Screening for non-small cell lung cancer

Lung cancer is the leading cause of cancer mortality and is usually discovered at an advanced stage, when treatment is generally not effective. Many researchers have investigated the value of screening for lung cancer, which would theoretically allow earlier detection and more effective treatment. Unfortunately, no trials of screening strategies for lung cancer have shown a mortality benefit, and as a result, no major medical organization currently recommends screening. Research continues to seek proof of the benefit of screening as new techniques are developed, including low-dose spiral computed tomography (CT), autofluorescence bronchoscopy, and advanced techniques of sputum analysis. Although there are promising data on the sensitivity of these newer screening methods, especially low-dose CT, for detecting early lung cancer, none of the published trials are controlled, and they have not yet proven a decrease in mortality. There are ongoing randomized, controlled trials aiming to demonstrate a mortality benefit. Patients who are interested in being screened for lung cancer should be encouraged to participate in well-designed clinical trials whenever possible.     

非小细胞肺癌的多次手术治疗

探讨非小细胞肺癌多次手术的经验、教训和疗效,以期提高中晚期肺癌生存率。方法对２６例复发、转移或出现第二原发癌的非小细胞肺癌再施以一到多次手术,２６例共施行５６次手术。观察这批患者的手术经过、术后并发症,用ＳＰＳＳ统计软件包的Ｋａｐｌａｎ－Ｍｅｉｅｒ法进行生存分析。结果首次手术的术后并发症为３．８％,１,３,５年累积生存率分别为８３．５％、５８．４％和３５．７％,中位生存时间４６个月。二次手术的术后并发症为２６．９％,手术死亡率为１１．５％,１,３,５年累积生存率分别为５５．８％、１７．１％和１７．１％,中位生存时间１５个月。２例三次手术的术后生存分别为１８个月和１７个月。四次手术和五次手术的为同一病人,均在与前一次手术相隔半年后进行,最后一次手术术后生存８个月。结论肺癌的多次手术是肺癌术后复发性或转移性肺癌的有效治疗方法。常规的肺功能检查不足以对病人的肺功能作出恰当的评价,术后应特别注意呼吸衰竭和胸腔出血这两大并发症     

时辰化疗治疗非小细胞肺癌的临床观察

为了对比观察CAP方案的时辰化疗与常规化疗的疗效及不良反应,对72例非小细胞肺癌患者,用抽签法随机分为时辰化疗组与常规化疗组,两组患者的治疗时间不同,但用药剂量及化疗周期相同.结果时辰化疗组38例,完全缓解率及总有效率分别为18.4%(7/38)及57.9%(22/38);常规化疗组34例,分别为2.9%(1/34)及32.3%(11/34).两组相比差异有统计学意义,P=0.005 6.时辰化疗组Ⅱ度以上的白细胞毒性、消化道毒性的发生率分别为15.8%(6/38)、23.7%(9/38),而常规化疗组分别为52.9%(18/34)、67.6%(23/34),两组相比差异有统计学意义,P＜0.001.初步研究结果提示,用CAP方案时辰化疗治疗非小细胞肺癌疗效高、毒副反应小,明显优于常规化疗,且费用低,值得临床推广应用.     

EGFR-TKI治疗非小细胞肺癌研究进展

吉非替尼和厄洛替尼均为小分子量表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）,已在化疗失败的晚期非小细胞肺癌（NSCLC）解救治疗中取得疗效,但仅对特定人群发挥作用。EGF冀。TKI联合化疗一线治疗NSCLC并未能提高疗效;正在进行的临床研究聚焦于优势人群EGFR-TKI一线治疗或联合化疗的研究。     

EGFR-TKI治疗非小细胞肺癌研究进展

吉非替尼和厄洛替尼均为小分子量表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI),已在化疗失败的晚期非小细胞肺癌(NSCLC)解救治疗中取得疗效,但仅对特定人群发挥作用。EGFR- TKI联合化疗一线治疗NSCLC并未能提高疗效;正在进行的临床研究聚焦于优势人群EGFR-TKI一线治疗或联合化疗的研究。     

非小细胞肺癌免疫治疗进展

肿瘤免疫理论经历一个多世纪的探索正逐渐走向成熟,并彰显出显著的临床疗效。免疫检查点抑制剂尤其是细胞毒T淋巴细胞抗原-4（cytotoxic T lymphocyte-associated protein-4,CTLA-4）和程序性死亡因子-1（programmed death-1,PD-1）/程序性死亡因子配体-1（programmed death-ligand 1,PD-L1）单克隆抗体单药治疗已在晚期肺癌的治疗中取得突破性进展,新的免疫检查点也开始获得关注。免疫联合治疗有望成为未来的发展方向。现阶段免疫治疗尚未实现广泛人群获益,对免疫耐药机制的理解将进一步推动个体化治疗。      

Surgical staging for non-small cell lung cancer

The treatment of non-small cell lung cancer is stage specific. Aggressive staging is associated with improved stage-specific prognosis. Available methods of surgical staging include scalene node biopsy, mediastinoscopy, anterior mediastinotomy, and thoracoscopy. In this article the various surgical staging methods are described and their respective roles are discussed.     

Preoperative chemotherapy for non-small cell lung cancer

Surgery has been considered the standard of care in patients with early-stage non-small cell lung cancer (NSCLC), as well as in some cases of stage III, for a long time. Poor survival after complete resection has led to the search for new therapeutic strategies such as combining anticancer treatments. However, at the present time, attempts to combine chemotherapy and radiotherapy after surgery have failed to show any significant impact on survival among patients with completely resected NSCLC.     

Second-line chemotherapy for non-small cell lung cancer

Several agents have been evaluated for the second-line treatment of patients with non-small cell lung cancer. The TAX 317 trial found that patients treated with docetaxel (Taxotere^®) 75 mg/m² had significantly longer survival than those treated with best supportive care alone. In addition, symptom control was better for patients who received chemotherapy. The TAX 320 trial found that treatment with docetaxel 75or 100 mg/m²resulted in significantly higher response rates than treatment with vinorelbine (Navelbine^®) or ifosfamide (Mitoxana^®), and the 1-year survival rate was also significantly better for patients treated with docetaxel 75 mg/m². A large randomized trial compared pemetrexed (LY-231514 or Alimta^®) 500 mg/m² with docetaxel 75 mg/m². Response and survival rates were similar in the two treatment arms, however, the toxicity profile of pemetrexed was superior to that of docetaxel with significantly less Grade 3/4 neutropenia and febrile neutropenia. Fewer patients in the pemetrexed arm required hospitalization. Topotecan (Hycamtin^®) 2.3 mg/m²/day orally for 5 days has been compared with docetaxel 75 mg/m²in a large 800-patient study. The results of this trial are awaited. Gemcitabine (Gemzar^®) and irinotecan (Campto^®) have been evaluated both as single agents and in combination with each other and study results do not suggest that either of these drugs is superior to docetaxel or pemetrexed. The vinca alkaloid vinorelbine has proved to be inferior to docetaxel in a randomized trial. The epidermal growth factor receptor inhibitors gefitinib (ZD1839, Iressa^®) and erlotinib (CP-358774, OSI 774, Tarceva^®) have been evaluated in Phase II trials in the second- and third-line setting. Both drugs have demonstrated interesting response rates ranging from 10 to almost 20%. The results of placebo-controlled randomized trials of this family of drugs are awaited. In summary, several studies have now found a definite role for the second-line treatment of patients with non-small cell lung cancer.     

Adjuvant chemotherapy for non-small cell lung cancer

Opinion statement Studies of adjuvant chemotherapy for non-small cell lung cancer (NSCLC) did not provide a consistent disease-free survival or overall survival benefit in the 1980s and early 1990s. However, recently reported studies have changed the practice of NSCLC treatment, for which adjuvant chemotherapy is now considered the standard of care. This review outlines the issues that may have limited the detection of beneficial effects of adjuvant chemotherapy in early trials and provides detailed analysis of the results of recently published trials of adjuvant chemotherapy for NSCLC.     

Targeted immunotherapy for non-small cell lung cancer

Targeted therapies that deliver the expected anti-tumor effects while mitigating the adverse effects are taking the cancer world by storm. The need for such therapies in non-small cell lung cancer (NSCLC), where systemic cytotoxic chemotherapies still remain the backbone of management, is felt more than ever before. Runway success of immunotherapies such as Ipilimumab for melanoma has brought excitement among oncologists. Immune-based treatments are in various stages of evaluation for NSCLC as well. Immunotherapies using strategies of antigen based or cell based vaccines, and blocking immune checkpoints are of substantial interest. Meaningful clinical responses are yet to be reaped from these new treatment modalities.     

Adjuvant chemotherapy for non-small cell lung cancer

Nearly half of all patients who undergo surgical resection of localized non-small cell lung cancer (NSCLC) will develop and ultimately die of recurrent disease. The postoperative radiotherapy (PORT) meta-analysis showed adjuvant thoracic radiotherapy to have a detrimental effect on survival in this patient population. A meta-analysis of early trials of adjuvant chemotherapy by the Non-Small Cell Lung Cancer Collaborative Group showed that while chemotherapy with alkylating agents was also detrimental, chemotherapy with cisplatin-based adjuvant chemotherapy was associated with an improved hazard ratio for death (HR = 0.87), equating to a 5 percent survival benefit at 5 years. However, the result was not statistically significant (p = 0.08). Recently, results have been reported for several large Phase III trials of adjuvant chemotherapy which differed with respect to the stage of resected disease included, the type of chemotherapy used and the use of post-operative radiotherapy. Three trials (IALT, JBR 10, and ANITA) that utilized cisplatin-based doublets showed a significantly positive survival benefit of adjuvant chemotherapy in patients with Stage II-IIIA NSCLC. The magnitude of this benefit, which was suggested to be 4-5 percent at 5 years in the meta-analysis and by the IALT study, may be as large as 8-15 percent as indicated by more recent studies with modern platinum-based doublet chemotherapy. These data indicate that medically fit patients with resected Stage II-IIIA NSCLC should be offered adjuvant chemotherapy with a modern cisplatin-based doublet.     

Hypofractionated irradiation for non-small cell lung cancer

Large radiation fractions are an effective way of killing tumour cells but have generally been avoided in curative treatment of patients because of concerns of a disproportionate increase in late normal tissue toxicity. Radiobiological modelling of the effect of radiation on lung tumours and late-reacting normal tissues, which are more sensitive to large radiation fractions, has been undertaken. The biological effect of radiation on tumours is increased as the overall treatment time is shortened but this is not true for late-reacting normal tissue. Sample data are shown in which the relative increases in radiation effect on the tumour and late-reacting normal tissues are similar after hypofractionation. A favourable therapeutic ratio can be achieved because the bulk of normal tissue will receive a lower dose of radiation at a lower dose per fraction than the tumour, especially with current techniques where the volume of normal tissue irradiated can be sharply reduced. The clinical evidence confirms that lung toxicity is volume-dependent. It is the small Stage I and II tumours which are most likely to benefit from hypofractionated regimens, as the volumes to be treated are smaller and they have a lower incidence of distant metastases. Patients with Stage III tumours with favourable prognostic factors are nowadays treated with combined chemotherapy and radiotherapy and so for this group more conservative hypofractionation regimens are being explored. However, more advanced tumours may be treated with hypofractionation to lower total doses to achieve palliation and a modest degree of survival benefit.     

Single-agent chemotherapy for non-small cell lung cancer

The survival and quality of life benefits of combination chemotherapy in patients with non-small cell lung cancer (NSCLC) are now well recognized. Since many clinical trials have been conducted in relatively young patients with good performance status, many elderly patients and patients with poor performance status are not offered chemotherapy because of concerns about higher risks of toxicity. The newer agents, including topotecan, are active as single agents in NSCLC, achieving response rates of up to 30%. Overall survival and symptoms may be improved when these agents are added to best supportive care. They are well tolerated in both elderly patients and patients with poor performance status. The major toxicity with the standard 5-day administration schedule of topotecan is myelosuppression, but weekly schedules may offer reduced toxicity while maintaining efficacy. Thus, single-agent therapy with newer agents is generally considered in elderly and poor performance status patients. However, combination chemotherapy may also be appropriate for some patients in these subgroups. Future studies of chemotherapy in NSCLC should not exclude elderly patients and patients with poor performance status.     

Adjuvant immunotherapy for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the biggest cancer killer in the United States and worldwide. In 2011, there are estimated to be 221,130 new cases of lung cancer in the United States. Over a million people will die of lung cancer worldwide this year alone. When possible, surgery to remove the tumor is the best treatment strategy for patients with NSCLC. However, even with adjuvant (postoperative) chemotherapy and radiation, more than 40% of patients will develop recurrences locally or systemically and ultimately succumb to their disease. Thus, there is an urgent need for developing superior approaches to treat patients who undergo surgery for NSCLC to eliminate residual disease that is likely responsible for these recurrences. Our group and others have been interested in using immunotherapy to augment the efficacy of current treatment strategies. Immunotherapy is very effective against minimal disease burden and small deposits of tumor cells that are accessible by the circulating immune cells. Therefore, this strategy may be ideally suited as an adjunct to surgery to seek and destroy microscopic tumor deposits that remain after surgery. This review describes the mechanistic underpinnings of immunotherapy and how it is currently being used to target residual disease and prevent postoperative recurrences after pulmonary resection in NSCLC.     

Gefitinib therapy for non-small cell lung cancer

Opinion statement Gefitinib is a small molecule that specifically inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) type 1 by interfering with the adenosine triphosphate (ATP) binding site. At doses that maximally inhibit EGFR tyrosine kinase activity chosen for phase II trials, the most common side effects of gefitinib are low-grade rash or diarrhea. An infrequent but serious side effect of gefitinib is interstitial lung disease (ILD). The Iressa dose evaluation for advanced lung cancer phase II trials (IDEAL 1 and IDEAL 2) of single agent gefitinib, 250 or 500 mg orally per day in pretreated patients with non-small cell lung cancer (NSCLC), found about 20% of patients on IDEAL-1 and 10% of patients on IDEAL-2 had major objective responses and improvement of symptoms. The data from the IDEAL trials and the extensive experience from the 21,000 patients treated on the expanded access program, suggests that the patients who have a major objective response probably have a significant survival benefit in addition to palliative benefit. In addition, approximately 40% of patients on the IDEAL trials experienced improvement in symptoms. Gefitinib was approved for third line treatment of NSCLC. Gefitinib is effective, safe, and well-tolerated single-agent therapy in previously treated NSCLC. Although there have been no direct comparisons, the small molecule inhibitors of EGFR gefitinib and erlotinib appear to have similar efficacy. Erlotinib has been shown to produce a survival advantage compared to best supportive care in an unselected group of previously treated patients with NSCLC. Until similar trials are completed comparing gefitinib to best supportive care, there is a similar survival advantage for gefitinib. Nonsmokers, women, and patients with adenocarcinoma, are more likely to have major objective responses than other patients. Bronchioalveolar lung cancer is a subtype of NSCLC that is more likely to respond to gefitinib. Several groups have now reported that most, but not all, tumors experiencing a major objective response to gefitinib have mutations associated with the ATP-binding site of EGFR. It is reasonable to move gefitinib in to second-line therapy for patients who are known to have a tumor that is more likely to respond to gefitinib. Also, I would treat such patients with gefitinib as first-line therapy on an appropriate clinical trial approved by the Institutional Review Board (IRB). Outside of a clinical trial, patients with advanced disease should initially be treated with a combination of doublet chemotherapy. There is strong evidence that there is no benefit to concurrent chemotherapy and gefitinib. Gefitinib should not be given concurrently with cytotoxic chemotherapy as initial treatment for NSCLC. Sequential therapy combining chemotherapy and gefitinib in advanced disease or as adjuvant therapy should only be done in the context of a clinical trial approved by the IRB. There is preclinical evidence suggesting that gefitinib is a radiosensitizer. Early results from trials combining radiation, or chemoradiotherapy with gefitinib have shown that these combinations are without excessive additive toxicity. There is no proven clinical benefit for concurrent Gefitinib and radiation. Gefitinib should only be given with radiation as part of an appropriate clinical trial approved by the IRB.     

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.     

局部晚期非小细胞肺癌的同步放化疗

局部晚期非小细胞肺癌(NSCLC)非手术治疗的标准手段为同步放化疗.同步放化疗中常用的化疗方案有EP方案、NP方案、DC方案及PC方案.新药联合方案及靶向治疗目前仍处于研究阶段.老年患者的耐受性下降,但并非同步放化疗的绝对禁忌人群.超分割及高剂量放疗虽然耐受性尚可,但其有效性及远期不良反应仍需进一步研究和评估.     

PET-CT影像引导非小细胞肺癌的放射治疗

CT等解剖影像在非小细胞肺癌(non-small cell lung cancer,NSCLC)影像引导放射治疗(image guided radiotherapy,IGRT)的靶区确定中发挥着重要作用,但在原发肿瘤范围的界定、区域淋巴结转移的判断及远处转移的发现等方面仍然存在局限性.以PET为代表的功能影像在NSCLC原发肿瘤范围的界定、区域淋巴结转移的判断、远处转移的发现及疗效预测等方面优于CT等解剖影像[1-2].作为同机融合的PET-CT,不仅具备了功能与解剖影像融合的特点,还可减少传统融合中的匹配误差.因此,PET-CT在NSCLC的靶区确定、计划制定和靶区修正等影像引导方面都会发挥更为重要的作用.