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Originally published as JCO Early Release 10.1200/JCO.2008.19.3839 on December 1 2008 © 2009 American Society of Clinical Oncology.
Blood-Based Early Detection of Malignant Mesothelioma
Research and Education Unit, Dust Diseases Board; and the School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
National Research Center for Asbestos Related Disease, Western Australian Institute of Medical Research, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia, Australia
Research and Education Unit, Dust Diseases Board, Sydney, New South Wales, Australia
National Research Center for Asbestos Related Disease, Western Australian Institute of Medical Research, University of Western Australia, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia, Australia
Research and Education Unit, Dust Diseases Board; and the Department of Thoracic Medicine, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales, Australia To the Editor: We were most interested to read the full report of the phase II trial on pemetrexed plus gemcitabine for patients with peritoneal mesothelioma in July 20, 2008, issue of Journal of Clinical Oncology.1 Australia has the highest incidence of malignant mesothelioma (MM) in the world, probably due to heavy asbestos usage during the 1950 to 1980s. MM is likely to become an increasingly common diagnosis in New South Wales (NSW) within the next 10 years, and we predict that numbers of cases of MM in NSW will peak in 2014.2 The predicted compensation cost for MM in Australia is 8.5 billion US dollars.3 In the most recent published data from NSW, the prognosis of peritoneal MM was still very poor with an average survival of approximately 5 months,2 but with a very wide range (0 to 220 months). Survival was significantly lower than that reported in the paper of Simon et al.1 We suggest that this difference in survival is probably the result of patient selection for the trial, which was of patients suitable for treatment rather than palliation, but may also reflect small numbers (n = 20). The authors did not present a power calculation, but we suggest that the study is significantly underpowered to reliably detect a real treatment effect. This is a real problem with a rare disease and not a criticism of an otherwise excellent study. We would be most interested in the comments of the authors on this point and those made below. Currently, there is no proven curative treatment for MM, although it is to be hoped that combined treatment including surgical resection and chemotherapy might prolong survival in the future. One recent large scale study of 409 patients with pleural MM showed that chemotherapy (without pemetrexed) seemed to have no benefit in extending survival in patients with pleural MM, but in addition, no overall effect on quality of life and possible benefit for some symptoms (eg, chest pain).4 Use of pemetrexed in combination with other agents may, in the future, have a beneficial effect, particularly in early disease.4 Early detection of MM is not easy and radiological surveillance is imperfect. Use of blood-based biomarkers might solve this difficulty and allow detection of MM at a stage when combined treatment involving surgery, chemotherapy, and radiation therapy might be effective.5 Soluble mesothelin related protein has been reported to be a promising biomarker in this respect.6,7 We have recently reported a prospective cohort study examining the utility of this biomarker in screening for MM in an asbestos exposed population.8 Unfortunately, we did not detect any MMs and a high false positive rate was observed, but follow-up to date has been limited. Blood-based biomarkers, possibly in combination with other new modalities, show some promise for cure in MM if detection is early. Given the high human and financial costs of past asbestos exposure, new treatments should be explored as a matter of urgency and we believe international collaboration is needed to obtain sufficient subject numbers to make progress in this area. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. NOTES published online ahead of print at www.jco.org on December 1, 2008 REFERENCES 1. Simon GR, Verschraegen CF, Jänne PA, et al: Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: Final report of a phase II trial. J Clin Oncol 21:3567-3572, 2008 2. Clements M, Berry G, Shi M, et al: Projected mesothelioma incidence in men in New South Wales. Occup Environ Med 64:747-752, 2007 3. Robinson BW, Lake RA: Advances in malignant mesothelioma. N Engl J Med 353:1591-1603, 2005 4. Muers MF, Stephens RJ, Fisher P, et al: MS01 Trial Management Group: Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): A multicentre randomised trial. Lancet 371:1685-1694, 2008[CrossRef][Medline] 5. O’Lone E, Park E-K, Sandrini A, et al: Early malignant pleural mesothelioma presenting with hydropneumothorax and detected by serum soluble mesothelin related protein measurement. Med J Australia 2008 (in press) 6. Robinson BWS, Creaney J, Lake R, et al: Mesothelin-family proteins and diagnosis of mesothelioma. Lancet 362:1612-1616, 2003[CrossRef][Medline] 7. Scherpereel A, Grigorlu B, Conti M, et al: Soluble mesothelin-related peptides in the diagnosis of malignant pleural mesothelioma. Am J Respir Crit Care Med 173:1155-1160, 2006 8. Park E-K, Sandrini A, Yates DH, et al: Soluble mesothelin related protein (SMRP) in an asbestos exposed population. Am J Respir Crit Care Med 178:832-837, 2008
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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