NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
November 28, 2006 • Volume 3 / Number 46 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Eye-Sparing Method Effective for Ocular Melanoma Diagnosis

A study published online November 15 in Ophthalmology found that use of fine-needle aspiration biopsy of the eye was a generally safe and effective means to obtain cells for genetic analysis from patients with ocular melanoma to determine whether they are at risk for metastatic spread of the disease.

Each of 18 patients at the University of California, Los Angeles' Jules Stein Eye Institute had the needle biopsy done during surgery to implant a radioactive plaque in the affected eye for localized radiation, which is the standard treatment of choroidal melanoma. It has been shown that patients with mutations in chromosome 3 (monosomy 3) are at high risk for metastatic spread, which has a poor prognosis. Until now, the only method for obtaining tumor cells for such genetic analysis involved removing the eye.

The researchers reported that the needle biopsy technique "was diagnostic of choroidal melanoma in 14 of 18 cases and resulted in viable cell cultures for fluorescent in situ hybridization (FISH) analysis in 9 cases." The genetic analysis for monosomy 3 was positive in four of the nine cases. "These findings are consistent with reports in the literature of an approximately 50 percent rate of monosomy 3 in choroidal melanoma," they noted.

"In our series, we observed only one complication: a patient developed a mild self-limited vitreous hemorrhage," the researchers reported. Identification of ocular melanoma patients with a poor prognosis may allow for the detection of metastasis at an earlier stage and will help select those best suited for clinical trials on new treatments, they added.

Nanoparticles Successfully Deliver Drugs to Brain Tumors in Mice

In a new study from the University of Michigan published in the November 15 Clinical Cancer Research, investigators designed targeted nanoparticles that successfully carried a photodynamic therapy compound to brain tumors in a mouse model, bypassing the blood-brain barrier.

The researchers designed the nanoparticles to bind to the cell-surface protein F3 because previous studies had shown that substances bound to this protein are taken up by cancer cells and their associated blood vessels. The nanoparticles were engineered to carry the photodynamic therapy drug Photofrin, which reacts with oxygen in the presence of light to form toxic compounds. The addition of a magnetic resonance imaging compound to the nanoparticles allowed the investigators to directly observe destruction of tumor tissue and blood vessels.

In vitro experiments showed that nanoparticles targeted to F3 were successfully taken up by cancer cells, and 4 hours of incubation with the nanoparticles caused the death of 90 percent of cells in culture when combined with exposure to laser light (to activate the encapsulated Photofrin). Nontargeted nanoparticles did not cause cell death under the same conditions.

Investigators then tested the nanoparticles in a mouse model of glioma, the most common type of brain tumor. Mice with xenograft tumors receiving targeted nanoparticles and laser exposure survived significantly longer than mice receiving either nontargeted nanoparticles or free Photofrin with laser exposure. Two out of five animals receiving the targeted nanoparticles remained disease free 6 months after treatment.

Targeted nanoparticles could potentially circumvent many problems with systemic delivery of photodynamic drugs, explained the authors, including damage to normal tissue and long-lasting skin sensitivity to light.

Risks Identified for New Solid Cancer after Stem Cell Transplants

Older patients who receive a stem cell transplant for blood cancer are at increased risk of developing a new solid cancer years after the transplant and patients who receive stem cells from a female donor are at even higher risk, according to a study in the November 27 online issue of Cancer.

The study was performed by the Leukemia/Bone Marrow Transplantation Program of British Columbia, which operates out of Vancouver General Hospital. Records were analyzed for 926 patients who had been treated at the hospital with allogeneic stem cell transplantation between 1985 and 2003. The median age of these patients was 39 years, ranging from 12 to 65 years.

The analysis showed that 10-year risk of recurrence-related mortality was 27 percent. Twenty-eight patients - all of whom received myeloablative preparation prior to their transplant - developed a total of 30 solid tumors after their procedure, most often in the skin, lungs, and mouth. The cumulative incidence in the study group of developing a second solid cancer 10 years after the initial treatment was 3.1 percent, nearly twice that of the general population in British Columbia.

Those younger than 40 had a second-cancer risk of 1.9 percent, versus 4.6 percent for those over 40. The sex of the stem cell donor was also a significant risk factor: 4.6 percent for female donors and 1.8 percent for male donors. "This observation [of donor sex and cancer recurrence] has not been reported previously in the literature," the authors wrote, "and its explanation is uncertain."

Study Suggests Survival Benefit for Tamoxifen-Anastrozole Combo

A meta-analysis that combined data from three randomized clinical trials indicates that, for postmenopausal women with hormone-sensitive early-stage breast cancer, switching to the aromatase inhibitor anastrozole (Arimidex) for adjuvant treatment after 2 to 3 years on tamoxifen significantly improves overall survival.

Each trial had compared a group of women who took tamoxifen for 5 years with a group who, after 2 to 3 years on tamoxifen, had switched to anastrozole for 2 years. Switching resulted in fewer cases of local or metastatic recurrence of disease and fewer cancer deaths. With the exception of bone fracture risk, it also had a better safety profile.

The question for researchers conducting the meta-analysis was whether improved event-free survival from the tamoxifen-anastrozole combination translated into better overall survival. The meta-analysis revealed that patients whose treatment included a switch to anastrozole after 2 to 3 years of tamoxifen had a 29 percent improvement in overall survival.

"A lot of people have been waiting to see whether aromatase inhibitors will show a survival advantage, and I think these data will assure them that 5 years of tamoxifen is no longer the standard of care," said the study's leader, Dr. Walter Jonat, of the University of Kiel in Germany, in a news release. "The best treatment for women with hormone-sensitive early-stage breast cancer should include an aromatase inhibitor."

The results of the study, released early online by The Lancet Oncology on November 17, reinforce recommendations from several professional oncology groups with regard to the treatment of this patient population. They also reflect what is already happening in clinical practice, explained Dr. Jennifer Eng-Wong of the NCI Center for Cancer Research (CCR) Medical Oncology Branch.

"Most clinicians are incorporating aromatase inhibitors into treatment," she said, "either starting adjuvant therapy with them or switching to them after 2 to 3 years of tamoxifen."