An article in the August 1 Journal of Clinical Oncology by researchers in NCI's Division of Cancer Prevention shows how effective Minority-Based Community Clinical Oncology Programs (MBCCOPs) have been in boosting minority enrollment in cancer clinical trials, and outlines steps that could be taken to see higher enrollments in the future. NCI funds 13 MBCCOPs in 10 states, the District of Columbia, and Puerto Rico to increase the number of underrepresented groups in cancer clinical trials. Begun in 1990, these programs are part of the larger network of 63 NCI-funded CCOPs based in clinical research facilities.
Although MBCCOPs make up less than 20 percent of all CCOPs, they contribute 33 percent of the overall minority recruitment for all trials in the CCOP network, and 44 percent of minority recruitment to cancer prevention and control trials. In the early years of prevention and control trials (1995-1999), between 51 and 60 percent of the participants at MBCCOPs were minorities; by 2003, 80 percent of participants in these trials were minorities.
"The MBCCOP program has been successful in improving both the visibility of and accessibility to clinical trials in minority communities," said Dr. Worta McCaskill-Stevens, program director. "In addition to increasing minority participation in trials, the program holds great potential to contribute to minority-focused research in a number of ways."
Some of the most critical factors that influence recruitment of minorities to clinical trials within the MBCCOPs are the availability of protocols targeting the most common cancers seen in minority communities, the level of institutional support for minority recruitment, and issues endemic to the communities themselves, such as cultural barriers and access to transportation.
During the past 20 years, results from randomized trials have led to the widespread adoption of screening mammography and clinical breast exams. However, a study in the July 20 Journal of the National Cancer Institute calls into question the mortality benefit of breast cancer screening as practiced in the real world, compared with the well-controlled situations of clinical trials.
Dr. Russell Harris of the University of North Carolina framed the question in an accompanying editorial: "To what extent is widespread screening in the United States in 2005 contributing to reducing breast cancer mortality?"
For the study, Dr. Joann Elmore and colleagues at the University of Washington reviewed the medical records of approximately 4,000 women from 6 health plans across 6 states. They identified 1,351 women who had died from breast cancer between 1983 and 1998, and 2,501 women, matched for age and risk factors, who had not been diagnosed with breast cancer.
The researchers found similar screening rates among the groups, but an advantage to screening was not clear. For example, 69.7 percent of the cancer patients aged 50-65 years with an average risk of developing the disease had gotten mammograms and/or breast examinations by a clinician in the past 3 years, compared with 69.2 percent of the cancer-free women of similar age and risk.
While the study results conclude that screening may have less impact on mortality in "real world" practice than it has proven to have in closely monitored clinical trials, the authors caution that their study is too small to verify that a modest reduction in mortality could be occurring in some subgroups. Additionally, they note, women who receive more than one screening within 3 years might have a greater benefit.
Breast cancer often metastasizes to the lungs, leading to a poor prognosis, but clinicians have no way of knowing which patients might be at risk for such metastases. Research from Memorial Sloan-Kettering Cancer Center, reported in the July 28 Nature, identifies a series of genes that mediate the spread of breast tumors to the lungs.
Dr. Andy Minn and colleagues developed a line of highly metastatic human breast cancer cells. When injected into mice, the cells developed into large lung tumors. Gene microarray analysis of the tumors highlighted a set of genes abnormally active in the cancer cells that migrated to the lungs compared with those that did not.
The team then examined tumors from 82 breast cancer patients. They found a subset of patients whose tumors seemed to abnormally express the newly identified genes. A close examination of the most crucial genes identified a clear split in risk among patients. Those with abnormal levels of the genes had an 89-percent risk of lung metastasis over 10 years versus a 56-percent risk among patients without the abnormal gene pattern.
Further analysis revealed that a separate set of genes is responsible for spreading breast tumors into bone - the second most common site of breast cancer metastases. The authors speculate that bone and lung metastasis are therefore different molecular processes. "In addition to providing...potential prognostic tools and possible targets for cancer treatment, the present findings shed light on the biology of breast cancer metastasis," they write.
Resistance to treatment with ONYX-015, a genetically modified virus that selectively attacks tumor cells, can be overcome by inducing a heat-shock response in tumor cells, according to a study in the July Cancer Cell.
ONYX-015, the first modified adenovirus to be approved for testing in human clinical trials, has proven in early stage clinical trials to be effective in shrinking tumors when combined with chemotherapy. The researchers sought to determine why some patients failed to respond to treatment with ONYX-015.
Dr. Clodagh O'Shea and colleagues at the University of California, San Francisco, reported that in laboratory studies, inducing a heat-shock response made tumor cells that were initially resistant to therapy with ONYX-015 amenable to treatment. The heat shock, the authors noted, "rescued" intracellular functions needed for the virus to replicate inside the tumor cell and induce cell death.
Specifically, they reported, heat shock restores late RNA export in resistant cells. The heat-shock response was induced both by pharmacologic induction with benzoquinoid ansamycins and by incubating the cells at elevated temperatures. In both cases, late RNA functions were rescued in resistant tumors, increasing viral yield 10-fold or more in 8 out of 10 resistant tumor cell lines. Moreover, viral activity in primary cells was not restored by the heat shock.
A clinical strategy that does not advocate suppression of fever, or that includes the heat-shock induction, they concluded, "could greatly augment ONYX-015's clinical utility as a cancer therapy."
Because the cure rates for men with stage I seminoma, a type of testicular cancer, are nearly 100 percent, clinicians focus on relapses and side effects in evaluating the best treatment. To this end, a European research team compared the standard adjuvant treatment, radiation, with single-dose carboplatin chemotherapy to see if adverse effects can be reduced. Their results are published in the July 23 Lancet.
Men in the study, who had their cancerous testicle removed before enrollment, were randomized to receive either a single intravenous dose of carboplatin or radiation of the groin dosed between 30 Gy in 15 sessions and 20 Gy in 10 sessions. The researchers used chest x-rays; chest, abdomen, and pelvic CT scans; and blood tests for tumor markers to monitor recurrence. Patients recorded side effects of treatment in a diary.
After a median of 4 years of follow-up, relapse-free survival was nearly the same in both groups: 96.7 percent in the radiation group and 97.7 percent in the carboplatin group after 2 years, and 95.9 percent versus 94.8 percent, respectively, after 3 years. Men who received carboplatin had less fatigue after treatment and returned to work more quickly than those who received radiation. "As well as carboplatin having fewer acute toxic effects than radiotherapy," the authors wrote, "some preliminary data indicate that carboplatin treatment delays and possibly reduces the incidence of contralateral second germ-cell tumours." They also noted that more follow-up is needed to confirm their findings.