Adds Badrinath Konety, MD, director of the Institute for Prostate and Urologic Cancers at the University of Minnesota, “This study may further enable scientists to separate patients with more aggressive disease in an effort to better customize treatment.” If researchers can identify a marker or genetic criteria for this group of younger men with aggressive disease, much could be learned not only about their specific cancer but also about the characteristics of the less aggressive subtype, says Dr. Denmeade. “If the signature for these men could be identified, it also would help us define the population that needs to be studied,” he says. “It would speed up research in this area and lead to stronger results.”
Additional Research Already, researchers at Johns Hopkins working in collaboration with the group at the University of Michigan (including Dr. Cooney), have identified a rare but recurrent mutation in the HOXB13 gene that is associated with a significantly increased risk of hereditary prostate cancer.3 The mutation accounts for approximately 4% to 5% of prostate cancer in families, Dr. Cooney notes, adding that she believes there are more rare mutations in hereditary prostate cancer that have yet to be discovered.
Most research programs either study the tumor or the inherited DNA, but we are looking at both in order to understand what the interactions might be. —Kathleen Cooney, MD “In breast cancer, there is a much more clear understanding of genes that contribute to the disease,” she says. “We don’t have the genetic germline studies, and we’re much further behind than we should be.” Although certain genomic tests provide additional information regarding the aggressiveness of a patient’s prostate cancer and may help to guide treatment decisions, they are not yet used routinely in practice as similar tests are in breast cancer, Dr. Denmeade notes. “At this point, it gives us a platform to incorporate into some of our clinical trials, to look at patterns and correlations with who’s responding and who isn’t, and eventually it will lead to more personalized medicine,” he says. On a broader level, research groups across the world and at the The Cancer Genome Atlas of the National Cancer Institute
have identified a number of genetic variations associated with prostate cancer. In addition, studies currently are underway to investigate how various techniques, ranging from immune checkpoint inhibitors to altering various genetic pathways, will improve treatment, but all are still in the testing phase, says Dr. Konety. “Several are already in phase 3 trials, but we don’t know if all of them will be approved by the FDA,” he says.
Emerging Tools One challenge in prostate cancer research, Dr. Konety notes, is that many patients survive 5 or more years, and therefore researchers must wait for some time before they can determine whether a particular treatment works. Nevertheless, many tools are emerging that will help scientists to better study biopsy samples and examine DNA in the blood to search for mutations. “We’re in the ‘Wild West’ stage,” says Dr. Denmeade. “There are a lot of different competing technologies, and eventually one will emerge that will become the standard.” His group, for example, has developed a method of measuring variants of androgen receptors in circulating tumor cells in the blood, which can help to determine whether patients will respond to androgen therapy. At the same time, 5 other groups are developing different platforms with the same end goal. “I think the treatment phase will start exploding in the next 5 to 10 years,” he says. Dr. Denmeade hopes that policymakers who have cut research funds will begin to see the wisdom of developing new, more effective treatments that could actually reduce health care costs in the long run. Meanwhile, with all the controversy over prostate cancer screening and whether to treat patients with early-stage disease, Dr. Cooney hopes that scientists, the public, and policymakers all keep one main point in mind. “What’s been forgotten about is that prostate cancer is still the second leading cause of cancer death [in men],” she says.
References 1. Salinas CA, Tsodikov A, Ishak-Howard M, Cooney KA. Prostate cancer in young men: an important clinical entity. Nat Rev Urol. 2014;11:317-323. 2. Lange EM, Johnson AM, Wang Y, et al. Genome-wide association scan for variants associated with early-onset prostate cancer. PLoS One. 2014;9:e93436. 3. Ewing CM, Ray AM, Lange EM, et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012;366:141-149. DOI: 10.1002/cncr.29156
ASCO, AACR Issue Joint Response to Proposed FDA Tobacco Rule
I
n a jointly written letter, the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR) voiced support of the US Food and Drug Administration (FDA)’s proposal to extend its regulatory authority over tobacco products, urging the agency to regulate electronic cigarettes (e-cigarettes), cigars, and all other tobacco 3848
products. They also called for strengthening the proposed regulations for newly deemed products. Both organizations applauded the FDA’s proposal to regulate electronic cigarettes. Peter Yu, MD, president of ASCO, notes that this effort is particularly important because the medical community does not know much about the health
Cancer
December 15, 2014
effects of e-cigarettes. “We are also quite concerned that e-cigarettes may increase the likelihood that nonsmokers or former smokers will use combustible tobacco products or that they will discourage smokers from quitting,” he adds in the statement. Roy Herbst, MD, PhD, chair of the AACR Tobacco and Cancer Subcommittee, notes that “any benefits of e-cigarettes are most likely realized in a regulated environment in which appropriate safeguards can be implemented.” ASCO and AACR urged the FDA to ban youth-oriented tobacco advertising and marketing, self-service product displays, and tobacco company sponsorship of youth-oriented events. In addition, they called for restricting sales to minors and implementing age verification procedures for Internet sales. Furthermore, the organizations stressed the importance of banning e-cigarette flavors or flavor names that are brand or trademarked names of candy, cookies, soda, and other similar products. They also urged the agency to prohibit e-cigarettes containing candy and other youth-friendly flavors, unless evidence demonstrates that these methods do not encourage young people to use these products.
ASCO and AACR also strongly discouraged the FDA from exempting “premium” cigars from regulation, which currently is under consideration. They pointed to the statistic that even cigar smokers who do not inhale have a risk of mouth and throat cancer that is overall 7 to 10 times higher than that of individuals who have never smoked. Both large and small cigars are increasingly appealing to youth and adult users. At the same time, ASCO and AACR expressed serious concerns that as premium cigars continue to be available in an unregulated market while the tobacco industry continues to market to youth and young adults, progress in reducing youth tobacco use could be reversed. In addition, both organizations called for the FDA to drop the “consumer surplus” discount for assessing the net impact of the proposed deeming rule. The discount allows the FDA to only consider 30% of the benefits achieved by tobacco cessation because of the costs associated with the proposed regulation, including the “lost pleasure” of smoking. ASCO and AACR counter that addiction is an unwelcome problem for tobacco users, many of whom are not making rational and fully informed choices concerning product use. DOI: 10.1002/cncr.26157
Wide Disparities Found in Lymphoma Survival atients with lymphoma who live in low socioeconomic status (SES) neighborhoods experienced significantly worse survival than patients living in higher SES neighborhoods, according to a study by the Cancer Prevention Institute of California.1 Researchers found that those patients living in the poorest communities had a 34% greater risk of dying of the disease and other causes than patients in the highest SES communities. The study focused on patients with diffuse large B-cell lymphoma, which is the most common form of non-Hodgkin lymphoma in adults. Diffuse large B-cell lymphoma is a curable disease, but it can be fatal if not treated properly. Researchers studied patients diagnosed in California between 1988 and 2000 as well as those diagnosed between 2001 and 2009, after rituximab was introduced as the first-line conventional chemotherapy for lymphoma. Survival improved substantially for all patients after 2001, regardless of age, sex, and SES. However, at the same time, the SES disparity in survival significantly increased. The study’s lead author, Li Tao, PhD, a scientist at the Cancer Prevention Institute of California, notes that the findings suggest barriers exist to effective treatment in poorer neighborhoods, including inadequate insurance coverage, which could lead to delays in treatment as well as limited care and follow-up. Despite improvements in the treatment of lymphoma, disadvantaged populations are not benefitting and are more
likely to die of complications other than cancer, the authors say. These patients are much less likely to receive the ongoing care required for their general health, as well as necessary monitoring and the complex management of drug regimens. Dr. Tao and her colleagues note that additional research must measure the living conditions, environmental exposures, and individual factors that may be preventing these patients from accessing the same level of care and follow-up as their counterparts residing in higher SES areas.
Reference 1. Tao L, Foran JM, Clarke CA, Gomez SL, Keegan TH. Socioeconomic disparities in mortality after diffuse large B-cell lymphoma in the modern treatment era. Blood. 2014;123:3553-3562. DOI: 10.1002/cncr.29158
© GEORGEMPHOTOGRAPHY, STEVEN FRAME | SHUTTERSTOCK.COM
P
Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2014.
Cancer
December 15, 2014
3849
Copyright of Cancer (0008543X) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Additional Research Already, researchers at Johns Hopkins working in collaboration with the group at the University of Michigan (including Dr. Cooney), have identified a rare but recurrent mutation in the HOXB13 gene that is associated with a significantly increased risk of hereditary prostate cancer.3 The mutation accounts for approximately 4% to 5% of prostate cancer in families, Dr. Cooney notes, adding that she believes there are more rare mutations in hereditary prostate cancer that have yet to be discovered.
Most research programs either study the tumor or the inherited DNA, but we are looking at both in order to understand what the interactions might be. —Kathleen Cooney, MD “In breast cancer, there is a much more clear understanding of genes that contribute to the disease,” she says. “We don’t have the genetic germline studies, and we’re much further behind than we should be.” Although certain genomic tests provide additional information regarding the aggressiveness of a patient’s prostate cancer and may help to guide treatment decisions, they are not yet used routinely in practice as similar tests are in breast cancer, Dr. Denmeade notes. “At this point, it gives us a platform to incorporate into some of our clinical trials, to look at patterns and correlations with who’s responding and who isn’t, and eventually it will lead to more personalized medicine,” he says. On a broader level, research groups across the world and at the The Cancer Genome Atlas of the National Cancer Institute
have identified a number of genetic variations associated with prostate cancer. In addition, studies currently are underway to investigate how various techniques, ranging from immune checkpoint inhibitors to altering various genetic pathways, will improve treatment, but all are still in the testing phase, says Dr. Konety. “Several are already in phase 3 trials, but we don’t know if all of them will be approved by the FDA,” he says.
Emerging Tools One challenge in prostate cancer research, Dr. Konety notes, is that many patients survive 5 or more years, and therefore researchers must wait for some time before they can determine whether a particular treatment works. Nevertheless, many tools are emerging that will help scientists to better study biopsy samples and examine DNA in the blood to search for mutations. “We’re in the ‘Wild West’ stage,” says Dr. Denmeade. “There are a lot of different competing technologies, and eventually one will emerge that will become the standard.” His group, for example, has developed a method of measuring variants of androgen receptors in circulating tumor cells in the blood, which can help to determine whether patients will respond to androgen therapy. At the same time, 5 other groups are developing different platforms with the same end goal. “I think the treatment phase will start exploding in the next 5 to 10 years,” he says. Dr. Denmeade hopes that policymakers who have cut research funds will begin to see the wisdom of developing new, more effective treatments that could actually reduce health care costs in the long run. Meanwhile, with all the controversy over prostate cancer screening and whether to treat patients with early-stage disease, Dr. Cooney hopes that scientists, the public, and policymakers all keep one main point in mind. “What’s been forgotten about is that prostate cancer is still the second leading cause of cancer death [in men],” she says.
References 1. Salinas CA, Tsodikov A, Ishak-Howard M, Cooney KA. Prostate cancer in young men: an important clinical entity. Nat Rev Urol. 2014;11:317-323. 2. Lange EM, Johnson AM, Wang Y, et al. Genome-wide association scan for variants associated with early-onset prostate cancer. PLoS One. 2014;9:e93436. 3. Ewing CM, Ray AM, Lange EM, et al. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012;366:141-149. DOI: 10.1002/cncr.29156
ASCO, AACR Issue Joint Response to Proposed FDA Tobacco Rule
I
n a jointly written letter, the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR) voiced support of the US Food and Drug Administration (FDA)’s proposal to extend its regulatory authority over tobacco products, urging the agency to regulate electronic cigarettes (e-cigarettes), cigars, and all other tobacco 3848
products. They also called for strengthening the proposed regulations for newly deemed products. Both organizations applauded the FDA’s proposal to regulate electronic cigarettes. Peter Yu, MD, president of ASCO, notes that this effort is particularly important because the medical community does not know much about the health
Cancer
December 15, 2014
effects of e-cigarettes. “We are also quite concerned that e-cigarettes may increase the likelihood that nonsmokers or former smokers will use combustible tobacco products or that they will discourage smokers from quitting,” he adds in the statement. Roy Herbst, MD, PhD, chair of the AACR Tobacco and Cancer Subcommittee, notes that “any benefits of e-cigarettes are most likely realized in a regulated environment in which appropriate safeguards can be implemented.” ASCO and AACR urged the FDA to ban youth-oriented tobacco advertising and marketing, self-service product displays, and tobacco company sponsorship of youth-oriented events. In addition, they called for restricting sales to minors and implementing age verification procedures for Internet sales. Furthermore, the organizations stressed the importance of banning e-cigarette flavors or flavor names that are brand or trademarked names of candy, cookies, soda, and other similar products. They also urged the agency to prohibit e-cigarettes containing candy and other youth-friendly flavors, unless evidence demonstrates that these methods do not encourage young people to use these products.
ASCO and AACR also strongly discouraged the FDA from exempting “premium” cigars from regulation, which currently is under consideration. They pointed to the statistic that even cigar smokers who do not inhale have a risk of mouth and throat cancer that is overall 7 to 10 times higher than that of individuals who have never smoked. Both large and small cigars are increasingly appealing to youth and adult users. At the same time, ASCO and AACR expressed serious concerns that as premium cigars continue to be available in an unregulated market while the tobacco industry continues to market to youth and young adults, progress in reducing youth tobacco use could be reversed. In addition, both organizations called for the FDA to drop the “consumer surplus” discount for assessing the net impact of the proposed deeming rule. The discount allows the FDA to only consider 30% of the benefits achieved by tobacco cessation because of the costs associated with the proposed regulation, including the “lost pleasure” of smoking. ASCO and AACR counter that addiction is an unwelcome problem for tobacco users, many of whom are not making rational and fully informed choices concerning product use. DOI: 10.1002/cncr.26157
Wide Disparities Found in Lymphoma Survival atients with lymphoma who live in low socioeconomic status (SES) neighborhoods experienced significantly worse survival than patients living in higher SES neighborhoods, according to a study by the Cancer Prevention Institute of California.1 Researchers found that those patients living in the poorest communities had a 34% greater risk of dying of the disease and other causes than patients in the highest SES communities. The study focused on patients with diffuse large B-cell lymphoma, which is the most common form of non-Hodgkin lymphoma in adults. Diffuse large B-cell lymphoma is a curable disease, but it can be fatal if not treated properly. Researchers studied patients diagnosed in California between 1988 and 2000 as well as those diagnosed between 2001 and 2009, after rituximab was introduced as the first-line conventional chemotherapy for lymphoma. Survival improved substantially for all patients after 2001, regardless of age, sex, and SES. However, at the same time, the SES disparity in survival significantly increased. The study’s lead author, Li Tao, PhD, a scientist at the Cancer Prevention Institute of California, notes that the findings suggest barriers exist to effective treatment in poorer neighborhoods, including inadequate insurance coverage, which could lead to delays in treatment as well as limited care and follow-up. Despite improvements in the treatment of lymphoma, disadvantaged populations are not benefitting and are more
likely to die of complications other than cancer, the authors say. These patients are much less likely to receive the ongoing care required for their general health, as well as necessary monitoring and the complex management of drug regimens. Dr. Tao and her colleagues note that additional research must measure the living conditions, environmental exposures, and individual factors that may be preventing these patients from accessing the same level of care and follow-up as their counterparts residing in higher SES areas.
Reference 1. Tao L, Foran JM, Clarke CA, Gomez SL, Keegan TH. Socioeconomic disparities in mortality after diffuse large B-cell lymphoma in the modern treatment era. Blood. 2014;123:3553-3562. DOI: 10.1002/cncr.29158
© GEORGEMPHOTOGRAPHY, STEVEN FRAME | SHUTTERSTOCK.COM
P
Content in this section does not reflect any official policy or medical opinion of the American Cancer Society or of the publisher unless otherwise noted. © American Cancer Society, 2014.
Cancer
December 15, 2014
3849
Copyright of Cancer (0008543X) is the property of John Wiley & Sons, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
