非小细胞肺癌肺叶袖状切除术手术安全性及远期疗效分析

背景与目的：长期以来,全肺切除术是治疗非小细胞肺癌的常用术式,仅少部分有适应证的肺癌患者选用肺叶袖状切除术。本研究评价肺叶袖状切除术在非小细胞肺癌治疗中的价值。方法：中山大学肿瘤防治中心1997年1月至2007年12月共施行非小细胞肺癌根治性袖状切除术93例,同期施行根治性全肺切除术571例。将两种手术方式的术后并发症发生率及术后死亡率进行比较．并回顾性分析两种手术方式的5年生存率。结果：袖状切除术术后并发症发生率为11．8％,全肺切除术术后并发症为20．7％,两组问差异有统计学意义（P=0．046）。术后死亡率袖状切除术组为2．1％,全肺切除术组为4．7％,两组间差异无统计学意义（P=0．259）。袖状切除术和全肺切除术术后5年生存率分别为42．0％、31．5％。组间差异有统计学意义（P=0．015）;其中N0、N1患者5年生存率袖状切除术组优于全肺切除术组（P=0．007,P=0．025）,N2患者5年生存率两组间差异无统计学意义（P=0．073）。支气管肺动脉双袖状切除术与全肺切除术组间5年生存率差异无统计学意义（P=0．092）。袖状切除术组与全肺切除术组之间的术后局部复发率差异无统计学意义（P=0．821）。结论：非小细胞肺癌袖状切除术手术安全性及远期疗效均优于全肺切除术．值得在临床上推广应用。     

Concurrent radiochemotherapy for patients with stage III non-small–cell lung cancer (NSCLC): long-term results of a phase II study

Purpose: To investigate the feasibility and activity of concurrent radiochemotherapy in patients with Stage III nonsmall-cell lung cancer (NSCLC).

Materials and Methods: Forty-one patients were treated with hyperfractionated radiation therapy (HfxRT) using 1.2 Gy bid, to a total of 69.6 Gy and concurrent low-dose daily chemotherapy (CHT) consisting of 30 mg of carboplatin (CBDCA) and 30 mg of etoposide (VP-16) given Mondays to Fridays during the RT course. On Saturdays and Sundays during the RT course, CBDCA and VP-16 were both given in a daily dose of 100 mg each.

Results: Median survival time was 25 months, and 3- and 5-year survival rates were 34% and 29%, respectively. Median relapse-free survival time was 22 months, and 3- and 5-year relapse-free survival rates were 32%, and 29%, respectively. Median time to local recurrence was 24 months and 3- and 5-year local recurrence-free survival rates were 41% and 38%, respectively. Median time to distant metastasis was 28 months, and 3- and 5- year distant metastasis-free survival rates were 44% and 44%, respectively. Acute high-grade (≥ 3) toxicity was mostly hematological (30%), esophageal (15%), and bronchopulmonary (12%). Late high-grade toxicity was infrequent.

Conclusion: This combined radiochemotherapy regimen produced promising results and warrants further studies with more patients before testing it in a prospective randomized fashion.     

支气管袖状成形肺切除术治疗支气管肺癌81例报告

目的 回顾分析我院1984－1999年间81例支气管袖状成形术,重点讨论各种袖状成形术的术式,总结经验。方法 术式包括左和右肺上叶支气管袖状切除术33例,右肺中叶袖状切除术6例,左和右肺下叶袖状切除术3例,右肺中叶及基底段支气管袖状切除术5例,右肺上叶、部分中叶及基底段支气管袖状切除术2例,左上叶及部分基底段支气管袖状切除术4例,左肺下叶及舌段袖状切除术5例,下叶背段袖状切除术8例,左肺舌段袖状切除术2例,主支气管袖状切除术4例,主支气管及上叶和中间支气管或下叶支气管袖状切除术3例,右中间和中叶支气管及下叶支气管袖状切除术3例,双袖状切除术3例。结果 本组81例无手术死亡,亦未出现严重的手术并发症。最常见的术后并发症为肺不张（共4例）,主要发生在段支气管袖状肺切除术（占3例）。经协助咳痰、纤支镜吸痰、抗炎治疗而治愈。结论 支气管解剖复杂,同时亦具有较大的可塑性。应根据具体病变的性质、位置、范围和解剖特点选择合理的术式,争取最佳的治疗效果。     

块型非小细胞肺癌放疗疗效分析

目的回顾性分析原发灶≥５ｃｍ的非小细胞肺癌放疗疗效及影响预后因素。材料与方法自１９７４年１月～１９８８年１２月共收治原发灶可测量、最小径≥５ｃｍ的非小细胞肺癌２７８例，男２３５例，女４３例。全部有组织学证实。Ⅰ期５例，Ⅱ期３７例，ⅢＡ期１７５例，ⅢＢ期６１例，伴有空洞４２例。照射方法采用６０Ｃｏ或８ＭＶ－Ｘ线外照射，常规前后野照射４０Ｇｙ／４周，然后避开脊髓缩野加量２０～３０Ｇｙ／２～３周。结果１，３，５年生存率分别为５１．０％，９．３％和５．０％。原发灶５ｃｍ×５ｃｍ～６ｃｍ×７ｃｍ和７ｃｍ×７ｃｍ～１０ｃｍ×１２ｃｍ的３，５年生存率分别为１１．６％，６．０％和３．８％，２．５％。Ⅰ，Ⅱ和Ⅲ期的３，５年生存率分别为８０．０％，６０．０％和１８．０％，１０．０％和６．０％，３．０％。空洞和非空洞３，５年生存率分别为２．４％，２．４％和１０．６％，５．０％。结论肿瘤≥５ｃｍ的情况下，肿瘤大小与空洞发生率无明显关系，预后与原发灶大小关系不大，而与临床分期、局部是否控制有关     

Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC)

The emergence of immunotherapy has dramatically changed how non–small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD-L1) expression is the current standard. The extent of PD-L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor-infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD-L1 as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy.     

肺癌根治性袖状切除术对非小细胞肺癌机体应激创伤反应、肺功能及生活质量的影响

目的:探讨肺癌根治性袖状切除术对非小细胞肺癌机体应激创伤反应、肺功能及生活质量的影响。方法:选取我院2014年2月至2017年12月期间收治的非小细胞肺癌患者96例,采用随机数字表法,将患者分为对照组和观察组。对照组接受全肺切除术,观察组行袖状切除术。记录两组患者气管插管时（T1）、手术进行60 min时（T2）、手术完成时（T3）,血清皮质醇（Cor）、肾上腺素（E）水平,心率（HR）和平均动脉压（MAP）,并记录术中出血量、手术时间、术后拔出胸管时间、住院时间和并发症情况,检测手术前后用力肺活量（FVC）、第一秒用力呼气容积（FEV1）、呼气峰流速（PEF）和生活质量。结果:与T1时比较,对照组患者在T2、T3时HR、MAP明显升高（P＜0.05）;观察组在T2、T3时HR、MAP较T1无明显变化（P＞0.05）。与T1时比较,两组T2、T3时Cor和E水平均升高,其中观察组Cor和E水平低于同期对照组（P＜0.05）。手术后,两组FVC、FEV1、PEF均明显降低,但观察组FVC、FEV1、PEF水平高于对照组（P＜0.05）。手术后,两组生活质量各项评分均升高,且观察组高于对照组（P＜0.05）。观察组术中出血量、术后拔出胸管时间、住院时间和并发症发生率少于对照组,手术时间多于对照组（P＜0.05）。结论:对非小细胞肺癌患者行袖状切除术,应激反应和肺功能影响小,术后并发症少,能有效提高生活质量。     

国产多西紫杉醇治疗晚期非小细胞肺癌的随机对照临床研究

背景与目的：多西紫杉醇已成为临床上治疗晚期非小细胞肺癌的主要药物之一。国外报道单药一线治疗晚期非小细胞肺癌的有效率20％,其主要毒性是骨髓抑制。本研究观察易优瑞康（Euruikang,国产多西紫杉醇）治疗晚期初治非小细胞肺癌的疗效和毒性。方法：共77例患者入组。随机分组,试验组38例,对照组39例。试验组接受易优瑞康75mg／m^2,对照组接受艾素75mg／m^2,1小时输注,两组均联合顺铂70mg／m^2,每3周重复疗程。在多西紫杉醇给药前1天开始口服地塞米松7．5mg,每天2次,连服3天预防过敏反应。所有患者均接受两个疗程以上的化疗。结果：试验组可评价37例,PR15例,SD16例,PD6例,总有效率40．54％。33例4周后再次复查评价,确认有效率为28．95％。对照组可评价疗效37例,PR13例,SD16例,PD8例,总有效率35．14％。34例4周后再次复查评价疗效,确认有效率为27．03％。两组疗效差异无统计学意义。易优瑞康主要的毒副作用为Ⅱ～Ⅲ度骨髓抑制,Ⅰ～Ⅱ度脱发、乏力和消化道反应,未见严重的过敏反应发生。结论：本研究所用的易优瑞康注射液是一种治疗晚期非小细胞肺癌安全有效的药物,与国内已上市的同类产品艾素疗效、毒副作用相当。     

A decade of EGFR inhibition in EGFR-mutated non small cell lung cancer (NSCLC): Old successes and future perspectives

The discovery of Epidermal Growth Factor Receptor (EGFR) mutations in Non Small Cell Lung Cancer (NSCLC) launched the era of personalized medicine in advanced NSCLC, leading to a dramatic shift in the therapeutic landscape of this disease. After ten years from the individuation of activating mutations in the tyrosine kinase domain of the EGFR in NSCLC patients responding to the EGFR tyrosine kinase inhibitor (TKI) Gefitinib, several progresses have been done and first line treatment with EGFR TKIs is a firmly established option in advanced EGFR-mutated NSCLC patients. During the last decade, different EGFR TKIs have been developed and three inhibitors have been approved so far in these selected patients. However, despite great breakthroughs have been made, treatment of these molecularly selected patients poses novel therapeutic challenges, such as emerging of acquired resistance, brain metastases development or the need to translate these treatments in earlier clinical settings, such as adjuvant therapy.The aim of this paper is to provide a comprehensive review of the major progresses reported so far in the EGFR inhibition in this molecularly-selected subgroup of NSCLC patients, from the early successes with first generation EGFR TKIs, Erlotinib and Gefitinib, to the novel irreversible and mutant-selective inhibitors and ultimately the emerging challenges that we, in the next future, are called to deal with.     

Apoptosis block as a barrier to effective therapy in non small cell lung cancer

Lung cancer, is the most common cause of cancer death in men and second only to breast cancer in women. Currently, the first line therapy of choice is platinum-based combination chemotherapy. A therapeutic plateau has been reached with the prognosis for patients with advanced non-small cell lung cancer (NSCLC) remaining poor. New biomarkers of prognosis as well as new therapies focusing on molecular targets are emerging helping to identify patients who are likely to benefit from therapy. Despite this, drug resistance remains the major cause for treatment failure. In this article we review the role of apoptosis in mediating drug resistance in NSCLC. Better understanding of this fundamental biological process may provide a rationale for overcoming the current therapeutic plateau.     

老年非小细胞肺癌患者全肺切除术后生存和预后分析

探讨老年肺癌患者行全肺切除的可行性和预后。方法自１９８５－１９９５年,我们对２３例６５岁以上非小细胞肺癌患者行全肺切除,选择同期小于６５岁行全肺切除的９９例ＮＳＣＬＣ患者对照,比较两组病５年生存率,手术并发症和死亡率,手术前后肺功能的改变,生存率分析采用Ｋａｐｌａｎ－Ｍｅｉｅｒ法。结果老年组５年生存率与对照组相似（２７．５６％比３０．５１％,Ｐ〉０．０５）,但手术并发症和死亡率明显高于对照组（１３     

Cisplatin and vinorelbine combination chemotherapy in inoperable non small cell lung cancer (NSCLC) : a multicenter phase II trial

Purpose

The present article reports the results of a multicentre phase II study analysing both activity and tolerance of the cisplatin vinorelbine combination in patients with inoperable NSCLC.

Materials and methods

87 consecutive patients from 6 Institutions were treated with vinorelbine 25 mg/m² on days 1 and 8, plus cisplatin 100 mg/m² on day 1, both intravenously, every 21 days. All patients were younger 75 years old, with unresectable non small cell lung cancer stages IIIA, IIIB and IV, who had a measurable or assessable disease, performance status ECOG 0–2 and had more than 12 weeks life expectancy. Response was assessed after 3 courses. Toxicity was assessed after every cycle.

Results

87 patients treated, all them were evaluable for response. Five patients (5.7%) had a complete response and twenty-two (25.3%) a partial one. The median overall survival was 8.03 months. The toxicity, evaluated on 262 cycles administered, was mainly haematological: 11,3% of courses grade 3–4 neutropenias and 3,8% grade 3 thrombocytopenias. There were 4 deaths due to toxicity (4.5%).

Discussion

The vinorelbine-cisplatin is active with manageable toxicity and response rates are in the range of results usually reported in the previous studies evaluating this combination. It suggest that this combination should be considered as a reference regimen in patients with advanced NSCLC.     

Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis

Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease [LD] and 18 with extensive disease [ED], the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression--especially thrombocytopenia. The frequency of previously described "acute radiation syndromes" and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques. The integration of SHB as a systemic therapy with combination chemotherapy and LRT is a feasible program for sequential administration of non-cross-resistant agents in SCLC and may be beneficial in patients with limited disease.     

含羟基喜树碱联合方案治疗中晚期非小细胞肺癌

目的 :观察含羟基喜树碱 (HCPT)联合方案治疗中晚期非小细胞肺癌 (NSCLC)患者的客观疗效及毒副作用。方法 :4 6例中晚期非小细胞肺癌患者为治疗组 ,应用含羟基喜树碱方案化疗 ,其中 2 5例肺腺癌患者接受HFAP方案 ,2 1例肺鳞癌患者接受HCAP方案 ,4周为一周期 ,2周期为一疗程 ;以同期住院的未用HCPT联合化疗的同类患者 4 2例作为对照组 ,其剂量、周期、疗程与治疗组相同 ,但不用HCPT。结果 :治疗组 4 3例患者完成一疗程治疗 ,肺腺癌有效率为 5 6 % ,CR 2例 ,PR 12例 ;肺鳞癌有效率为 5 5 5 % ,CR为 0 ,PR 10例 ,总有效率 (CR +PR)为 5 5 8% ;对照组 4 2例均完成一疗程治疗 ,肺腺癌有效率为37 5 % ,CR 1例 ,PR 9例 ;肺鳞癌有效率为 33 3% ,PR 6例 ,有效率 35 7% ;两组间差异显著 (P <0 0 5 )。治疗组和对照组的毒副反应主要表现为食欲不振、脱发、恶心呕吐和白细胞及血小板减少 ,两组毒副反应发生率无显著性差异 (P >0 0 5 )。结论 :羟基喜树碱联合化疗治疗中晚期非小细胞肺癌疗效确切 ,副作用可耐受 ,该药是治疗非小细胞肺癌较为有效的药物 ,值得进一步在临床中观察和研究。     

Ⅲ期非小细胞肺癌手术与非手术综合治疗对照性临床研究

背景与目的局部晚期非小细胞肺癌的综合治疗中手术加入是否对生存期有益仍无定论。本研究的目的是评价Ⅲ期非小细胞肺癌综合治疗计划中有手术加入和无手术加入的生存期之差别。方法自1992年5月至1999年5月，114例局部晚期非小细胞肺癌被分成两组。A组：共56例，ⅢA期39例，ⅢB期17例；中位KPS为80（70～90）；综合治疗计划包括手术、化疗、放疗和中医药治疗；术式：肺叶切除加纵隔淋巴结系统清扫或淋巴结取样49例，袖式切除加纵隔淋巴结清扫5例，右侧全肺切除2例；术前或术后辅助化疗方案包括MVP、NP、TC及GP等，每4周重复，共4～6周期；肺内病灶或纵隔野放射治疗总剂量5000～6000cGy。B组：共58例，ⅢA期23例，ⅢB期35例；中位KPS为70（60～90）；综合治疗计划除不作手术外，其余大致与A组相同。结果A组：①随访期内转移部位依次为淋巴结、胸膜-肺、骨、脑、肝、心包、皮肤和。肾上腺；②中位存活时间27个月，1、2、5年生存率分别为82．1％、60．7％和25．0％。B组：①随访期内转移部位依次为淋巴结、胸膜肺、骨、脑、肝、心包、皮肤、。肾上腺、胰腺和食管；②中位存活时间13个月，1、2、5年生存率分别为53．4％、31．0％和1．7％。A组中位生存期明显优于B组（P=0．0001），两组间1、2、5年生存率差异亦均有统计学意义（x^2=9．4，P〈0．01；x^2=8．9，P〈0．01；x^2=11．5，P〈0．01）。结论局部晚期非小细胞肺癌的综合治疗有手术加入者与不手术者相比，前者可明显改善生存期。     

CT-guided permanent brachytherapy for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC)

Seven patients with early stage T1N0M0 NSCLC who had medical contraindications for surgical resection were treated with CT-guided percutaneous implantation of (103)Pd or (125)I seeds. After the procedure, two patients developed pneumothorax and hemo/pneumothorax that was managed with aspirative drainage. One patient developed a focal pneumonitis 3 months after the procedure. After a median follow-up of 13 months (4.6-41.0+ months), no patient has developed local or regional failure.     

紫杉醇卡铂周方案同步化疗联合三维适形放射治疗局部晚期非小细胞肺癌的临床研究

目的观察紫杉醇卡铂周方案同步化疗联合三维适形放疗(3D-CRT)治疗局部晚期非小细胞肺癌(NSCLC)的毒性反应及疗效。方法采用前瞻性非随机对照方法,将52例局部晚期NSCLC患者分为同步组(21例):采用紫杉醇和卡铂周方案化疗联合同步3D-CRT;序贯组(31例):采用紫杉醇和卡铂序贯化疗联合3D-CRT。同步组紫杉醇40 mg/m2,静脉滴注1h;卡铂AUC 1.5。序贯组在放疗前行2周期的紫杉醇和卡铂辅助化疗,紫杉醇150 mg/m2,第1天、第21天;卡铂AUC 5,第1天、第21天。3D-CRT 1.8～2.0 Gy/d,总剂量60～66 Gy/6～8周。结果52例患者全部完成治疗。有12例患者在治疗过程中由于白细胞减少而导致治疗时间延长1周以上,其中同步组5例,序贯组7例。同步组中,肺原发灶完全缓解(CR)为9.5%(2/21),部分缓解(PR)为71.4%(15/21),无变化和进展(NC PD)为19.0%(4/21),有效率(CR PR)为81.0%。序贯组中,肺原发灶CR为6.5%(2/31),PR为67.7%(21/31),NC PD为25.8%(8/31),CR PR为74.2%。同步组和序贯组患者的Ⅱ～Ⅲ级急性放射性食管炎、Ⅱ～Ⅲ级急性放射性肺炎和Ⅱ～Ⅲ级白细胞减少发生率分别为61.9%(13/21)和41.9%(13/31)、23.8%(5/21)和22.6%(7/31)及42.9%(9/21)和19.4%(6/31)。同步组有1例患者出现Ⅳ级白细胞减少。52例患者的中位生存时间为17.5个月(同步组19.0个月,序贯组15.8个月),1、2年总生存率分别为72.0%和37.0%,1、2年局部控制率分别为75.0%和75.0%。结论同步放化疗是一种安全有效的治疗方法,绝大多数患者能耐受治疗。同步组与序贯组相比,有提高有效率和延长生存率的趋势,但差异并无统计学意义。