Maintaining a healthy lifestyle lowered the likelihood of developing metastatic disease or dying of prostate cancer among men with high genetic risk, according to data from a study presented during the 2021 Virtual AACR Annual Meeting.

The research also showed, however, that maintaining a healthy lifestyle was not associated with a lower risk of overall prostate cancer among patients in any of the 4 genetic risk categories defined by the study.

“In our study, a healthy lifestyle did not attenuate genetic risk of overall prostate cancer. However, a healthy lifestyle did attenuate the genetic risk of lethal disease in men at highest genetic risk,” one of the study’s lead authors, Anna Plym, PhD, a postdoctoral research fellow at Brigham and Women's Hospital and Harvard T. H. Chan School of Public Health, said when presenting the results during the AACR meeting.

“While further studies are needed, this suggests that modifiable factors can mitigate the consequences of having a genetic susceptibility to prostate cancer,” added Plym.

The study included 10,443 men with available genotype data from the Health Professionals Follow-up Study, a prospective cohort study that accrues data from participating healthcare professionals. The investigators quantified the genetic risk of prostate cancer in these men using a validated polygenic risk score (PRS) for overall prostate cancer. The researchers then applied a validated lifestyle score for lethal prostate cancer. Elements factored into the score included healthy weight, vigorous physical activity, not smoking, reduced intake of processed meat, and high consumption of tomatoes and fatty fish.

The investigators assessed the incidence of overall prostate cancer and lethal prostate cancer (metastatic disease or prostate cancer-specific death). Men were followed from the date of DNA collection (1993-1994 or 2005-2006) until prostate cancer event or death.

“To account for the genotype sampling strategy within the Health Professionals Follow-up Study, in which not all recruited men were genotyped, we applied an inverse probability weighted Cox regression model, adjusting for [several] factors, including [age, year of inclusion, genetic ancestry, PSA screening, other cancers, diabetes, medication use, and total energy intake,” said Plym.

Using multivariable Cox proportional hazards models, the investigators estimated the overall and lethal prostate cancer risk by joint categories of a time-varying lifestyle score and genetic risk (PRS quartiles). The investigators used both inverse probability weighted (IPW) and unweighted models for their analysis, and estimated lifetime cumulative incidence using regression standardization.

At a median follow-up of 18 years, there were 2111 prostate cancer events; at a median follow-up of 22 years there were 238 lethal prostate cancer events.

The risk of overall prostate cancer was 5.4 times higher in men whose PRS score placed them in the highest genetic risk quartile versus those in the lowest genetic risk quartile (HRipw, 5.39; 95% CI, 4.59-6.33). The risk of lethal prostate cancer was 3.5 times higher in the highest versus the lowest genetic risk quartile (HRipw, 3.53, 95% CI, 2.34-5.32) compared with men in the lowest genetic risk quartile.

Maintaining a healthy lifestyle was significantly associated with a reduced risk of developing lethal prostate cancer compared with men living the least healthy lifestyle (HRipw, 0.54; 95% CI, 0.31- 0.94). In contrast, there was no link between maintaining a healthy lifestyle and a reduced risk of overall prostate cancer (HRipw, 1.01; 95% CI, 0.84-1.22).

Also of note, among men maintaining a healthy lifestyle at study entry who had the highest genetic risk, there was a 3% lifetime cumulative occurrence of lethal prostate cancer. This was half of the 6% lifetime cumulative incidence for men with the least healthy lifestyle. It is also comparable to the 3% population average.

In a statement included in a press release made available during the AACR meeting, Plym stated, “Our findings add to current evidence suggesting that men with a high genetic risk may benefit from a targeted prostate cancer screening program, aiming at detecting a potentially lethal prostate cancer while it is still curable.”

Commenting on the results during the AACR meeting, moderator Charles Swanton MBPhD, FRCP, FMedSci, FRS, FAACR, Royal Society Napier Professor, The Francis Crick Institute and UCL Cancer Institute, Cancer Evolution and Genome Instability Lab, London, England, said, “Healthy lifestyle did not associate with prostate cancer risk overall, but was associated with lethal prostate disease in those with the highest PRS risk. So, the question is, why did a healthy lifestyle only protect those in the highest PRS category? And so I think we need future validation in larger cohorts using similar thresholds and a biological mechanism that might explain an interaction between the healthy lifestyle and a highest genetic risk and the risk of lethal prostate cancer.”

Plym A, Zhang Y, Stopsack K, et al. Can the genetic risk of prostate cancer be attenuated by a healthy lifestyle? Presented at: 2021 AACR Virtual Annual Meeting Week 1; April 10-15, 2021; Virtual. Abstract 822.

Healthy lifestyle may offset risk of lethal prostate cancer in men with high genetic risk. Published online April 10, 2021. Accessed April 10, 2021.

Articles

Maintaining a healthy lifestyle was found to reduce the likelihood of developing metastatic disease or dying of prostate cancer among men who had a high genetic risk.

Healthy Lifestyle May Reduce Likelihood of Lethal Prostate Cancer Among Those With High Genetic Risk

The American Society of Clinical Oncology (ASCO) updated its 2003 recommendations for genetic testing to keep pace with exponential progress in genetic science. The new guidelines encompass developments in genetic testing from the past 7 years, including direct-to-consumer (DTC) genetic testing and public access to genetic tests with unproven clinical benefit. A podcast and article summarizing the recommendations are available at www.cancer.net.

“The awareness of individual genetic differences within the population has sparked a number of significant developments and an unprecedented level of raw information being made available, not only to health professionals, but also to the public in the form of DTC tests,” said Kenneth Offit, MD, MPH, chief of Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center, and chair of ASCO’s Ethics Committee, in a press release. “ASCO’s updated recommendations on genetic and genomic testing attempt to get back to the basics— patient safety and clinical utility&mdash;for the individuals considering genetic testing and the doctors who offer testing or may be asked by patients to interpret DTC test results,” he said.

Genetic testing can help assess the risk of disease, identify genetic carriers, diagnose disease, or predict the course of a disease. Currently, genetic tests are available for malignancies of the breast, ovaries, and colon, and for some rare cancers. Most tests have been professionally mediated and have proven clinical usefulness. DTC genetic testing and those tests for which clinical usefulness has not been demonstrated scientifically fall short of the new ASCO standards. ASCO believes that tests with unproven clinical utility, like tests to identify genetic variations and assess cancer risk, need to be evaluated in clinical trials. ASCO also supports indicating which tests have personal, but not clinical, utility.

In 2004, the Centers for Disease Control and Prevention (CDC) established the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) to help evaluate genetic tests and genomic applications and their transition from research to practice. The EGAPP Working Group has developed processes for assessing the validity and utility of a genetic test in clinical practice, but the CDC has no authority to regulate genetic testing, which falls under the purview of the FDA. ASCO proposes that the FDA and Centers for Medicare and Medicaid Services develop standards to assess the accuracy, validity, and quality of genetic tests and genetic testing facilities. According to ASCO, creating a compulsory public registry that requires manufactures of genetic tests to make full disclosure would facilitate better oversight.

ASCO advises individuals to use caution when using genetic technologies that do not meet the new standards. According to ASCO, people using DTC tests should consult their healthcare provider for assistance with interpreting results and for advice on follow-up care, based on established cancer risk factors. As the price of genetic testing continues to fall, with recent full screening now available for $5000, more people may request genetic screening to assess their risk for various cancers, making it increasingly important to develop guidelines and regulations for those who manufacture and distribute genetic tests.

ASCO urges renewed focus on establishing higher standards for genetic testing in oncology. Beyond professional mediation and clinical practicality, ASCO advocates the following: genetic tests need interpretable results, individuals tested should demonstrate genetic cancer susceptibility, and individuals should receive pre- and post-test counseling.

The American Society of Clinical Oncology (ASCO) updated its 2003 recommendations for genetic testing to keep pace with exponential progress in genetic science.

ASCO Updates Guidelines for Genetic Testing

As the United States descended into the Great Recession in 2008, healthcare spending slowed and the growth rate in healthcare spending dropped to the lowest it has been since 1960, according to an article in the journal 

. Despite the decline, the 4.4% growth rate in healthcare spending managed to surpass the 2.6% growth in the nominal gross domestic product (GDP). The United States spent $2.3 trillion ($7681 per person) on healthcare in 2008, with costs continuing to outstrip available resources. As a share of GDP, healthcare spending rose from 15.9% in 2007 to 16.2% in 2008.

“Healthcare spending is usually somewhat insulated from the immediate impact of a downturn in the economy, but this recession has exerted considerable influence on the healthcare sector,” Micah Hartman, a statistician with the Centers for Medicare and Medicaid Services and co-author of the report, said in a press release.

The federal government was the only sector with a healthcare spending rate increase in 2008. Federal revenue appropriated to healthcare jumped 8% over 2007. The increase resulted in large part from the American Reinvestment and Recovery Act of 2009, which awarded states an additional $7 billion in Medicaid funds. This contributed to an 8.4% increase in federal Medicaid spending. Medicare spending reached $469.2 billion, a growth rate of 8.6%, up from 7.1% in 2007.

Both Democrats and Republicans used the study to sound off on proposed national healthcare legislation. Democrats say the public’s inability to afford rising healthcare costs necessitates reform legislation. Republicans maintain that proposed efforts to overhaul healthcare will actually increase costs. Congress continues to seek a compromise on healthcare legislation. If and when legislation will pass, and what provisions of current proposals will survive remains to be seen.

Hartman M, Martin A, Nuccio O, et al. Health Spending Growth at a Historic Low in 2008. 

The economic downturn reduced the growth in healthcare spending by businesses, individuals, and state and local governments. Private business healthcare spending grew only 1.2% in 2008, partly because businesses shifted more responsibility for insurance premiums to employees. Household healthcare spending growth rates declined from 5.9% in 2007 to 4.3% in 2008. Unemployed Americans’ loss of insurance coverage, in particular, affected consumer spending. State and local spending growth slowed to 3.4% in 2008, down from 6.6% in 2007. Spending reductions in these major economic segments fueled decreased spending on hospital services, physician and clinical services, retail prescription drugs, nursing homes, and private health insurance.

The United States spent $2.3 trillion ($7681 per person)
on healthcare in 2008, with costs continuing to
outstrip available resources.

2008 Healthcare Spending Massive Despite Decline in Growth Rate

The FDA Center for Devices and Radiological Health, in collaboration with the National Cancer Institute Enterprise Vocabulary Service, launched a Website (http://tinyurl.com/mlptu7) updating its coding system for reporting adverse events related to medical devices. The new system aims to improve overall report quality, facilitate manufacturer reporting, and enhance the FDA’s response capability. The Website provides updated codes and advice on transitioning to the new system. Old codes will no longer be accepted starting April 2, 2010.

The Safe Medical Devices Act of 1990 mandated that user facilities report device-related deaths to both the FDA and the manufacturer. Device-related serious injuries must be reported to the manufacturer or to the FDA if the manufacturer is unknown. With no quality control mechanisms in place, inefficiencies had plagued the FDA’s current medical device reporting system. According to the agency, the following concerns necessitated the changes:

• Code meanings were ambiguous and several were created for unique situations

• One concept might have multiple synonyms, causing confusion about the preferred code

• No procedures existed for adding, deleting, or updating terms

• The agency had limited communication with reporters regarding coding updates

• Current terms were not accessible online and could not be downloaded automatically.

Under the new system, one term refers to one device, and component codes identify specific device parts. Additionally, individuals reporting adverse events can access code definitions and hierarchies. These modifications simplify code selection, enhance report accuracy, and maximize efficiency. The FDA believes that the new Website and quality control mechanisms will ensure continued progress going forward.

The FDA Center for Devices and Radiological Health, in collaboration with the National Cancer Institute Enterprise Vocabulary Service, launched a Website (http://tinyurl.com/mlptu7) updating its coding system for reporting adverse events related to medical devices.

New FDA Website Updates Medical Device Report Codes

Researchers at the University of Oklahoma (OU) have been investigating focused microwave thermotherapy (FMT), a microwave treatment capable of destroying large cancer tumors in patients with breast cancer. They reviewed data from four multi-institutional studies and found that when administered with neoadjuvant chemotherapy, FMT reduced the need for mastectomies by ~90% in women with invasive carcinomas. “This therapy is a major advancement for women with later stage breast cancer. Right now, most patients with large tumors lose their breast. With this treatment along with chemotherapy, we were able to kill the cancer and save the breast tissue,” said William Dooley, MD, researcher at the OU Cancer Institute and the director of surgical oncology at OU Medicine, in a press release.

The FDA-approved technique adapts the microwave technology behind former President Ronald Reagan’s “Star Wars” defense system. In a phase I study involving 10 patients with breast cancer, a single dose of FMT produced tumor shrinkage in 8 patients. Another study randomized patients with early stage invasive breast cancer to FMT at ablative temperatures prior to breast conserving surgery (n = 34) or to breast conserving surgery alone (n = 41). None of the patients treated with FMT had positive tumor margins compared with 4 patients in the group that did not receive FMT (P = .13). Another study randomized patients with large tumors ranging from 1 to 1.5 inches, which ordinarily necessitate mastectomy, to FMT within 2 hours of receiving neoadjuvant chemotherapy or chemotherapy alone. Median tumor volume was reduced by 88.4% (n = 14) for patients in the FMT arm compared with 58.8% (n = 10) for the chemotherapy-only group (P = .048). The percentage of patients requiring mastectomies declined from 75% to 7%. According to Dooley, FMT could theoretically be applied to any organ capable of being held “relatively still.”

Researchers hope to build on this breakthrough treatment by testing FMT on even larger tumors in the next phase of clinical trials, scheduled to start this year. “The trial was very successful. We were able to completely reverse those odds,” Dooley said. “We redesigned the machine and will begin clinical trials this year to determine whether the therapy works on tumors that are larger than 1.5 inches and smaller than 5 inches.”

The team wants to integrate heat-sensitive nanotechnology to target cancer cells more precisely. They also plan to study whether deposits of cancer proteins in the bloodstream following rapid tumor disintegration affect immune resistance to cancer recurrence. The study was published in 

Dooley WC, Vargas HI, Fenn AJ, et al. Focused microwave thermotherapy for preoperative treatment of invasive breast cancer: A review of clinical studies. 

Researchers at the University of Oklahoma (OU) have been investigating focused microwave thermotherapy (FMT), a microwave treatment capable of destroying large cancer tumors in patients with breast cancer.

Star Wars Strikes Back: Microwave Technology from Reagan-era Program Reduces Mastectomies

In January, New Jersey became the 14th state in the nation to legalize marijuana use for certain chronic illnesses. Other states where the use of medical marijuana is permitted include Alaska, California, Colorado, Hawaii, Maine, Michigan, Montana, Nevada, New Mexico, Oregon, Rhode Island, Vermont, and Washington; around a dozen more states are weighing pending bills. The New Jersey law is the most restrictive in the nation and authorizes prescribed marijuana for only a handful of chronic illnesses, such as multiple sclerosis, cancer, glaucoma, epilepsy, Crohn’s disease, AIDS, muscular dystrophy and Lou Gehrig’s disease. Unlike other states, physicians in New Jersey will not be able to prescribe medical marijuana for anxiety, headaches, or chronic pain.

The state plans to authorize 6 dispensaries, and patients will receive identification cards authorizing them to purchase the drug. They will not be able to grow their own marijuana or use it in public, however. And individuals without a prescription will still be subject to criminal prosecution if caught in possession of marijuana.

Richard J. Rosenbluth, MD, is medical director of the Hospice Program and division chief of Geriatric Oncology at John Theurer Cancer Center at Hackensack University Medical Center in New Jersey. He is also the editor of the 

t, and he supports New Jersey’s decision to legalize marijuana for medical use, predicated on a physician’s determination that good clinical evidence exists to prescribe it. “I believe any drug that might be beneficial should be decriminalized, if currently not available,” he said. “Marijuana should be available and doctors should treat it as any other drug, as per the Medical Board of California’s 2004 recommendations,” said Rosenbluth.

Shifting attitudes toward medical marijuana

According to Patrick Stack and Claire Suddath, authors of “A Brief History of Medical Marijuana,” published in 

, medicinal marijuana can be traced back to Emperor Shen Neng of China, who prescribed marijuana tea in 2737 BCE as a treatment for gout, rheumatism, malaria, and poor memory. Its use became widespread throughout Asia and the Middle East. As of the late 18th century, medical journals in Britain and the United States were recommending hemp seeds for everything from inflamed skin to incontinence and venereal disease. Marijuana for medical use eventually fell out of favor in the United States, however, as state and federal regulators imposed increasingly harsh criminal penalties for growing, possessing, using, and selling marijuana.

Paul M. Zeltzer, MD, clinical professor in neurosurgery, David Geffen School of Medicine, University of California Los Angeles, explained that medical marijuana has been tainted with an association between marijuana and criminal enterprise. “Smoking medical, ordinary marijuana helps to alleviate many symptoms of pain and depression in persons who have cancer,” he said, but he noted that marijuana use has been commingled with “an underground that involves crime syndicates and domestic/foreign nationals who may kill and maim in the process of cultivation, acquisition, and distribution.” Some people have had trouble divorcing these two issues. “One alternative,” Zeltzer suggests, “would be for [marijuana] to be [completely] legalized, thus sidestepping or eliminating the crime connection and adding to our country’s tax base.”

Although a minority of Americans support legalizing marijuana outright, 81% do support legalizing marijuana for medical purposes, according to an ABC News/Washington Post poll. Presidential administrations have differed on what approach to take toward medical marijuana, which remains a federal crime. Under the Obama administration, the Justice Department formally announced that it will not prosecute people who are using marijuana in compliance with state laws that permit its use for medicinal purposes. This is a reversal of the position taken by the previous administration, which dispatched federal agents to raid marijuana dispensaries and farms in states with legalized medical marijuana. Operators were charged under federal drug laws.

The FDA maintains that “marijuana has a high potential for abuse, has no currently accepted medical use in treatment in the United States, and has a lack of accepted safety for use under medical supervision.” Though the FDA bans the use of raw marijuana, delta-9- tetrahydrocannabinol (THC) is the herb’s most active ingredient and has been available by prescription as dronabinol (Marinol) since 1985. It is sometimes used to treat chemotherapy-induced nausea and vomiting. Rosenbluth said in terms of patient benefit, research fails to show either dronabinol or raw marijuana as superior to one another. He added that “anecdotally, patients who have prior history of smoking marijuana seem to get more benefit from smoking than from oral preparations.” The NCI advocates THC use only when first-line therapies prove ineffective.

How does medical marijuana affect patients?

Despite marijuana being available for centuries, years of study have failed to elucidate its curative and palliative properties. Some studies have provided pretty strong evidence that marijuana reduces nausea and improves appetite in patients on chemotherapy. It also relieves aching and numbness in patients with AIDS and may alleviate some neurological problems associated with multiple sclerosis.

In patients with cancer, Rosenbluth said, “Several benefits have been attributed to marijuana, including improvement in anorexia/cachexia (cancer wasting syndrome), anti-nausea [properties], and help with depression and anxiety.” Rosenbluth said there have not yet been any good clinical trials that confirm these benefits, however. “What trials do exist have generally not used smoked marijuana—only dronabinol.” Rosenbluth said he is not convinced that marijuana is superior to other approved agents and suggested it may be significantly less effective than many of them.

Adverse effects associated with marijuana use are few and manageable, Rosenbluth said. “They include dysphoria, depersonalization syndromes, drowsiness, dizziness, and mild cardiac and circulatory side effects. These effects may be less apparent in younger patients and more so in the elderly.”

“There is a good deal of interest in some basic laboratory research indicating anti-tumor effects of cannabinoids,” Rosenbluth said. Some researchers are experimenting with THC to reduce tumor growth. These studies are all in their early phases, but Rosenbluth said preliminary findings are interesting, and he hopes relaxation of medical marijuana laws will allow “cannabis and its components to be studied freely throughout the country, as any other potentially beneficial drug.”

Despite the Obama administration’s relaxation on prosecutions, many researchers are still having difficulty getting approval to conduct studies that involve smoking marijuana. Requests to conduct the studies must go through the National Institute on Drug Abuse (NIDA), which controls supply from a plantation at the University of Mississippi, the only federally approved source of marijuana. NIDA routinely turns down study requests unless they are designed to evaluate the potential harm from smoking marijuana. The Drug Enforcement Agency has also declined petitions from researchers requesting permission to grow their own marijuana for use in studies.

Legalizing medical marijuana has not been without problems. Law enforcement officials in states where it is legalized complain that many healthy people take advantage of the law to procure marijuana and that growers are spreading from rural areas into the city. The city of San Jose, California, which has as many as 30 dispensaries operating within the city limits, recently announced it would be forcing all dispensaries to close. Related crime has also been a concern, and several states and municipalities are tightening regulations on marijuana dispensaries.

Most states with medical marijuana laws allow employers to refuse employment to individuals who use medical marijuana. In some states, like Colorado, the laws are ambiguous and employers are unclear as to whether they can forbid employees to use medical marijuana outside of work. Schools are also grappling with the issue, as well, with more high school students— particularly in areas with less restrictive medical marijuana laws&mdash;receiving prescriptions for marijuana, increasingly to treat ADHD. In addition, some facilities that perform organ transplants acknowledge denying transplants to patients who use medical marijuana.

In the absence of any proven benefits from smoking marijuana, physicians in the 14 states where it is legal may want to discuss some of the pros and cons with their patients prior to issuing a prescription. Patients need to be aware of the potential impact of medical marijuana on all facets of life and should be wary of letting the anecdotal hype surrounding medical marijuana use dissuade them from first trying a proven treatment option.

Nevada legalized medical marijuana in 2000. First, physicians determine whether patients have a qualifying medical condition such as cancer, AIDS, or glaucoma. The Nevada Department of Health and Human Services then verifies an applicant is in compliance with the law and, if so, issues a registration card authorizing medical marijuana use.

Medical Oncology Comprehensive Cancer Centers of Nevada-Siena Henderson, Nevada

Dr Nguyen is on the editorial advisory board of

 Oncology & Biotech News, Oncology Net Guide, and Contemporary Oncology.

A small number of patients with cancer I treat report medical marijuana alleviates symptoms of cachexia, anorexia, and severe nausea. I suspect its use and benefit are likely underreported due to fear of legal consequence and the stigma attached to marijuana. In Nevada, a state registry program within the Nevada Department of Health and Human Services, Nevada State Health Division, allows patients diagnosed with a chronic or debilitating medical condition, including cancer, to obtain a registry identification card authorizing medical marijuana use.

Overall, marijuana is not a routine drug I recommend up front for severe nausea, cachexia, or anorexia. In my practice, patients benefiting from medical marijuana usually arrive already possessing the drug and simply notify me of their use. Typically, I do not ask whether they have a state registry card or where they obtained the marijuana. I simply request that they update me on any drugs or herbal supplements they are taking, so that I may determine any harmful drug interactions with their current treatment plan. Oral intake of cannabis may have a high first-pass effect in the liver, creating the potential for pharmacokinetic interaction with others drugs.

I approach medical marijuana with the same open-mindedness with which I approach all integrative oncology. I believe that medical marijuana has helped alleviate symptoms of cachexia and anorexia in some of the patients with cancer I treat. The main reason I have not adopted a routine practice in completing applications for medical marijuana is my lack of training in its use. Medical marijuana use is not typically taught to oncology students. I also believe oncologists have not adopted routine medical marijuana recommendations because of a general unfamiliarity with varying state legislation governing its use. An additional hindrance is a paucity of clinical trial data; the majority of medical marijuana evidence is anecdotal.

When our home state of New Jersey became the 14th state in the nation to legalize medical marijuana, OBTN decided to take a closer look at the herbal remedy. With help from oncologists on our advisory
board, we sought to filter through the smoke and examine the ealities of medical marijuana.

Medical Marijuana: Smoke & Mirrors?

Chemotherapy recipients have long complained of decreased mental function during and after treatment, yet the medical community has only recently acknowledged the reality of chemo brain, the term for chemotherapy’s degenerative effect on normal cognitive function. In an article in 

, researchers at the University of Rochester Medical Center (URMC) in New York said the cause of chemo brain remains a mystery but numerous studies have shown that patients undergoing chemotherapy demonstrate “memory lapses, trouble concentrating, difficulty in word association, confusion, trouble multitasking, and slow thinking and information processing,” and these effects often persist ≥5 years after discontinuing therapy.

Neuroimaging studies support the clinical evidence of chemo brain, showing restricted blood flow and other abnormalities in areas of the brain where many cognitive functions transpire. Using mice, the URMC researchers have isolated a possible cause for chemo brain and identified insulin-like growth factor 1 (IGF-1), known to increase neural cell proliferation, as a possible treatment.

The team had hypothesized that chemotherapy drugs such as cyclophosphamide (Cytoxan) and fluorouracil (5-FU), known to cross the blood-brain barrier, were responsible for impairing neural cell proliferation and that agents like paclitaxel and doxorubicin (Adriamycin), which cross the bloodbrain barrier infrequently, would be less likely to cause chemo brain. Instead, the researchers found all four drugs significantly reduced brain cell proliferation, contradicting the study’s hypothesis. Mice received one of the chemotherapy drugs or saline. Data showed a 15.4% reduction in cell regeneration associated with paclitaxel, 30.5% for 5-FU, 22.4% for cyclophosphamide, and 36% for doxorubicin compared with saline (P <.05).

In a press release, Robert Gross, MD, PhD, professor of Neurology and Pharmacology and Physiology at URMC and principal investigator of the study, said, “It could be that all of the chemo drugs cross into the brain after all, or that they act via peripheral mechanisms such as inflammation that could open up the blood-brain barrier.”

While the study failed to isolate a drug attribute responsible for chemo brain, the results with IGF-1 were more auspicious. Preclinical studies had demonstrated that IGF-1 facilitates neurogenesis, leading the URMC researchers to test it in mice to see whether it might mitigate chemotherapy-related cognitive impairment. The team administered IGF-1 before and after a conventional multiple-dose regimen of cyclophosphamide and a single high-dose regimen. IGF-1 appeared to increase brain cell proliferation in both treatment groups compared with the mice who received saline, but the effects of IGF-1 on the mice that received the low-dose regimen were not significant. The high-dose model results proved more effective, with a mean increase in new cells of 27.5% compared with saline.

“It is not yet clear how our results can be generally applied to humans, but we have taken a very significant step toward reproducing a debilitating condition and finding ways to treat it,” said Gross. 

The research team intends to examine further the effects of IGF-1 and other chemotherapy drugs on brain cell growth. “Neurogenesis can also be altered by stress, sleep deprivation, and depression, all of which are common among cancer patients,” said Michelle Janelsins, PhD, research assistant professor of Radiation Oncology at the James P. Wilmot Cancer Center and co-investigator and lead author of the study. “More thorough studies are needed to understand the interplay of these factors and the long-term effects of chemotherapy on the brain.”

Chemotherapy recipients have long complained of decreased mental function during and after treatment, yet the medical community has only recently acknowledged the reality of chemo brain, the term for chemotherapy's degenerative effect on normal cognitive function.

By Jason M. Broderick