Non-surgical therapy for the patients with advanced non-small cell lung cancer

Abstract Radiation therapy (RT) and chemotherapy have been the two main treatment modalities for advanced non-small cell lung cancer (NSCLC). New techniques in RT, including hyperfractination and 3-dimensional conformal RT (3-DCRT), have changed conventional RT, which has been regarded as standard modality for locally advanced NSCLC. Introduction of cisplatin into chemotherapeutic regimens for NSCLC has changed the status of chemotherapy to standard therapy for patients with stage IV or stage IIIb with effusion. Radiation therapy or chemotherapy alone have already showed their limitations, even although they could improve the survival of NSCLC patients. Combined treatments with these two have become powerful alternatives for patients with unresectable and locally advanced NSCLC. Sequential or concurrent chemoradiotherapy could improve the response rate and survival rate without a remarkable increase in toxicities. Gene therapy is a novel therapeutic approach based on molecular oncology and tumour immunology. The practical contribution of gene therapy to clinical oncology is still minimal. From the research data, gene therapy has shown its potential to become a new treatment modality or to lead us to as yet undiscovered novel approaches to the treatment of lung cancer.     

The relative survival of COPD patients on long-term oxygen therapy in Australia: A comparative study

OBJECTIVE: The survival of patients with COPD on long-term oxygen therapy (LTOT) has been studied using both univariate and multivariate procedures. There has been only one previous report of relative survival. Relative survival takes into account the risk of death due to increasing age. The objective of this study was to determine the relative survival of a group of South Australian patients prescribed home oxygen therapy for COPD. METHODOLOGY: A method proposed by Hakulinen was used to determine relative survival. The results were compared with the relative survival of a similar group of French COPD patients. RESULTS: A total of 505 COPD patients (249 males, 256 females) were included in the survival analysis. Relative survival corrected for life expectancy was 78.1%, 56.7%, 23.1% and 1.1% at 1, 2, 5 and 10 years, respectively, which was less than that reported in a recent French study of comparable patients. Our patients were similar with respect to age, severity of hypoxaemia and oxygen usage to those in the French study. CONCLUSIONS: Using relative survival analysis, Australian LTOT patients with COPD have worse outcomes than some European patients. Factors contributing to the excess mortality in South Australian COPD patients need to be investigated.     

血栓弹力图在晚期肺癌初诊患者凝血功能状态评估中的应用

目的 探讨血栓弹力图（TEG）在晚期肺癌初诊患者凝血功能状态评估中的应用价值。方法回顾性分析90例晚期肺癌初诊患者的血栓弹力图和常规凝血功能检测结果,比较两种检测方法对凝血功能异常检出的差异。结果经TEG检测发现38例（42.2%）患者存在凝血功能异常,经常规凝血功能检测方法发现85例（94.4%）患者存在凝血功能异常,两种检测方法对晚期肺癌初诊患者凝血功能异常检出率的差异有显著统计学意义（P〈0.01）。结论晚期肺癌患者经TEG检测存在高凝状态的比例低于常规凝血功能检测结果。     

Tailored therapy in lung cancer

Historically, all non-small cell lung cancers were essentially grouped together and considered to be a single disease. However, it is now recognized that non-small cell lung cancer actually comprises a genetically diverse group of tumours. This, in turn, affords a new opportunity for the development of effective treatments tailored to individual tumours and patients. Advances in molecular biology have made possible the development of drugs against specific molecular targets on cancer cells, most notably the tyrosine kinase inhibitors. The relevant literature and current practice guidelines are discussed. In addition, other related areas of active investigation, including tumour vaccines and pharmacogenetics, are briefly reviewed.     

Identifying an optimum treatment strategy for patients with advanced non-small cell lung cancer

Owing to the slow but sustained progress made in lung cancer treatment over the last 20 years, several therapeutic options are now available in the first-line setting as well as for patients who have progressed after one or more previous lines of treatment. Considering the growing array of choices currently confronting clinicians involved in the treatment of advanced non-small cell lung cancer (NSCLC), an effort should be made to define the optimal treatment option in each disease setting and to identify a logical therapeutic strategy after initial disease progression. This is especially crucial in the management of young, fit patients, who may be suitable candidates for two or more lines of therapy. At present, a rational treatment strategy for advanced NSCLC may be designed on the basis of patient clinicopathological features and rely on evidence from large, well-conducted clinical trials. In a near future the results of prospective validation studies will provide more sophisticated approaches for the classification of lung cancer patients, allowing clinicians to make individualised treatment decisions based on tumour molecular profile and on novel, more refined predictive/prognostic factors.     

Non-surgical therapy for patients with advanced non-small cell lung cancer

Abstract Non-small cell lung cancer is the major cancer problem in the Western World. Treatment and prognosis are highly stage dependent, although overall only 5–10% of patients will be alive 5 years after diagnosis. Patients with early stage disease are treated with surgery alone. However, for patients with locally advanced disease there is increasing evidence that combined modality approaches, incorporating chemotherapy, radiotherapy and/or surgery result in modest improvements in survival. For patients with metastatic non-small cell lung cancer there is evidence from metaanalyses and randomised studies that chemotherapy results in improvements in both duration and quality of life. Despite these advances, there is substantial room for further improvement and therefore, wherever possible, patients should be enrolled in well designed clinical studies.     

Proton beam radiotherapy for patients with early-stage and advanced lung cancer: a narrative review with contemporary clinical recommendations

Although lung cancer rates are decreasing nationally, lung cancer remains the leading cause of cancer related death. Despite advancements in treatment and technology, overall survival (OS) for lung cancer remains poor. Proton beam therapy (PBT) is an advanced radiation therapy (RT) modality for treatment of lung cancer with the potential to achieve dose escalation to tumor while sparing critical structures due to higher target conformality. In early and late-stage non-small cell lung cancer (NSCLC), dosimetric studies demonstrated reduced doses to organs at risk (OARs) such as the lung, spinal cord, and heart, and clinical studies report limited toxicities with PBT, including hypofractionated regimens. In limited-stage SCLC, studies showed that regimens chemo RT including PBT were well tolerated, which may help optimize clinical outcomes. Improved toxicity profiles may be beneficial in post-operative radiotherapy, for which initial dosimetric and clinical data are encouraging. Sparing of OARs may also increase the proportion of patients able to complete reirradiation for recurrent disease. However, there are various challenges of using PBT including a higher financial burden on healthcare and limited data supporting its cost-effectiveness. Further studies are needed to identify subgroups that benefit from PBT based on prognostic factors, and to evaluate PBT combined with immunotherapy, in order to elucidate the benefit that PBT may offer future lung cancer patients.     

家庭氧疗对COPD患者肺功能影响研究

目的 探讨不同临床分级慢性阻塞性肺疾病（COPD）患者经过长期家庭氧疗（LTOT）后肺功能变化情况.方法 选取220例COPD患者按照肺功能分级不同分为四组,所有患者均进行长期家庭氧疗,四年后复测所有患者的肺功能及相关生化、动脉血气指标.结果 四年后肺功能I、Ⅱ级患者的FEV1、FEV1/FVC%、FEV1%预计值及日间SaO2有下降趋势,且有统计学意义（P＜0.05）.而在肺功能Ⅲ、Ⅳ级患者中上述指标然也有下降趋势,但这种趋势无统计学差异.结论长期家庭氧疗对于所有COPD患者均有益处,尤其对于肺功能Ⅲ、Ⅳ级患者其延缓肺功能恶化的作用更为显著.     

晚期非小细胞肺癌化疗的若干问题

肺癌的发生率和病死率均占据恶性肿瘤之首。手术、放疗和化疗仍然是现阶段治疗肺癌的主要手段,而分子靶向治疗的出现则使肺癌治疗观念和模式发生了革命性的变革。基于分子生物标志物的个体化综合治疗策略有望延长肺癌患者的生存期。但现阶段,化疗仍然是治疗晚期非小细胞肺癌患者的基石,这需贯彻"三结合"辩证施治方针,即全身结合局部、常规结合个体、祛邪结合扶正。     

Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG-ps) in patients receiving palliative chemotherapy for gastroesophageal cancer

Aim:  The aim of the present study was to compare an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) with performance status (ECOG-ps) in patients receiving platinum-based chemotherapy for palliation of gastroesophageal cancer.
Methods:  Sixty-five patients presenting with gastroesophageal carcinoma to the Royal Infirmary, Glasgow between January 1999 and December 2005 and who received palliative chemotherapy or chemo-radiotherapy were studied. ECOG-ps, C-reactive protein, and albumin were recorded at diagnosis. Patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS of 1 and patients with a normal C-reactive protein and albumin were allocated a score of 0. Toxicity was recorded using the Common Toxicity Criteria.
Results:  The minimum follow up was 14 months. During the follow-up period, 59 (91%) of the patients died. On univariate and multivariate survival analysis, only the GPS (hazard ratios 1.65, 95% CI 1.10–2.47, P  < 0.05) was a significant independent predictor of cancer survival. In addition, in comparison with patients with GPS of 0, those patients with a GPS of 1 or 2 required more frequent chemotherapy dose reduction ( P  < 0.05), were less likely to exhibit a clinical response to treatment ( P  < 0.05), and had shorter survival ( P  < 0.05).
Conclusion:  The presence of a systemic inflammatory response, as evidenced by the GPS, appears to be superior to the subjective assessment of performance status (ECOG-ps) in predicting the response to platinum-based chemotherapy in patients with advanced gastroesophageal cancer.     

吉非替尼治疗晚期非小细胞肺癌的临床观察

目的 观察吉非替尼单药治疗晚期非小细胞肺癌的疗效与不良反应.方法 24例Ⅲ～Ⅳ期非小细胞肺癌患者口服吉非替尼(易瑞沙)250 mg/d,1次顿服,不限疗程,直至出现严重不良反应或因经济问题或死亡而终止.观察临床症状改善情况、不良反应,通过CT扫描判断疗效.结果 24例患者中完全缓解2例,部分缓解12例,稳定6例,进展4例,有效率为58.3%,疾病控制率为83.3%,主要不良反应为腹泻.结论 吉非替尼应用于放、化疗失败或不能耐受放、化疗的非小细胞肺癌患者是安全的,患者耐受性好.     

Factors associated with long-term survival of patients with advanced non-small cell lung cancer

Background and objective: Only a small proportion of patients with advanced non‐small cell lung cancer (NSCLC) have a life expectancy greater than 2 years. The aim of this study was to identify the factors associated with long‐term survival of patients with advanced NSCLC. Methods: Patients who had received chemotherapy for stage IIIb or IV NSCLC that was not amenable to radiotherapy were studied retrospectively. Data were gathered prospectively from a comprehensive database. Long‐term survivors (>2 years) were compared with the other patients, with respect to clinical, biological and tumour–node–metastasis criteria. Results: Data for 245 consecutive patients were collected. Thirty nine patients (15.9%) survived for more than 2 years. Long‐term survivors were more likely to have had metastases at fewer sites (P = 0.008), an absence of bone metastases (P = 0.01), a performance status (PS) of 0–1 at first progression of the tumour (P = 0.002), a tumour that was controlled with first (P < 0.0001) and second‐line (P = 0.004) chemotherapy, maintenance therapy (P = 0.001), curative surgery (P < 0.0001), time to first progression of the tumour of >3 months (P < 0.0001), normal LDH levels at diagnosis (P = 0.049), and a haemoglobin concentration >110 g/L at first progression of the tumour (P = 0.02). In multivariate analysis, surgery, maintenance treatment, time to first progression of the tumour of >3 months, a PS of 0–1 at first progression, the number of chemotherapy agents received, and LDH levels, were significant predictors of long‐term survival. Conclusions: Assessment of these factors, and the use of maintenance therapy, when possible, may identify a population of patients with NSCLC that is likely to have a prolonged life expectancy.     

肺癌综合治疗的选择

肺癌患者在确诊时绝大多数已属晚期，应用现有的任何一种治疗均不能获得满意疗效。应根据每位患者的不同情况，有计划地进行综合治疗。目前，肺癌的综合治疗已形成了一些较为成熟的模式，可显著提高肺癌5年生存率。不断涌现的新技术及新药为肺癌的综合治疗提供了更多，更好的选择。     

洛铂联合足叶乙甙治疗晚期小细胞肺癌的临床研究

目的观察评价新一代铂类抗癌药物洛铂（LBP）联合足叶乙甙（VP-16）组成的LE方案治疗晚期小细胞肺癌（SCLC）的有效性和安全性。方法26例经病理组织学和／或细胞学检查确诊SCLC,均为初治患者,其中男性22例,女性4例;年龄42～74岁,中位年龄61岁,TNM分期：ⅢA11例,ⅢB6例,Ⅳ期9例。应用LE方案,即LBP30mg／m^2静滴d1;VP-16100mg静滴d1～5;21～28d为一周期,至少接受2个周期化疗。按照WHO标准评价客观疗效和毒性。结果26例患者中,可评价疗效的患者有25例。其中CR3／25,PR20／25,NC2／25,有效率（RR）92．0％。主要毒性反应为可逆性的骨髓抑制和胃肠道反应。结论LBP联合VP-16组成LE方案治疗SCLC疗效好,毒性反应可以耐受,值得进一步研究观察。     

埃克替尼联合放疗治疗晚期非小细胞肺癌的研究进展

研究证实埃克替尼治疗表皮生长因子受体突变的非小细胞肺癌(NSCLC)患者疗效明确,并具有放疗增敏效果。国内有大量的研究表明埃克替尼联合放疗能显著提高NSCLC患者生存时间,特别是对老年患者或脑转移患者,且不良反应较小。因此,埃克替尼联合放疗有可能成为治疗晚期NSCLC患者的有效治疗手段。现对其相关研究进展作一综述。     

Immune checkpoint inhibitors combined with chemotherapy/bevacizumab therapy for patients with advanced lung cancer and heavily treated with EGFR mutation: a retrospective analysis

BackgroundEGFR-mutated lung cancer poorly responded to anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy. Whether patients with EGFR-mutated lung cancer can benefit from anti-PD-1/PD-L1 therapy combined with other drugs remains controversial. We retrospectively evaluated the safety and efficacy of the PD-1 inhibitor combined with other drugs (chemotherapy and/or bevacizumab) in patients with EGFR-mutated lung cancer, who have progressed on EGFR–TKI treatment to determine the activity of the anti-PD-1/PD-L1 therapy combined with chemotherapy or/and bevacizumab therapy in heavily treated patients with EGFR-mutated lung cancer.MethodsWe identified 56 patients with EGFR-mutated lung cancer treated with PD-1/PD-L1 inhibitors alone or combined with the chemotherapy/bevacizumab therapy. The objective response rates were assessed using RECIST v1.1. Adverse events (AEs) were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Academic Ethics Committee of Jiangsu Cancer Hospital. (NO. 2019 160), and individual consent for this retrospective analysis was waived.ResultsObjective responses were observed in 6 of 56 (10.7%) patients, and the disease control rate was 53.6% (30/56). The median progression-free survival (PFS) was 3.33 months with 95% CI of 1.58–5.08 months. No patient achieved a complete response. All six patients that achieved PR were treated with the PD-1 inhibitor combined with chemotherapy or bevacizumab therapy. Three of the six patients who achieved PR were treated with radiotherapy combined with PD-1 inhibitor-based therapy. Patients treated with the PD-1 inhibitor-based therapy as second-line therapy showed relatively longer PFS and higher objective response rates than those treated with PD-1 inhibitor-based therapy as third- or late-line therapy (PFS: 5.50 vs. 3.27 months, P=0.301; objective response rates: 25.0% vs. 6.82%, P=0.071). No additional AE profile was observed.ConclusionsThe PD-1 inhibitor combined with the chemotherapy/bevacizumab therapy showed acceptable toxicity profile and moderate efficacy on heavily treated advanced EGFR-mutated lung cancer after the exhaustion of target therapy.     

肺癌合并静脉血栓栓塞症的风险评估

静脉血栓栓塞症(venous thromboembolism,VTE)是癌症常见的并发症和最常见的死亡原因之一,主要包括深静脉血栓栓塞症和肺血栓栓塞症.近年来,随着血栓栓塞性疾病研究的深入,肺癌相关性VTE已引起关注.其中,肺癌患者的预防性抗凝治疗具有很大争议性.初级预防能使肺癌相关性VTE发生风险减少,但相关研究同时提示患者出血风险提高.目前尚不推荐对肺癌患者进行常规抗凝,但对血栓风险高、出血风险低的肺癌患者进行选择性抗凝可使其获益.因此,肺癌相关性VTE的风险评估和分级可提高预防性抗凝的临床获益,减少相关出血事件.