimental, clearly offers encouraging results. However, there is no evidence of its superiority over adjuvant chemotherapy. Moreover, for adjuvant therapy a benefit has not been established yet. Possibly current ongoing or recently finished trials may change the recommendations on adjuvant or neoadjuvant therapy for completely resected or resectable early disease in the future.     

Patterns of failure and overall survival in patients with completely resected T3 N0 M0 non-small cell lung cancer.

BACKGROUND: Previous studies of patients with surgically resected non-small cell lung cancer and chest wall invasion have shown conflicting results with respect to prognosis. Whether high-risk subsets of the T3 N0 M0 population exist with respect to patterns of failure and overall survival has been difficult to ascertain, owing to small numbers of patients in most series. METHODS AND MATERIALS: A retrospective review was performed to determine patterns of failure and overall survival for patients with completely resected T3 N0 M0 non-small cell lung cancer. From 1979 to 1993, 92 evaluable patients underwent complete resection for T3 N0 M0 non-small cell lung cancer. The following potential prognostic factors were recorded from the history: tumor size, location, grade, histology, patient age, use of adjuvant radiation therapy (18 of 92 patients), and type of surgical procedure (chest wall or extrapleural resection). RESULTS: The actuarial 2- and 4-year overall survival rates for the entire cohort were 48% and 35%, respectively. The actuarial local control at 4 years was 94%. Neither the type of surgical procedure performed nor the addition of thoracic radiation therapy impacted local control or overall survival. CONCLUSION: Patients with completely resected T3 N0 M0 non-small cell lung cancer have similar local control and overall survival irrespective of primary location, type of surgery performed, or use of adjuvant radiation therapy. Additionally, the tumor recurrence rate and overall survival found in this study support the placement of this group of patients in Stage IIB of the 1997 AJCC lung staging classification.     

Surgery for Small Cell Lung Cancer

Retrospective analyses have shown that, following surgical resection, patients with early-stage small cell lung cancer have a survival rate comparable to that seen with non-small cell lung cancer, especially if combined modality therapy is used. Surgery has been employed in three specific instances: primary surgery followed by postoperative chemotherapy and, when indicated, mediastinal irradiation for tumors presenting as peripheral nodules; multimodality therapy including induction chemotherapy followed by surgery; and radiotherapy in "resectable," very limited disease and "salvage surgery" for patients with limited disease previously treated, recurring at the primary site. The results of such surgery in very selected patients yields the best reported results in the treatment of small cell lung cancer. These approaches are worthy of further study.     

Therapeutic strategies in superior sulcus tumors: a model for combined modality therapy in non-small cell lung cancer]

Superior sulcus tumors have been individualized among other non-small cell lung cancers because of their characteristic clinical presentation in connection with their local extension to the chest wall and the brachial plexus. For a long time considered as marginally resectable, superior sulcus tumors have been treated since the early 1960's, with a combined approach including preoperative radiotherapy and curative-intent surgery. Surgical resection includes both thoracic, cervical and neurosurgical approach, and aims at obtaining complete resection, which has been identified as a determining prognostic factor in most reported series. Two recent phase II trials showed the benefit, both regarding resectability and local control rates, and survival of combined therapeutic strategies including induction platinum-based chemoradiation, extensive surgical resection, and adjuvant chemotherapy. Adjuvant radiotherapy is not recommended at the time, but needs to be re-evaluated regarding its recent technical optimisation. Similarly to other locally advanced non-small cell lung cancers, exclusive chemoradiation is the standard treatment of unresectable superior sulcus tumors. In this way, radiotherapy has shown to offer a prolonged analgesia in more than 75% of cases, and is associated with concurrent or sequential chemotherapy, with comparable results to those observed in stage III lung cancer. These developments make superior sulcus tumors a therapeutic model for locally advanced non-small cell lung cancer, whereby the benefit of combined multimodal strategies including induction chemoradiation and surgical resection are currently evaluated in phase III trials.     

高龄肺癌58例的外科治疗及围手术期处理

目的：探讨高龄肺癌外科治疗与围手术期处理的有关问题。方法：回顾分析手术治疗的58例70岁以上肺癌病例。结果：手术切除56例(96．6％)，其中根治性切除48例(85．7％)，姑息性切除8例(14．3％)。探查2例(3．4％)。术后并发症50例(86．2％)，围手术期手术死亡2例，病死率3．4％。结论：高龄并非是决定肺癌患者采取手术治疗的禁忌。重视合并症的诊断和治疗、充分的术前准备、合理选择手术时机与手术方式、加强术中与术后监测和防治并发症，是减少术后并发症和病死率、提高根治性切除率、生存率和改善生存质量的关键。     

Treatment options for brain metastases in patients with non-small cell lung cancer

Opinion statement Brain metastases are a common complication for patients with non-small cell lung cancer and a significant cause of morbidity and mortality. In the past, treatment of brain metastases and lung cancer focused on symptom palliation with whole brain radiotherapy (WBRT) and steroids because of the grim outlook for patients. However, recent advances in technology and surgical techniques have created more options for the management of brain metastases, which include surgery, irradiation, stereotactic radiosurgery, and chemotherapy. These aggressive approaches have resulted in an improvement of neurologic outcomes and survival rates of patients with non-small cell lung cancer. Central nervous system (CNS) metastases can be divided into three groups: solitary CNS metastases with controlled or controllable primary disease, oligometastatic disease (fewer than three metastases), and multiple metastases. For patients with solitary CNS metastases, long-term survival is possible. A radical treatment approach involving surgical resection or radiosurgery, followed by WBRT, is recommended. For patients with oligometastatic disease, surgical resection or radiosurgery is considered in selected cases and WBRT is indicated. For patients with multiple metastases, WBRT is recommended. For patients with oligometastatic disease and patients with multiple metastases, recent evidence indicates that systemically effective chemotherapy may produce responses and can be instituted safely before radiotherapy. The treatment timing of chemotherapy and radiotherapy should be individualized.     

简单肺功能评价对Ⅰ、Ⅱ期非小细胞肺癌术式选择的价值

目的 探讨简单肺功能评价对Ⅰ、Ⅱ期非小细胞肺癌手术患者手术方式选择的指导价值.方法 选取Ⅰ、Ⅱ期非小细胞肺癌手术患者60例,应用常规肺功能检查仪检测患者的最大通气量(maximum voluntary ventilation,MVV)、肺活量(vital capacity,VC)、用力肺活量(forced vital capacity,FVC)、第1秒用力呼气容积(forced expiratory volume in one second,FEV1),评价患者的通气功能,并选择相应的手术方法.同时观察患者肺功能水平与术后并发症的相关性.结果 肺功能指标中MVV>80.0%、VC>96.5%、FVC>48.1%、FEV1>2.4 L的24例患者实施左或右全肺切除术,MVV为47.5%~77.8%、VC为41.8%~97.5%、FVC为51.8%~74.3%、FEV1为2.3~3.0 L的20例行单肺叶切除术,而MVV<41.7%、VC为36.3%~94.7%、FVC为30.1%~57.8%、FEV1为0.7~1.0 L的4例不适行任何开胸手术.在呼吸衰竭、死亡严重并发症方面,正常通气功能组发生率低于轻中度损伤与重度损伤组(P<0.05),但轻中度损伤与重度损伤组比较差异无统计学意义.肺部感染、心律失常与低氧血症的发生率随着肺通气功能损伤程度的加重而增高(P<0.05).结论 对Ⅰ、Ⅱ期非小细胞肺癌手术患者术前简单评估肺功能,可积极指导患者术式的选择,同时肺通气功能较差的患者术后并发症较严重,应提前有效预防.     

局部晚期非小细胞肺癌治疗的争议与共识

肺癌是发病率和死亡率增长最快 ,对人类健康和生命威胁最大的恶性肿瘤。完全性切除是目前治疗肺癌的最好方法。但是 ,仅有约 1/3的肺癌适合于外科治疗 ,另 2 /3的肺癌由于伴有远处转移或侵犯邻近器官而被视为不可手术。近年来 ,随着心血管外科理论和技术在肺癌外科中的应用 ,使得肺切除合并受侵的左心房、胸主动脉、上腔静脉和肺动脉的整块切除成为可能。这些过去被视为外科禁忌证和无治愈希望的局部晚期肺癌 ,不但获得肿瘤完全切除、无肿瘤复发转移 ,而且获得长期生存和良好的生活质量。     

280例非小细胞肺癌患者围手术期输血与否的预后关系

目的：研究非小细胞肺癌术后的预后因素及围手术期输血对术后无病生存的影响。方法：回顾性调查了280例手术切除的非小细胞肺癌患者，其中145例（51．8％）患者围手术期接受了输血治疗，采用单因素对数秩检验（log—ranktest）多因素Cox比例风险回归模型进行分析。结果：多因素分析表明，影响预后的主要因素有分化程度、术后分期、围手术期输血。围手术期输血是无病生存的独立预后因素。结论：围手术期输血是非小细胞肺癌独立的不利预后因素，应当尽量避免围手术期输血。     

Surgical strategies in the therapy of non-small cell lung cancer

Lung cancer represents the leading cause of cancer mortality worldwide. Despite improvements in preoperative staging, surgical techniques, neoadjuvant/adjuvant options and postoperative care, there are still major difficulties in significantly improving survival, especially in locally advanced non-small cell lung cancer (NSCLC). To date, surgical resection is the primary mode of treatment for stage I and II NSCLC and has become an important component of the multimodality therapy of even more advanced disease with a curative intention. In fact, in NSCLC patients with solitary distant metastases, surgical interventions have been discussed in the last years. Accordingly, this review displays the recent surgical strategies implemented in the therapy of NSCLC patients.     

Chemotherapy is the cornerstone of the combined surgical treatment of lung cancer with synchronous brain metastases

BACKGROUND: Lung cancer accounts for about 50% of brain metastases, of which nearly 25% are eligible for neurosurgery, providing a neurological control rate of up to 70% when followed by whole brain radiation therapy. How to manage the primary lung carcinoma remains elusive. METHODS: We undertook a retrospective study of consecutive patients who underwent surgical resection for synchronous brain metastases from non-small cell lung cancer in a single institution, to determine overall survival and prognostic factors, with particular attention to the treatment of the primary lung tumor. RESULTS: Fifty-one patients underwent surgical resection of synchronous brain metastases from non-small cell lung cancer. Median survival was 13.2 months. Prognosis mainly depended of the treatment of the lung tumor, with a marked survival advantage in the 29 patients receiving a focal treatment (thoracic surgery or radiotherapy), compared to the 22 other patients: median, 1-year, and 2-year survival were 22.5 months, 69%, and 42%, versus 7.1 months, 33%, and 5%, respectively (p<0.001); response to pre-operative chemotherapy before focal treatment was the main favorable prognostic factor (p=0.023), and further identified patients who had benefit from resection of the lung tumor, with a significantly better outcome. CONCLUSIONS: Chemotherapy, by its therapeutic and prognostic value, may be considered as the cornerstone of the combined medical and surgical therapeutic sequence whereby brain metastasectomy is followed by chemotherapy and further focal treatment of the primary lung tumor in responders to chemotherapy.     

新曼彻斯特评分系统对早期非小细胞肺癌患者术后预后的评估价值

目的:探讨术前曼彻斯特评分系统(NMSS)对非小细胞肺癌(NSCLC)患者术后预后的评估价值。方法:本研究纳入2015年12月至2018年12月在河南省胸科医院确诊为早期NSCLC并进行手术切除的患者共278例。NMSS 评分系统根据乳酸脱氢酶（LDH）、碱性磷酸酶（ALP）、血钠、血碳酸氢盐、分期和卡式评分（KPS）分为良好、中等和不良三组，分析NMSS 不同分组以及其他临床指标与术后生存时间之间的关系。结果:278例 NSCLC 患者中，46 例(16.5%)为中等组，70例(25.2%)为不良组，高龄、晚期、未接受放化疗与预后相关，NMSS评分为不良组是预后差的独立危险因素。结论:术前高NMSS评分是影响非小细胞肺癌术后预后的独立危险因素，NMSS评分高提示预后不良。在进行非小细胞肺癌治疗相关选择时，可根据患者的辅助检查结果进行相应的预测评估。     

Is there a role for surgery in stage Ⅲ A-N2 non-small cell lung cancer?

The role of surgery in stage ⅢA-N2 non-small cell lung cancer(NSCLC) remains controversial.Most important prognostic factors are mediastinal downstaging and complete surgical resection.Different restaging techniques exist to evaluate response after induction therapy and these are subdivided into non-invasive,invasive and alternative or minimally invasive techniques.In contrast to imaging or functional studies,remediastinoscopy provides pathological evidence of response after induction therapy.Although technically more challenging than a first procedure,remediastinoscopy can select patients for subsequent thoracotomy and provides prognostic information.An alternative approach consists of the use of minimally invasive staging procedures as endobronchial or endoscopic esophageal ultrasound to obtain an initial proof of mediastinal nodal involvement.Mediastinoscopy is subsequently performed after induction therapy to evaluate response.In this way,a technically more difficult remediastinoscopy can be avoided.Stage ⅢA-N2 NSCLC represents a heterogenous spectrum of locally advanced disease and different subsets exist.When N2 disease is discovered during thoracotomy after negative,careful preoperative staging a resection should be performed if this can be complete.Postoperative radiotherapy will decrease local recurrence rate but not overall survival.Adjuvant chemotherapy increases survival and is presently recommended in these cases.Most patients with pathologically proven N2 disease detected during preoperative work-up will be treated by induction therapy followed by surgery or radiotherapy.In two large,recently completed,phase Ⅲ trials there was no difference in overall survival between the surgical and radiotherapy arm,but in one trial there was a difference in progression-free survival in favor of the surgical arm.In the surgery arm the rate of local recurrences was also lower in both trials.Surgical resection may be recommended in those patients with proven mediastinal downstaging after induction therapy who can preferentially be treated by lobectomy.Pneumonectomy has a significantly higher mortality and morbidity rate,especially after induction chemoradiotherapy.Patients with bulky N2 disease are mostly treated with combined chemoradiotherapy although the precise treatment scheme has not been determined yet.     

术前支气管动脉灌注化疗在肺癌手术中的临床研究

Objective： How to improve the postoperative 5-year survival rate for lung cancer and to give more patients a chance of surgery have become research hotspots. The aim of this research is to evaluate the clinical and pathohistological responses and effects of preoperative bronchial artery infusion （BAI） chemotherapy in patients with locally advanced （stage Ⅲ） non-small cell lung cancer （NSCLC）. Methods： A total of 92 patients with locally advanced NSCLC were randomly divided into two groups. BAI group received BAI chemotherapy for 2 cycles before surgical resection. Surgery group received operation only. The complete resection rate and clinical response were compared between the two groups. Results： In the BAI group, the clinical response rate and the pathohistological response rate were 68.3% and 51.3%, respectively. The complete resection rate in the BAI group was 89.7%, which was significantly higher than that in the surgery group （72.5%） （P 〈 0.05）. The 1- and 2-year survival rate was 100.0% and 80.6% in the BAI group, and 94.1% and 60.0% in the surgery group. Conclusion： BAI neoadjuvant chemotherapy is safe and effective, which has a good clinical and pathohistological response. It might increase the complete resection rate of the tumor and improve the long term survival rate of stage Ⅲ NSCLC patients.     

老年非小细胞肺癌的治疗

目前老年非小细胞肺癌（NSCLC）发病率及死亡率呈上升趋势。治疗的主要手段是手术治疗、放疗、化疗以及靶向治疗,其治疗目的在于延长患者生命的同时提高其生活质量。但老年NSCLC的治疗目前尚无统一标准。     

Surgery versus stereotactic radiosurgery for single synchronous brain metastasis from non-small cell lung cancer

Objective: The aim of this study is to compare the effectiveness of surgery with stereotactic radiosurgery (SRS) for patients with a single synchronous brain metastasis from successfully treated non-small cell lung cancer.Methods: Between 1995 and 2002, 53 patients underwent resection of both primary non-small cell lung cancer and the associated single brain metastasis. There were 33 men and 20 women with a mean age of 57 years (range, 32(85 years). At the time of diagnosis, 42 patients experienced lung cancer related symptoms, whereas 11 patients experienced brain metastases-related symptoms. 42 patients had received thoracic surgery first, and 11 patients had undergone neurosurgery or radiosurgery first. Pneumonectomy was performed in 9 out of 42 patients (21.4%), lobectomies in 30 (71.4%), and wedge resection in 3 (7.2%). 48 patients (90.5%) underwent complete lymphadenectomy. 35 patients underwent brain metastasectomy. 18 underwent SRS.Results: There was no postoperative mortality and severe complications after either lung or brain surgery. Histology showed 34 adenocarcinomas, 16 squamous cell carcinomas, and 3 large cell lung cancers. 15 patients (28.3%) had no evidence of lymph node metastases (N0), 20 patients (37.7%) had hilar metastases (N1), and 18 patients (34%) had mediastinal metastases (N2). The 1-, 2-, 3- and 5-year overall survival rates were 49%, 19%, 10%, and 5%, respectively. The corresponding data for neurosurgery group were 55%, 17%, 11%, and 6%, respectively. The median survival time was 13 months. For SRS group the corresponding data were 44.8%, 20.9% 10.5%, and 2%, respectively. The median survival time was 14 months. The differences between the two groups were not significant (P>0.05). In lymph node negative patients (N0), the overall 5-year survival rate was 10%, as compared with a 1% survival rate in patients with lymph node metastases (N1(2). The difference was significant (P<0.01). For adenocarcinomas, the 5-year survival rate was 5%. The correspondent data for squamous cell lung cancers was 3%. The difference was not significant (P>0.05).Conclusion: Although the overall survival rate for patients who have brain metastases from NSCLC is poor, surgical resection or radiosurgery may be beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.     

腔镜下肺段切除治疗Ib期老年非小细胞肺癌的疗效观察

目的:探讨电视胸腔镜下解剖性肺段切除治疗老年（≥65岁）高危Ib期(pT状态:>2 cm,≤3 cm)非小细胞肺癌患者的疗效。方法:368例Ib期老年非小细胞肺癌患者,分为高危组:182例,伴严重心、肺功能及其他系统器官的功能障碍,接受胸腔镜下解剖性肺段切除+系统性淋巴结清扫术;常规风险组:186例,心肺功能储备好,无合并其他系统器官功能障碍,接受胸腔镜下肺叶切除+系统性淋巴结清扫术。结果:高危组手术时间和失血量［（73.0±25.0） min,（58.0±25.0） ml］ 明显低于常规风险组［（102.0±17.0) min,(98.0±16.0) ml］。高危组5年生存率、无瘤生存率和复发率分别为62.09%、30.22%和13.74%,常规风险组为62.90%、32.80%和12.90%,两组无统计学差异(P＞0.5)。结论:解剖性肺段切除联合系统性淋巴结清扫治疗老年、高危、Ib期非小细胞肺癌创伤小,安全可行。     

153例经外科干预的非小细胞肺癌伴胸膜播散患者的预后研究

  目的  探讨经不同外科治疗方式干预的非小细胞肺癌（non-small cell lung cancer,NSCLC）伴胸膜播散患者的预后。  方法  回顾性分析2002年5月至2011年5月153例在中国医学科学院肿瘤医院胸外科接受外科手术并于术中或术后确诊NSCLC伴胸膜播散患者的临床资料。  结果  全组患者,3年和5年生存率分别为38.5%和24.2%,中位生存时间29.0个月。其中31例接受胸膜结节活检术,122例接受原发肿瘤切除术,两组患者5年生存率分别是16.1%和26.2%,中位总生存时间分别为24.0个和29.0个月,两组间生存差异均无统计学意义（P>0.05）。122例接受原发肿瘤切除术患者中,是否行淋巴结清扫和转移结节切除,以及行部分肺叶或肺叶切除对患者预后影响无显著性差异（P>0.05）。  结论  NSCLC伴胸膜播散患者预后较差,行不同外科干预方式生存未显示出显著性差异,外科干预的主要作用是除外及证实胸膜播散以明确病理诊断,指导后续治疗,肿瘤切除应慎重,其意义有待进一步探讨。