Johns Hopkins University and Washington University in Saint Louis

Multi-Modality Quantitative Imaging for Evaluation of Response to Cancer Therapy

Eric Frey, Ph.D
efrey1@johnshopkins.edu
Johns Hopkins University
Grant Number: U01 CA140204

The spread of cancer to bones is an important area of cancer research, and there are currently no widely used quantitative imaging methods for evaluating the response to therapy in metastatic bone lesions, complicating the evaluation of new therapies. This project seeks to develop, validate, and translate into clinical practice quantitative imaging methods based on relatively easily implemented changes to bone scintigraphy protocols, the current standard of care for evaluating bone metastases.

Bone metastases are common in advanced cancers including prostate adenocarcinoma, where there is evidence of bone metastases in more than 70% of patients with advanced disease. Despite their prevalence and the important clinical implications, there is currently no widely accepted quantitative imaging assessment for response to therapy. Assessment of response or progression is typically made based on visual interpretation of bone scintigraphy in conjunction with CT and serum markers. The goal of this QIN project is to develop, validate, and advance to clinical practice multi-modality quantitative metrics for assessing response of bone metastases to therapy. Combined SPECT-CT systems and the implementation of robust compensation methods has enabled the development of quantitative SPECT imaging methods, which have recently become clinically available. In this project the Johns Hopkins team aims to exploit the nexus of these developments via three aims: (1) Using simulation and phantom studies, the team endeavors to first optimize and evaluate methods for quantitative SPECT/CT (QSPECT) imaging of Tc-99m MDP. Additionally, they propose to expand the phantom studies to a QIN cooperative project in order to evaluate the methods across different scanners and centers. (2) Based on these QSPECT methods, the team will develop, optimize, and characterize quantitative bone SPECT indices for assessing response to therapy. Computing these indices will involve semi-automatic segmentation of bone and bone lesions, implemented in an integrated software tool. The indices calculated will include the number of lesions, bone lesion burden, and change in lesion uptake with therapy. They will characterize the variability of the indices using realistic simulations and in pre-therapy test-retest studies. (3) Finally, the team aims to apply the methods and validate them in current clinical trials of new therapeutic regimens for bone metastatic castrate-resistant prostate cancer. In these studies, they will evaluate the methods in terms of time to progression and will compare the methods in vivo to similar quantitative metrics estimated from Na18F PET/CT. The Hopkins team will also investigate the amount of additional information provided by whole-body MRI and PSMA PET/CT. The team plans to make the methods and images available to the QIN and propose to organize challenges of segmentation and response metrics to take advantage of the QIN-wide interest in these areas. Taken together, these quantitative imaging tools and studies will provide a validated approach for quantitative imaging-based evaluation of response in bone metastases that is readily clinically implementable with only a minor increase in cost relative to clinical standard bone scintigraphy.

Recent Publications

TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer.
Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V.
J Clin Oncol. 2019 Mar 20;37(9):714-722. doi: 10.1200/JCO.2018.78.7986. Epub 2019 Feb 5. PMID: 30721110

Reply to E. Hindié et al.
Connolly RM, Huang CY, Stearns V, Wahl RL.
J Clin Oncol. 2019 Jun 28:JCO1901078. doi: 10.1200/JCO.19.01078. [Epub ahead of print] No abstract available. PMID: 31251693

Jones, K. M., L. B. Solnes, S. P. Rowe, M. A. Gorin, S. Sheikhbahaei, G. Fung, E. C. Frey, M. E. Allaf, Y. Du and M. S. Javadi (2018). "Use of quantitative SPECT/CT reconstruction in (99m)Tc-sestamibi imaging of patients with renal masses." Ann Nucl Med 32(2): 87-93.

Vicente, E. M., M. A. Lodge, S. P. Rowe, R. L. Wahl and E. C. Frey (2017). "Simplifying volumes-of-interest (VOIs) definition in quantitative SPECT: Beyond manual definition of 3D whole-organ VOIs." Med Phys 44(5): 1707-1717.

Jha, A. K., E. Mena, B. Caffo, S. Ashrafinia, A. Rahmim, E. Frey and R. M. Subramaniam (2017). "Practical no-gold-standard evaluation framework for quantitative imaging methods: application to lesion segmentation in positron emission tomography." J Med Imaging (Bellingham) 4(1): 011011.

Rowe, S. P., E. Vicente, N. Anizan, H. Wang, J. P. Leal, M. A. Lodge, E. C. Frey and R. L. Wahl (2015). "Repeatability of Radiotracer Uptake in Normal Abdominal Organs with 111In-Pentetreotide Quantitative SPECT/CT." J Nucl Med 56(7): 985-988.