Impact of symptom burden in post-surgical non-small cell lung cancer survivors

Purpose

Pain, fatigue, dyspnea, and distress are commonly reported cancer-related symptoms, but few studies have examined the effects of multiple concurrent symptoms in longer-term cancer survivors. We examined the impact of varying degrees of symptom burden on health-related quality of life (HRQOL) and performance status in surgically treated non-small cell lung cancer (NSCLC) survivors.

Methods

A sample of 183 NSCLC survivors 1–6 years post-surgical treatment completed questionnaires assessing five specific symptoms (pain, fatigue, dyspnea, depression, and anxiety), HRQOL, and performance status. The number of concurrent clinically significant symptoms was calculated as an indicator of symptom burden.

Results

Most survivors (79.8 %) had some degree of symptom burden, with 30.6 % reporting one clinically significant symptom, 27.9 % reporting two symptoms, and 21.3 % reporting three or more symptoms. Physical HRQOL significantly decreased as the degree of symptom burden increased, but mental HRQOL was only significantly decreased in those with three or more symptoms. Receiver-operating characteristic (ROC) curves showed that having multiple concurrent symptoms (two or more) was most likely associated with limitations in functioning (area under a ROC curve?=?0.75, sensitivity?=?0.81, specificity?=?0.54).

Conclusions

Two or more clinically significant symptoms are identified as the “tipping point” for showing adverse effects on HRQOL and functioning. This highlights the need for incorporating multiple-symptom assessment into routine clinical practice. Comprehensive symptom management remains an important target of intervention for improved post-treatment HRQOL and functioning among lung cancer survivors.     

The symptom burden of patients with hematological malignancy: a cross-sectional observational study

Context

Current literature suggests that contact with specialist palliative care for patients diagnosed with hematological malignancy is infrequent. As part of an investigation into patterns of care, the symptom profile of this patient group required elucidation.

Objectives

The purpose of this study was to determine the patterns of symptoms and level of distress in patients diagnosed with a hematological malignancy.

Methods

One hundred eighty patients diagnosed with a hematological malignancy attending a tertiary referral hospital completed the Memorial Symptom Assessment Scale-Short Form. Comparisons were made to published symptom prevalence studies of those with nonhematological malignancies.

Results

Patients with hematological malignancy had a considerable physical and psychological symptom burden, with an overall mean of 8.8 (±5.9) symptoms. The mean number of symptoms was significantly greater in those on treatment (P < 0.05), those with poorer performance status (P < 0.001), inpatients (P < 0.01), and those with a more advanced disease stage (P < 0.001) than their respective counterparts. Symptom prevalence ranged from 69% for fatigue to 9% for vomiting. Global, physical, and psychological distress scores were high and varied significantly according to disease stage, Eastern Cooperative Oncology Group status, and patient location. The mean number of symptoms and level of distress were comparable to those patients with metastatic nonhematological malignancy.

Conclusion

Patients with hematological malignancy are likely to have symptom control needs similar to those with metastatic cancer. Because such symptom burden appears to affect those at all phases of illness, comprehensive symptom assessment is suggested throughout. The introduction of palliative care services during times of increased symptom burden may assist hematologists and other carers in the management of their patients’ distress and quality of life.     

同步放化疗治疗非小细胞肺癌的临床研究

目的观察同步放化疗治疗非小细胞肺癌的疗效及毒性反应。方法 32例Ⅱ~Ⅲb期非小细胞肺癌患者接受同步放化疗。6MVX线加速器常规分割放射治疗,2 Gy/次,5次/周,总计量为60~66 Gy(6~7周)。放疗开始后同步进行EP方案:VP-16 100 mg/m2,第1~3天;DDP 30 mg/m2,第1~3天,3周为1个周期,共化疗4个周期。结果近期有效率为84.38%,1年生存率为68.75%。主要的毒副反应为骨髓抑制(71.88%),胃肠道反应(75.00%),放射性食管炎(56.25%)和放射性肺炎(21.88%)。结论 EP方案同步放疗治疗非小细胞肺癌疗效确切,毒副反应可耐受,值得在临床上进一步推广。     

Updates in non-small cell lung cancer

Lung cancer is the leading cause of cancer death in both men and women. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing more than 80% of lung cancer diagnoses. Five-year survival remains at 15%, but new strategies for prevention, early detection, and treatment may improve survival rates. This article provides an overview of updates in NSCLC, with an emphasis on advances in treatment strategies. Newer targeted therapies, as well as advances in genetic blueprinting, will be discussed. Nurses play a pivotal role in the assessment and management of patients with NSCLC and, therefore, must remain abreast of the most current prevention, screening, and treatment options.     

Independent prognostic value of whole-body metabolic tumor burden from FDG-PET in non-small cell lung cancer

Purpose

To determine whether whole-body metabolic tumor burden, measured as either metabolic tumor volume (MTV_WB) or total lesion glycolysis (TLG_WB), using FDG-PET/CT is an independent prognostic marker in non-small cell lung cancer (NSCLC).

Methods

328 patients with histologically proven NSCLC were identified for this retrospective analysis. This study was approved by our Institutional Review Board. All patients underwent baseline ¹⁸F-FDG-PET/CT scan imaging before therapy. The MTV_WB, TLG_WB, maximum standardized uptake value (SUV_maxWB) and mean standardized uptake value (SUV_meanWB) of tumors throughout the whole body were measured from FDG-PET images with semi-automated 3D contouring software.

Results

In univariate analysis, there was a statistically significant association of overall survival (OS) with the MTV_WB (hazard ratio (HR) = 1.62, p < 0.001), TLG_WB (HR = 1.47, p < 0.001). The patients with a MTV_WB ≤ median of 65.7 ml and TLG_WB ≤ median of 205.11 SUV_mean * ml had a median OS of 41.1 and 35.4 months compared with 9.5 and 9.7 months for those with a MTV_WB > 65.7 ml and TLG_WB > 205.11 SUV_mean * ml, respectively. From a series of multivariate Cox regression models, the MTV_WB and TLG_WB were significantly better than SUV_maxWB and SUV_meanWB at prognostication and significantly associated with patients’ OS with HRs of 1.50 (p < 0.001) and 1.42 (p < 0.001), respectively, after adjustment for patient’s age, gender and treatment intent as well as the tumor SUV_maxWB, histology and stage.

Conclusions

MTV_WB and TLG_WB as metabolic tumor burden measurements in ¹⁸F-FDG-PET/CT are independent prognostic markers and are significantly better than SUV_maxWB and SUV_meanWB at prognostication.     

Cetuximab in non-small cell lung cancer

Advanced non-small cell lung carcinoma (NSCLC) remains a challenge to treat due to its high local and systemic recurrence. The overall survival remains poor despite the approval of several new chemotherapeutic agents in the management of advanced NSCLC. Overexpression or mutations in the EGFR have been shown to be associated with a significant percentage of NSCLC. The development of targeted agents, such as cetuximab, against the EGFR is therefore a rational objective. Several preclinical and clinical studies suggest that cetuximab is active against NSCLC. This paper reviews the application of cetuximab in NSCLC.     

肺癌分子分期的循证医学研究

目的 评估常见的非小细胞肺癌(NSCLC)基因标记物与NSCLC预后的关系,在TNM分期的基础上,进行分子分期,提供有预见性、针对性的个性化量体裁衣式的治疗方案.方法 计算机检索PubMed、Ovid.Cochrane library online,查找与NSCLC预后有关的基因标记物的临床随机对照试验、系统评价、Meta分析等,循证评价检索得到的相关文献.结果 检索到原始文献83篇,相关参考文献266篇.在NSCLC中检测p53突变率为45%~75%.p53基因突变在Ⅰ～Ⅳ期NSCLC中现提示预后不良,尤其对Ⅰ期腺癌患者预后意义更强;K-ras在NSCLC中突变率 15%~50%.对于各期NSCLC中的腺癌,应用PCR方法 检测到K-ras突变,提示预后不良;血管内皮生长因子(VEGF)在NSCLC中表达率为66%～72%.VEGF是NSCLC的不良预后因素;Cyclin E在NSCLC中表达率为41%～53%.cyclin E高表达与NSCLC预后不良相关,尤其是Ⅰ～Ⅱ期肺腺癌更有意义;Survivin在NSCLC中表达率为40%～85%.Survivin在Ⅰ～ⅢA期NSCLC高表达提示患者预后不良,且对鳞癌的预后意义更大.结论 将p53.K-ras.VEGF.Survivin.Cyclin E组成一个分子分期模型系统进行分子分期是切实可行的.     

免疫化学联合疗法治疗中晚期非小细胞肺癌的Meta分析

目的：系统评价树突状细胞共培养细胞因子诱导的杀伤细胞（Dendritic cell-cytokine-induced killer cell, DC-CIK）联合化疗治疗中晚期非小细胞肺癌（Non-Small Cell Lung Cancer,NSCLC）的临床疗效及安全性,同时评价患者的生存质量及免疫功能。方法计算机检索 PubMed、Cochrane Library、CNKI、维普和万方数据库,并辅手工检索,收集所有DC-CIK联合化疗与单纯化疗治疗中晚期 NSCLC的随机对照试验（randomized controlled trials,RCT）。结合研究特点对纳入研究进行质量评价后,采用 RevMan 5．2和 Stata 12．0软件分别进行 Meta分析和发表偏倚分析。结果共纳入11个 RCT,769例患者。Meta分析结果显示,与单纯化疗组比较,DC-CIK联合化疗组生存率（overall survival,OS）、临床疗效[客观反应率（obj ective response rate,ORR）及疾病控制率（disease control rate,DCR）]、生存质量[Karnofsky（KPS）评分提高率]及免疫功能（治疗后血清中T淋巴细胞亚型CD3＋、CD4＋与CD4＋／CD8＋）均有所提高,且差异有统计学意义;两组在安全性（骨髓抑制、消化道反应与肝肾功能损害发生率）方面的差异无统计学意义。生存率和临床疗效观察指标显示无发表偏倚。结论在中晚期 NSCLC治疗中,与单纯化疗比较,DC-CIK联合化疗能提高生存率和临床疗效,未增加严重的不良反应,同时有改善患者生活质量和免疫功能的趋势。     

厄洛替尼治疗非小细胞肺癌的系统评价

目的 评价厄洛替尼治疗非小细胞肺癌的效果和安全性.方法 采用Cochrane系统评价方法,检索Cochrane图书馆、MEDLINE、VIP、CNKI、CBM disc等电子资料库.由2名评价者共同评价纳入研究质量,对同质研究进行Meta分析.结果 共纳入6个随机对照研究、3184例非小细胞肺癌患者.纳入的6个研究均表明采用了随机的方法,1个研究实施了切实有效的盲法,所有研究未提及分配隐藏,所有纳入研究均进行ITT意向性分析;Meta分析显示厄洛替尼联合化疗的反应率[OR 1.10,95%CI(0.91～1.34)]、1年生存率[OR 1.04,95%CI(0.88～1.24)]均无统计学意义,厄洛替尼单药口服显示出生存优势,中位无进展生存期、中位生存期分别为2.2个月和6.7个月(P<0.001).结论 现有研究结果显示厄洛替尼是一种有效安全的靶向抗肿瘤药物,但由于纳入研究存在选择性偏倚和测量性偏倚的可能性,势必影响结果的强度.     

The development of immunotherapies for non-small cell lung cancer

Standard of care for non-small cell lung cancer (NSCLC) (surgery, chemotherapy and radiation) may enhance patient survival but the enhancement is typically transient and quite uncommon with advanced disease. Researchers and medical professionals are using new approaches to improve patient mortality and morbidity. One of these approaches, immunotherapy, seeks to stimulate antitumour immunity above a threshold level needed for tumour regression or to induce stability in the face of progression. Among the most established approaches are vaccines involving monoclonal antibodies (mAbs) or immune effector cells. These approaches stimulate the humoral and cell-mediated arms of the immune system, respectively. As the development of humanised or fully human antibodies has spurred exploration of radioimmunoconjugates and immunotoxins, mAbs have enjoyed a revival of sorts. Cell-based therapies using the tumour cell itself as a vaccine component has resulted in disease stabilisation or regression. In addition, immune cells (e.g., T-lymphocytes and dendritic cells [DCs]) are the focal point of numerous patient trials in which meaningful clinical impact was achieved. In general, there are many tactics under development for the treatment of NSCLC. This review primarily concerns immunotherapeutic cancer treatments that are either already in clinical trial or well progressed into preclinical studies.     

吉非替尼治疗晚期非小细胞肺癌疗效分析

目的观察吉非替尼对晚期非小细胞肺癌患者的疗效。方法对吉非替尼治疗的非小细胞肺癌22例进行分析。结果22例中可评估的14例中(5例疾病稳定,2例完全缓解,1例部分缓解)有效率21.4%,临床获益率8/14(57.2%)。结论吉非替尼对晚期非小细胞肺癌疗效较好,其副反应相对小,耐受性好。     

The development of immunotherapies for non-small cell lung cancer

Standard of care for non-small cell lung cancer (NSCLC) (surgery, chemotherapy and radiation) may enhance patient survival but the enhancement is typically transient and quite uncommon with advanced disease. Researchers and medical professionals are using new approaches to improve patient mortality and morbidity. One of these approaches, immunotherapy, seeks to stimulate antitumour immunity above a threshold level needed for tumour regression or to induce stability in the face of progression. Among the most established approaches are vaccines involving monoclonal antibodies (mAbs) or immune effector cells. These approaches stimulate the humoral and cell-mediated arms of the immune system, respectively. As the development of humanised or fully human antibodies has spurred exploration of radioimmunoconjugates and immunotoxins, mAbs have enjoyed a revival of sorts. Cell-based therapies using the tumour cell itself as a vaccine component has resulted in disease stabilisation or regression. In addition, immune cells (e.g., T-lymphocytes and dendritic cells [DCs]) are the focal point of numerous patient trials in which meaningful clinical impact was achieved. In general, there are many tactics under development for the treatment of NSCLC. This review primarily concerns immunotherapeutic cancer treatments that are either already in clinical trial or well progressed into preclinical studies.     

Emepepimut-S for non-small cell lung cancer

Introduction: Immunotherapy as a possible therapeutic option for cancer has been of great importance due to the innovative development of vaccines. Various molecules have been tested and emepepimut-S (Biomira Liposomal Peptide 25 (BLP 25)) has emerged as an option, particularly in lung cancer.

Areas covered: A PubMed literature and ClinicalTrials.gov search was conducted using the terms: emepepimut, BLP25, NSCLC, cancer immunotherapy, cancer vaccine and MUC1. This review covers how emepepimut-S acts against the mucin 1 (MUC1) tumor-associated antigen producing a cellular immune response against the cells that express MUC1 and the most important clinical data available that led to the ongoing Phase III trial.

Expert opinion: The results obtained in the Phase I/II trials are promising, showing a favorable toxicity with a benefit in survival in NSCLC patients. As future trials develop, demonstration of the long-term survival benefit, understanding of the various mechanisms of immune response initiated by the drug and the selection of patients that will highly benefit from the immunotherapy will be elucidated. The safety and extension in survival makes emepepimut-S a very interesting drug and could, therefore, offer a possibility of treatment and maintenance, particularly for good performance status patients with locally advanced NSCLC.     

Adjuvant chemotherapy in non-small cell lung cancer

Adjuvant chemotherapy is considered a standard of care for many malignancies, the most well known being breast and colon cancer. Unfortunately, less than a third of patients with non-small cell lung cancer (NSCLC) present with resectable disease and despite resection outcomes are often poor with a median 5-year survival of 40-50%. Modern chemotherapy for NSCLC provides both a survival advantage and an improvement in quality of life in the palliative setting. Several large studies using modern platinum-based regimens have been presented since the 1995 meta-analysis. This demonstrated a nonsignificant benefit for older platinum-based regiments. These studies have consistently shown a survival benefit across all stages of resection with acceptable toxicity. The absolute magnitude of benefit is consistent with that achieved in other malignancies where adjuvant chemotherapy is offered as a standard of care.     

非小细胞肺癌中甲基转移酶的研究

目的:探讨非小细胞肺癌中DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶基因的过甲基化状况及表达的关系.方法:采用甲基化特异性PCR及免疫组织化学法检测96例经病理确诊的非小细胞肺癌中DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶基因及蛋白表达.结果:96例非小细胞肺癌组织DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶基因过甲基化率36.5%,DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶蛋白的阳性表达率为33.3%,DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶基因过甲基化与蛋白的表达呈负相关(Rs=-0.536,P＜0.05).结论:在非小细胞肺癌中,DNA修复酶O6-甲基鸟嘌呤-DNA甲基转移酶基因过甲基化导致蛋白表达的降低,可能与肺癌的发生、发展相关.     

Emepepimut-S for non-small cell lung cancer

INTRODUCTION: Immunotherapy as a possible therapeutic option for cancer has been of great importance due to the innovative development of vaccines. Various molecules have been tested and emepepimut-S (Biomira Liposomal Peptide 25 (BLP 25)) has emerged as an option, particularly in lung cancer. AREAS COVERED: A PubMed literature and ClinicalTrials.gov search was conducted using the terms: emepepimut, BLP25, NSCLC, cancer immunotherapy, cancer vaccine and MUC1. This review covers how emepepimut-S acts against the mucin 1 (MUC1) tumor-associated antigen producing a cellular immune response against the cells that express MUC1 and the most important clinical data available that led to the ongoing Phase III trial. EXPERT OPINION: The results obtained in the Phase I/II trials are promising, showing a favorable toxicity with a benefit in survival in NSCLC patients. As future trials develop, demonstration of the long-term survival benefit, understanding of the various mechanisms of immune response initiated by the drug and the selection of patients that will highly benefit from the immunotherapy will be elucidated. The safety and extension in survival makes emepepimut-S a very interesting drug and could, therefore, offer a possibility of treatment and maintenance, particularly for good performance status patients with locally advanced NSCLC.     

Necitumumab for non-small cell lung cancer

Introduction: Targeting the EGFR pathway is a rational approach to treat patients with advanced NSCLC. Necitumumab, a second-generation recombinant fully human immunoglobulin G1 monoclonal antibody directed against EGFR, has recently been assessed in combination with first-line cisplatin-based chemotherapy.

Areas covered: This article reviews literature on necitumumab development, from preclinical data to results of Phase III clinical trials, either published or presented in international scientific conferences. Ongoing clinical trials were searched with the clinical-trials.gov website.

Expert opinion: During the last decade, advances in treatment of metastatic NSCLC have been exclusively achieved in patients with non-squamous histology. In this context, any treatment improvement, even modest, was eagerly awaited for patients with squamous NSCLC. In this patient’s population, the SQUIRE Phase III study demonstrated a relatively small, but statistically significant survival benefit in patients treated with necitumumab in combination with standard chemotherapy (cisplatin and gemcitabin) compared with those treated with chemotherapy alone. However, the identification of predictive biomarker for treatment outcome is still needed to select the patients who will experience a large benefit from the targeted treatment.     

晚期非小细胞肺癌综合治疗的前瞻性研究

目的探讨提高Ⅲ期非小细胞肺癌治疗效果的方法。方法85例Ⅲ期非小细胞肺癌患者随机分为3组,并进行不同顺序的治疗,A组(化疗+手术+放疗)28例,放疗后配合辅助化疗;B组(手术+化疗+放疗)28例;C组(手术+放疗+化疗)29例。比较各组3年生存率、局部区域复发率和远处转移率的差异性。结果A、B、C3组3年生存率分别为75.00%,53.57%,44.83%,其中A组与C组比较差异有显著性意义(P<0.05);3组局部区域复发率分别为7.14%,32.14%,17.24%,其中A组与B组比较差异有显著性意义(P<0.05);各组远处转移率分别为7.14%,10.71%,37.93%,其中A组与C组及B组与C组比较,差异均有显著性意义(P<0.05)。结论术前化疗再手术,配合术后放疗及辅助化疗,可提高治疗Ⅲ期非小细胞肺癌的疗效。     

非小细胞肺癌治疗进展

肺癌是目前全球死亡率最高的肿瘤之一，其中80％的患者为非小细胞肺癌（non—small cell lung cancer，NSCLC）。由于化疗和分子靶向药物的开发应用，以及多学科综合治疗模式的发展，NSCLC的治疗效果较前有所提高，但患者总体预后仍然较差。近年来，随着对肿瘤分子生物学特性的深入研究，NSCLC的治疗越来越强调个体化。多学科综合治疗发挥越来越重要的作用。