Cancer Research Highlights
Type of Surgery Affects Long-Term Survival in Early-Stage Kidney Cancer
Older patients with early-stage kidney cancer lived longer if only the tumor, and not the entire kidney, was removed, according to a new study. Cancer-specific survival, however, was similar regardless of whether patients had a partial nephrectomy or a radical nephrectomy. The findings were published April 18 in JAMA.
Dr. David Miller of the University of Michigan Comprehensive Cancer Center and his colleagues used NCI’s SEER-Medicare Linked Database to analyze data from approximately 7,100 Medicare beneficiaries who had surgical treatment for kidney tumors that were 4 cm or smaller (stage T1a) between 1992 and 2007.
The authors used a statistical model to adjust for differences between the two treatment groups. This analysis showed that patients who had a partial nephrectomy had a 46 percent lower risk of death from any cause. Based on the model, the research team estimated that one death was averted during 8 years of follow-up for every seven patients treated with partial nephrectomy instead of radical nephrectomy.
Radical nephrectomy can substantially increase the risk of developing chronic kidney disease, studies have shown. The survival difference seen in the JAMA study and others, explained Dr. Miller, may be due to a greater frequency of long-term complications from chronic kidney disease, including cardiovascular adverse events, among patients who received radical surgery. He cautioned, however, that further research is needed to demonstrate whether complications are, in fact, the cause of the survival difference.
Although clinical guidelines now recommend partial nephrectomy for most patients with early-stage kidney cancer, the procedure has not been widely adopted. In this study, only 27 percent of the patients had undergone a partial nephrectomy. Choosing which type of surgery to have, Dr. Miller acknowledged, can involve a trade-off because partial nephrectomy is more technically challenging than radical nephrectomy and can be associated with more short-term complications.
Active surveillance—forgoing immediate treatment after diagnosis and closely monitoring the tumor—is another option for some patients. And minimally invasive robotic surgery is also increasingly being used to perform partial nephrectomy, added Dr. Miller. “From my view, the robotic platform has made partial nephrectomy a much more technically accessible procedure.”
Survival Differences Persist Between Black and White Children with Cancer
Despite substantial improvements in childhood cancer survival over the past several decades, racial disparities in survival rates persist—and, in fact, have worsened for some cancer types—according to a study published online April 30 in the Journal of Clinical Oncology.
The study, by researchers from St. Jude Children’s Research Hospital, showed that over two different study periods, black children diagnosed with cancer in the United States were less likely to survive 5 years after diagnosis than white children. But when the researchers analyzed survival rates for children treated at St. Jude specifically, there was no survival difference between black and white patients. St. Jude accepts and treats all patients regardless of ability to pay and absorbs all costs not covered by third-party insurers.
To conduct the study, the research team analyzed data from NCI’s Surveillance, Epidemiology, and End Results (SEER) database and from St. Jude’s own patient registry. The researchers looked at data for two periods: 1992 to 2000 and 2001 to 2007. The analysis included only black and white patients.
Although survival rates improved substantially for several cancers from the earlier to the later study period, the SEER data analysis “showed significantly inferior outcomes for black patients in the vast majority of disease categories,” the researchers reported. The survival disparity narrowed over time for acute lymphoblastic leukemia and Hodgkin lymphoma but expanded for acute myeloid leukemia and neuroblastoma. At St. Jude, survival rates also improved between the two time periods for most types of cancer but were similar in blacks and whites.
Although information on participants' socioeconomic status was not available, when the researchers looked at insurance coverage as a proxy for socioeconomic status, black patients were far more likely to have public insurance and far less likely to have private insurance.
The study’s lead investigator, Dr. Ching-Hon Pui, chair of St. Jude Department of Oncology, said he was “disappointed” to see that survival disparities between black and white patients in the United States had not narrowed but was encouraged by the results at St. Jude showing that this disparity can be overcome.
Lack of access to team-oriented care with strong medical and psychosocial support is clearly a driving factor behind the continued disparities, Dr. Pui added. He cited, for example, lower rates of adherence to treatments among underprivileged patients. “It takes a lot of time and effort to explain to parents or guardians how to take the medicine and to make sure that patients actually get their medicine,” he said. “[At St. Jude] we have a team of nurse practitioners, nurses, social workers, and doctors of pharmacy to help with those sorts of things.”
For more information about cancer disparities research, visit NCI’s Center to Reduce Cancer Health Disparities.
Hispanics Have Lower Death Rates for Common Lung Cancer
A large population-based analysis of U.S. patients diagnosed with non-small cell lung cancer (NSCLC) indicates that Hispanic white patients have better overall survival than non-Hispanic whites and blacks, according to a report published online April 23 in Cancer. The researchers also found that Hispanic whites had higher rates than non-Hispanic whites of a subtype of NSCLC that has a more favorable prognosis than other subtypes of the disease.
Dr. Brian Lally and his colleagues at the University of Miami analyzed data from more than 172,000 patients in NCI’s Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with NSCLC between 1988 and 2007. Among the clinical variables that could account for the differences in survival, the investigators found that the NSCLC subtypes associated with better survival, particularly the bronchioalveolar carcinoma subtype, were more common in Hispanic whites.
The authors noted that previous studies have indicated that Hispanic white patients have better survival than non-Hispanic white and black patients for several diseases, including cardiovascular disease, breast cancer, and prostate cancer. “This finding was previously termed the ‘Hispanic paradox,’ because [Hispanic whites] in the United States tend to have fewer resources and less access to care than [non-Hispanic whites] and also tend to have a poverty rate similar to that of blacks,” the authors noted.
“The results of our analysis suggest that different molecular phenotypes of NSCLC may be the product of an interaction between genetic and environmental factors that could be related to ethnicity,” the researchers said. Further studies into these factors are needed, they concluded.
Women at High Risk for Breast Cancer May Benefit from Starting Mammography at Age 40
For women with twice the average risk of developing breast cancer, the benefits and harms of beginning biennial (every-other-year) screening mammography at age 40 are similar to those for average-risk women aged 50 to 74 screened biennially, according to a new modeling study. These results, published May 1 in the Annals of Internal Medicine, may provide important information to move toward individualized, risk-based screening, the study authors wrote.
A companion paper published in the same issue of Annals identified women aged 40 to 49 with a first-degree relative with breast cancer or with extremely dense breasts (Breast Imaging Reporting and Data System category 4 breast density) as having double the average risk of breast cancer.
To determine which women younger than 50 might benefit from mammography at a level similar to those aged 50 to 74, Nicolien van Ravesteyn of Erasmus Medical Center in the Netherlands and her colleagues used four breast cancer models developed by the NCI-funded Cancer Intervention and Surveillance Modeling Network (CISNET). These models allowed the authors to estimate the benefits and harms associated with mammography screening for women in their 40s under a variety of different assumptions about a woman’s risk of developing breast cancer. The models also incorporated additional data on film and digital mammography use in community practices from the Breast Cancer Surveillance Consortium.
Among younger women, screening mammography prevents fewer deaths because their risk of breast cancer is lower to begin with, explained the authors. Thus, for most younger women, the harms of screening mammography may outweigh the benefits.
According to the models, for women with twice the average risk of developing breast cancer, “the balance of benefits and harms…of starting biennial screening at age 40 years approximates that of biennial screening for average-risk women starting at age 50 years,” wrote the authors. In the models, annual screening added little benefit, and the risk of false-positive results was higher with digital mammography than with film mammography.
“Decisions related to screening women in their 40s on a personal or public policy level are complex, and these results add to the body of knowledge available to inform these decisions,” said Dr. Kathy Cronin of NCI’s Surveillance Research Program and scientific coordinator of the CISNET breast cancer group. “The results do not directly answer the question of which women should be screened in their 40s, but rather highlight the importance of including individual risk in the discussion between women and their physicians.”
Combination Targeted Therapy for Liver Cancer Shows Promise in Mice
New findings show that a combination of two drugs that act on the same target by different mechanisms is more potent than either drug alone in shrinking tumors and reversing altered gene expression in a mouse model of liver cancer. On the basis of these unexpected findings, published online April 25 in Science Translational Medicine, researchers have initiated an early-phase clinical trial of the drug combination in patients with liver cancer and other solid tumors.
The two drugs—everolimus, which is already approved for the treatment of a number of cancers, and an experimental drug being tested in clinical trials known as BEZ235—inhibit mTOR, a protein that controls cell growth, proliferation, and autophagy. The mTOR signaling pathway is overly active in many human cancers, including 40 to 50 percent of liver cancers. Everolimus and other related mTOR inhibitors, called rapamycins, are being tested in patients with liver cancer in clinical trials.
However, the rapamycins now in clinical use do not completely block the effects of mTOR signaling in cells, explained Dr. Sara Kozma of the University of Cincinnati, who led the new study. She and her colleagues originally set out to determine whether BEZ235 was more effective than the rapamycins. To their surprise, they found that the two drugs had synergistic effects when used together at low doses.
Further experiments showed that the two-drug combination increased autophagy, a process thought to suppress liver tumors, compared with a placebo or either drug alone. More studies are needed to explore how increased autophagy could contribute to tumor regression, Dr. Kozma commented.
“The fact that we could find synergy of BEZ235 with a drug that is already approved for clinical use may facilitate [BEZ235’s] introduction into the clinic,” Dr. Kozma said. Furthermore, she noted, adverse side effects would be reduced if lower doses of the two-drug combination prove effective in treating human cancers.