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Our radiation sciences team includes members of the departments of radiology, radiation oncology, and medical physics. Our clinical research is focused on developing the latest state-of-the-art technologies for cancer diagnosis and treatment.
We participate in all disease management teams at Memorial Sloan-Kettering, and we collaborate with basic science researchers working in the laboratory.
Among our recent research accomplishments:
Radiation Therapy Advances
Radiation Oncology Learn more about the work of our radiation oncology staff
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- We are continuing efforts to improve target homogeneity in the breast and to decrease exposure to surrounding normal tissues, using intensity-modulated radiation therapy (IMRT) and a prone treatment board designed at MSKCC. Long-term local control in the prone position matches data in the conventional supine position with a more favorable toxicity profile for lung, heart, and skin tissue. Given the cardiotoxicity of commonly used adjuvant systemic agents, this approach may lead to a decreased risk of late effects.
- Based on both the decreased risk of local failure in older women and the feasibility of single-dose partial breast irradiation demonstrated by investigators in Milan, Italy, we developed a technique called intra-operative partial breast radiation using a high-dose rate remote afterloader for use during breast conserving surgery, a procedure which is performed in a shielded operating room. A specially designed HAM applicator was produced for this study, and the feasibility of the approach was demonstrated in our first patient cohort (limited to women 60 years or older). Both the surgery and the single-dose radiation are delivered together on an outpatient basis. Int J Radiat Oncol Biol Phys. 2007;68(1):73-81. [PubMed Abstract]; Int J Radiat Oncol Biol Phys. 2007;69(1):19-24. [PubMed Abstract]
- Our radiation oncologists have been investigating ways of effecting more precise delivery of high-dose radiation through better control of tumor motion and the integration of PET and cone-beam imaging. Integrating PET into treatment planning improves the reproducibility of tumor delineation. A phase I dose-escalation trial using 3D conformal radiotherapy for inoperable non-small cell lung cancer established that a dose of 84 Gy can be safely delivered in patients and reported very favorable survival and local control rates in patients receiving greater than 80 Gy. Int J Rad Oncol Biol Phys 2005;62:70-75. [PubMed Abstract]; Cancer 2005;103:2118-2127. [PubMed Abstract]
Imaging Studies
Radiology Learn more about the work of our radiology staff
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- Three-dimensional tumor assessment techniques developed at MSKCC for evaluating response to treatment are now being widely evaluated in clinical trials and in the National Cancer Institute/Food and Drug Administration/Centers for Medicare & Medicaid Services Oncology Biomarker Qualification Initiative. This work has resulted in recognition that Rapid Evaluation Criteria in Solid Tumors (RECIST) and other methods of response assessment are not equivalent; that volumetrics may provide a more meaningful measure of response; that automated computational techniques may decrease variability and enhance reproducibility; and that other treatment effects (such as necrosis) may be quantified along with size changes. Annals Oncol. 2006;17:1018-1023. [PubMed Abstract]
- Our investigators demonstrated that fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) scanning can distinguish between indolent and aggressive lymphoma and can be used to detect histological transformation of indolent to aggressive lymphoma. J Clin Oncol. 2005;23:4643-4651. [PubMed Abstract]
- In the area of interventional radiology, we are developing techniques for fusing multiple imaging modalities to help guide therapy with tools that contain electromagnetic position sensors displaying the position of the tool on the fused images. We are developing treatment-planning software that is integrated into robotic systems for accurate needle delivery for thermal ablation. With General Electric Healthcare, we are designing a real-time, open computed tomography (CT) system that will enable access to the patient in a four-dimensional imaging system. Heart Rhythm. 2005;2:413-415. [PubMed Abstract]; J Vasc Interv Radiol. 2005;16:445-447. [PubMed Abstract]; J Vasc Interv Radiol. 2006;17:903-907. [PubMed Abstract]
- With immunology researchers, our interventional radiologists are developing mouse models in which thermal ablation, which leaves dead cells in place, creates a systemic antitumor effect. Clinical applications thus far include the use of a PET-detectable antibody against clear-cell renal cancer to assess the postablation tumor bed for residual disease. With the Thoracic Disease Management Team, they are building a lung ablation registry, and they expect to begin a multicenter bone ablation study shortly. Finally, the interventional radiology team assists multiple research groups with research-related tissue acquisition. PLoS Med. 2005;2:e73. [PubMed Abstract]
- In the area of image analysis, our researchers are developing methodologies for improving the information yield of imaging for clinical oncology. We are evaluating imaging modalities and techniques, postprocessing algorithms, and other metrics for evaluating response, especially early response to therapy. We have documented and quantified limitations of current response assessment criteria and have proposed solutions and modifications. For thin-section multislice CT, we have developed disease-specific and organ-specific segmentation algorithms to segment tumors in several anatomic sites rapidly, accurately, and reproducibly. Finally, we are evaluating functional imaging techniques for assessing response, including FDG-PET, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and perfusion CT, and have applied these methods in clinical trials. The goal is to qualify these imaging biomarkers by demonstrating biological relevance, accuracy, and reproducibility, so that they may ultimately be validated in larger multicenter clinical trials. Annals Oncol. 2006;17:1018-1023. [PubMed Abstract]; Invest Radiol. 2006;41:753-762. [PubMed Abstract]; Med Phys. 2006;33:2452-2460. [PubMed Abstract]; Radiology. 2005;234:934-939. [PubMed Abstract]; J Nucl Med. 2006;47:901-903. [PubMed Abstract]; J Clin Oncol. 2006;24:4293-4300. [PubMed Abstract]
- We also have a growing program in the discovery and development of informative imaging probes. For imaging the central nervous system of model systems, some of the models have already had a direct impact on clinical research directions. Our E2F1 luciferase mouse was used with the PDGF-induced glioma model to demonstrate that tumors driven by PDGF respond to inhibition of signaling through the PDGF receptor or mTOR. As a consequence, both PTK787 (a PDGF inhibitor) and CCI779 (an mTOR inhibitor) are being evaluated in multicenter trials for patients with gliomas. We also tested the new Akt-inhibiting drug perifosine and identified its effects in gliomas in mouse models; these data were instrumental in convincing the manufacturer to sponsor a clinical trial in glioma patients at MSKCC. Cancer Res. 2005;65:7429-7435. [PubMed Abstract]
- New radiolabeled cell proliferation probes may differentiate low-grade from high-grade gliomas and afford earlier detection of treatment response than is currently possible, as well as better localization of brain tumors than is afforded by FDG-PET or contrast MRI. Patient studies with 11C-methionine and the novel MSKCC-generated amino-acid ligand 18F-FACBC are nearing completion.
- Building on extensive therapeutic and pharmacodynamic studies with single-photon emitters, our researchers have embarked on PET tracer studies of antibodies for improved dosimetry of targeted therapy and in vivo immunotyping. Clinical trials with the positron-emitting antibodies 124I-G250 and 124I-A33 are underway; the ability to define tumor histology with imaging appears to be a promising guide to surgical planning for renal cancer.
- Clinical trials of the novel hypoxia probe 124I-IAZGP have begun, initially to establish safety and define biodistribution, pharmacokinetics, radiation dosimetry, and the optimal imaging time post-injection. Clinical trials comprising both colorectal and head and neck cancer patients will involve a head-to-head comparison of 124I-IAZGP and 18F-FMISO to assess their prognostic value for predicting treatment outcome in each disease. Positive results would suggest the approach may have value in developing adjunctive treatment strategies, such as guiding the use of the hypoxic cell-specific cytotoxic agent tirapazamine or exploring a clinical extension of our preclinical radio-gene therapy studies. A second study is planned to validate PET against direct pO2 measurements and immuohistochemical analysis of hypoxia-related proteins (such as CAIX, VEGF, HIF-Alpha 1, and GLUT-1) on tumor biopsies of distally located rectal cancer. This study will be based on a recently developed methodology to relate spatially tumor hypoxia data from different sources.
- Although imaging of the thyroid with radioactive iodine is perhaps the oldest application of functional imaging in medicine, striking improvements are still possible by varying the emission characteristics of the probe. Our thyroid and nuclear medicine groups have pioneered the utility of 124I PET-based imaging as an effective means of restaging patients who develop subsequent thyroid cancer metastases. They have also shown that 124I PET-based, patient-specific three-dimensional dosimetry is feasible, and that sequential PET can be used to obtain accumulated activity images for three-dimensional dosimetry. In addition, in all thyroid cancer subtypes, FDG-PET scanning is an effective means of restaging patients who develop subsequent metastases, assigning them to groups that are either at low (FDG-negative) or high (FDG-positive) risk of cancer-associated mortality. J Clin Endocrinol Metab. 2006;91:498-505. [PubMed Abstract]
- MRI and magnetic resonance spectroscopic imaging (MRSI) have substantial value in staging. Specifically, our investigators have demonstrated in large studies (of more than 300 patients) that MRI and MRSI contribute significant incremental value to clinical variables and clinical staging nomograms in the prediction of extracapsular extension and seminal vesicle invasion in prostate cancer. MRI can detect cancer in the transition zone as well as recurrent disease. We have also demonstrated the importance of sub-specialization in image interpretation and the utility of MRI for improving surgical planning. In addition, we have learned that MRI/MRSI can provide an indication of tumor aggressiveness and can contribute incremental value to nomograms for the prediction of indolent cancer. Radiology 2006;239:784-792. [PubMed Abstract]; Radiology 2006;238:176-183, 2006. [PubMed Abstract]; Radiology 2005;234:804-814. [PubMed Abstract]
- In women with a high risk of developing breast cancer, screening breast MRI can identify cancer that is not detected by mammography or physical examination in 4 percent of women. We have quantified the frequency of cancer as a function of specific MRI features, including lesion size. In collaboration with the Department of Surgery, we have developed and refined biopsy methods for lesions identified only by MRI, using preoperative localization for surgical biopsy and vacuum-assisted needle biopsy. AJR 2005; 185:183-193. [PubMed Abstract]; AJR 2006; 186: 426-430. [PubMed Abstract]
- As an adjunct to breast MRI, MRSI of the breast has the potential to decrease the number of benign biopsies performed for MRI-detected lesions, while missing virtually none of the cancers. We now plan now to identify subpopulations of patients who are most likely to benefit from breast MRI; to prospectively study the sensitivity and specificity of spectroscopy in a variety of settings; and to refine MRI-guided intervention methods. We will study MRSI to monitor the response to chemotherapy, and will evaluate MRI-guided high-focused ultrasound for the percutaneous ablation of breast lesions -- a technique that holds promise for nonsurgical treatment. Radiology 2006; 239:686-692. [PubMed Abstract]
- Multiple retrospective and prospective studies conducted at MSKCC have demonstrated the value of PET standardized uptake value for predicting prognosis in patients with resectable non-small cell lung cancer, mesothelioma, and small cell lung cancer. These studies were either the initial or most persuasive studies. Our results in patients with mesothelioma led directly to the incorporation of PET imaging into a multicenter trial of multimodality therapy for the initial staging, prognostic stratification, and assessment of response to induction chemotherapy. Ann Thorac Surg. 2006;81:1076-1081. [PubMed Abstract]; J Thorac Cardiovasc Surg. 2006;132:763-768. [PubMed Abstract]
- Our imaging specialists are investigating the efficacy of DCE-MRI and MRSI as an a priori predictor or early marker of tumor response. In bone sarcoma, the hypothesis is that MRI technologies can identify lack of response early enough to allow effective change in chemotherapy. Early results suggest a promising correlation with pathology and that pretreatment ATP levels (perhaps a surrogate of hypoxia) in the soft-tissue components of bone sarcomas predict outcome. We are currently trying to broaden applicability by focusing on detecting lactate, which would allow extension of the studies to smaller soft-tissue components. Researchers are also beginning clinical trials in patients with head and neck tumors using 1H spectroscopy studies of metabolism, DCE-MRI, and imaging 18F-fluoromisonidazole with PET.
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