Lung cancer referral patterns in the former Yorkshire region of the UK

The purpose of this study was to find out what proportion of patients are referred as lung cancer guidelines assume, whether different referral pathways result in different management and what proportion of patients are seen within recommended time intervals between referral and treatment. A randomly selected sample of 400 lung cancer cases registered with the former Yorkshire Cancer Registry database in 1993 was selected for casenote analysis. Mode of presentation, speciality of initial referral, treatment by specialist, time intervals for key points in the referral pathways were analyzed. A total of 362 (90.5%) of case-notes were available. Less than half of lung cancer patients (173, 47.8%) presented to hospital with a chest X-ray diagnosis of lung cancer. Forty-one (11.3%) presented as self-referrals to Accident and Emergency and the remainder were referred without a diagnosis of lung cancer by other routes, mainly via GPs. Patients who did not present initially with a lung cancer diagnosis were less likely to receive specialist care (62%:96%), or have their diagnosis histologically confirmed (57.1%:80.3%) or receive surgery or radical radiotherapy (6.9%:13.9%). Nine per cent of all 362 patients did not receive a specialist opinion. Eighty per cent of patients referred by a GP with CXR suspected lung cancer were seen at hospital within 2 weeks. Only 32.4% of those receiving active treatment were treated within 8 weeks of clinical diagnosis or first hospital visit. Lung cancer patients presenting to hospital without a suspicious CXR are less likely to have specialist care, histological confirmation of their cancer and have lower rates of active treatment (surgery, any radiotherapy or chemotherapy).     

癌/睾丸抗原在肺癌中的研究进展

肺癌传统的诊治手段难以达到满意的效果。寻找新的早期诊断和治疗方法迫在眉睫。很多研究表明癌/睾丸抗原（CTA）与肺癌的分期、病理类型、转移、复发等密切相关，在肺癌的免疫治疗中，CTA备受瞩目，其表达特性对肺癌诊疗方法的发展有着重要意义。现就CTA与肺癌关系的研究进展做如下综述。     

miRNA expression profiles associated with diagnosis and prognosis in lung cancer

miRNAs, which are small single-stranded RNA molecules composed of 18–23 nts, act as oncogenes or tumor suppressor genes playing important roles in the processes of tumor formation, infiltration and metastasis. Lung cancer currently has the highest morbidity and mortality among all malignant tumors; yet, lack of early specific diagnostic markers and effective treatments hinders its proper management. In lung cancer, about 40–45 abnormal expression patterns of miRNAs have been discovered and are involved in lung cancer development. miRNAs have functions together with oncogenes and tumor suppressor genes of lung cancer. miRNAs-based tests can be used for early clinical diagnosis and prediction of clinical outcomes of lung cancer. Studying the role of miRNAs in lung cancer development and its relationship with diagnostic and prognostic parameters might help to improve the sensitivity of diagnosis and the efficacy of lung cancer treatment.     

The Emerging Role of “Liquid Biopsies,” Circulating Tumor Cells,and Circulating Cell-Free Tumor DNA in Lung Cancer Diagnosis and Identification of Resistance Mutations

Therapeutic advances in the treatment of lung cancer are in part due to a more complete understanding of its genomic portrait. The serial monitoring of tumor genotypes, which are instable and prone to changes under selective pressure, is becoming increasingly needed. Although tumor biopsies remain the reference standard for the diagnosis and genotyping of lung cancer, they are invasive and not always feasible. The “liquid biopsies” have the potential to overcome many of these hurdles, allowing a rapid and accurate identification of de novo and resistant genetic alterations and a real-time monitoring of treatment responses. In this review, we provide insights into new liquid diagnostic platforms and discuss the role of circulating tumor cells and circulating tumor DNA in the diagnosis and identification of resistance mutations in lung cancer.     

生物标志物在肺癌早筛早诊应用中的研究现状

肺癌是全球范围内恶性程度最高的肿瘤之一.在我国,肺癌的死亡率已连续多年处于首位.早筛早诊是延长肺癌患者生存期的前提.近年来,被认为具有发展前景的液体活检技术逐渐受到关注,其在肺癌早期诊断中的价值值得我们探讨.本文通过综述生物标志物在肺癌筛查和早期诊断中的应用,从多组学寻找特异生物标志物,探讨其在肺癌早期诊断的意义.     

肺癌早期诊断相关标志物研究进展

肺癌是死亡率居于我国首位的肿瘤,早发现、早诊断是影响肺癌治疗效果的关键,但目前仍然缺乏精准安全的肺癌早期诊断方法,这极大地影响了肺癌患者的生存期。肺癌作为一种高度恶性肿瘤,其诊断生物标志物的相关研究受到了极大的关注。这些诊断生物标志物具有多样性,在肺癌早期诊断中的价值有待进一步探讨。     

Has lung cancer in the elderly different characteristics at presentation?

Lung cancer is the first cause of cancer death for males aged > or =35 years, and the second for females aged between 35 and 70 years. Elderly patients seem to have the worst performance status (PS) and earlier stage of disease at diagnosis. We analyzed data concerning 1,035 patients with lung cancer referred to the National Cancer Institute of Naples. The variables considered in the analysis were: gender; type of cancer [small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC)]; ECOG (Eastern Cooperative Oncology Group) PS, the stage of disease at diagnosis, the histological type, age at diagnosis. In order to better assess the relevance of age at diagnosis in lung cancer patients we categorized the age into two groups (young < or =70; old >70 years). The statistical analyses were performed using chi2 trend test with corresponding p-value and odds ratios (OR) for the examined variables, with a corresponding 95% confidence interval. These were derived using multiple logistic regression, fitted by the maximum likelihood method. For all the 1035 patients the risk between the age at diagnosis and the performance status was not statistically significant (OR=1.1, 95%CI 0.8-1.5). We repeated the same risk distinguishing the histological type and we analyzed the performance status for the SCLC (OR=1.0, 95%CI 0.4-2.5) and the stage at diagnosis (OR=1.0, 95%CI 0.4-3.0), without any significant difference. Our study showed that elderly patients with lung cancer do not seem to have different characteristics at presentation, particularly related to stage of disease, PS and histology, as compared to their younger counterpart. Other characteristics such as type and number of co-morbidities and organ function differ in the two groups of populations.     

General practitioner assessment of stage and performance status in lung cancer patients at a population level: implications for prognosis and radiotherapy needs analyses

BACKGROUND: Stage, weight loss, and performance status (PS) are important prognostic factors and eligibility factors for curative intent therapy for lung cancer patients. Details of stage, weight loss, and PS are often not collected until referral to a cancer specialist, and since not all patients are referred to cancer specialists these important variables are not well defined at a population level. PATIENTS AND METHODS: Data on stage, weight loss, PS and referral pattern were requested from general practitioners (GPs) on all lung cancer patients diagnosed between May and June of 2002 in the province of British Columbia, Canada. Outcomes were analyzed in relation to survival and referral to a cancer centre. RESULTS: 395 patients were identified, and GP questionnaires were returned on 85% of the cases. Patients referred to a cancer centre shortly after diagnosis differed from those who were not referred. Patients who were not referred to a cancer centre consisted of two groups-patients with localized disease and good PS who tended to have a better survival than those who were referred, and patients with advanced disease and poor performance status who tended to have a worse survival than those who were referred. GP assessed stage and PS are prognostic factors for survival. CONCLUSIONS: GP assessed stage and PS are prognostic factors for survival in lung cancer patients. The case mix of patients who are not referred to a cancer centre shortly after their diagnosis differs from those that are referred.     

Influence of sex on lung cancer histology, stage, and survival in a midwestern United States tumor registry

BACKGROUND: A study was performed to identify differences between men and women with regard to lung cancer type, stage at diagnosis, and survival in a single hospital system cancer registry. PATIENTS AND METHODS: A retrospective cohort study was designed based on a study population drawn from the lung cancer tumor registry at a single hospital system composed of 2 independent hospitals in the Midwestern United States. This database included all patients from 1996 to 2002 with known lung cancer or abnormal findings on chest radiography or computed tomography (N=2618). Patients with adenocarcinoma or squamous cell, small-cell, or large-cell carcinoma were included in the study. Data were collected on patient sex, age, cancer type, stage at diagnosis, and survival status. RESULTS: A total of 1216 men and 997 women met inclusion criteria for the study. There was no significant difference in age between sexes at diagnosis. Women were significantly more likely to have adenocarcinoma or small-cell carcinoma but less likely to have squamous cell carcinoma compared with men. There were no significant differences between sexes in the incidence of large-cell carcinoma. No significant differences were found between men and women in terms of cancer stage at diagnosis. There were significant differences in survival between the histologic types at years 3, 4, and 5. Only patients with stage I disease showed a difference between sexes and only for years 2, 3, 4, and 5. CONCLUSION: Overall differences in lung cancer histology and survival were found between men and women. Because a high mortality rate of lung cancer exists in both sexes, it is important to understand its occurrence and survival rates in both sexes.     

The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients

RationaleAirflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American populationObjectiveTo describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and to evaluate their impact on the management and outcome of lung cancer.MethodsMedical records of 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan, were reviewed. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment, and outcome. Computed tomographies (CT) of the chest about the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CTs and/or airflow obstruction by spirometry.ResultsThere were no differences by sex for age at lung cancer diagnosis (P = .78) and tumor histology (P = .43). The men were more likely to present at a later stage of lung cancer diagnosis compared with the women (P = .04), and the women were more likely to have surgery than the men (P = .03). Overall, 94% of the men and 78% of the women in this population had spirometry and/or CT evidence of COPD. The men were somewhat more likely to have COPD diagnosed by either CT or spirometry than were the women (P = .06), but the Global Obstructive Lung Disease Classification scores did not differ by sex among those with spirometry-diagnosed COPD (P = .34). Seventy-eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (P = .03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (P = .82) or emphysema diagnosis (P = .51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (P = .30 and P = .06, respectively), nor did treatment modality (P = .54 and P = .10, respectively). Patients with lung cancer and with COPD, diagnosed either via spirometry or CT, did not show an increased risk of death compared with patients with lung cancer and without COPD after adjusting for age at diagnosis, sex, and stage (hazard ratio, 1.31 [95% CI, 0.68-2.53]).ConclusionThere is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.     

以转移症状为主要临床表现的肺癌──附64例分析

以转移症状为主要临床表现的肺癌并不少见。因其原发灶小、起病隐袭、临床表现复杂、涉及临床多个科室，又缺少呼吸道症状、易致漏诊、误诊。本文分析６４例以转移症状为主要临床表现的肺癌，重点探讨其诊断问题。强调临床医师应不断扩大知识面，提高对肺癌转移症状的识别能力，有助于肺癌的早期诊断。     

Immunochemistry and lung cancer: application in diagnosis, prognosis and targeted therapy

Immunochemistry is now an established ancillary technique in lung cancer diagnosis. Not only does it help in supporting the morphological diagnosis of malignancy, but its role now extends to the determination of cell lineage, ascertaining the primary site of tumour origin and contributing to decisions on prognosis and treatment. Early detection and confirmation of lung cancer facilitate early treatment decisions. Lung cancer management now has a multidisciplinary approach which includes cytopathologists and clinicians. Some clinicians may not understand what immunochemistry is and what its role is in lung cancer diagnosis, prognosis and therapy. The purpose of this paper is to define immunochemistry, on the background of basic respiratory airway epithelial structure and cancer biology, and discuss its application in the diagnosis, treatment and determination of prognosis of lung cancer.     

The value of cytologic examination in the management of lung cancer

Cytologic examination of sputum and other material from the lung is of great value in the diagnosis of lung cancer. If the patient does not expectorate, material can be obtained by bronchoscopic aspiration of secretions, bronchial brushings, bronchial washings, transthoracic needle aspiration and thoracocentesis. Cytologic examination makes it possible not only to diagnose lung cancer but also to determine the exact cell type of the cancer in most cases. Furthermore, such cytologic examinations are of value in cancer metastatic to the lung as well as for primary lung cancer. The risk of a false positive diagnosis is small, especially in laboratories within which sufficient numbers of examinations are performed to maintain the skill of technicians and pathologists.Studies are in progress to evaluate the cost-effectiveness of frequent sputum examinations, along with roentgenograms of the thorax, to detect asymptomatic lung cancer in men at special risk because of their smoking habits. Present data are inadequate to determine the ultimate value of such screening tests for lung cancer. For the time being, each physician must evaluate the risk of lung cancer and recommend what seems reasonable for each patient.     

The radiological diagnosis of branched cancer of the lung

The data on 36 patients with branched cancer of the lung are reported, which made 0.8% of the total number of lung cancer patients. A detailed analysis of radiological manifestations of branched lung cancer, presented in the article, indicated that at early stages of the disease its diagnosis is especially difficult and must be based only on the results of bronchoscopy together with biopsy. Clinical signs, as a rule, are followed by radiological symptoms which make possible to establish a reliable diagnosis of branched lung cancer. Tomograms made in the typical bronchial planes of bronchograms yield the most valuable information.     

Resection of small indeterminate lung nodules by video-assisted thoracoscopic surgery (VTS). Implications for the early diagnosis of lung cancer

Small indeterminate lung nodules are increasingly detected because of the extensive use of chest x-rays and of computed tomography scans. In evaluating a small solitary pulmonary nodule the main concern is whether the nodule is benign or malignant. Resection by video-assisted thoracic surgery is the standard treatment for solitary pulmonary nodules, especially if they are small and not accessible by bronchoscopy or by percutaneous transthoracic needle aspiration. In this prospective study the personal experience in the diagnosis and treatment of lung nodules by video-assisted thoracic surgery and its implications in early diagnosis of lung cancer, are illustrated In the reported series video-assisted lung wedge resection was carried out successfully in (94%) of lung nodules, with low morbidity and no mortality. A definitive pathologic diagnosis was achieved in all cases. These findings indicate that indeterminate lung nodules > 1 cm in diameter have a high probability (65%) of being malignant and therefore need to be resected to establish a definitive diagnosis.     

A study of the volatile organic compounds exhaled by lung cancer cells in vitro for breath diagnosis

BACKGROUND: The specific volatile organic compounds (VOCs) exhaled by lung cancer cells in the microenvironment are the source biomarkers of lung cancer and also serve as direct evidence that the diagnosis of lung cancer by breath is possible. However, to the authors' knowledge, few articles published to date have provided accurate VOCs in the microenvironment, thereby leading to different points of view with regard to searching for biomarkers in the breath from lung cancer patients In this article, an innovative pathologic analysis method of lung cancer and the early diagnosis of lung cancer at the cellular level were introduced for this purpose. METHODS: Solid-phase microextraction combined with gas chromatography is used as the detection system to determine the VOCs in the culture medium of several target cells, including different kinds of lung cancer cells, bronchial epithelial cells, tastebud cells, osteogenic cells, and lipocytes. As a result, each kind of cells has a unique chromatogram. There are 4 special VOCs that were found to exist in all culture mediums of lung cancer cells, which are the metabolic products of lung cancer cells and can be viewed as markers of lung cancer. RESULTS: The authors were able to determine a correlation between VOCs in the metabolic products of lung cancer cells and VOCs in the breath of lung cancer patients, some of whom had stage I and II disease, and eventually hope to certify the biomarkers in the breath of lung cancer patients. CONCLUSIONS: This research is significant and provides the basis for the noninvasive detection and the breath diagnosis of lung cancer using an electronic nose.     

Early Detection of Lung Cancer Risk Using Data Mining

Background: Lung cancer is the leading cause of cancer death worldwide Therefore, identification of geneticas well as environmental factors is very important in developing novel methods of lung cancer prevention.However, this is a multi-layered problem. Therefore a lung cancer risk prediction system is here proposed whichis easy, cost effective and time saving. Materials and Methods: Initially 400 cancer and non-cancer patients’data were collected from different diagnostic centres, pre-processed and clustered using a K-means clusteringalgorithm for identifying relevant and non-relevant data. Next significant frequent patterns are discovered usingAprioriTid and a decision tree algorithm. Results: Finally using the significant pattern prediction tools for alung cancer prediction system were developed. This lung cancer risk prediction system should prove helpful indetection of a person’s predisposition for lung cancer. Conclusions: Most of people of Bangladesh do not evenknow they have lung cancer and the majority of cases are diagnosed at late stages when cure is impossible.Therefore early prediction of lung cancer should play a pivotal role in the diagnosis process and for an effectivepreventive strategy.     

The role of imaging in screening,diagnosis and staging of Non-Small Cell Lung Cancer (NSCLC)

Imaging plays a vital role in the management of NSCLC including diagnosis, staging and follow up. Computerised tomography (CT) is of value not only in the diagnosis of lung cancer, but also for screening and guiding intervention. CT and magnetic resonance imaging (MRI) are used in staging and provide anatomical information but have well known limitations in differentiating reactive from malignant nodes, fibrosis from active disease and in defining the extent of invasion. MRI, with its superior soft tissue contrast provides optimal information on brachial plexus and central nervous system involvement. Functional imaging using 2-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) is increasingly being used to provide unique information and when combined with anatomic imaging will provide better staging information for both local disease and the extent of metastases. FDG-PET or ^99mTc-depreotide may help in deciding which lesions need further investigation and the most appropriate lesion to biopsy. Multidetector CT is being used to detect lung cancer at an early stage when it is potentially curable by surgery although many problems exist, particularly the high false positive rates requiring further investigation, which will have implications on cost effectiveness for lung cancer screening programs.     

Local thermal ablative therapies for extracranial oligometastatic disease of non-small-cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Clinically, 40–50% of patients with NSCLC are found to have systemic metastasis at the initial diagnosis. Meanwhile, 30–75% of patients with lung cancer who have undergone radical surgical resection have local recurrence and distant metastases. However, not all distant metastases are multiple, and some are potentially curable. In this study, among the patients with NSCLC having distant organ metastasis, approximately 7% showed extrapulmonary solitary metastasis and remained in this relatively stable state for a long time. This form of metastasis is known as NSCLC oligometastases. This review describes the concept and classification of oligometastases, as well as the local treatment and prognosis of extracranial oligometastases.     

Proteomics-based identification of protein gene product 9.5 as a tumor antigen that induces a humoral immune response in lung cancer.

We used a proteomic approach to identify proteins that commonly induce an antibody response in lung cancer. Sera from 64 newly diagnosed patients with lung cancer, 99 patients with other types of cancer, and 71 noncancer controls were analyzed for antibody-based reactivity against lung adenocarcinoma proteins resolved by two-dimensional PAGE. Unlike controls, autoantibodies against a protein identified by mass spectrometry as protein gene product 9.5 (PGP 9.5) were detected in sera from 9 of 64 patients with lung cancer. Circulating PGP 9.5 antigen was detected in sera from two additional patients with lung cancer, without detectable PGP 9.5 autoantibodies. PGP 9.5 is a neurospecific polypeptide previously proposed as a marker for non-small cell lung cancer, based on its expression in tumor tissue. Using A549 lung adenocarcinoma cell line, we have demonstrated that PGP 9.5 was present at the cell surface, as well as secreted. Thus, the findings of PGP 9.5 antigen and/or antibodies in serum of patients with lung cancer suggest that PGP 9.5 may have utility in lung cancer screening and diagnosis.