Loading...

Follow Colorado Cancer Blogs on Feedspot

Continue with Google
Continue with Facebook
or

Valid

Philip Owens, PhD

When prostate cancer metastasizes to bone, it can become especially dangerous – not only with its action in the bone but, interestingly, with increased aggressiveness of the overall cancer itself. Now, research presented at the American Association for Cancer Research (AACR) Annual Meeting 2018 hints at why: Cells involved in these bone metastases may release signals that drive the progression of the disease.

“With prostate cancer, often a patient will come in with new bone growth, which can be really painful. What we show is that some of the same things that cause this new bone growth may help the cancer grow and spread,” says Philip Owens, PhD, investigator at the University of Colorado Cancer Center and Denver Veterans Administration Hospital Research Program.

Specifically, Owens looked at growth factors called bone morphogenetic proteins (BMPs). As the name implies, BMPs aid the growth of healthy bone – and are even used to grow new bone in procedures like spinal fusion. But mutations that dysregulate BMP – both turning up or turning down its activity – have been implicated in many cancer types. For example, low BMP signaling seems to drive some colorectal cancers, while high BMP signaling is associated with esophageal cancer.

Owens explored BMP signaling in a special kind of cell found in bone and bone marrow known as myeloid cells. These cells are multipotent, able to differentiate into new cell types that form components of bone and blood, especially cell types of the immune system. The current study knocked out the gene BMPR1a, one of these BMPs, specifically in myeloid cells. Mouse models of prostate cancer in which BMPR1a was removed formed fewer, smaller tumors than mice with active BMPR1a. Specifically, it seemed that conditional deletion of BMPR1a removed some of these myeloid cells’ stem-like abilities, restricting the kinds of cells they could produce (and in turn, restricting the ability of myeloid cells to drive cancer).

The team had previously shown that the experimental BMP inhibitor, DMH1, had dampened the growth of cancer cells and Owens calls the current study “genetic proof” showing not only that the drug happens to work, but also showing how the drug likely works in cells that are not the tumor themselves.

“We think there’s evidence that in many tissues, the BMP that is driving cancer is in fact coming from these myeloid cells. This is an emerging body of evidence showing the anti-cancer benefit of inhibiting BMP signaling in myeloid cells,” Owens says.

Owens’ continuing work at CU Cancer Center, CU School of Medicine and Denver VA Hospital hopes to continue making the case for BMP inhibition in myeloid cells as a component of prostate cancer treatment, possibly leading to a human trial of this strategy with DMH1 or another BMP inhibitor for patients with metastatic disease.

The post When prostate cancer reaches bone, bone cells may drive overall growth of the disease appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

James Costello, PhD

The chemotherapy docetaxel is widely accepted as a standard therapy for metastatic castration-resistant prostate cancer. But 10-20 percent of patients will have adverse side effects that force discontinuation of treatment. These patients may have been better off with another treatment in the first place, but who’s to know before trying the drug which patients will go on to experience debilitating side effects? A crowdsourced competition asked this as an open question. Today in the Journal of Clinical Oncology Clinical Cancer Informatics, competition organizers and participating teams report their findings: Using open data from four previously conducted clinical trials, teams of international researchers designed mathematical models predicting the likelihood that a patient will discontinue docetaxel treatment due to adverse events. These results represent the first comprehensive effort to make such predictions based on patient clinical characteristics.

Specifically, the challenge was to connect any of 129 baseline clinical measurements to the chance of docetaxel discontinuation. In all, 34 international teams submitted 61 models. Seven of these teams submitted models with similarly high predictive ability and so technically “won” the challenge. The five clinical factors that were most predictive were measures of hemoglobin, alkaline phosphatase, aspartate aminotransferase, prostate specific antigen, and ECOG performance status. The seven successful models all integrated these five factors into various computational frameworks.

Interestingly, after the competition officially ended, these top seven teams decided to collaborate outside the framework of the competition, resulting in refinements that led to a combined model that was more predictive than any of the submissions alone.

“The seven groups from around the world – Finland, Germany, Canada, Israel and the U.S. – had never formally met before the challenge. It’s a really exciting example of the power of scientific collaboration,” says James Costello, PhD, senior author of the paper, investigator at the University of Colorado Cancer Center, assistant professor in the Department of Pharmacology at the CU School of Medicine, and director of Computational and Systems Biology Challenges within the Sage Bionetworks/DREAM organization.

The combined model stratified patients into groups with low and high risk of discontinuing docetaxel due to adverse events, with the high group having more than double the likelihood of discontinuation as the low group.

“Not only could a model like this help identify patients who might benefit more from a different treatment, it also has the potential to immediately impact future clinical trials by improving patient selection through the use of novel patient selection designs. In doing so, the number of patients needed for clinical trials could be reduced, making more efficient use of available resources,” says Devin Koestler, PhD, assistant professor of Biostatistics at the University Kansas Medical Center, and one of the first authors of the paper.

The challenge was built to promote and capitalize on the potential of an open question paired with open data.

“The field is definitely moving toward a much more open sharing model of clinical trial data. This project is a great example of how you can gain new knowledge from existing data and how making clinical data open and freely accessible can maximize the use of these valuable data for the benefit of patients,” says Laura Elo, PhD, one of the senior authors of the paper, adjunct professor in Biomathematics and research director in Computational Biomedicine and Bioinformatics at Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, Finland.

The project was overseen as a collaborative effort between 16 institutions, led by academic research institutions including CU Cancer Center, open-data initiatives including Project Data Sphere, Sage Bionetworks, and the DREAM Challenges, and industry and research partners including Sanofi, AstraZeneca, and the Prostate Cancer Foundation.

Because only 10-20 percent of patients discontinue treatment due to adverse events, no single trial has enrolled enough patients to predict with statistical significance who would discontinue docetaxel – commonly, these trials tested the effectiveness of treatments in the population that was able to finish the regimen and were not designed to answer this secondary question of who would be unable to finish. Had clinical trial results remained firewalled by the academic or industry sponsors, this secondary question would have remained unanswered; however, the decision to open these clinical trial data allowed the current researchers to combine the numbers from four previous trials, pooling over 2,000 patients – enough to start identifying statistically significant patterns.

“The number of clinical trials in Project Data Sphere continue to grow. At the time of this study, there were about 10,000 patients in their database. Now there are over 66,000, meaning that we will be able to explore future questions with even greater accuracy and ask questions that have been unaddressable due to restricted data access,” Costello says.

The project takes place in the context of a debate between research factions, one of which holds that studies should generate new data designed to specifically explore study questions, and another faction that sees value in mining previously generated data for new insights. This study bridges the gap between these factions, involving both the clinicians who generated original data from clinical trials and also researchers using new tools to draw novel conclusions from these data.

“Ultimately what we’d like to do is have a much more dynamic interaction with the clinical trial design. As patients are coming in, we could use these statistical models to help match the right person with the right trial,” Costello says.

Chalk one up for research symbiosis: International, multi-institution research collaboration to mine previously generated, open data now offers a tool that can better leverage patient clinical characteristics and ease the process of clinical trials.

The post Research symbiosis makes mathematical crystal ball to gaze into future of prostate cancer treatment appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Elizabeth Kessler, MD

Androgen drives many prostate cancers. But the body uses androgen for muscle growth and maintenance, among other functions. An ongoing study published in the Journal of Clinical Oncology along with the American Society for Clinical Oncology (ASCO) Annual Meeting 2017 evaluates the effects of androgen deprivation therapy not just on patients’ physical function but on global geriatric health, including skills of daily living. Because the study is longitudinal, following individual patients from before treatment through the course of their care, findings can help to define not only the characteristics of men who will need supportive care, but when in treatment this care should begin.

Seventeen patients were enrolled on the study with a median age of 75 years and 14 with metastatic disease. Two tools were used to measure function and vulnerability, namely the Vulnerable Elders Survey (showing overall daily function), and the short physical performance battery (a common tool defining physical health in the context of oncology). On both scales about half of these patients were identified as vulnerable at baseline, reflecting the combined effects of age-related frailties and the influence of cancer.

Differences between these two measures emerged as early as three months after treatment. On the short performance battery, seven patients had seen declines at three months, with the most dramatic impairment being in patients’ ability to stand from a chair without using hands (reflecting loss of large muscle strength with androgen deprivation therapy). However, while three patients showed decreases on the Vulnerable Elders Survey, six showed increases at three months, likely due to the effect of anti-androgen therapy against their cancer. Of the 10 patients who were followed for at least six months, five had worsening scores on the Vulnerable Elders Scale whereas only two had worsening on the short physical performance battery.

“Oncologists use measures of a patient’s functional status to inform fitness for treatment, but there may be nuances you’re missing,” says Elizabeth Kessler, MD, oncology fellow at the University of Colorado Cancer Center and the paper’s first author. “What we wanted to know is the relationship between overall geriatric health and functional status. Results of this ongoing study are beginning to show that, first, because many of these men show baseline vulnerability due to their age and cancer, androgen deprivation therapy can show almost immediate improvement in functioning. But then, second, we do see effects of androgen deprivation on things like muscle strength that could be improved with intervention.”

Kessler points out that interventions already exist to support overall functioning in geriatric prostate cancer patients, often including components of cardiovascular and strength training.

“We even imply that some of these patients might benefit from pre-habilitation, starting physical interventions a few weeks before the start of anti-androgen therapy,” Kessler says. She points out that both tests used in this ongoing study can be administered by clinicians in an exam room without the need for specialized gym equipment or other specific resources.

“We’ve known that androgen deprivation affects physical function, but we haven’t known when that effect took place,” Kessler says. “This can tell us when to start interventions.”

The group’s next step will explore the influence of supportive health interventions in this population.

The post Study evaluates overall geriatric health during androgen deprivation therapy appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

A University of Colorado Cancer Center clinical trial is now recruiting prostate cancer patients who would otherwise be on a watch-and-wait protocol to test the ability of grape seed extract to slow the rise of prostate-specific antigen (PSA), a common marker of prostate cancer progression. The trial is the result of a series of CU Cancer Center studies demonstrating the promise of grape seed extract in preclinical models of prostate cancer, in collaboration with doctors at University of Colorado Hospital who treat the condition. In addition to testing grape seed extract, the trial provides the framework to test other promising compounds in this setting, potentially including additional compounds derived from natural sources.

“In this window, we would only be watching these patients – our trial is an alternative to observation, not an alternative to treatment – and we’ve shown that grape seed extract is unlikely to cause side effects. So why not take this opportunity to test some of these promising compounds, starting with grape seed extract?” says Paul Maroni, MD, investigator at the CU Cancer Center and associate professor of Surgery at the CU School of Medicine.

The trial will enroll 40 men with asymptomatic, non-metastatic prostate cancer with rising PSA, who will take 150 mg of grape seed extract by mouth twice daily. These men will then be evaluated every 6 weeks for a year to measure the progress of their cancer.

“Our hope it that the PSA will not rise as quickly as it has in the past for this patient,” says Maroni. “If we would expect it to go from 1 to 2 in next six months, but it only goes up to 1.5 in the grape seed extract group, that would be a significant improvement.  This might help them avoid needing other treatments with side effects.”

Because prostate cancer tends to be an especially slow-growing form of the disease, it may only take slowing the disease’s acceleration by a small amount to push back the date at which the cancer would be expected to become problematic far past a patient’s predicted lifespan.

“For many prostate cancer patients, the goal is to die with the disease rather than from it. We see the potential for grape seed extract to help us reach this goal,” Maroni says.

His optimism is built largely on the laboratory work of CU Cancer Center investigator Rajesh Agarwal, PhD, professor in the CU Skaggs School of Pharmacy and Pharmaceutical Sciences. Agarwal’s lab has primarily focused on using the tools of molecular medicine to evaluate compounds derived from natural products in the same ways that researchers would evaluate any promising anti-cancer agent.

For example, Agarwal’s 2012 paper in the journal Carcinogenesis shows that grape seed extract creates oxidative stress that damages cancer cell DNA and also interrupts the pathways that would repair this damage (as seen by decreased levels of the DNA repair molecules Brca1 and Rad51 and DNA repair foci). A 2015 paper in the journal Molecular Carcinogenesis looks even closer at this mechanism to show how grape seed extract initiates this oxidative stress, namely by targeting the energy-producing mitochondria in cancer cells. Another 2015 paper, in Current Cancer Drug Targets, shows that grape seed extract targets prostate cancer progenitor cells by slowing their ability to grow new blood vessels needed to supply the cancer with nutrients.

“I think the whole point is that cancer cells have a lot of defective pathways and they are very vulnerable if you target those pathways. The same is not true of healthy cells,” Agarwal says.

The Agarwal lab has followed this line of reasoning to show that grape seed extract does indeed use these mechanisms to slow the growth of cancers in mouse models, setting the stage for the current clinical trial which will test, for the first time, the effect of grape seed extract in human cancer patients.

In fact, ongoing work at the Agarwal lab is unpacking mechanics of a few other compounds derived from natural sources including milk thistle extract and bitter melon.

“Ultimately, if grape seed doesn’t change how we approach these patients, then we’ve built a program to examine other complimentary or low-side-effect medicines. If grape seed extract doesn’t work, we can take this protocol, put in a new background – bitter melon, milk thistle, etc.  – and examine that,” Maroni says.

Many drugs currently used against cancer originated from substances found naturally. Now this approach that uses the tools of Western medicine to evaluate what some would consider Eastern ideas may allow doctors to add to this list of naturally-derived compounds that aid our fight against cancer.

The post New clinical trial framework tests ‘natural’ cures for cancer appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Isabel Schlaepfer, PhD

Patients with castration resistant prostate cancer (CRPC) usually have a poor prognosis. In part, this is due to the cancer’s ability to resist anti-androgen therapy. A University of Colorado Cancer Center study published today in Oncotarget shows that combining a CPT1A inhibitors with anti-androgen therapy increases the cancer’s sensitivity to the anti-androgen drug enzalutamide.

“This is a huge development for men with CRPC that previously did not have many options,” says Isabel Schlaepfer, PhD, CU Cancer Center member, assistant professor in the Division of Medical Oncology and senior author of the study. “There is a critical need for improved therapies for this specific cancer type.”

Most cells use the energy of glucose (sugar). Some prostate cancers evolve to use energy from lipids (fat). Previous work shows that metabolizing lipids helps prostate cancer escape anti-androgen therapy. However, there are many steps involved in lipid metabolism and researchers have been working to break prostate cancer’s ability to harness this energy source. In this study the researchers focused on the CPT1A enzyme. CPT1A helps facilitate the entry of long chain fatty acids into the cell’s mitochondria for oxidation. This oxidation is vital to lipid metabolism and has been shown to aid cancer cell survival, resistance to radiation, oxidative stress, and activation of oncogenic signaling pathways.

“We had to find a way to block this pathway so that the cancer would not be able to burn lipid in the mitochondria to acquire energy to resist therapy,” explains Schlaepfer.

In fact, we are already able to block the action of the CPT1A enzyme. The drug ranolazine is a fat oxidation inhibitor that earned FDA approval in 2006 to treat angina. When Schlaepfer and colleagues experimented with fat burning inhibitors and anti-androgens in cancer cell lines,  they found that the addition of ranolazine to anti-androgen therapy made tumors more sensitivity to the anti-androgen drug enzalutamide.

“This finding may have a huge impact on patients with CRPC that had very few options before,” says Schlaepfer. “Since the drugs are clinically safe, a clinical trial can be designed in patients for whom enzalutamide is prescribed.”

The post Breakthrough study stops fat-eating prostate cancer cells appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Thomas W. Flaig, MD

Patients with metastatic prostate cancer whose PSA levels remain high despite initial hormone treatments have historically had poor prognosis, with survival typically in the 1-2 year range. Results of a 40-person clinical trial published in JAMA Oncology show that 13 percent of these patients deemed “hormone refractory” did, in fact, have strong responses to treatment with the next-generation hormonal drug abiraterone acetate, with PSA levels falling from above 4.0 ng/ml to below 0.2 ng/ml. An additional 33 percent of patients showed partial response to the drug, achieving PSA levels between 0.2 and 4 ng/ml.

“We set an especially high bar with our goal of reducing PSA to below 0.2, which is very low, especially for this high-risk population. The trial did not meet its success criteria of six full responders, but we feel that with five full responders and evidence that many more patients also received some benefit from the drug, abiraterone acetate deserves more study in this population,” says Thomas W. Flaig, MD, investigator at the University of Colorado Cancer Center and the trial’s national primary investigator.

Flaig also points to this trial as important evidence of the evolution of hormone therapy in prostate cancer.

“We used to think that if a patient’s cancer progressed despite traditional hormone therapy, that was it for hormone therapy. Now we see that’s not the case. It may just be that the first drug wasn’t strong enough, or that cancer became hypersensitive to any remaining androgen. Now with drugs like abiraterone we can almost completely cut off a cancer’s ability to drive its growth with androgen and we see this drug working even after the initial, standard hormone therapy has failed,” Flaig says.

The trial is one of many exploring the use of abiraterone acetate in various prostate cancer settings, including uses earlier in the sequence of treatment, and in patients with less progressed disease.

“This is one of the first studies to focus on this high-risk group of patients with early failure of hormone induction therapy. Seeing this level of response in patients that had previously been dubbed ‘hormone resistant’ reinforces our hope that this drug will help many kinds of patients in many settings,” Flaig says.

The post Trial shows responses to abiraterone acetate in some prostate cancer patients with initial hormone induction failure appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Brandon Bernard, MD

Brandon Bernard, MD, a medical oncologist, is joining University of Colorado Cancer Center’s elite team of physician/scientists treating and researching genitourinary cancers like prostate cancer.  

Bernard has big plans during his time at the Cancer Center. In addition to continuing his research in prostate and testicular cancers, he wants to dig deeper into other interests.

“My interests range from population studies, looking at outcomes of patients with urologic cancers both in Colorado and the country, to translational work looking at new biomarkers to guide drug development and further assist in understanding the different diseases,” he says. “I also plan on being heavily involved with clinical trials, so building up a portfolio on that front is definitely a priority!”

According to Dr. Bernard communication with his patients is also at the top of his priority list. He has embraced social media, particularly Twitter, as one of the most effective ways to reach not only his patients but also other doctors. 

 “I think social media can be an incredibly powerful resource and tool in academic medicine. It allows for rapid correspondence among peers, the quick dissemination of ideas, and boundless potential for networking and collaborative efforts,” he explains. “However, I think one has to be responsible on social media, as occasionally a tweet may be misleading due to the inherent brevity. As with everything, I think it’s important for doctors and patients alike to be thoughtful, conscientious, and respectful with how we communicate and interact online.”

Bernard completed his medical training in Canada, where he was born and raised. Eventually he traveled to the United States for genitourinary medical oncology fellowship at the Dana-Farber Cancer Institute in Boston in 2014.

“Cancer biology has always fascinated me,” says Bernard. “I did my undergraduate in biochemistry so there were a lot of examples of cancer as molecular workings gone wrong. From then on, I always saw myself as someone who could advance the field, and after exploring a few different options during medical school and residency, I invariably returned to oncology as the career for me.”

Before deciding on his specialty Bernard volunteered with crisis lines and counseling groups. It was after his experience working with families affected by all types of cancer that he decided to pursue urologic oncology.

“I decided to focus on urologic cancers as they comprise a diverse group of different cancer types and patient populations, pose an area of great research opportunity, and provide an environment for great teamwork and collaboration with colleagues in the field,” he explains.

Bernard moved to Colorado in November 2016 and is looking forward to the active, outdoor lifestyle that the state is known for.

“Outside of medicine, I love to travel, try new restaurants, explore the urban landscape, and maintain some semblance of physical fitness,” he says. “There’s definitely no shortage of outdoor things to do in Colorado! It’s actually quite similar to Canada in that sense, so it made for an easy transition.”

The post University of Colorado Cancer Center welcomes Brandon Bernard, MD appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

E. David Crawford, MD, reports 15-year PLCO results in the journal Cancer.

Starting in 1993 and ending in 2001, ten academic medical centers in the United States screened 76,685 men and 78,216 women for prostate, lung, colorectal and ovarian cancers. The question was whether yearly screening could catch cancers early and thus decrease mortality from these diseases. Fifteen-year follow-up results focusing on prostate cancer were published this month in the journal Cancer, and show little difference in mortality between men screened annually and the control group, some of whom chose to be screened occasionally. According to researchers, the results don’t necessarily negate the value of prostate cancer screening, but imply that within the data of this massive trial are clues that inform personalized decisions for subsets of this prostate cancer population.

“What we can see from these results is that most men diagnosed with prostate cancer will not die from their disease. In 15 years, people on the study died from lots of other things. However, we can also see that now we need to focus on discovering the men that will,” says E. David Crawford, MD, investigator at the University of Colorado Cancer Center and study co-author.

Specifically, in the intervention arm that received annual prostate cancer screening, 255 men have died of prostate cancer since the start of the trial. In all, 244 men in the control arm, who did not receive annual screening (but may have received self-directed intermittent screening), died of prostate cancer. By comparison, 1,933 and 1,882 men in the experimental and control arms, respectively, died of other cancers. Slightly more in each group died of heart-related conditions.

According to Crawford, these data imply that some men need not be screened for prostate cancer.

“For example, we have since shown that men with PSA lower than one have only about a 0.5 percent chance of being diagnosed with prostate cancer within 10 years,” Crawford says. Administering a PSA test first and then not screening men with PSA less than one would save billions of dollars in healthcare costs every year.

However, in addition to discovering no decreased mortality with yearly prostate cancer screening compared with intermittent screening, Crawford suggests that these results could be used to discover men who do, in fact, benefit from careful monitoring.

“I treated a guy who’d been diagnosed in his 40s,” says Crawford. “We did surgery, but then a year later he was diagnosed with melanoma. It turned out that at the same time, his sister was diagnosed with triple-negative breast cancer and died within the year. Being diagnosed with prostate cancer in your 40s is a red flag that there might be a germline mutation to blame, predisposing these men and maybe family members who share the mutation to more, and more aggressive cancers. The PLCO shows that most men don’t benefit from screening, but if we could have used the data to spot this guy, maybe we could have even tested his sister as well.”

And so the takeaway from this retrospective on a massive study, 15 years after the completion of data gathering, is that despite what many have characterized as failure – after all, yearly screening did not result in overall lives saved – is that inside this data (or in related, follow-up studies) may still exist clues that could stratify prostate cancer risk.

Alongside the risks and costs of over-diagnosis and over-treatment that come with screening the entire population of men for prostate cancer still exists hope that screening only those with higher risk, at the right schedule, could save lives.

The post Prostate cancer patients more likely to die of other diseases, say 15-year PLCO results appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Knowing the likely course of cancer can influence treatment decisions. Now a new prediction model published today in Lancet Oncology offers a more accurate prognosis for a patient’s metastatic castration-resistant prostate cancer. The approach was as novel as the result – while researchers commonly work in small groups, intentionally isolating their data, the current study embraces the call in Joe Biden’s “Cancer Moonshot” to open their question and their data, collecting previously published clinical trial data and calling for worldwide collaboration to evaluate its predictive power. That is, researchers crowdsourced the question of prostate cancer prognosis, eventually involving over 550 international researchers and resulting in 50 computational models from 50 different teams. The approach was intentionally controversial.

“Scientists like me who mine open data have been called ‘research parasites’. While not the most flattering name, the idea of leveraging existing data to gain new insights is a very important part of modern biomedical research. This project shows the power of the parasites,” says James Costello, PhD, senior author of the paper, investigator at the University of Colorado Cancer Center, assistant professor in the Department of Pharmacology at the CU School of Medicine, and director of Computational and Systems Biology Challenges within the Sage Bionetworks/DREAM organization.

The project was overseen as a collaborative effort between 16 institutions, led by academic research institutions including CU Cancer Center, open-data initiatives including Project Data Sphere, Sage Bionetworks, and the National Cancer Institute’s DREAM Challenges, and industry and research partners including Sanofi, AstraZeneca, and the Prostate Cancer Foundation. Challenge organizers made available the results from five completed clinical trials. Teams were challenged to connect a deep set of clinical measurements to overall patient survival, organizing their insights into novel computational models to better predict patient survival based on clinical data.

“The idea is that if a patient comes into the clinic and has these measurements and test results, can we put this data in a model to say if this patient will progress slowly or quickly. If we know the features of patients at the greatest risk, we can know who should receive standard treatment and who might benefit more from a clinical trial,” Costello says.

The most successful of the 50 models was submitted by a team led by Tero Aittokallio, PhD, from the Institute for Molecular Medicine Finland, FIMM, at University of Helsinki, and professor in the Department of Mathematics and Statistics at University of Turku, Finland.

“My group has a long-term expertise in developing multivariate machine learning models for various biomedical applications, but this Challenge provided the unique opportunity to work on clinical trial data, with the eventual aim to help patients with metastatic castration-resistant prostate cancer,” Aittokallio says.

Basically, the model depended on not only groups of single patient measurements to predict outcomes, but on exploring which interactions between measurements were most predictive – for example, data describing a patient’s blood system composition and immune function were only weakly predictive of survival on their own, but when combined became an important part of the winning model. The model used a computational learning strategy technically referred to as an ensemble of penalized Cox regression models, hence the model’s name ePCR. This model then competed with 49 other entries, submitted by other teams working independently around the world.

“Having 50 independent models allowed us to do two very important things. First when a single clinical feature known to be predictive of patient survival is picked out by 40 of the 50 teams, this greatly strengthens our overall confidence. Second, we were able to discover important clinical features we hadn’t fully appreciated before,” Costello says.

In this case, many models found that in addition to factors like prostate-specific antigen (PSA) and lactate dehydrogenase (LDH) that have long been known to predict prostate cancer performance, blood levels of an enzyme called asparate aminotransferease (AST) is an important predictor of patient survival. This AST is an indirect measure of liver function and the fact that disturbed levels of AST are associated with poor patient performance implies that studies could evaluate the role of AST in prostate cancer.

“The benefits of a DREAM Challenge are the ability to attract talented individuals and teams from around the world, and a rigorous framework for the assessment of methods. These two ingredients came together for our Challenge, leading to a new benchmark in metastatic prostate cancer,” says paper first author, Justin Guinney, PhD, director of Computational Oncology for Sage Bionetworks located at Fred Hutchinson Cancer Research Center.

“A goal of the Project Data Sphere initiative is to spark innovation – to unlock the potential of valuable data by generating new insights and opening up a new world of research possibilities. Prostate Cancer DREAM Challenge did just that. To witness cancer clinical trial data from Project Data Sphere be used in research collaboration and ultimately help improve patient care in the future is extremely rewarding!” says Liz Zhou, MD, MS, director of Global Health Outcome Research at Sanofi.

The goal now is to make the ePCR model publicly accessible through an online tool with an eye towards clinical application. In fact, the National Cancer Institute (NCI) has contracted the winning team to do exactly this. Soon, when patients face difficult decisions about the best treatment for metastatic castration-resistant prostate cancer, ePCR tool could be an important piece of the decision-making process.

###

Challenge winners and results can be found on the Prostate Cancer DREAM Challenge homepage. The clinical trial data can be found at Project Data Sphere. The research article describing this work can be found at The Lancet Oncology. Additional papers that describe individual team methods can be found in the DREAM Channel at F1000Research. A companion paper covering prognosis models in prostate cancer can be found at bioRxiv.

About University of Colorado Cancer Center

The University of Colorado Cancer Center, located at the Anschutz Medical Campus, is Colorado’s only National Cancer Institute-designated comprehensive cancer center, a distinction recognizing its outstanding contributions to research, clinical trials, prevention and cancer control. CU Cancer Center’s clinical partner University of Colorado Hospital is ranked 15th by US News and World Report for Cancer and the CU Cancer Center is a member of the prestigious National Comprehensive Cancer Network®, an alliance of the nation’s leading cancer centers working to establish and deliver the gold standard in cancer clinical guidelines. CU Cancer Center is a consortium of more than 400 researchers and physicians at three state universities and three institutions, all working toward one goal: Translating science into life. For more information visit Coloradocancercenter.org and follow CU Cancer Center on Facebook and Twitter. A companion paper covering prognosis models in prostate cancer can be found at bioRxiv.

About the DREAM Challenges Initiative

Founded in 2006 by A. Califano (Columbia University) and Gustavo Stolovitzky (IBM Research) the Dialogue on Reverse Engineering Assessment and Methods (DREAM) Challenges Initiative poses fundamental questions about systems biology and translational medicine. Designed and run by a community of researchers from a variety of organizations, the DREAM challenges invite participants to propose solutions — fostering collaboration and building communities in the process. Expertise and institutional support are provided by Sage Bionetworks, along with the infrastructure to host challenges via their Synapse platform. Together, the leaders of the DREAM Challenges Initiative share a vision allowing individuals and groups to collaborate openly so that the “wisdom of the crowd” provides the greatest impact on science and human health. More information is available at: http://dreamchallenges.org/.

About the Project Data Sphere Initiative

Project Data Sphere, LLC, an independent, not-for-profit initiative of the CEO Roundtable on Cancer’s Life Sciences Consortium (LSC), operates the Project Data Sphere® platform (www.ProjectDataSphere.org). Launched in April 2014, the Project Data Sphere platform provides one place where the cancer community can broadly share, integrate, analyze and discuss historical patient-level comparator arm data sets (historical patient-level cancer phase III) from multiple providers, with the goal of advancing research. With its broad-access approach, the initiative brings diverse minds and technology together to help unleash the full potential of existing clinical trial data and speed innovation by generating collective insights that may lead to improved trial design, disease modeling and beyond. The platform currently contains 27,600 patient lives of data; 9,400 of those are across a wide spectrum of prostate cancer populations. In order to ensure that researchers can realize the full potential of this data, PDS teamed with CEO Roundtable on Cancer Member, SAS Institute Inc. SAS, a leader in data and health analytics, developed and hosts the site and provides free state-of-the-art analytic tools to authorized users within the Project Data Sphere environment.

About Sage Bionetworks

Sage Bionetworks is a nonprofit biomedical research organization, founded in 2009, with a vision to promote innovations in personalized medicine by enabling a community-based approach to scientific inquiries and discoveries. Sage Bionetworks strives to activate patients and to incentivize scientists, funders and researchers to work in fundamentally new ways in order to shape research, accelerate access to knowledge and transform human health. It is located on the campus of the Fred Hutchinson Cancer Research Center in Seattle, Washington and is supported through a portfolio of philanthropic donations, competitive research grants, and commercial partnerships. More information is available at www.sagebase.org.

The post Crowdsourcing a better prostate cancer prediction tool appeared first on Colorado Cancer Blogs.

Read Full Article
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Scott (left) and fellow cancer wellness participant George (right).

Scott Monserud, sports editor for the Denver Post, has been active all his life. He played sports of all kinds growing up with five older siblings on a farm. So, when he suddenly felt extreme fatigue and lower back pain a year ago, Scott knew something was not right. He was not expecting the stage IV metastatic prostate cancer diagnosis that he received in August, 2015.

Scott grew up on a small farm in northeast Iowa. He made Colorado his home in 2001, moving from Grapevine, Texas, where he had been a sports editor for the Fort Worth Star-Telegram.   He has been a sports editor his entire professional career, including the past 15 years at The Denver Post, the last 10 as assistant managing editor/sports.  He has one daughter, Alison, who is enrolled in nursing school.

Last August Scott made an appointment with his primary care physician after he had been feeling extremely fatigued.

“I worked all week but was totally exhausted at day’s end, and had no appetite,” Monserud recalled. “I would get home and go to bed, without eating. I felt if the condition continued into the following week, I needed to get a checkup.”

A blood draw the next week showed that his PSA had elevated to an extremely high level, at which point he was told he likely had prostate cancer. A biopsy soon after determined the cancer had spread outside his prostate to his skeletal system and his lymph nodes.

“I was devastated, and terrified,” Monserud said. “I had prepared myself mentally before going to the urologist that I might have cancer but was not ready to be told it had spread outside my prostate.”

Almost immediately after his diagnosis Scott was put on Lupron, an injectable drug that helps decrease the testosterone produced by the prostate, which feeds the cancer, and Casodex, a pill he takes daily.  He began chemotherapy and had six sessions, each three weeks apart, the last on December 30, 2015.

While undergoing chemotherapy, Scott sought second opinions from experts at the  University of Colorado Anschutz Medical Campus in Aurora. He was put in touch with E. David Crawford, a surgeon, who recommended he have cyrotherapy surgery after he was done with his chemotherapy. The purpose of the surgery is to destroy cancer cells in the prostate by freezing them with extremely cold liquid nitrogen or argon gas.

Scott had the surgery the day after returning from the Super Bowl in California, where he directed The Denver Post’s coverage of the Denver Broncos’ victory over Carolina.

Soon after the surgery, Scott enrolled in a three-month exercise program for cancer patients at the University of Colorado Health and Wellness Center under the care of Nicole Klochak, BS, CES, CPT, a personal trainer.

Cancer Exercise Program: Scott's Story - YouTube

Scott is continuing to work out six days a week, run 5Ks, play basketball, hike and lift weights. He never stopped working during his treatment. He is thankful that his PSA has dropped to a normal level and that his bone scans are vastly improved from a year ago.

“I never expected to be dealing with stage IV cancer,” says Scott. “My advice for anyone going through a similar situation would be to try not to panic and assess all of your options. Don’t rush into a decision, be your own doctor, ask questions and if you don’t get the answer you’re looking for, keep asking. Doctors are very smart but they don’t always have time to explain things clearly. Finally, try to stay positive and work to improve your diet. Attempt to exercise and lift weights. You’ll feel better and I believe it helps your body fight cancer.”

The post Cancer never slowed me down: Scott’s story appeared first on Colorado Cancer Blogs.

Read Full Article

Read for later

Articles marked as Favorite are saved for later viewing.
close
  • Show original
  • .
  • Share
  • .
  • Favorite
  • .
  • Email
  • .
  • Add Tags 

Separate tags by commas
To access this feature, please upgrade your account.
Start your free month
Free Preview