Cancer Research Highlights

A promising new way to treat superficial tumors, such as tumors of the scalp or of the chest wall after a mastectomy, is a procedure called modulated electron therapy (MERT). That’s because the radiation dose of an electron beam falls off rapidly with distance, which allows the tumor to be irradiated at doses sufficient to kill cancerous cells, but spares the healthy tissue beneath from exposure to too much radiation.

Murat Surucu , a Postdoctoral Research Associate in the Radiation Oncology Department at the Washington University School of Medicine in St. Louis, and his colleagues have developed a number of tools that make MERT more effective and customizable to individual patients. Their protocol includes an automated field-shaping method to modulate the intensity of the electron beam and improve the ability to deliver an appropriate dosage to the tumor, a graphic user interface that can modify automated fields and energy selection, simulations that calculate dose distribution, and a second graphical user interface to optimize the overall dose distribution in the patient.

Surucu is the winner of the Jack Fowler Junior Investigator Competition, established in honor of Jack Fowler, Emeritus Professor of Human Oncology and Medical Physics at the University of Wisconsin. Talk (MO-D-351-01), “Optimization Tools for Modulated Electron Radiotherapy” is at 1:30 p.m. on Monday, July 28, 2008 in room 351.

A familiar problem in cancer radiation therapy is the persistence of tumors that do not respond to standard doses. Tumors that are low in oxygen (“hypoxic”) are in this category. They resist the curative effects of both radiation and chemotherapy-but that may change as a result of preliminary work by a group of New York researchers.

While much research is devoted to molecular manipulations to reverse or block the hypoxic tumor-promoting environment, the New York team is taking a new tactic: They are using the low-oxygen chemical signal to guide an adjustable-strength radiation treatment called Intensity Modulated Radiation Therapy (IMRT). The intensity modulation approach not only uses the low-oxygen environment to locate zones of radiation resistance, it then delivers extra radiation doses to the zones in hopes of overcoming resistance to standard doses. Researchers can also scale back the dose to minimize damage to tissues characterized by normal oxygen levels.

N. Lee, M.D. , from Memorial Sloan-Kettering Cancer Center in New York, is the lead researcher. She explains the significance of the team’s work this way: “Our results are able to visualize variable levels of hypoxia within tumors, which is potentially important for future therapies because it suggests this is a feasible approach to locating pockets of resistance and gaining local control over head and neck cancers.”

Dr. Lee’s group tested this approach in 10 patients with head and neck cancer. To visualize the tumors’ oxygen environments they radioactively labeled tracers and gave them intravenously to patients. The tracers were detected and displayed as an image by a technology known as 18F-fluoromisonidazole positron emission tomography (PET) scanning. Low oxygen zones were revealed based on a tumor zone’s uptake of the tracers. Regions of elevated 18F-fluoromisonidazole were identified as low in oxygen, and then treated with an intensity-modulated radiation boost to overcome the resistant zones.

Talk (WE-D-AUD C-2), “Hypoxia-Guided Intensity-Modulated Radiation Therapy for Head and Neck Cancer” is at 1:30 p.m. on Wednesday, July 30, 2008 in Auditorium C.

Tumors are notoriously heterogeneous. Although the cells of a tumor may descend from the same progenitor cell, they can mutate to become genetically unique, displaying distinct characteristics and behavior, and responding differently to environmental assaults. Some cancer cells, for example, may be highly resistant to radiation therapy, while others are insensitive to the drugs used in chemotherapy, all of which can confound cancer therapy. But does tumor heterogeneity change because of cancer treatment?

Chihwa Song , a postdoctoral researcher in the Department of Medical Physics at the University of Wisconsin, Madison, has with his colleagues taken the first steps toward finding an answer. The scientists conducted a statistical analysis of heterogeneity and its progression in nine people undergoing radiotherapy and six people getting chemotherapy, for various types of cancer. Each patient underwent diagnostic imaging prior to, and during, treatment.

Using a special type of positron emission tomography scan, the researchers looked for variation within tumors in the rates at which clumps of cells proliferate, which could be visualized as clusters of rapidly growing cells. A rapid rate of cell proliferation is one characteristic of highly malignant tumors. Song and colleagues found no major changes in proliferation heterogeneity over the course of radiotherapy treatment, but a large decrease in the amount of heterogeneity during chemotherapy. A larger decrease in heterogeneity could mean that the patients were becoming more responsive to their treatment.

The study, Song says, “seems to show that tumor heterogeneity changes over the time course of treatment, with response to treatment related to that change,” although the reasons why remain unclear. “If this is true, a change in tumor heterogeneity will serve as a prognostic tool.”

Talk (TH-D-AUD C-05), “Assessment of Heterogeneity Change in Tumors over Time Course of Treatment” is at 1:18 p.m. on Thursday July 31, 2008 in Auditorium C.

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