Research Projects
CSTR Lab
PAC-AI
Chemotherapy-related cognitive impairment (CRCI) affects an estimated 60% of patients, negatively impacting quality of life. Currently, there is no established method for predicting which patients will develop CRCI.
This information could be practice-changing by assisting clinicians with treatment decision-making for individual patients. We have shown that the brain network (“connectome”) is significantly altered in patients with CRCI. Therefore, we measured the connectome in patients prior to any treatment and demonstrated that these connectome properties could be used in combination with machine learning to predict 1 year post-chemotherapy cognitive impairment with 100% accuracy.
The proposed project aims to test this preliminary prediction model in a new, larger sample with the overarching goal of validating its use for clinical practice. We will enroll 50 newly diagnosed patients with primary breast cancer scheduled for adjuvant chemotherapy who will be assessed prior to any radiation or chemotherapy treatment, 1 month after chemotherapy treatment and again 1 year later. We will also enroll 50 women with breast cancer who have completed chemotherapy treatment.
Additionally, we will enroll matched healthy female controls who will be assessed at yoked intervals. We will combine these data with retrospective data we obtained during a prior study for a total sample of 150 in each group. Data from healthy controls will be used to determine impairment status in patients with breast cancer and to provide a template of typical connectome organization for comparison.
We hypothesize that our machine learning model will accurately predict 1 year post- chemotherapy cognitive impairment and that it will be more accurate than a model that includes patient- related and medical variables alone. We will also examine longitudinal changes in connectome organization associated with impairment subtypes (i.e. persistent vs. late onset impairment) as well as changes in specific functional networks (e.g. default mode, salience,executive-attention and sensory- motor networks). This information will provide novel insights regarding the neural mechanisms of CRCI and may also help us refine our prediction models.
Status: Active and Recruiting
Funded by the National Cancer Institute #R01CA226080-01A1
Brief Behavioral Therapy for Cancer Related Insomnia (BBT-CI) and Healthy Eating Education Learning (HEAL)
Insomnia is defined as difficulty falling or staying asleep, poor sleep quality and/or quantity, and it is one of the most frequently reported side effects resulting from cancer treatment. Nearly 80% of cancer patients undergoing chemotherapy report insomnia symptoms, and 30 to 50% of newly diagnosed cancer patients meet the criteria for an insomnia diagnosis.
Our prospective study identified low sleep efficiency as a prognostic factor for significantly shorter survival in women with advanced breast cancer independent of other factors. Despite the high prevalence and risk of insomnia in cancer patients, it is commonly undertreated and does not respond to traditional talk therapy. While cancer survivors have been studied extensively, behavioral interventions in cancer patients have been rare because of the lack of behavioral models uniquely suited for people suffering from neuropsychiatric symptoms who are also medically ill.
Participants will receive either Brief Behavioral Therapy for Cancer Related Insomnia (BBT-CI) or Healthy Eating Education Learning (HEAL) for a total of approximately 6 weeks. We developed the former as a behavioral intervention that is brief, requires no extensive training (can be delivered by clinical staff), and can be conducted in the clinic while patients are undergoing chemotherapy infusion. Furthermore, BBT-CI addresses circadian disruption directly by providing education about cancer-associated circadian disruption, adverse effects of circadian disruption on sleep, effects of melatonin on sleep and sleep consolidation, and behavioral instruction on how to entrain circadian rhythms.
This phase III trial aims to determine the efficacy of BBT-CI compared to HEAL for treating insomnia as measured by the Insomnia Severity Index(ISI) at post-intervention. We will enroll a total of 400 participants across all research sites, randomized to receive either BBT-CI or HEAL interventions.
Status: Active and Recruiting
Funded by the National Cancer Institute #
ProBC2: Prefrontal Cortex Abnormalities Associated With Breast Cancer Chemotherapy-2
Chemotherapy-related cognitive impairment (CRCI), or a decline in memory and other neurocognitive functions that occurs during and after chemotherapy, is associated with reduced quality of life and survival yet remains understudied. Research by our group and others has demonstrated that CRCI is linked to altered brain structure and function from pretreatment to post treatment with neurocognitive impairments being found 20+ years post-treatment. Additionally, breast cancer survivors treated with chemotherapy have accelerated brain aging phenotypes. We have also observed that patients may demonstrate unique trajectories of cognitive impairment that require further study.
Existing prospective studies of cancer and cognition have been limited to relatively short-term post- treatment follow-ups (e.g. 6-12 months), including our past prospective study (CA172145) investigating cognitive function and brain structure/function pre-surgery, 1-month post chemotherapy, and 1-year post chemotherapy. To better understand the long-term trajectory of neurocognitive outcomes in breast cancer survivors, we aim to expand our past prospective study to assess cohorts of women treated with chemotherapy, chemotherapy naïve patients, and healthy controls at yearly intervals for 5 additional years (up to 10 years).
Using non-invasive neuroimaging methods and standardized neuropsychological testing, we will measure long-term changes in neural connectivity, rather than specific regional changes, and cognitive outcomes. Finally, we will explore different trajectories or subtypes of impairment and their neural phenotypes.
By extending our knowledge of long-term neurobiological outcomes and different subtypes of cognitive impairments following breast cancer chemotherapy, the proposed project will significantly advance the understanding of chemotherapy-related cognitive impairments.
Public Health Relevance Statement:
During the last decade there has been progress in defining the neurocognitive changes associated with breast cancer from pretreatment to post treatment, but little is known about these changes after 3 years post treatment. It is possible that cancer-related cognitive impairments result from accelerated aging processes, so we need a better understanding of survivors’ neurocognitive changes beyond 3 years. To begin addressing these limitations, we aim to extend our current prospective study (CA172145), which longitudinally examines cognitive function and brain structure/function pre-surgery to 1-year post chemotherapy. In the proposed study, we will continue to assess our breast cancer cohort at yearly intervals for 5 additional years providing unique longitudinal data up to 10 years post-chemotherapy. The project will extend our knowledge on long-term neurocognitive outcomes following breast cancer chemotherapy
Status: Active But Not Recruiting at Virginia Commonwealth University
Funded by the National Cancer Institute #5R01CA172145-04
Past Research Projects
Not currently recruiting
MOSAIC: Management of Insomnia in Breast Cancer Patients
This research is designed to determine the efficacy of the BBT-I in comparison with the attention-matched behavioral control in reducing insomnia, fatigue, and cognitive difficulties in breast cancer patients. In addition, this study will examine the potential involvement of moderators (age, depression, anxiety, and hot flashes), specific behavioral mechanisms (maladaptive sleep behaviors, dysfunctional beliefs and attitudes), and physiological mechanisms (dysregulated circadian rhythms, disrupted wake-sleep cycles, and autonomic tone) as potential mediators of intervention-related changes in insomnia and the secondary outcomes of fatigue and cognitive difficulties. To address these aims, 180 breast cancer patients with acute insomnia during chemotherapy treatment will be recruited and randomized to receive either BBT-I or a behavioral control focused on Healthy Eating Education. Each intervention condition will consist of 2 face-to-face sessions + 4 phone calls, delivered over a period of six weeks. Assessments will include sleep diary, questionnaires, neuropsychological testing, actigraphy, heart rate variability measurement, and salivary cortisol collection at baseline, post-intervention, and 6- and 12 months follow ups. By offering this intervention during chemotherapy when patients are just beginning to develop insomnia, we hope to alleviate and avoid the development of chronic insomnia in the survivorship phase.
Status: Not Recruiting
Funded by the National Cancer Institute. #5R01CA181659-02
ProBC: Prefrontal Cortex Abnormalities Associated With Breast Cancer Chemotherapy
Our laboratory, along with others, has demonstrated abnormalities in brain structure and function associated with breast cancer chemotherapy, most consistently in the prefrontal cortex. The prefrontal cortex is critical for skills such as multitasking, attention, processing speed and memory; skills that are often impaired in patients who have undergone breast cancer chemotherapy. Because prefrontal cortex changes have also been observed in patients prior to chemotherapy treatment as well as in those treated with radiation and/or hormonal blockade, the specific effects of chemotherapy on prefrontal cortex remain unclear. It is also currently unknown why some patients treated with chemotherapy show improvement in cognitive function over time while others do not.
The proposed research will examine prefrontal cortex structure and function as well as cognitive status in 50 patients with primary breast cancer scheduled for chemotherapy. These patients will be evaluated across the treatment course, from pre-surgery to 12 months post-chemotherapy. We will compare the chemotherapy-treated group to 50 patients who do not receive chemotherapy and to 50 healthy females who are all assessed at the same time intervals as the chemotherapy-treated group. We will utilize non-invasive neuroimaging (MRI) methods to measure prefrontal cortex volume and functional activation in combination with neuropsychological measures of executive function, memory, processing speed and attention. We will also explore possible predictors of individual outcome such as demographic, disease, psychiatric and treatment factors.
Increasing our understanding regarding the neurobiologic mechanisms underlying chemotherapy-related cognitive impairments may improve identification of patients at highest risk for cognitive deficit and aid the development of treatments for these impairments.
Funded by the National Cancer Institute. #5R01CA172145-04
Did you participate in this research study? See our follow-up project, ProBC-2
Better Sleep for BMT
Sleep disturbance in the BMT population has been described in a small number of studies, typically noted in conjunction with reporting quality of life and/or fatigue post-BMT. A similar finding to cancer patients receiving standard chemotherapy, BMT recipients have a greater incidence of sleep disturbance than the normal population. However, the sleep disturbance persisted in approximately a third of patients 3 months to several years post-BMT. In addition, reports note a statistically significant correlation between fatigue and sleep disturbance in the post-BMT patient. Although one study suggests Cognitive Behavior Therapy to manage post-BMT fatigue, none of these studies investigated interventions to alleviate fatigue or sleep disturbance.
Behavioral intervention may be an effective approach to reducing insomnia in cancer patients during and following therapy, suggested by two pilot studies completed by Dr. Palesh. Based on this preliminary information and the multidisciplinary collaboration between a cancer behavioral scientist (Dr. Palesh), a BMT clinical researcher (Dr. Johnston) and a neuroscientist (Dr. Kesler), an open label, single arm clinical trial in BMT recipients is proposed. This team brings a unique expertise in all 3 clinical areas allowing the investigation of behavioral therapy for BMT recipients with sleep disturbance. The expected accrual is 40 patients over one year, with all eligible BMT patients receiving the brief behavioral intervention (BBT-I). The BBT-I is modeled on standard cognitive behavioral therapy for insomnia (CBT-I) and includes both stimulus control and sleep scheduling, modified to make it more suitable for cancer patients with recently developed insomnia symptoms.
Assessment of Symptoms and Side Effects in Pancreatic Adenocarcinoma Patients
Patients diagnosed with pancreatic adenocarcinoma suffer from multiple side effects of their cancer and cancer treatments. Relatively little is known about the supportive care needs of this population, and when those needs can be most effectively addressed. In order to eventually conduct a randomized control trial of early supportive care in this population, and in order to most effectively implement supportive care with
limited resources, we aim to better understand the symptomatic needs over time of the Stanford Cancer Center pancreatic adenocarcinoma patients.
Patients receiving treatment at the Stanford Cancer Center will be assessed for presence of side effects as measured by a symptom inventory survey originally developed for this study based on MD Anderson Symptom Inventory and adapted through focus groups of pancreatic cancer patients, their medical providers, and our team for medical and psychiatric symptomatology and treatments. We expect to recruit 80 participants for this study.
Acupuncture for Sleep Disruption in Cancer Survivors
Acupuncture is well known to be effective as a pain treatment, but several recent studies have examined its efficacy for insomnia. Three recent reviews of randomized controlled trials concluded that acupuncture may have a beneficial effect on subjective measures of sleep, but also highlight methodological limitations of the quality of extant research. Among the methodological issues identified by the recent reviews are: imprecise diagnostic procedures, problems with randomization, blinding issues, and insufficient safety data. We propose to address these methodological concerns using individualized acupuncture treatments.
Currently, there are no studies on the efficacy of needle acupuncture for insomnia in cancer patients. The mechanism by which it is presumed to promote sleep is by stimulating the release of neurotransmitters involved in the sleep-wake system or through its effects on melatonin secretion. This study enrolled 64 women with breast cancer from the Stanford Cancer Center and local communities who finished undergoing treatment and who complain of persistent insomnia problems. The eligible women with sleep disruption were randomized into one of two arms: Acupuncture vs. Sham Acupuncture.
