Originally published as JCO Early Release 10.1200/JCO.2008.16.2545 on December 1 2008

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Tumor Cavitation: Impact on Objective Response Evaluation in Trials of Angiogenesis Inhibitors in Non–Small-Cell Lung Cancer

Simon J. Crabb, Demetris Patsios, Eric Sauerbrei, Peter M. Ellis, Andrew Arnold, Glenwood Goss, Natasha B. Leighl, Frances A. Shepherd, Jean Powers, Lesley Seymour, Scott A. Laurie

From the Cancer Research UK Clinical Centre, University of Southampton, Southampton, United Kingdom; and National Cancer Institute of Canada Clinical Trials Group, Kingston, Ontario, Canada

Corresponding author: Simon J. Crabb, PhD, Cancer Research UK Clinical Centre, Somers Cancer Research Bldg (MP824), Southampton General Hospital, Tremona Rd, Southampton, SO16 6YD, United Kingdom; e-mail: S.J.Crabb{at}soton.ac.uk

Purpose We have observed cavitation of lesions in clinical trials of an angiogenesis inhibitor combined with chemotherapy for non–small-cell lung cancer (NSCLC). We hypothesized that cavitation might alter response assessment in such clinical trials.

Patients and Methods We performed a retrospective radiologic review of patients with NSCLC enrolled onto three National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) trials of platinum-based chemotherapy with or without a small-molecule angiogenesis inhibitor (vascular endothelial growth factor receptor inhibitor [VEGFRI]). Response was assessed both by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and a novel alternate method in which the longest diameter of any cavity was subtracted from the overall longest diameter of that lesion to measure target lesions. Rates of cavitation were documented.

Results Marked cavitation of pulmonary lesions was seen in 24% of 33 patients treated with VEGFRI combined with platinum-based chemotherapy but in none of 18 patients treated with platinum-based chemotherapy alone. Use of the alternate method for response assessment resulted in an alteration of response assessment, time to best response, duration of response, and time of disease progression in a minority of patients compared with RECIST.

Conclusion Cavitation of target and nontarget lesions is common in NSCLC patients treated with VEGFRIs and platinum-based chemotherapy. Impact on response and time to event outcomes occurred but seems to be less common. Response assessment might be improved by incorporating cavitation into volume assessment for target lesions, potentially altering outcomes of key efficacy parameters in clinical trials. This should be prospectively assessed in clinical trials of angiogenesis inhibitors.

published online ahead of print at www.jco.org on December 1, 2008

Supported by the Canadian Cancer Society.

Presented in part at the 12th World Conference on Lung Cancer, September 2-6, 2007, Seoul, South Korea.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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