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Background: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy., Methods: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell)., Results: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively., Conclusions: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening., Competing Interests: Conflict of interest: S.G. Spiro has nothing to disclose. Conflict of interest: P.L. Shah has nothing to disclose. Conflict of interest: R.C. Rintoul has nothing to disclose. Conflict of interest: J. George has nothing to disclose. Conflict of interest: S. Janes reports personal fees for advisory board work from BARD1, Achilles Therapeutics and AstraZeneca, personal fees for conference travel from AstraZeneca, outside the submitted work. Conflict of interest: M. Callister has nothing to disclose. Conflict of interest: M. Novelli has nothing to disclose. Conflict of interest: P. Shaw has nothing to disclose. Conflict of interest: G. Kocjan has nothing to disclose. Conflict of interest: C. Griffiths has nothing to disclose. Conflict of interest: M. Falzon has nothing to disclose. Conflict of interest: R. Booton has nothing to disclose. Conflict of interest: N. Magee has nothing to disclose. Conflict of interest: M. Peake reports personal fees for lectures from Roche Products Ltd, grants and personal fees for lectures from MSD Ltd, personal fees for advisory board work from BMS and Pfizer Ltd, outside the submitted work. Conflict of interest: P. Dhillon has nothing to disclose. Conflict of interest: K. Sridharan has nothing to disclose. Conflict of interest: A.G. Nicholson has nothing to disclose. Conflict of interest: S. Padley has nothing to disclose. Conflict of interest: M.N. Taylor has nothing to disclose. Conflict of interest: A. Ahmed has nothing to disclose. Conflict of interest: J. Allen has nothing to disclose. Conflict of interest: Y. Ngai has nothing to disclose. Conflict of interest: N. Chinyanganya has nothing to disclose. Conflict of interest: V. Ashford-Turner has nothing to disclose. Conflict of interest: S. Lewis has nothing to disclose. Conflict of interest: D. Oukrif has nothing to disclose. Conflict of interest: P. Rabbits has nothing to disclose. Conflict of interest: N. Counsell has nothing to disclose. Conflict of interest: A. Hackshaw has nothing to disclose., (Copyright ©ERS 2019.)

Background: Initial studies on the use of ultrasound in the detection and sampling of supraclavicular lymph nodes in patients with suspected lung cancer show this to be a promising technique, giving both a cytological diagnosis and pathological N3 (pN3) stage. Leicester published its initial experience in 2005 and the aim of this study was to establish if this had been embedded into the diagnostic pathway, and further to examine the use of ultrasound in diagnosing and staging lung cancer by imaging other areas including pleural effusions, chest wall, bone and liver lesions., Methods: All patients diagnosed with lung cancer, registered on the Leicester lung cancer database over a two year period between January 2007 and December 2008, had their imaging and pathology retrospectively reviewed; 996 primary lung cancer patients were identified (n=996). Of these, 318 patients underwent an ultrasound examination (n=318), consisting of ultrasound of the neck, pleural cavity, and metastatic lesions potentially amenable to ultrasound guided aspiration/biopsy., Results: The overall malignant yield was 45% of patients scanned (95% CI 39.5% to 50.4%) and 81.3% of patients sampled (95% CI 75.5% to 87%). Of the 996 patients, 14.4% (n=143) had a positive ultrasound guided cytological diagnosis (95% CI 12.2% to 16.5%). Of all the pathological diagnoses (n=765), 18.7% were ultrasound guided (95% CI 15.9% to 21.5%). In particular, 32.2% of patients with CT detected neck or mediastinal nodes had a diagnosis and stage achieved by neck ultrasound., Conclusion: The use of ultrasound gives a rapid and less invasive method of diagnosing and staging lung cancer and has become embedded into the diagnostic pathway. We advocate its increased use and availability in patients with lung cancer.

Background: Lung cancer is the leading cause of death from cancer in the UK. Pathological diagnosis traditionally requires invasive procedures such as bronchoscopy, mediastinoscopy, or image guided biopsy. Ultrasound of the neck with fine needle aspiration cytology (FNAC) of enlarged but impalpable supraclavicular nodes has been used in patients with suspected lung cancer who have N2 or N3 disease on staging computed tomography (CT). If positive, this technique helps to both stage the patient and provide a cytological diagnosis., Methods: 101 patients were enrolled prospectively over a 1 year period. FNAC was performed on all supraclavicular nodes over 5 mm in size using the capillary aspiration technique., Results: Sixty one of the 101 patients had enlarged supraclavicular nodes and underwent FNAC. The overall malignant yield was 45.5% of patients scanned and 75.4% of patients sampled. As a result of FNAC, 43 patients (42.6%) avoided more invasive procedures., Conclusion: Ultrasound guided FNAC is a promising, relatively non-invasive technique for the staging and diagnosis of patients with lung cancer.

Study Objective: This study investigates variation in management and treatment of lung cancer patients and determines the impact of any variation in treatment on survival., Design: A retrospective study of population based data held by the Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing active treatment rates for lung cancer with survival by districts. SETTING The then 17 districts in Yorkshire and South Humber, England., Patients: 22 654 patients registered with lung cancer between 1986 and 1994 and followed up until end of 1996., Results: The overall rates of active treatment (surgery, radiotherapy, and chemotherapy) varied between districts from 37% to 56%. One year survival (with 95% CI) was significantly better in the districts with highest rates of active treatment 23% (22% to 24%) compared with 19% (17% to 20%) for those with lowest treatment rates. Non-small cell lung cancer patients (55%) in the districts with highest active treatment rates had an age adjusted relative risk of death during the follow up period, relative to risk of death in the districts with the lower treatment rates of 0.88 (0.83 to 0.92). Clinically diagnosed patients (34%) had an age adjusted RR of 0.92 (0.86 to 0.96). RR in small cell cancer (11%) was not significant., Conclusion: This study has shown wide variations in the rates of active treatment for lung cancer patients within districts across one large region of England. Active treatment was strongly associated with improved survival, especially in non-small cell lung cancer.

A randomized trial was conducted to determine whether administration of Amifostine with chemotherapy for small cell lung cancer could decrease the toxicity. 84 patients with small cell lung cancer of favourable prognosis (limited disease, performance status 0-1; limited disease with performance status 2 but normal sodium and alkaline phosphatase, or extensive disease with performance status 0-1, normal sodium and alkaline phosphatase) received treatment with Ifosfamide 3 g/m(2)intravenously, Carboplatin (Glomerular filtration rate + 25) x6 mg intravenously, Etoposide 50 mg orally, twice daily, for 7 days, every 3 weeks. Patients were randomized to receive amifostine 740 mg/m(2)immediately prior to the intravenous drugs (n = 42) or to receive chemotherapy alone (n = 42). The two groups were similar with respect to baseline prognostic factors. There was no significant difference in the occurrence of grade III or IV neutropenia or thrombocytopenia between the two groups, nor in the response rate or overall survival, for which the median was 11 months in the chemotherapy only group and 14 months in the group treated with amifostine. This study has not shown a protective effect from the use of amifostine with this regimen and there does not appear to be any effect upon the efficacy of treatment., (Copyright 2001 Cancer Research Campaign.)

A total of 30 with good prognosis small cell lung cancer were treated with a modified 'ICE' (ifosfamide, carboplatin and etoposide) chemotherapy regimen in an attempt to achieve a high response rate with less toxicity than is seen with the full 'ICE' regimen. This was given every 4 weeks for a maximum of six cycles. In total 25 patients (83%, 95% CI (70-97%)) experienced a partial or complete response at some stage of their treatment. Of these patients, 12 (40%, 95% CI (22-58%)) showed a complete response. A total of 19 patients (63%) had to have their dose reduced and/or delayed at some point due to toxicity. Nadir blood counts showed that 19 patients (63%, 95% CI (46-81%)) had WHO grade 3 or 4 thrombocytopenia, and 24 (86%, 95% CI (73-99%)) had grade 3 or 4 neutropenia. A total of 17 patients (53%) completed six cycles of chemotherapy. In total 3 patients died during treatment all due to treatment-related complications. Median survival was 12.6 months (95% CI (11.6, 14.7 months)). Nausea, vomiting, dysphagia, activity, mood and overall condition, as recorded using daily diary cards, were worse at the beginning of each chemotherapy cycle. Both response rates and survival were clinically acceptable. However, neutropenia and thrombocytopenia, although reduced from rates reported with the full ICE regimen, were still high. A prospective randomised controlled trial is now needed to assess this regimen in more detail.

A retrospective evaluation of serial measurements of neuron-specific enolase (NSE) has been performed in 58 patients with small cell lung cancer (SCLC). All 58 patients received first-line chemotherapy and 11 patients received also second-line treatment after relapse. Samples were obtained every 3-4 weeks during treatment before each cycle of chemotherapy and every 6 or 12 weeks during follow-up. NSE values were depicted on semi-logarithmic paper. Fifty-one times a major response (complete or partial remission) was observed and 49 times the NSE level reached a plateau between 3.5-10 ng/ml. The NSE level did not discriminate between a complete or a partial remission. Seven times stable disease was obtained and the NSE level declined but remained above the normal plateau of 3.5-10 ng/ml. On 50 occasions progressive disease was found. In 3 cases progressive disease was due to a histologically-proven non-small cell lung cancer and NSE levels did not change. In only 5 out of the remaining 47 occasions NSE levels were normal at the time of relapse but rose later in 4. On 42 occasions of progressive SCLC an exponential rise of NSE was found, often within the range of 3.5-20 ng/ml. None of 6 patients, who are still incomplete remission for 1-5 years, showed a consistent rise of NSE. Serial measurements of serum NSE, can predict the occurrence of a major response, stable disease and progressive disease outside the brain with a very high accuracy and seem to be at least a useful addition to standard investigational methods to guide the treatment of SCLC.

During a retrospective analysis of the value of neuron specific enolase (NSE) in patients with small cell lung cancer (SCLC) it became apparent that at progressive disease (PD) NSE rose exponentially with a doubling time (NSE-Td) varying from 10 - 94 days. In this study the influence of the NSE-Td on the survival of 29 SCLC-patients has been investigated. A significant correlation between survival from the start of rise of NSE at PD and NSE-Td was observed. By extrapolating the exponential rise of NSE to the start of treatment a theoretical logarithmic value of NSE, called Yr, could be calculated. When the patients were grouped according to the Yr value greater than -1, between -1 and -4 and less than or equal to -4 a highly significant correlation between the survival from the start of treatment and NSE-Td was found in all 3 groups. These preliminary data suggest that by means of NSE-Td and Yr value the survival of an SCLC-patient from the time of rise of NSE and from the start of treatment may be predicted within certain limits.

Serum samples were collected from 115 small-cell lung cancer patients before each course of chemotherapy and during follow-up. Levels of neuron-specific enolase (NSE) were measured and compared to the clinical assessments of the course of the disease, which were done by the responsible physician without knowledge of NSE-values. The predictive accuracy of an increase or decrease of NSE for a major response (CR + PR), SD or PD was 98%. Importantly no false-positive rises of NSE were observed. On the basis of this large number of data it seems justified to conclude that in common clinical practice the treatment of small-cell lung cancer patients can be monitored by serial measurements of NSE alone.

A radioimmunoassay for neuron specific enolase (NSE), a marker of neuroendocrine differentiation, has been evaluated in small cell lung cancer (SCLC). In untreated patients 25/38 (68%) with localized SCLC had raised blood levels of NSE (greater than 13 ng ml-1), in extensive disease 34/39 (87%) patients had raised NSE levels. In patients with non-small cell lung cancer (NSCLC) the serum levels were raised in 16/94 (17%). In extensive tumours of non-pulmonary origin NSE levels were increased in 24/116 (20%) patients. Longitudinal studies indicated a good correlation between the response to chemotherapy and fall of NSE levels. Tumour progression was accompanied by a rising NSE in 25/29 patients, with doubling times of 7-90 days. In patients with progression with a normal NSE the recurrence was a NSCLC. Cerebral metastases occurring as the only recurrence during clinical complete remission were not accompanied by a rise of NSE. Serum NSE levels provides a valuable monitor for SCLC during and after chemotherapy.