Clinical Outcomes in T4 and/or N2 Rectal Cancer Treated With Neoadjuvant Chemoradiotherapy: A Retrospective Study.

INTRODUCTION: Total neoadjuvant therapy (TNT) in the management of locally advanced rectal cancer (LARC) did not show survival benefit over the standard long course chemoradiotherapy. Trials of TNT did not address the impact of each risk feature in isolation from other high-risk features. METHODOLOGY: In this retrospective study, we describe the clinical outcomes of patients with T4 and/or N2 rectal adenocarcinoma who were treated with chemoradiotherapy followed by total mesorectal excision (TME). After obtaining the local regulatory approvals, demographic and clinical data were collected for patients in Manitoba between January 2007 and December 2019. RESULTS: The cohort included 331 patients. 61 patients had T4-only disease and 218 had N2-only disease. Mean age was 59.65 years. 74.3% received adjuvant chemotherapy (ACT), but only 56.5% completed the planned course. R0 resection was achieved in 93.4% of patients (78.7% and 97.2% in T4 and N2, respectively). Median follow up was 4.93 years. 3-year overall recurrence rate was 29%. 3-year locoregional recurrence (LRR) rate was 8% (16% and 6% in T4 and N2, respectively). 3-year overall survival (OS) rate was 84% in the whole cohort (72.6% and 87.1% in T4 and N2, respectively). Incomplete surgical resection was a poor prognostic factor for both OS and LRR. ACT was associated with a survival benefit in the whole cohort (P = .001) and in the N2 sub-cohort (P = 003) but there was no survival benefit observed in T4 sub-cohort. ACT did not have an impact on LRR. CONCLUSIONS: Achieving R0 resection in LARC with neoadjuvant therapy improves recurrence and survival rates. T4 disease carries a worse clinical outcome than N2 and consideration should be given to upstage T4 to stage III. Different high-risk features in LARC predict different clinical outcomes. In the era of TNT, personalization of treatment strategy based on these factors could potentially improve outcomes.

Prolonged Early Food Insecurity and Child Feeding Practices among a Low-Income Hispanic Population: Role of Parenting Stress.

OBJECTIVE: To examine associations between prolonged early household food insecurity (FI) during pregnancy, infancy, and toddlerhood, and child feeding practices, and the mediating role of dysfunctional parent-child interactions. METHODS: We conducted secondary longitudinal analyses of data from the Starting Early Program (StEP) randomized controlled trial, which studied a primary care-based child obesity prevention program for low-income Hispanic families. Our independent variable was FI, using the USDA Food Security Module, during the third trimester of pregnancy and at child ages 10- and 19-months. Frequency of reported FI was defined by the number of periods with FI (0, 1, 2, or 3). Our dependent variables were feeding practices at child age 28-months using the Comprehensive Feeding Practices Questionnaire. Our mediating variable was dysfunctional parent-child interactions using the Parenting Stress Index subscale at age 19-months. We used linear regression to determine associations between frequency of reported FI and feeding practices adjusting for covariates, and mediation analyses to determine if dysfunctional parent-child interactions mediate these associations. RESULTS: 344 mothers completed assessments at child age 28-months. Of the 12 feeding practices examined, higher frequency of reported FI was positively associated with using food as a reward, restriction of food for weight control, and using food for emotional regulation, and was negatively associated with monitoring of less healthy foods. There was a significant indirect effect of frequency of reported FI on these practices through dysfunctional parent-child interactions. CONCLUSION: Higher frequency of reported FI was associated with four feeding practices, through dysfunctional parent-child interactions. Understanding these pathways can inform preventive interventions.

The effects of parent-child dysfunctional interactions on early childhood weight: A serial mediation model through emotional feeding and child appetite traits.

Parent-child dysfunctional interactions (PCDI) are known to contribute to children's weight status. However, the underlying mechanisms in how dysfunctional interactions between parent and child influence child weight are not clear. This study investigates the impact of PCDI on toddlers' weight, focusing on the potential serial mediation by maternal emotional feeding and child appetite traits. We conducted a secondary analysis of longitudinal data from a larger intervention trial to prevent childhood obesity in low-income Hispanic families. A total of 241 mother-child dyads were included in these analyses. Measurements were taken at various stages: PCDI at child age 19 months, maternal emotional feeding at 28 months, and both child appetite traits and weight-for-age z-score (WFAz) at 36 months. Serial mediation analyses revealed a significant indirect effect of early PCDI on later child WFAz through maternal emotional feeding and two child food approach traits (food responsiveness, emotional overeating) out of the eight child appetite traits assessed. PCDI at 19 months was associated with increased use of emotional feeding in mothers at 28 months, which was associated with heightened food responsiveness and emotional overeating in children at 36 months, which in turn was linked to greater child WFAz at 36 months. The findings of this study expand the understanding of the mechanisms underlying PCDI and child weight, emphasizing the interplay between maternal feeding practices and child appetite in the context of adverse parent-child interactions during early childhood.

Different patterns of endorsement of intensive mothering beliefs: Associations with parenting guilt and parental burnout.

The unrealistic expectations rooted in intensive mothering beliefs can negatively impact maternal well-being. The present study investigates associations between intensive mothering beliefs, parenting guilt, and parental burnout using a person-centered approach. We first examined whether different profiles of mothers exist based on their endorsement of the five subbeliefs of the Intensive Parenting Attitudes Questionnaire. We then tested associations between these profiles and parenting guilt and parental burnout and whether mothers' demographic characteristics predicted profile membership. Using data from 291 mothers (61% White, 15% Black/African American) with at least one child under 6 years old, we identified four profiles of mothers. Two distinct patterns of intensive mothering endorsement emerged: mothers who exhibited consistent levels of endorsement across the five subbeliefs (i.e., high endorsement, moderate endorsement, and low endorsement) and mothers who were characterized by higher endorsement on fulfillment, stimulation, and child-centered but lower endorsement on essentialism and challenging (i.e., selective endorsement). Profile membership contributed to differences in parenting guilt and parental burnout. Parenting guilt was the highest in the profile characterized by the high levels of endorsement across all five subbeliefs (high endorsement) and was significantly higher than low endorsement. Parental burnout was the lowest in the selective endorsement and was significantly lower than in the high endorsement and moderate endorsement. These results highlight the heterogeneity of subscribing to intensive mothering beliefs and suggest that magnitude and patterns of endorsement of intensive mothering beliefs differentially contribute to parenting-related well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Rapid, biochemical tagging of cellular activity history in vivo.

Intracellular calcium (Ca2+) is ubiquitous to cell signaling across all biology. While existing fluorescent sensors and reporters can detect activated cells with elevated Ca2+ levels, these approaches require implants to deliver light to deep tissue, precluding their noninvasive use in freely-behaving animals. Here we engineered an enzyme-catalyzed approach that rapidly and biochemically tags cells with elevated Ca2+ in vivo. Ca2+-activated Split-TurboID (CaST) labels activated cells within 10 minutes with an exogenously-delivered biotin molecule. The enzymatic signal increases with Ca2+ concentration and biotin labeling time, demonstrating that CaST is a time-gated integrator of total Ca2+ activity. Furthermore, the CaST read-out can be performed immediately after activity labeling, in contrast to transcriptional reporters that require hours to produce signal. These capabilities allowed us to apply CaST to tag prefrontal cortex neurons activated by psilocybin, and to correlate the CaST signal with psilocybin-induced head-twitch responses in untethered mice.

Social Determinants of Premature Birth.

Social determinants of health have received increasing attention in public health, leading to increased understanding of how social factors-individual and contextual-shape the health of the mother and infant. However, racial differences in birth outcomes persist, with incomplete explanation for the widening disparity. Here, we highlight the social determinants of preterm birth, with special attention to the social experiences among African American women, which are likely attributed to structural racism and discrimination throughout life.

Machine learning-guided engineering of genetically encoded fluorescent calcium indicators.

Here we used machine learning to engineer genetically encoded fluorescent indicators, protein-based sensors critical for real-time monitoring of biological activity. We used machine learning to predict the outcomes of sensor mutagenesis by analyzing established libraries that link sensor sequences to functions. Using the GCaMP calcium indicator as a scaffold, we developed an ensemble of three regression models trained on experimentally derived GCaMP mutation libraries. The trained ensemble performed an in silico functional screen on 1,423 novel, uncharacterized GCaMP variants. As a result, we identified the ensemble-derived GCaMP (eGCaMP) variants, eGCaMP and eGCaMP+, which achieve both faster kinetics and larger ∆F/F0 responses upon stimulation than previously published fast variants. Furthermore, we identified a combinatorial mutation with extraordinary dynamic range, eGCaMP2+, which outperforms the tested sixth-, seventh- and eighth-generation GCaMPs. These findings demonstrate the value of machine learning as a tool to facilitate the efficient engineering of proteins for desired biophysical characteristics.

Prenatal and Pediatric Primary Care-Based Child Obesity Prevention: Effects of Adverse Social Determinants of Health on Intervention Attendance and Impact.

Background: Adverse social determinants of health (SDoHs), specifically psychosocial stressors and material hardships, are associated with early childhood obesity. Less is known about whether adverse SDoHs modify the efficacy of early childhood obesity prevention programs. Methods: We conducted a secondary analysis of publicly insured birthing parent-child dyads with Latino backgrounds participating in a randomized controlled trial of the Starting Early Program (StEP), a child obesity prevention program beginning in pregnancy. We measured baseline adverse SDoHs categorized as psychosocial stressors (low social support, single marital status, and maternal depressive symptoms) and material hardships (food insecurity, housing disrepair, and financial difficulties) individually and cumulatively in the third trimester. Logistic regression models tested effects of adverse SDoHs on StEP attendance. We then tested whether adverse SDoHs moderated intervention impacts on weight at age 2 years. Results: We observed heterogeneous effects of adverse SDoHs on outcomes in 358 parent-child dyads. While housing disrepair decreased odds of higher attendance [adjusted odds ratio (aOR) 0.52, 95% confidence interval (CI): 0.29-0.94], high levels of psychosocial stressors doubled odds of higher attendance (aOR 2.36, 95% CI: 1.04-5.34). Similarly, while certain adverse SDoHs diminished StEP impact on weight (e.g., housing disrepair), others (e.g., high psychosocial stress) enhanced StEP impact on weight. Conclusions: Effects of adverse SDoHs on intervention outcomes depend on the specific adverse SDoH. Highest engagement and benefit occurred in those with high psychosocial stress at baseline, suggesting that StEP components may mitigate aspects of psychosocial stressors. Findings also support integration of adverse SDoH assessment into strategies to enhance obesity prevention impacts on families with material hardships. Trial Registration: This study is registered on clinicaltrials.gov: Starting Early Obesity Prevention Program (NCT01541761); https://clinicaltrials.gov/ct2/show/NCT01541761.

Optimizing pharmacogenomic decision-making by data science.

Healthcare systems have made rapid progress towards combining data science with precision medicine, particularly in pharmacogenomics. With the lack of predictability in medication effectiveness from patient to patient, acquiring the specifics of their genotype would be highly advantageous for patient treatment. Genotype-guided dosing adjustment improves clinical decision-making and helps optimize doses to deliver medications with greater efficacy and within safe margins. Current databases demand extensive effort to locate relevant genetic dosing information. To address this problem, Patient Optimization Pharmacogenomics (POPGx) was constructed. The objective of this paper is to describe the development of POPGx, a tool to simplify the approach for healthcare providers to determine pharmacogenomic dosing recommendations for patients taking multiple medications. Additionally, this tool educates patients on how their allele variations may impact gene function in case they need further healthcare consultations. POPGx was created on Konstanz Information Miner (KNIME). KNIME is a modular environment that allows users to conduct code-free data analysis. The POPGx workflow can access Clinical Pharmacogenomics Implementation Consortium (CPIC) guidelines and subsequently be able to present relevant dosing and counseling information. A KNIME representational state transfer (REST) application program interface (API) node was established to retrieve information from CPIC and drugs that are exclusively metabolized through CYP450, and these drugs were processed simultaneously to demonstrate competency of the workflow. The POPGx program provides a time-efficient method for users to retrieve relevant, patient-specific medication selection and dosing recommendations. Users input metabolizer gene, genetic allele data, and medication list to retrieve clear dosing information. The program is automated to display current guideline recommendations from CPIC. The integration of this program into healthcare systems has the potential to revolutionize patient care by giving healthcare practitioners an easy way to prescribe medications with greater efficacy and safety by utilizing the latest advancements in the field of pharmacogenomics.

Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function.

The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralization, Abs can clear infected cells and induce immunomodulatory functions through engagement of their crystallizable fragment (Fc) with complement proteins and Fc receptors on immune cells. Little is known about the role of Fc effector functions of neutralizing Abs in the context of encephalitic alphavirus infection. To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab with intact Fc function (hF5-WT) or containing the loss of function Fc mutations L234A and L235A (hF5-LALA) in the context of VEEV infection. We observed significantly reduced binding to complement and Fc receptors, as well as differential in vitro kinetics of Fc-mediated cytotoxicity for hF5-LALA compared to hF5-WT. The in vivo efficacy of hF5-LALA was comparable to hF5-WT at -24 and + 24 h post infection, with both Abs providing high levels of protection. However, when hF5-WT and hF5-LALA were administered + 48 h post infection, there was a significant decrease in the therapeutic efficacy of hF5-LALA. Together these results demonstrate that optimal therapeutic Ab treatment of VEEV, and possibly other encephalitic alphaviruses, requires neutralization paired with engagement of immune effectors via the Fc region.

Long-term Survival Among Patients With De Novo Human Epidermal Growth Receptor 2-Positive Metastatic Breast Cancer in Manitoba.

OBJECTIVES: Although metastatic breast cancer (MBC) is considered incurable, human epidermal growth receptor 2 (HER2)-directed therapy has improved outcomes significantly, with some patients experiencing durable responses to treatment. The aim of this study was to identify potential predictors of long-term survival (LTS) among patients with de novo HER2-positive MBC who received HER2-directed treatment. METHODS: Eligible patients from 2008 to 2018 were identified using the Manitoba Cancer Registry. LTS was defined as survival ≥5 years from the time of diagnosis. Univariate logistic regression models were performed to assess variables of clinical interest and the odds of LTS. Overall survival (OS) was defined as the time from diagnosis of MBC to death of any cause. OS was estimated using the Kaplan-Meier method with log-rank comparative analyses as a univariate analysis. A Cox proportional hazards model was used for OS estimates in a univariate analysis. RESULTS: A total of 62 patients were diagnosed with de novo HER2-positive MBC and received HER2-directed therapy. Eighteen (29%) achieved LTS. The median OS of the whole cohort was 50.2 months (95% CI: 28.6-not reached). Radiographic response to first-line treatment was associated with LTS; complete and partial responses were both associated with higher odds of LTS (odds ratio: 28.33 [95% CI: 2.47-4006.71, P = 0.0043] and odds ratio: 7.80 [95% CI: 0.7317-1072.00, P = 0.0972], respectively). The best radiographic response was associated with improved OS. CONCLUSIONS: Radiographic response to first-line HER2-directed therapy is a predictor for LTS in patients with de novo HER2-positive MBC. Larger studies are needed to identify patients who can safely discontinue HER2-targeted therapy.

Province-Wide Ascertainment of Lynch Syndrome in Manitoba.

BACKGROUND & AIMS: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years. METHODS: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT). Data were stratified and compared before and after the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP vs clinic referrals (CRs). RESULTS: Between 2014 and 2021, 50 of 101 (49.5%) index cases were identified by the LSSP compared with 51 of 101 (50.5%) from CRs. The proportion of PMS2 variants was 34% (17 of 50) for LSSP index cases compared with 21.6% (11 of 51) for CRs from 2014 to 2021 (P < .001). Among CRs from 2014 to 2021, 24 of 51 (47.1%) families met the Amsterdam criteria, compared with 11 of 50 (22.0%) for the LSSP (P = .01). CGT occurred among 46.8% (95 of 203; average, 1.9 relatives/index) of first-degree relatives of CR index cases vs 36.5% (84 of 230; average, 1.7 relatives/index) of first-degree relatives of LSSP index cases (P = .03). Daughters were most likely to undergo CGT. CONCLUSIONS: A tumor screening program is more effective at detecting individuals with lower penetrant gene variants and families who do not meet traditional family history-based criteria. Cascade genetic testing is higher among clinic referrals compared with the screening program. These findings suggest a complementary role of these 2 ascertainment methods for Lynch syndrome.

Promoting toddlers' self-regulation and healthy eating habits among families living in poverty: A randomized controlled trial of Recipe 4 Success.

The Recipe 4 Success preventive intervention targeted multiple factors critical to the health and well-being of toddlers living in poverty. This randomized controlled trial, which was embedded within Early Head Start home visits for 12 weeks, included 242 racially and ethnically diverse families (51% girls; toddler mean age = 2.58 years; data collected 2016-2019). Compared to parents in usual practice home visits, parents in Recipe 4 Success displayed greater sensitive scaffolding of toddlers' learning and more responsive food parenting practices (Cohen's d = .21-.30). Toddlers in Recipe 4 Success exhibited greater self-regulation and had healthier eating habits (Cohen's d = |.16-.35|). Results highlight the value of Recipe 4 Success in promoting parent and toddler behavior change that could have life-long benefits.

Breast Cancer Polygenic-Risk Score Influence on Risk-Reducing Endocrine Therapy Use: Genetic Risk Estimate (GENRE) Trial 1-Year and 2-Year Follow-Up.

Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors. PREVENTION RELEVANCE: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

Household Food Insecurity and Maternal-Toddler Fruit and Vegetable Dietary Concordance.

OBJECTIVE: To examine whether prenatal or concurrent household food insecurity influences associations between maternal and toddler fruit and vegetable (FV) intake. DESIGN: Application of a life-course framework to an analysis of a longitudinal dataset. SETTING: Early childhood obesity prevention program at a New York City public hospital. PARTICIPANTS: One-hundred and fifty-six maternal-toddler dyads self-identifying as Hispanic or Latino. VARIABLES MEASURED: Maternal and toddler FV intake was measured using Centers for Disease Control and Prevention dietary measures when toddlers were aged 19 months. Household food insecurity (measured prenatally and concurrently at 19 months) was measured using the US Department of Agriculture Food Security Module. ANALYSIS: Regression analyses assessed associations between adequate maternal FV intake and toddler FV intake. Interaction terms tested whether prenatal or concurrent household food insecurity moderated this association. RESULTS: Adequate maternal FV intake was associated with increased toddler FV intake (B = 6.2 times/wk, 95% confidence interval, 2.0-10.5, P = 0.004). Prenatal household food insecurity was associated with decreased toddler FV intake (B = -6.3 times/wk, 95% confidence interval, -11.67 to -0.9, P = 0.02). There was a significant interaction between the level of maternal-toddler FV association (concordance or similarity in FV intake between mothers and toddlers) and the presence of food insecurity such that maternal-toddler FV association was greater when prenatal household food insecurity was not present (B = -11.6, P = 0.04). CONCLUSIONS AND IMPLICATIONS: Strategies to increase FV intake across the life course could examine how the timing of household food insecurity may affect intergenerational maternal-child transmission of dietary practices.

Tagging neurons with light.

Molecular circuits for activity-guided optogenetics.

The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership.

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.

Engineered allostery in light-regulated LOV-Turbo enables precise spatiotemporal control of proximity labeling in living cells.

The incorporation of light-responsive domains into engineered proteins has enabled control of protein localization, interactions and function with light. We integrated optogenetic control into proximity labeling, a cornerstone technique for high-resolution proteomic mapping of organelles and interactomes in living cells. Through structure-guided screening and directed evolution, we installed the light-sensitive LOV domain into the proximity labeling enzyme TurboID to rapidly and reversibly control its labeling activity with low-power blue light. 'LOV-Turbo' works in multiple contexts and dramatically reduces background in biotin-rich environments such as neurons. We used LOV-Turbo for pulse-chase labeling to discover proteins that traffic between endoplasmic reticulum, nuclear and mitochondrial compartments under cellular stress. We also showed that instead of external light, LOV-Turbo can be activated by bioluminescence resonance energy transfer from luciferase, enabling interaction-dependent proximity labeling. Overall, LOV-Turbo increases the spatial and temporal precision of proximity labeling, expanding the scope of experimental questions that can be addressed with proximity labeling.

The impact of early palliative care on the quality of life of patients with advanced pancreatic cancer: The IMPERATIVE case-crossover study.

PURPOSE: Pancreatic cancer is a lethal disease. Many patients experience a heavy burden of cancer-associated symptoms and poor quality of life (QOL). Early palliative care alongside standard oncologic care results in improved QOL and survival in some cancer types. The benefit in advanced pancreatic cancer (APC) is not fully quantified. METHODS: In this prospective case-crossover study, patients ≥ 18 years old with APC were recruited from ambulatory clinics at a tertiary cancer center. Patients underwent a palliative care consultation within 2 weeks of registration, with follow up visits every 2 weeks for the first month, then every 4 weeks until week 16, then as needed. The primary outcome was change in QOL between baseline (BL) and week 16, measured by Functional Assessment of Cancer Therapy - hepatobiliary (FACT-Hep). Secondary outcomes included symptom control (ESAS-r), depression, and anxiety (HADS, PHQ-9) at week 16. RESULTS: Of 40 patients, 25 (63%) were male, 28 (70%) had metastatic disease, 31 (78%) had ECOG performance status 0-1, 31 (78%) received chemotherapy. Median age was 70. Mean FACT-hep score at BL was 118.8, compared to 125.7 at week 16 (mean change 6.89, [95%CI (-1.69-15.6); p = 0.11]). On multivariable analysis, metastatic disease (mean change 15.3 [95%CI (5.3-25.2); p = 0.004]) and age < 70 (mean change 12.9 [95%CI (0.5-25.4); p = 0.04]) were associated with improved QOL. Patients with metastatic disease had significant improvement in symptom burden (mean change -7.4 [95%CI (-13.4 to -1.4); p = 0.02]). There was no difference in depression or anxiety from BL to week 16. CONCLUSION: Palliative care should be integrated early in the journey for patients with APC, as it can improve QOL and symptom burden. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03837132.