Using PET for therapy monitoring in oncological clinical trials: challenges ahead.

Molecular imaging with PET has emerged as a powerful imaging tool in the clinical care of oncological patients. Assessing therapy response is a prime application of PET and so the integration of PET into multicentre trials can offer valuable scientific insights and shape future clinical practice. However, there are a number of logistic and methodological challenges that have to be dealt with. These range from availability and regulatory compliance of the PET radiopharmaceutical to availability of scan time for research purposes. Standardization of imaging and reconstruction protocols, quality control, image processing and analysis are of paramount importance. Strategies for harmonization of the final image and the quantification result are available and can be implemented within the scope of multicentre accreditation programmes. Data analysis can be performed either locally or by centralized review. Response assessment can be done visually or using more quantitative approaches, depending on the research question. Large-scale real-time centralized review can be achieved using web-based solutions. Specific challenges for the future are inclusion of PET/MRI scanners in multicentre trials and the incorporation of radiomic analyses. Inclusion of PET in multicentre trials is a necessity to guarantee the further development of PET for routine clinical care and may yield very valuable scientific insights.

Validation of novel imaging methodologies for use as cancer clinical trial end-points.

The success or failure of a clinical trial, of any phase, depends critically on the choice of an appropriate primary end-point. In the setting of phases II and III cancer clinical trials, imaging end-points have historically, and continue presently to play a major role in determining therapeutic efficacy. The primary goal of this paper is to discuss the validation of imaging-based markers as end-points for phase II clinical trials of cancer therapy. Specifically, we outline the issues that must be considered, and the criteria that would need to be satisfied, for an imaging end-point to supplement or potentially replace RECIST- defined tumour status as a phase II clinical trial end-point. The key criteria proposed to judge the utility of a new end-point primarily relate to its ability to accurately and reproducibly predict the eventual phase III end-point for treatment effect, which is usually assessed by a difference between two arms on progression free or overall survival, both at the patient and more importantly at the trial level. As will be demonstrated, the level of evidence required to formally and fully validate a new imaging marker as an appropriate end-point for phase II trials is substantial. In many cases, this level of evidence will only become available by conducting a series of coordinated prospectively designed multicentre clinical trials culminating in a formal meta-analysis. We also include a discussion of situations where flexibility may be required, relative to the ideal rigorous evaluation, to accommodate inevitable real-world feasibility constraints.

Superiority of iodine-123 compared with iodine-131 scanning for thyroid remnants in patients with differentiated thyroid cancer.

PURPOSE: Iodine-123 is a pure gamma emitter and has excellent characteristics for imaging with modern scintillation cameras. The goal of this study was to compare the performance of I-123 and I-131 as imaging agents for whole-body scanning in patients with differentiated thyroid cancer undergoing ablation for thyroid remnants after initial surgery. METHODS: Fourteen patients with differentiated thyroid cancer who had undergone near-total thyroidectomy and had serum thyroid-stimulating hormone levels greater than 40 mU/I underwent diagnostic scanning 5 hours after administration of 48 to 56 MBq (1.3 to 1.5 mCi) I-123 and 48 hours after administration of 111 MBq (3 mCi) I-131. After receiving ablative I-131 therapy, they also underwent whole-body planar imaging 7 days later. The diagnostic I-123 and I-131 scans were compared with each other and with the post-therapy images by two nuclear medicine physicians and one endocrinologist. RESULTS: The diagnostic scans revealed 35 foci in the thyroid bed and neck. The I-123 images showed all 35 foci, but only 32 of the 35 foci (91 %) were seen on the I-131 scans. The findings of pre- and post-therapy scans were concordant in 11 of 13 patients, and the same general sites of uptake (left and right thyroid bed, midline) were revealed on both sets of images. In one patient, a focus seen on the diagnostic I-123 and I-131 images was not visualized on the post-therapy scan and was thought to represent possible stunning. An additional area of uptake in the lower right neck and upper mediastinum was present on the post-therapy scan of another patient, but it was not seen on diagnostic images. CONCLUSION: These results show improved quality of imaging with 50 MBq (1.5 mCi) I-123 compared with 111 MBq (3 mCi) I-131 for whole-body scanning in patients with differentiated thyroid cancer undergoing thyroid remnant ablation. I-123 imaging may prove to be the preferred procedure in such settings in patients with differentiated thyroid cancer.