The clinical impact of integrated FDG PET-CT on management decisions in patients with lung cancer.

PURPOSE: To retrospectively evaluate the clinical impact of FDG PET-CT on the management pathway of patients with lung cancer. PATIENTS AND METHODS: One hundred and sixty-one patients with suspected lung cancer undergoing FDG PET-CT during the study period were analyzed. Before PET-CT, lung cancer MDT recorded scan indication, conventional clinical stage, and proposed treatment plan. The accuracy of integrated PET-CT compared with stand alone CT in preoperative staging of lung cancer was evaluated with pathological staging used as the reference standard. The effect of PET-CT on the subsequent management of patients was also evaluated. RESULTS: The agreement between CT and integrated PET-CT in preoperative staging of lung cancer was significant (p<0.001). In 16 (10%) patients PET-CT excluded tumour as there was no FDG uptake. PET-CT revealed occult metastasis in 25 (16%) patients. It was also a better overall predictor for T status (64% vs. 58%) and N status (78% vs. 65%). For N staging PET-CT was more accurate for N1 (82% vs. 72%) and N2 (85% vs. 80%) disease. Regression analyses suggested that PET-CT was a better predictor of overall TNM staging for lung cancer. FDG PET scanning changed or influenced management decisions in 66 (41%) patients with lung cancer. Changes in TNM staging following PET-CT were significant predictors (p=0.02) in making a decision to abandon thoracotomies. CONCLUSION: Addition of PET-CT to comprehensive evaluation of lung cancer can have significant clinical impact. There is marked improvement in staging the disease. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted. PET permits reduction in the number of thoracotomies performed for non-resectable disease with predicted reduction in the morbidity rate and cost associated with unnecessary interventions.

Population based epidemiology and prognosis of mesothelioma in Leeds, UK.

INTRODUCTION: Malignant mesothelioma is a fatal neoplasm, which is rapidly increasing in incidence throughout Western Europe. To date there have been no studies reporting on the natural history and interventional practices on a comprehensive unselected population, as opposed to reports from referral institutions or compensation claimants. We present a population based study capturing data on all patients with mesothelioma presenting within a defined geographical area over a 4 year period in the UK. METHOD: Data of all cases occurring in Leeds with a population of 750 000 were collected retrospectively from 2002 to 2003 and prospectively from 2004 to 2005. All patients' hospital records and the Trust histology database were reviewed, as well as coroner's reports on all patients with a post mortem diagnosis of mesothelioma. RESULTS: Over the 4 year study period, there were a total of 146 cases in Leeds; 77% were male. Median age was 74 years (range 36-93). Median survival from diagnosis was 8.9 months. 92% and 8% had histological or cytological confirmation, respectively. 85% had documented evidence of definite or probable exposure to asbestos. 110/146 (75%) had symptomatic pleural effusions at presentation. Twice the number of patients (42 vs 17) were managed with surgical rather than bedside pleurodesis and these had a lower recurrence rate (14% vs 47%; p = 0.02). 122 patients had video assisted thoracoscopic surgery/cutting CT biopsies or chest drains. 73/122 (60%) had prophylactic radiotherapy to these sites. There were seven cases (5%) of tract invasion by tumour and six of these had received prophylactic radiotherapy. Median time to seeding was 174 days. 92/146 (63%) had a performance status of 2 or better at diagnosis but only 54/146 were considered fit for chemotherapy. Of these, 28 (52%) declined chemotherapy; the overall uptake of chemotherapy or entry into a trial was 18%. No patient had radical surgery. CONCLUSION: This comprehensive population based audit has shown that the median age at presentation of malignant mesothelioma is increasing and baseline performance status and survival is worse than in selected series. 37% of patients were considered suitable for palliative chemotherapy but less than 20% accepted this offer. Thorascopic pleurodesis appears to be associated with fewer recurrences. The role of prophylactic radiotherapy to chest drain and biopsy sites needs reappraisal.

Psychological distress and concerns of elderly patients treated with palliative radiotherapy for lung cancer.

We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Psychological distress and concerns were measured before and after treatment using the Hospital Anxiety and Depression Scale (HADS) and a Concerns Checklist. Psychosocial morbidity was common, however, prevalence was similar in both age groups. There was a trend towards worsening of both anxiety and depression scores after treatment, but this did not reach statistical significance. Younger patients reported more concerns than the older group (median 12 vs 10) but this too was not statistically significant. Concerns about the illness and symptoms were more likely to have been addressed by the care team than were concerns about psychosocial issues such as the family and the future. People of all ages have similar concerns and levels of anxiety and depression whilst receiving palliative radiotherapy for lung cancer. Further research is needed to explore the use of screening tools, like those used in this study, to identify patients' difficulties and target interventions to improve their quality of life.

Do elderly people with lung cancer benefit from palliative radiotherapy?

The median age at diagnosis of patients with lung cancer is currently around 70 and is rising, yet the trials on which treatment is based included few elderly people. We conducted a prospective observational cohort study of 83 elderly patients (aged 75 and above) being treated with palliative radiotherapy for lung cancer, with a comparison group of 49 younger patients (aged 65 and under). Response to treatment was evaluated by patient-assessed symptom and quality of life scores using the EORTC QLQ-C30 and its companion lung module LC17. This is to date the largest prospective study of elderly lung cancer patients in routine practice. We found no significant differences in response or toxicity between the two groups. Elderly people with lung cancer should be offered palliative radiotherapy the same as younger patients, with the same expectation of benefit.

BTS randomised feasibility study of active symptom control with or without chemotherapy in malignant pleural mesothelioma: ISRCTN 54469112.

BACKGROUND: The incidence of mesothelioma is rising rapidly in the UK. There is no generally accepted standard treatment. The BTS recommends active symptom control (ASC). It is not known whether chemotherapy in addition prolongs survival or provides worthwhile palliation with acceptable toxicity. Palliation as recorded by patients has been fully reported for only two regimens: mitomycin, vinblastine, and cisplatin (MVP), and vinorelbine (N). The BTS and collaborators planned to conduct a phase III randomised trial comparing ASC only, ASC+MVP, and ASC+N in 840 patients with survival as the primary outcome measure. The aim of the present study was to assess the acceptability of the trial design to patients and the suitability of two standard quality of life (QL) questionnaires for mesothelioma. METHODS: Collaborating centres registered all new patients with mesothelioma. Those eligible and giving informed consent completed EORTC QLQ-C30+LC13 and FACT-L QL questionnaires and were randomised between all three or any two of (1) ASC only, (2) ASC+4 cycles of MVP, and (3) ASC+12 weekly doses of N. RESULTS: During 1 year, 242 patients were registered of whom 109 (45%) were randomised (55% of the 197 eligible patients). Fifty two patients from 20 centres were randomised to an option including ASC only. This translates into a rate of 312 per year from 60 centres interested in collaborating in the phase III trial. The EORTC QL questionnaire was superior to FACT-L in terms of completeness of data and patient preference. Clinically relevant palliation was achieved with ASC. CONCLUSION: The planned phase III trial is feasible.

Do newly diagnosed lung cancer patients feel their concerns are being met?

Lung cancer is the leading cause of cancer death worldwide. It has a poor prognosis and the majority of those affected are elderly. Evidence suggests that providing clear, relevant information and addressing patients' concerns can make a worthwhile difference to patients. This study aimed to: explore the concerns of lung cancer patients shortly after diagnosis; and enquire whether these concerns had been discussed by their care teams. Eighty patients with a new diagnosis of primary lung cancer were interviewed 14-28 days after the date on which they were told the diagnosis. Interviews were conducted either in the hospital ward, outpatient clinic or at home. Participants were asked to rate 17 specific items of concern from 1 = 'not a worry' to 5 = 'extremely worried', plus one non-specific item. Patients rated at least two items as worrying them to some degree with a median of nine concerns being reported. Major concerns for patients were the illness itself; the future relating to the illness and concerns about the family. Overall, patients in the study felt that less than half of their concerns (43%) had been discussed by the care team. Although levels of concern about physical symptoms were relatively low, these had been more frequently addressed than the psychosocial issues, which were rated higher by patients. There were some differences in the number of concerns reported between males/females and younger/older age groups, but the pattern of concerns was similar. There were no differences in the level of concerns between treatment groups; the location of the interview nor in the interval between diagnosis and delivery of the checklist. This study supports previous findings that there is a need for health professionals to provide emotional support and respond to the psychosocial needs of patients by eliciting their concerns and attempting to address them in the early stages of the disease process.

Lung cancer: district active treatment rates affect survival.

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.

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).

Genetic alterations in bronchial mucosa and plasma DNA from individuals at high risk of lung cancer.

Evidence suggests that the majority of lung cancer patients have tumour-derived genetic alterations in circulating plasma DNA, and that this may be developed as a diagnostic tool. To this end, we have studied 60 individuals attending bronchoscopy clinic, with symptoms suspicious of lung cancer, for genetic alterations in bronchial mucosa biopsy (n = 47) and plasma (n = 40) DNA. Thirteen of 47 individuals from whom biopsies were taken displayed allelic loss of heterozygosity (LOH) in biopsy DNA for at least 1 of 4 markers. All 13 of these individuals had neoplastic tumour cells in their biopsies and were subsequently diagnosed with cancer. Thirteen of 40 individuals from whom plasma was taken displayed a plasma DNA LOH, and 12 of these 13 individuals were subsequently diagnosed with cancer. LOH in plasma was generally representative of LOH in the corresponding biopsy. In terms of sensitivity, using just 4 markers, biopsy LOH and plasma LOH were found in 13 of 44 (30%) and 12 of 29 (41%), respectively, of those patients subsequently diagnosed with cancer. Two patients were positive for LOH in plasma samples that pre-dated a diagnosis of cancer by several months. These data suggest that assay of genetic alterations in circulating plasma DNA may be developed as a useful addition to conventional techniques for the diagnosis of lung cancer.

A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for 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.

Non-tuberculous mycobacterial lung infection complicated by chronic necrotising pulmonary aspergillosis.

We report four cases of pulmonary mycobacterial disease (three due to Mycobacterium malmoense and one to Myco- bacterium avium intracellulare) complicated by the development of chronic necrotising pulmonary aspergillosis. Difficulties with treatment and the potential benefits of steroids are discussed.