Medical Bulletin 10/ October/ 2024

A blood test, performed when metastatic prostate cancer is first diagnosed, can predict which patients are likely to respond to treatment and survive the longest. It can help providers decide which patients should receive standard treatment versus who might stand to benefit from riskier, more aggressive new drug trials. The research, part of a phase 3 clinical trial funded in part by the National Cancer Institute (NCI) of the National Institutes of Health, was just published in JAMA Network Open.

A new study found that measuring circulating tumor cells, rare cancer cells shed from tumors into the blood, is a reliable way to predict later treatment response and survival prospects. circulating tumor cells have been studied in prostate cancer before, but only in its later stages.

The research leveraged CellSearch (Menarini, Inc.), an FDA-cleared liquid biopsy technology at the Norris Comprehensive Cancer Center, to detect and measure circulating tumor cells in blood samples. Patients with more circulating tumor cells had shorter median survival lengths and a greater risk of death during the study period. Those with more circulating tumor cells also had less “progression-free survival,” which refers to the length of time when a patient’s disease is controlled by treatment without getting worse.

The research was part of a phase 3 clinical trial of the NCI-funded SWOG Cancer Research Network, a group of more than 1,300 institutions around the country that collaborate to study various cancers. Baseline blood samples from 503 patients with metastatic prostate cancer, who were participating in a new drug trial, were sent to the Keck School of Medicine team for analysis.

To analyze the blood samples, the researchers used the CellSearch platform at the Norris Comprehensive Cancer Center’s Liquid Biopsy Research Core. CellSearch uses immunomagnetic beads, antibodies attached to small magnetic particles, which bind to circulating tumor cells in the blood and pull them out to be detected and counted by specialized equipment.

Patients with five or more circulating tumor cells in their blood sample had the worst outcomes. Compared to patients with zero circulating tumor cells, they were 3.22 times as likely to die during the study period and 2.46 times as likely to have their cancer progress. They were only 0.26 times as likely to achieve a complete prostate-specific antigen (PSA) response, meaning they responded poorly to treatment.

Men with five or more circulating tumor cells had a median survival length of 27.9 months following the blood test, compared to 56.2 months for men with one to four circulating tumor cells and at least 78 months for men with zero circulating tumor cells

The bottom line: more circulating tumor cells meant that patients survived for less time, progressed much more quickly and were unlikely to respond to standard treatments.

Reference: Goldkorn A, Tangen C, Plets M, et al. Circulating Tumor Cell Count and Overall Survival in Patients With Metastatic Hormone-Sensitive Prostate Cancer. JAMA Netw Open. 2024;7(10):e2437871. doi:10.1001/jamanetworkopen.2024.37871

The duration of breastfeeding is shorter than average among mothers with a fear of childbirth – regardless of the mode of delivery, a new study from Finland shows. According to the researchers, the fear of childbirth can also be an indication of a greater need for breastfeeding support. Using data from the Kuopio Birth Cohort study, KuBiCo, the study examined factors related to childbirth that may affect the success and duration of breastfeeding in the child’s first year of life.

The researchers analysed data collected in 2013–2020, which included 2,521 women who had given birth in Kuopio University Hospital. During pregnancy, expectant mothers filled out various questionnaires, and they also responded to a questionnaire about the duration of breastfeeding at the time when their child was one year old. 98% of mothers participating in the study initiated breastfeeding during the first neonatal week, and three out of four mothers continued to breastfeed their child for at least six months. Mothers who had a vaginal delivery without any complications most frequently met the breastfeeding recommendation.

Fear of childbirth may affect the duration of breastfeeding regardless of the mode of delivery

A key finding of the study was the observed association between the fear of childbirth and the duration of breastfeeding.

“In mothers who feared childbirth, the duration of breastfeeding, either exclusively with their own milk or with formula, was three times more likely to be shorter than recommended,” says Maija Vasanen, Lic.Med., the first author of the study.

The researchers also found that twin pregnancy, maternal overweight and obesity, high blood pressure, and smoking were associated with a shorter duration of breastfeeding. Of mothers with twins, 40% breastfed their children for at least six months. Other factors associated with a shorter duration of breastfeeding were young maternal age, first-time childbirth, single parenthood, and lower level of education.

Increasing number of mothers are breastfeeding for more than six months

According to the researchers, the study also found a delightfully positive trend in the duration of breastfeeding. The proportion of mothers breastfeeding for more than six months increased from around 71% to 85% between 2013 and 2020. At the same time, the proportion of those breastfeeding for a shorter duration decreased from 27% to 15%.

Reference: Maija Vasanen, Anni Kukkonen, Katri Backman, Sari Hantunen, Leea Keski-Nisula. Fear of Childbirth Impairs Breastfeeding Success Independent of Mode of Birth. Breastfeeding Medicine 2024, published online 2.10.2024. https://doi.org/10.1089/bfm.2024.0024

Investigators have determined that a substantial portion of topical benzoyl peroxide (BPO) acne and rosacea treatments currently on the market are unstable and contain unacceptably high levels of benzene, a known human carcinogen. Degradation of these products and formation of benzene appear to occur when sitting on shelves at room temperature, at elevated temperatures, and when exposed to ultraviolet (UV) levels representative of sunlight. Drug stabilization techniques like encapsulation do not appear to prevent the formation of benzene in benzoyl peroxide drug products. Recent research in the Journal of Investigative Dermatology, published by Elsevier, details the findings of this study.

The study also showed that in addition to elevated temperatures expected during use and transportation, exposure to UV light at outdoor levels is another concerning mechanism through which benzoyl peroxide drug products degrade into benzene, and one that appears to occur more rapidly than heated storage and transportation conditions. These products are frequently used by consumers over extended periods of time, thereby likely increasing their exposure to benzene; there is no safe level or duration of exposure to benzene.

Co-investigator Christopher G. Bunick, MD, PhD, Department of Dermatology and Program in Translational Biomedicine, Yale University School of Medicine, New Haven, CT, explains, “The potential degradation of benzoyl peroxide into benzene has been a topic of concern in dermatology. Our research demonstrates that benzoyl peroxide products can generate benzene at typical room and store shelf temperatures, while cold storage significantly reduces this formation. These findings suggest a need to recommend refrigeration of benzoyl peroxide products throughout the supply chain—from manufacturing to patient use—to limit benzene exposure. Until formulations are developed to prevent benzene formation, refrigeration may serve as a practical solution to minimize unnecessary exposure. Additionally, dermatologists should continue to advise patients on the appropriate use of benzoyl peroxide, including potential risks associated with UV exposure.”

Mass spectrometry methods were used to detect benzene in 111 new, unopened products stored at room temperature on shelves of major US retailers, and the air surrounding them with and without UV exposure. It is the first time benzoyl peroxide drug products have been shown to degrade into benzene via a mechanism other than heat, and furthermore, it shows that benzene formation can occur independently of the starting benzene concentration in new or cold temperature stored benzoyl peroxide drug products.

Reference: Evaluation of Benzene Presence and Formation in Benzoyl Peroxide Drug Products Kucera, Kaury et al. Journal of Investigative Dermatology, Volume 0, Issue 0

A cognitive behavioural therapy (CBT) app has been found to significantly prevent increases in depression in young people who are at high risk - and could be implemented as a cost effective public mental health measure.

Globally, concern is growing about the high and steadily increasing rates of anxiety and depression in young people. Effective and scalable ways of preventing poor mental health in this group are needed, and digital tools such as mobile apps have been proposed as part of the solution.

Whilst there is emerging evidence for mental health apps being effective in treating anxiety and depression, this project led by the University of Exeter is the first to rigorously test a mental health app on such a large scale across four countries. Two linked papers published in Lancet Digital Health report the results of the ECoWeB-PREVENT and ECoWeB-PROMOTE trials, which ran concurrently in the four-year study funded by Horizon 2020. Critically, these studies found that a CBT self-help app can protect vulnerable young people against depression.

In one of the largest studies of its kind, 3,700 young people took part across the UK, Germany, Belgium, and Spain and were allocated into two trials based on their emotional competence abilities at the start of the study. That resulted in 1,200 young people with reduced emotional competency scores that confer increased risk for depression such as increased worry and overthinking going into one trial focused on prevention, whilst 2,500 without such risk went into the other trial focused on wellbeing promotion.

Those two groups were then randomised in equal numbers to three different apps developed by the study. There was a self-monitoring app where people can report their emotions every day, a self-help app that provided personalised training in emotional competence skills, and a self-help app based on CBT principles. Participants were then followed up at three months and 12 months to see how their wellbeing and depression symptoms changed.

The trials found the CBT app prevented an increase in depression, relative to self-monitoring in the higher risk sample, but that there was no difference between any of the interventions in their effects for the lower risk sample.

Reference: Emotional competence self-help app versus cognitive behavioural self-help app versus self-monitoring app to prevent depression in young adults with elevated risk (ECoWeB PREVENT): an international, multicentre, parallel, open-label, randomised controlled trial Watkins, Edward R et al. The Lancet Digital Health, Volume 0, Issue 0