Summary of the UPICT Protocol for 18F-FDG PET/CT Imaging in Oncology Clinical Trials.

The Uniform Protocols for Imaging in Clinical Trials (UPICT) (18)F-FDG PET/CT protocol is intended to guide the performance of whole-body FDG PET/CT studies within the context of single- and multiple-center clinical trials of oncologic therapies by providing acceptable (minimum), target, and ideal standards for all phases of imaging. The aim is to minimize variability in intra- and intersubject, intra- and interplatform, interexamination, and interinstitutional primary or derived data. The goal of this condensed version of the much larger document is to make readers aware of the general content and subject area. The document has several main subjects: context of the imaging protocol within the clinical trial; site selection, qualification, and training; subject scheduling; subject preparation; imaging-related substance preparation and administration; imaging procedure; image postprocessing; image analysis; image interpretation; archiving and distribution of data; quality control; and imaging-associated risks and risk management.

New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy.

OBJECTIVE: The purpose of this article is to compare the recently published revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1) to the original guidelines (RECIST 1.0) for advanced non-small cell lung cancer (NSCLC) after erlotinib therapy and to evaluate the impact of the new CT tumor measurement guideline on response assessment. MATERIALS AND METHODS: Forty-three chemotherapy-naive patients with advanced NSCLC treated with erlotinib in a single-arm phase 2 multicenter open-label clinical trial were retrospectively studied. CT tumor measurement records using RECIST 1.0 that were generated as part of the prospective clinical trial were reviewed. A second set of CT tumor measurements was generated from the records to meet RECIST 1.1 guidelines. The number of target lesions, best response, and time to progression were compared between RECIST 1.1 and RECIST 1.0. RESULTS: The number of target lesions according to RECIST 1.1 decreased in 22 patients (51%) and did not change in 21 patients (49%) compared with the number according to RECIST 1.0 (p < 0.0001, paired Student's t test). Almost perfect agreement was observed between best responses using RECIST 1.1 and RECIST 1.0 (weighted kappa = 0.905). Two patients with stable disease according to RECIST 1.0 had progressive disease according to RECIST 1.1 criteria because of new lesions found on PET/CT. There was no significant difference in time to progression between RECIST 1.1 and RECIST 1.0 (p = 1.000, sign test). CONCLUSION: RECIST 1.1 provided almost perfect agreement in response assessment after erlotinib therapy compared with RECIST 1.0. Assessment with PET/CT was a major factor that influenced the difference in best response assessment between RECIST 1.1 and RECIST 1.0.

Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate.

PURPOSE: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney were investigated. Tissue perfusion was measured using oxygen-15 (15O)-labeled water and blood volume was measured using 15O-labeled carbon monoxide (C15O). Scans were performed immediately before, and 30 minutes and 24 hours after the first infusion of each dose level of CA4P. All statistical tests were two sided. RESULTS: PET data were obtained for 13 patients with intrapatient dose escalation. Significant dose-dependent reductions were seen in tumor perfusion 30 minutes after CA4P administration (mean change, -49% at >or= 52 mg/m2; P =.0010). Significant reductions were also seen in tumor blood volume (mean change, -15% at >or= 52 mg/m2; P =.0070). Although by 24 hours there was tumor vascular recovery, for doses >or= 52 mg/m2 the reduction in perfusion remained significant (P =.013). Thirty minutes after CA4P administration borderline significant changes were seen in spleen perfusion (mean change, -35%; P =.018), spleen blood volume (mean change, -18%; P =.022), kidney perfusion (mean change, -6%; P =.026), and kidney blood volume (mean change, -6%; P =.014). No significant changes were seen at 24 hours in spleen or kidney. CONCLUSION: CA4P produces rapid changes in the vasculature of human tumors that can be assessed using PET measurements of tumor perfusion.