LOS ANGELES, Sep 05: A new study led by Cedars-Sinai Health Sciences University investigators found that prostate-specific antigen levels in the blood, which are used to track the effectiveness of prostate cancer treatment, need to be 10 times lower than most physicians generally target for the best patient outcomes.
The study, published in Cancer, could help doctors better manage treatment of prostate cancer patients, maximizing patients’ chances of survival.
“PSA levels drop dramatically when patients receive hormone therapy,” said Stephen Freedland, MD, professor of Urology and director of the Center for Integrated Research in Lifestyle and Cancer at Cedars-Sinai, and first author of the study. “Our study found that the optimal PSA level was less than 0.2 nanograms per milliliter of blood. However, fewer than half of patients given hormone therapy alone reached that optimal level for overall survival.”
Investigators reviewed Veterans Health Administration data on 4,090 prostate cancer patients. They found that even if PSA dropped 90%, if it did not get below 0.2 nanograms per milliliter of blood, outcomes were not good.
Importantly, the study found that if doctors added drugs called androgen receptor pathway inhibitors to their hormone therapy, patients were much more likely to reach PSA levels below 0.2 nanograms per milliliter of blood.
“Many physicians don’t offer patients additional treatment because hormone therapy alone lowers their PSA levels below 2 nanograms per milliliter, which we previously showed was many physicians’ target level,” Freedland said. “We hope these data will change that practice.”
Additional authors include Wei Gao, PhD; Maëlys Touya, PharmD, MSc; Hongbo Yang, PhD; David Russell, MD, FACS; Jingyi Chen, MS; Grace Chen, MS; and Jasmina I. Ivanova, MA.
Funding: Sponsored by Pfizer Inc. and Astellas Pharma Inc.
Disclosures: Stephen J. Freedland reports consulting or advisory roles with Astellas Pharma Inc., AstraZeneca, Bayer, Candel, Eli Lilly, Johnson & Johnson Innovative Medicine (formerly Janssen), Merck, Novartis, Pfizer Inc., Sanofi, Sumitomo Pharma America, Inc. (formerly Myovant Sciences), and Tolmar.
New Tool Measures Thyroid Cancer Patients’ Anxiety
A new tool created by Cedars-Sinai Health Sciences University investigators is the first to measure anxiety in patients with thyroid cancer. Described in Thyroid, the Thyroid Cancer Modified Anxiety Scale (TC-MAX) could help doctors clarify patients’ expectations, better match their treatment to their needs, and improve patient outcomes.
“A patient’s distress greatly influences which thyroid cancer treatment the patient prefers and what their doctor recommends,” said Allen Ho, MD, professor of Surgery, co-director of the Thyroid Cancer Program at Cedars-Sinai Cancer and senior author of the study. “We found that our tool effectively assesses patient concerns to help doctors better determine the best course of treatment. This is especially important when the treatment options have similar likely outcomes but patient preferences vary widely.”
The tool includes 18 questions that measure a patient’s general cancer-related anxiety, their anxiety around ultrasound testing, which is used to monitor thyroid cancer progression, and their fear about whether their cancer will progress or come back. Investigators created TC-MAX in collaboration with Thyroid Cancer Survivors’ Association, the world’s largest thyroid cancer patient consortium. They relied on medical literature, physician expertise and the perspectives of more than 1,000 thyroid cancer patients.
The study showed that the extent of each patient’s anxiety mirrored the extent of surgery they chose, Ho said. When active surveillance, partial thyroid removal and total thyroid removal were all options, patients with the highest TC-MAX anxiety scores chose to have their entire thyroid removed, while those with lower average TC-MAX scores generally selected partial thyroid removal. Patients with the lowest scores chose active surveillance.
Ho said that the tool is now ready for use in clinical trials and patient care.
Additional Cedars-Sinai authors include Amanda J. Bastien MD, Sungjin Kim MS, Cynthia Zalt, Iris Cong PhD, Jewel Ng, Caroline Marshall, Christopher V. Almario MD MSHPM, Omer Liran MD, Brennan M.R. Spiegel MD, MSHS, Jon Mallen-St. Clair MD, PhD, Evan Walgama MD, Kevin S. Scher MD, Julie K. Jang MD, Yufei Chen MD, Samuel Zhang MD, Linnea Peterson MD, Wendy L. Sacks MD, and Zachary S. Zumsteg MD.
Other authors include Gary Bloom and Michelle M. Chen MD.
Funding: AAOHNS CORE Grant; Cedars-Sinai Jim and Eleanor Randall Department of Surgery Research Award.
Reducing Unnecessary Fluid Testing Could Lower Cancer Care Costs
Doctors might be able to safely reduce healthcare costs by skipping unnecessary laboratory tests for patients with advanced gynecologic cancers, according to a Cedars-Sinai Health Sciences University study. The paper, published in JAMA Network Open, examined testing on fluid drained from the abdomen or around the lungs.
Patients with advanced gynecologic cancer often experience fluid buildup in these areas. Draining the fluid helps relieve pain, pressure and other symptoms, but the investigators found that laboratory testing of the fluid is frequently unnecessary.
Cedars-Sinai gynecologic oncology fellow Yingao Zhang, MD, and obstetrics and gynecology resident Olivia Foy, MD, are co-first authors of the study.
“We undertook this study to determine how often unnecessary tests may be safely skipped, and to estimate how much this would help reduce healthcare costs,” Zhang said.
Investigators reviewed 976 fluid-draining procedures performed on gynecologic cancer patients at one hospital over 10 years. Laboratory testing was ordered in 40% of cases, a common practice done to rule out infection, check for the presence of cancer cells, and determine the cause of fluid buildup.
Nearly 80% of those orders included at least one test the researchers determined was likely unnecessary—either because a cancer diagnosis had already been confirmed or a patient had no symptoms that would prompt further fluid testing. The estimated cost of these tests was roughly $1million over 10 years.
The investigators found that unnecessary tests were more likely to be ordered in the emergency department or for hospitalized patients than in outpatient clinics. They also found that non-oncology care providers were more likely to order unneeded fluid tests than oncologists.
“Avoiding automatic lab testing on fluid from patients with known cancer diagnoses represents a low-risk opportunity to reduce healthcare costs,” Foy said.
The investigators identified clinician education as a way to reduce unnecessary testing and related costs, and suggested that similar analyses in other cancer types and other institutions could uncover additional cost-reducing opportunities.
Additional Cedars-Sinai authors include Grace Pipes, MD; and Margaret I. Liang, MD, MSHPM.
Funding: The Cedars-Sinai Honest Enterprise Research Broker (HERB) Committee, which assisted with cohort building, is supported by the NIH National Center for Advancing Translational Science UCLA CTSI Grant Number UL1TR001881.
Disclosures: Dr. Liang reported grants from Merck, grants from Foundation for Women’s Cancer, and personal fees from Association of Cancer Care Centers outside the submitted work.
How Your Brain Stays Focused on a Goal
Cedars-Sinai Health Sciences University investigators have discovered how the brain maintains focus when a person is working toward a goal. The study, published in Nature Human Behaviour, sheds light on how a person’s brain actively maintains task goals in working memory while that person responds to changes in their environment.
“Our findings show that the brain maintains memories of task goals by keeping certain neurons persistently active over minutes,” said Ueli Rutishauser, PhD, professor of Neurosurgery, at Cedars-Sinai and senior author of the study. “The two different brain regions we studied maintained such memories in two different formats, thereby giving people the flexibility to adapt while continuing to pursue the same goal.”
The study concentrated on two brain regions: the medial frontal cortex, which supports planning, decision-making and long-term goal achievement, and the hippocampus, which plays an important role in learning and memory.
Investigators recorded the activity of individual brain cells while study participants completed tasks designed to test how the brain remembers goals over many minutes without reminders.
By analyzing activity patterns in different brain regions, investigators found that task goals are stably and persistently represented by brain cells in the medial frontal cortex many minutes after instructions were given to the participants. In contrast, the hippocampus continuously updated task goal information as circumstances changed on the timescale of seconds. This allows a person to adapt quickly to change without losing sight of a desired long-term outcome.
Additional Cedars-Sinai authors include Hristos Courellis, Michael Kyzar, Juri Minxha and Adam Mamelak.
Other authors include Araceli R. Cardenas, Taufik Valiante and Ralph Adolphs.
Funding: This work was supported by the BRAIN Initiative through the NIH Office of the Director (U01NS117839 to U.R.), the Simons Foundation Collaboration on the Global Brain (to U.R. and R.A.), and by a merit scholarship from the Josephine De Karman Fellowship Trust .
Small Bowel Microbiome Offers Clues to Women’s Health
A new study by investigators at Cedars-Sinai Health Sciences University has identified differences in the makeup and organization of the small bowel microbiome between women and men. The findings, published in iScience, could offer new insights into why some conditions are more prevalent in women.
The small bowel microbiome comprises a community of microorganisms that coexist in this part of the digestive tract and play vital roles in immune function, metabolism and hormonal regulation.
“One intriguing finding was a bacterial community containing Granulicatella, which we found only in women,” said Ruchi Mathur, MD, director of Clinical Research and Clinical Operations for the Medically Associated Science and Technology Program at Cedars-Sinai and corresponding author of the study. “Bacteria in this community appear at increased levels in women with polyendocrine metabolic ovarian syndrome, formerly known as polycystic ovary syndrome.”
Investigators also found sex differences related to how small bowel microbes produce fructans, complex carbohydrates known for triggering digestive symptoms in irritable bowel syndrome, a condition far more common in women than men.
“Our findings show that biological sex is a critical variable in the small bowel microbiome,” said Mathur, also a professor of Medicine. “We must consider it as we move toward more personalized approaches to understanding and treating disease.”
Other Cedars-Sinai authors include Mohamad Rashid, Gabriela Leite, Gillian M. Barlow, Ava Hosseini, Daniel Brimberry, Dilara Flor, Gonzalo Parodi, Maritza Sanchez, Ignacio Rivera, Angel Trujillo, Maria Jesus Villanueva-Millan, Walter Morales, Stacy Weitsman and Mark Pimentel.
Funding: This study was supported by the Monica Lester Charitable Trust and the Elias, Genevieve and Georgianna Atol Charitable Trust in support of Ruchi Mathur’s research, and the National Philanthropic Trust in support of Mark Pimentel’s research.
Boosting the Accuracy of Disease Risk Prediction From Genetic Data
Investigators at Cedars-Sinai Health Sciences University have developed a new computational framework for improving how genetic data is used to estimate the inherited risk that an individual will develop conditions like Alzheimer's disease, Type 2 diabetes, high blood pressure and breast cancer.
The framework, called Adaptive Boosting of Pre-trained Polygenic Risk Scores (AB-PRS) and described in Nature Communications, builds on existing polygenic risk scores, tools that estimate disease risk based on many genetic variants across the genome, and identifies additional genetic signals that may not be fully captured by current scoring methods.
"As more people undergo genetic testing, it's becoming increasingly important to make the best use of that information," said Ruowang Li, PhD, co-corresponding author of the study and assistant professor of Computational Biomedicine at Cedars-Sinai. "Our findings aim to improve the accuracy of genetic risk prediction, allowing us to better predict disease risk and guide more personalized care."
Polygenic risk scores are increasingly used in research and clinical settings to estimate genetic susceptibility to common diseases, but their accuracy varies across diseases, datasets and populations. Investigators trained AB-PRS to identify genetic signals that existing risk scores may miss. They tested the approach using genetic data from the UK Biobank and validated the findings in three independent biobanks. The method consistently matched or outperformed existing polygenic risk scores across multiple diseases. The researchers say additional validation, particularly in more diverse populations, will be needed before the approach can be widely used in clinical care.
