Patricia Fisher

Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial

Summary Background Malignant pleural mesothelioma is almost always fatal, and few treatment options are available. Although active symptom control (ASC) has been recommended for the management of this disease, no consensus exists for the role of chemotherapy. We investigated whether the addition of chemotherapy to ASC improved survival and quality of life. Methods 409 patients with malignant pleural mesothelioma, from 76 centres in the UK and two in Australia, were randomly assigned to ASC alone (treatment could include steroids, analgesic drugs, bronchodilators, palliative radiotherapy [n=136]); to ASC plus MVP (four cycles of mitomycin 6 mg/m2, vinblastine 6 mg/m2, and cisplatin 50 mg/m2 every 3 weeks [n=137]); or to ASC plus vinorelbine (one injection of vinorelbine 30 mg/m2 every week for 12 weeks [n=136]). Randomisation was done by minimisation, with stratification for WHO performance status, histology, and centre. Follow-up was every 3 weeks to 21 weeks after randomisation, and every 8 weeks thereafter. Because of slow accrual, the two chemotherapy groups were combined and compared with ASC alone for the primary outcome of overall survival. Analysis was by intention to treat. This study is registered, number ISRCTN54469112. Findings At the time of analysis, 393 (96%) patients had died (ASC 132 [97%], ASC plus MVP 132 [96%], ASC plus vinorelbine 129 [95%]). Compared with ASC alone, we noted a small, non-significant survival benefit for ASC plus chemotherapy (hazard ratio [HR] 0·89 [95% CI 0·72–1·10]; p=0·29). Median survival was 7·6 months in the ASC alone group and 8·5 months in the ASC plus chemotherapy group. Exploratory analyses suggested a survival advantage for ASC plus vinorelbine compared with ASC alone (HR 0·80 [0·63–1·02]; p=0·08), with a median survival of 9·5 months. There was no evidence of a survival benefit with ASC plus MVP (HR 0·99 [0·78–1·27]; p=0·95). We observed no between-group differences in four predefined quality-of-life subscales (physical functioning, pain, dyspnoea, and global health status) at any of the assessments in the first 6 months. Interpretation The addition of chemotherapy to ASC offers no significant benefits in terms of overall survival or quality of life. However, exploratory analyses suggested that vinorelbine merits further investigation. Funding Cancer Research UK and the Medical Research Council (UK).

The impact of virtual simulation in palliative radiotherapy for non-small-cell lung cancer.

BACKGROUND AND PURPOSE Radiotherapy is widely used to palliate local symptoms in non-small-cell lung cancer. Using conventional X-ray simulation, it is often difficult to accurately localize the extent of the tumour. We report a randomized, double blind trial comparing target localization with conventional and virtual simulation. METHODS Eighty-six patients underwent both conventional and virtual simulation. The conventional simulator films were compared with digitally reconstructed radiographs (DRRs) produced from the computed tomography (CT) data. The treatment fields defined by the clinicians using each modality were compared in terms of field area, position and the implications for target coverage. RESULTS Comparing fields defined by each study arm, there was a major mis-match in coverage between fields in 66.2% of cases, and a complete match in only 5.2% of cases. In 82.4% of cases, conventional simulator fields were larger (mean 24.5+/-5.1% (95% confidence interval)) than CT-localized fields, potentially contributing to a mean target under-coverage of 16.4+/-3.5% and normal tissue over-coverage of 25.4+/-4.2%. CONCLUSIONS CT localization and virtual simulation allow more accurate definition of the target volume. This could enable a reduction in geographical misses, while also reducing treatment-related toxicity.

Accelerated Radical Radiotherapy for Non-small Cell Lung Cancer using Two Common Regimens: a Single-centre Retrospective Study of Outcome

AIMS A variety of radical radiotherapy regimens are in use for non-small cell lung cancer. Continuous hyperfractionated accelerated radiotherapy (CHART: 54 Gy in 36 fractions over 12 days) and accelerated hypofractionated radiotherapy using 55 Gy in 20 fractions over 4 weeks are standard fractionations in our centre. The primary aim of this retrospective study was to evaluate survival outcome seen in routine clinical practice. MATERIALS AND METHODS All case notes and radiotherapy records of radically treated patients between 1999 and 2004 were retrospectively reviewed. Basic patient demographics, tumours, characteristics, radiotherapy and survival data were collected. RESULTS In total, 277 patients received radical radiotherapy: 137 and 140 patients received CHART and hypofractionated radiotherapy, respectively. There were differences noted in the demographics between the two treatment schedules: median age 65 years (range 41-83) vs 73 years (range 33-87); histological confirmation rates 90% vs 76%; prior chemotherapy 34% vs 19% for CHART and hypofractionated treatment, respectively. For CHART patients, stages I, II, III and unclassified were 12, 8, 68 and 12% and the staging for the hypofractionated regimen was 54, 11, 34 and 2%, respectively. The median overall survival from the time of diagnosis was 20.4 months with a 40% 2-year survival rate. For the two fractionations the median survival was 16.6 months vs 21.4 months and 34% vs 45% of patients were alive at 2 years in the CHART and hypofractionated groups, respectively. On multivariate analysis, stage was the only factor affecting overall survival - no difference was seen according to radiotherapy regimen. CONCLUSION This single-centre study reflects the outcome of unselected consecutively treated non-small cell lung cancer patients. Adjusting for stage, there was no significant difference in survival seen according to regimen. Encouragingly, CHART outcome shows reproducibility with the original CHART paper. Our hypofractionated outcome is similar to that previously reported, but despite this being the UKs most common regimen, 55 Gy in 20 daily fractions remains unvalidated by phase III trial data.

Oral presentation of malignant mesothelioma

We report a case of metastatic mesothelioma presenting as an oral metastasis in a 46-year-old patient. The patient presented with 2 polypoid lesions that appeared to be benign on the dorsum of the tongue. Excisional biopsy showed the presence of metastatic carcinoma that on further investigation proved to be mesothelioma. The initial presentation of mesothelioma as an oral metastasis is not previously reported. This article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of the general dental practitioner in screening for oral neoplasms.

Non-small cell lung cancer

This patient describes his experience of multidisciplinary care after his diagnosis of non-small cell lung cancer when he was 15 years old

P1.17-05 Accelerated Radiotherapy for Non-Small Cell Lung Cancer: A 12 Year Retrospective Review of Two Dose Fractionation Schedules

Study (GWAS) was carried out to look for potential SNPs associated with risk of RP grade 2. Result: The incidence of RP of grade 2 was 29.2%. Using SNP information by Genomes-Wide Association Study (GWAS), we discovered 73 SNPs that showed significant difference with cutting off p-value of 0.001. Most of them are previously not reported. Conclusion: This result established a set of biomarkers which can be used for prognosis predictions for radiation-induced pneumonitis.