Image-Guided Cancer Therapy
Image-Guided Percutaneous Tumor Ablation / Treatment
Matthew Callstrom, M.D.; J. W. Charboneau, M.D.; Thomas Atwell, M.D.; Michael Farrell, M.D.; and Stephanie Carlson, M.D.; lead a very active research program, developing and testing a variety of methods for imaged-guided percutaneous ablation of malignant tumors in multiple protocols. Methods of image guidance include ultrasound, CT, and MRI and combine modalities. Ablation/treatment technologies that are being tested include RF thermal, microwave thermal, laser thermal, cryotherapy, alcohol/sclerotic agent injection, chemotherapy injection, targeted immune systemic therapy, and gene therapy injection. Clinical goals range from palliation and pain relief to complete tumor eradication, depending on application. Interprogrammatic collaborators in these protocols include Svetomir Markovic, M.D.; Joseph Rubin, M.D.; Matthew Goetz, M.D.; Henry Pitot, M.D.; David Patterson, M.D.; Bradley Leibovich, M.D.; George Chow, M.D.; David Nagorney, M.D.; and Florencia Que, M.D.
Some of their current research initiatives include:
Dr. Callstrom has other ongoing research initiatives into the efficacy of cryoablation for pain. He is collaborating on project to develop software and hardware necessary for fusion of previously acquired CT with real-time ultrasound image data. This will allow rapid, confident correlation of CT findings with ultrasound imaging. In addition, this software and hardware system will allow ablation of masses in the liver and kidney that may not be well visualized with ultrasound imaging. And in another study, he is evaluating radiofrequency ablation of hepatic colorectal metastases to see if there is a correlation between tumor-free margin dimension and local recurrence rates following radiofrequency ablation of liver tumors.
- Endogenous Heat-Shock Vaccines for Melanoma Phase I/Feasibility Study – Dr. Markovic is hoping to induce a systemic response to cell surface antigens present on melanoma cancer cells. Sub-lethal radiofrequency ablation or cryoablation is used to induce and release heat-shock protein. Serum cell markers and specific lymphocyte markers will be analyzed to determine the specificity of the reaction to the ablation treatment.
- David Kallmes, M.D., is conducting a National Institutes of Health-funded study of the efficacy of percutaneous, image-guided vertebroplasty to improve the quality of life for patients suffering from painful vertebral compression fractures. This project focuses on patients with osteoporotic compression fractures, but is relevant to management of cancer patients, since the procedure is increasingly being applied for instance to palliate compression fractures in patients with multiple myeloma.
MR-Guided Focused Ultrasound Tumor Ablation
Joel Felmlee, Ph.D., leads research in the technical development of magnetic resonance (MR) image-guided focused ultrasound tumor ablation. The basic concept is to use a large, steerable ultrasound array located outside the body to create cautery-level temperatures at a tiny, well-defined focal spot within a target lesion. The temperature and location of the focal spot can be monitored non-invasively using MRI techniques, providing real-time targeting and thermal dosimetry. A computer-controlled actuator is used to raster the tiny focal spot in three dimensions, so that a lesion can be fully ablated.
Kathy Brandt, M.D., is Principal Investigator of a project entitled “Pilot Study of MR Guided Focused Ultrasound for Tissue Coagulation in Women with Breast Cancer: MR Imaging and Histopathologic Correlation, an Assessment of Target Accuracy and Patient Acceptance.” Dr. Brandt’s study utilizes the latest prototype of this MR-guided focused ultrasound ablation system. Her long-term goal is to develop a reliable non-invasive image-guided ablation therapy for breast cancer. Joel Felmlee, Ph.D.; Gina Hesley, M.D.; Kimberly Amrami, M.D.; Bradley Lewis, M.D.; Marilyn Morton, M.D.; Richard Ehman, M.D.; Clive Grant, M.D.; James Ingle, M.D.; and Paula Schomberg, M.D.; are collaborators in this project.
Dr. Hesley leading a project entitled “MR Guided Focused Ultrasound Surgery in the Treatment of Uterine Leiomyomas.” This protocol is testing the capacity of the MR-guided focused ultrasound ablation system to treat (debulk) symptomatic benign pelvic tumors. Preliminary results have been excellent in terms of symptom relief and no significant complications. Drs. Brandt, Felmlee, Ehman, and Bobbie Gostout, M.D., are collaborators on this project.
Dr. Felmlee’s research with MR-guided, focused ultrasound ablation has revealed important challenges in controlling the ablation dose to reach an appropriate histologic endpoint. He is working to develop MR elasticity imaging to measure focused ultrasound-excited tissue displacement as a means to directly monitor FUS thermal ablation during each treatment; and verify after all treatments are complete that the targeted tissue volume is entirely ablated. This research will provide data using the viscoelastic properties of thermally treated tissue to improve the MRI-guided, focused ultrasound thermal treatment of cancer through reliable monitoring and immediate assessment of tissue coagulation.
Image-Guided Prostate Brachytherapy
Brian Davis, M.D., Ph.D., is conducting research focused on the use of imaging as an aid in prostate brachytherapy and other minimally invasive prostate cancer therapies. He served as principal investigator on an NIH-funded R21 grant entitled “Real-time prostate brachytherapy using image fusion.” Dr. Davis also supports the Mayo Clinic Prostate SPORE, which has 2 of 6 projects related to image-guided therapy of locally recurrent prostate cancer following external beam radiotherapy where co-investigators from the Division of Radiation Oncology are providing input.
Dr. Fatemi is collaborating with Dr. Davis in a study of ultrasound visualization and evaluation of brachytherapy seeds during their placement in the prostate. It may be possible to evaluate these seeds by vibro-acoustography.
The goals of this study are to:
- Measure the relative ultrasound backscatter of different seed types as a function of seed orientation which affects their detectability and visibility in pulse-echo (in C-scan mode) imaging
- Evaluate the corresponding vibro-acoustic imaging of these seeds
Two Department of Defense grants related to prostate cancer therapy and imaging research were submitted in the past three years. One grant proposal was similar to the R21 funded grant described above and the other grant related to trans-urethral imaging of the prostate during brachytherapy.
Image-Guided Gene and Virotherapy
Dr. Carlson is incorporating radiologic imaging and interventional techniques to develop an innovative approach for the treatment of pancreatic cancer using intratumoral injection of a measles virus genetically-modified with the sodium-iodide symporter (NIS) gene (MV-NIS). MV-NIS is a highly potent oncolytic agent against all human tumor models that have been tested, and NIS gene expression allows the use of radioiodine-based in vivo imaging and therapy techniques. This work is conducted in collaboration with Stephen Russell, M.D., Ph.D., Gene and Virus Therapy Program. Dr. Carlson is also conducting a clinical trial comparing CT fluoroscopy-guided biopsies of mobile tumors in the lung or upper abdomen with or without the use of the respiratory monitoring system. Preliminary results show a decrease in procedure time and radiation exposure with the system. The use of the system allows the patient to consistently reproduce the same breath hold level during biopsy procedures. This allows consistent access to smaller mobile tumors than previously achieved. Co-investigators include: Michael Farrell, M.D.; C. Daniel Johnson, M.D.; Matthew Callstrom, M.D.; Joel Felmlee, Ph.D.; and Richard Ehman, M.D.
Radio-Immunotherapy
Gregory Wiseman, M.D., is a leader in radio-immunotherapy and radioisotope tumor therapy research at Mayo. He also has worked to develop new radio-labeled metabolic imaging techniques for tumor imaging.
In collaboration with Thomas Witzig, M.D., Hematology Malignancy Program, Dr. Wiseman is using radio-immunotherapy to treat patients with indolent non-Hodgkin lymphoma (NHL). To date, over 150 patients have been treated in a Phase I/II trial, two Phase II trials and a Phase III trial of radio-labeled IDEC Y-90 Y2B8 monoclonal antibody. He is also conducting a trial using I-131 anti-CD20 monoclonal antibody for treatment of CD20-expressing multiple myeloma; and another using sequential doses of Zevalin radio-immunotherapy and growth factors with radio-immunotherapy in the treatment of lymphoma.
Principal Investigator for a number of other clinical trial collaborations, Dr. Wiseman is collaborating with Angela Dispenzieri, M.D., to evaluate high dose Sm-153 Ethylene Diamine Tetramethylene Phosphonate (EDTMP) for autologous stem cell transplant for multiple myeloma. The study is nearing completion and a follow-up study with radiation sensitizers is planned.
He has also collaborated on a recent Phase I trial used Sm-153 EDTMP in high doses to treat bone tumors, and a second one is ongoing using Sm-153 EDTMP to treat bone tumors along with gemcitabine chemotherapy as a radiation sensitizer.
Imaging-based Assessment of Vascular Biology
Dr. Kallmes employs tissue engineering, gene therapy, and hemodynamic modeling techniques in his research. While his work has a neurovascular focus, his research in endothelial cell physiology has clear implications in the important area of tumor angiogenesis. One promising collaboration with Sanjay Misra, M.D., and Erik Ritman, M.D., Ph.D., is exploring vascular biology relevant to oncology.
