Compliance with PET acquisition protocols for therapeutic monitoring of erlotinib therapy in an international trial for patients with non-small cell lung cancer
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The Response Evaluation Criteria in Solid Tumors (RECIST) are widely used but have recognized limitations. Molecular imaging assessments, including changes in 18F-deoxyglucose (FDG) or 18F-deoxythymidine (FLT) uptake by positron emission tomography (PET), may provide earlier, more robust evaluation of treatment efficacy.
A prospective trial evaluated on-treatment changes in FDG and FLT PET imaging among patients with relapsed or recurrent non-small cell lung cancer treated with erlotinib to assess the relationship between PET-evaluated response and clinical outcomes. We describe an audit of compliance with the study imaging charter, to establish the feasibility of achieving methodological consistency in a multicentre setting.
Patients underwent PET scans at baseline and approximately day 14 and day 56 of treatment (n = 73, 66 and 51 studies, and n = 73, 63 and 50 studies for FDG PET and FLT PET, respectively). Blood glucose levels were within the target range for all FDG PET scans. Charter-specified uptake times were achieved in 86% (63/73) and 89% (65/73) of baseline FDG and FLT scans, respectively. On-treatment scans were less consistent: 72% (84/117) and 68% (77/113), respectively, achieved the target of ±5 min of baseline uptake time. However, 96% (112/117) and 94% (106/113) of FDG and FLT PET studies, respectively, were within ±15 min. Bland-Altman analysis of intra-individual hepatic average standardized uptake value (SUVave), to assess reproducibility, showed only a small difference in physiological uptake (−0.006 ± 0.224 in 118 follow-up FDG scans and 0.09 ± 0.81 in 111 follow-up FLT scans).
It is possible to achieve high reproducibility of scan acquisition methodology, provided that strict imaging compliance guidelines are mandated in the study protocol.
KeywordsCompliance PET acquisition protocols Erlotinib therapy Non-small cell lung cancer
We would like to thank all the patients who participated in the study, and the clinical site teams: (in Australia) Peter MacCallum Cancer Centre, East Melbourne, Victoria; Austin Hospital, Heidelberg, Victoria; Royal Brisbane Women’s Hospital, Herston, Queensland; Prince Charles Hospital, Brisbane, Queensland; (in the USA) USC Medical Center Kenneth Norris Cancer Center, Los Angeles, CA; Pacific Cancer Medical Center, Inc, Anaheim, CA; St. Joseph Hospital, Regional Cancer Center, Orange, CA; and the Wilshire Oncology Medical Group, Inc., Corona, CA. We would like to acknowledge the site investigators Timothy Byun, Veena Charu, Barbara Gitlitz, Jeffrey Goh, Frank Howard, Brett Hughes, Samuel Kipper, Kai Lee, Paul Mitchell, and Hui Trung.
This work was supported financially by Genentech, Inc., South San Francisco, CA, USA. Drs. Pirzkall, Yu and Fine are employees at Genentech, Inc., and own stock with F. Hoffmann-La Roche, Ltd.
Genentech, Inc. provided assistance with preparation of the manuscript.
- 1.Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–16.PubMedCrossRefGoogle Scholar
- 5.Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999;35:1773–82.PubMedCrossRefGoogle Scholar
- 14.Erlotinib (Tarceva®) (package insert). South San Francisco: Genentech, Inc., 2007.Google Scholar
- 16.Calvert H, Twelves C, Ranson M, Anthoney A, Plummer R, Fettner S, et al. The effect of erlotinib on CYP3A4 activity, as quantified by the erythromycin breath test and oral midazolam kinetics in cancer patients: preliminary results. J Clin Oncol 2005;23 (June 1 Supplement):3076.Google Scholar