Cancer Research Highlights

The discomfort of a mammogram can drive some women to avoid the valuable screening, occasionally with dire consequences. Now a new procedure, dedicated breast computed tomography (CT), promises to take the pain out of breast cancer detection.

In the cone beam breast CT scanner, which was first developed at the University of California, Davis, a woman lies face down on a special table with one breast suspended through an opening. A CT scanner rotates around the breast, collecting data that are reconstructed into a three-dimensional image. The total dose of radiation is the same as in a conventional mammogram.

Since 2004, the UC Davis researchers, led by John M. Boone , Professor and Vice Chair of Radiology and Professor of Biomedical Engineering, have scanned 160 women with their prototype scanner. In early 2008, the researchers began operating a second prototype device, into which the researchers have incorporated a positron emission tomography (PET) scanner. The PET scanner tracks the metabolic activity of a tumor, if present, so the hybrid CT/PET breast scanner would allow clinicians to, among other uses, precisely localize and monitor the response of a tumor to chemotherapy, determine the extent (or staging) of tumors, and help guide radiologists conducting biopsies.

The clinical trials show that the scanner “is better mammography for mass detection,” Boone says, while “offering improved comfort to the patient and a better three-dimensional understanding of pathological lesions when they are present.” The scanner, however, is less efficient than regular mammography at detecting the tiny clusters of calcium (or microcalcifications) that can sometimes signal breast cancer. This is because it uses X rays at higher energies than do mammograms, reducing the contrast of the images and the ability to distinguish the calcium clusters. “Thus, we are not making the claim that breast CT is “better” than mammography-yet,” Boone says.

Scientists at The Ohio State University (OSU) have identified a way to predict very early in the treatment process the outcome of radiation and chemotherapy for cervical cancer patients - based on oxygen levels within the tumor.

The oxygenation of a tumor is critical for the success of cancer treatment. That’s because the amount of oxygen in a cell is directly correlated with the ability of that cell to repair radiation damage. When the oxygen level is low, a state called hypoxia, the biological changes in tumor cells produced by radiation - that will hopefully destroy the cells - can be repaired, and tumor recurrence is more likely. But when oxygen is present, it reacts with free radical molecules to produce organic peroxide, which causes that damage to be “permanent and irreparable,” says study head Jian Z. Wang, Ph.D. , an Assistant Professor at OSU and the Director of the Radiation Response Modeling Program at the OSU James Cancer Hospital and Solove Research Institute. Inevitably, those well-oxygenated tumor cells die, tumors are less likely to return, and patient survival rates rise, says Wang.

In their study of 88 women with cervical cancer, Dr. Wang and his colleagues measured the level of hemoglobin, the oxygen-carrying molecule in blood, and measured blood supply to the tumor through magnetic resonance imaging (MRI) scans. Blood tests were conducted weekly beginning prior to treatment, and MRI scans were performed before radiation treatment, during radiation at 2-2.5 and 4-5 weeks, and 1-2 months after treatment. Cancer recurrence rates were tracked for up to 9 years. This study was supported by a NIH R01 grant led by the principal investigator Nina A. Mayr, M.D., Professor of Radiation Medicine at the OSU James Cancer Hospital and Solove Research Institute.

Measurements of tumor oxygenation just 2 weeks into treatment provided the best predictor of tumor control and disease-free survival. That early glimpse into the future can identify individuals at the greatest risk of having their cancer return, Mayr says, giving doctors the opportunity to adopt more aggressive therapies to improve the prognosis. Wang predicts that, with further testing, the technique also will prove useful for other types of cancer.

An integrated, multi-modality molecular imaging system, invented in 1999 by Martin Tornai, Associate Professor of Radiology and Biomedical Engineering of Duke University, and developed by Priti Madhav and other of Tornai’s grad students over the years, may improve detection, diagnosis and treatment monitoring of breast cancer, while also relieving some of the discomfort often associated with breast exams. The system allows subjects to lie prone while both a dedicated SPECT and CT scan are taken of the breast. Because these are three-dimensional imaging techniques, there is no need to compress the breast (often painfully) as is done during a two-dimensional mammography.

To generate the SPECT image, the nuclear medicine technologist injects the subject with a radio-tracer associated with metabolism. Cancer cells are more active than normal cells, so they take up more of the gamma-ray-emitting tracer. The SPECT camera detects this gamma ray emission and produces an image of the 3D distribution of metabolic activity. To help physically localize the source, a dedicated breast CT scan, also developed in Tornai’s lab, with 0.5 millimeter resolution is obtained. When the two scans are fused together, the doctor has both functional (SPECT) and anatomical (CT) information in one picture. In a handful of patient imaging trials, the combined image highlighted cancerous cells that might have been missed in a CT scan by itself.

Although full body SPECT-CT already exists, this is the first dedicated SPECT-CT apparatus for breast imaging. The advantage of tailoring the machine to the breast is that the SPECT camera gets a better picture by being closer to the breast. Moreover, the CT scan is targeted, thus reducing the amount of radiation to other parts of the body. An added bonus is that the patient never has to move while the two scans are taken.

Talk (TU-C-332-04), “Pilot Patient Studies Using a Dedicated Dual-Modality SPECT-CT System for Breast Imaging” is at 10:36 a.m. on Tuesday, July 29, 2008 in room 332.

Nearly a third of leukemia patients do not respond to chemotherapy, but this is not usually discovered until they have already endured a week-long chemotherapy treatment and waited a month to see whether it has worked. A new study shows that PET scans could tell how well a patient is responding after just one day of chemotherapy.

Treating leukemia primarily involves killing the cancerous cells where they originate in the bone marrow. Chemotherapy can knock out bone marrow cells, but it also kills healthy cells, causing such side effects as immunodeficiency and weight loss. Doctors traditionally take a bone marrow biopsy after the treatment to assess how well the drugs have worked. This is unfortunately rather late for those who do not respond to chemotherapy. And even for those who do, the single biopsy is not always representative of how the entire bone marrow is responding.

A PET scan can detect cancerous activity in a full-body image, but it had previously never been used to assess leukemia treatment. As an investigative study, Matt Vanderhoek (.(JavaScript must be enabled to view this email address)) of the University of Wisconsin and his colleagues imaged eight people with leukemia at different stages of their chemotherapy. They used a PET radio-tracer called FLT (fluoro-L-thymidine), which is readily taken up by cells during cell division. Since leukemia cells divide more than normal cells, they should absorb a lot of FLT and appear brighter in the bone marrow of a PET scan. However, if chemotherapy is able to kill these over-proliferative cells, then the bone marrow should appear dark.

In their sample, the researchers found that brightness and non-uniformity in bone marrow PET scans was an indication that the subject was not responding to the chemotherapy. This assessment, which apparently can be made as early as day one, could potentially spare 30 percent of people with leukemia from a treatment that is wrong for them.

Talk (TH-D-AUD C-6), “Early Assessment of Treatment Response in Hematopoietic Disease Using [18F]FLT PET Imaging ” is at 1:30 p.m. on Thursday July 29, 2008 in Auditorium C.

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