Alzheimer's disease-related biomarkers and cancer-related cognitive decline: the thinking and living with cancer study.

PURPOSE: We evaluated whether plasma Alzheimer's Disease (AD)-related biomarkers were associated with cancer-related cognitive decline (CRCD) among older breast cancer survivors. METHODS: We included survivors 60-90 years with primary stage 0-III breast cancers (n = 236) and frequency-matched non-cancer controls (n = 154) who passed a cognitive screen and had banked plasma specimens. Participants were assessed at baseline (pre-systemic therapy) and annually for up to 60-months. Cognition was measured using tests of attention, processing speed and executive function (APE) and learning and memory (LM); perceived cognition was measured by the FACT-Cog PCI. Baseline plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), beta-amyloid 42/40 (Aß42/40) and phosphorylated tau (p-tau181) were assayed using single molecule arrays. Mixed models tested associations between cognition and baseline AD-biomarkers, time, group (survivor vs control) and their two- and three-way interactions, controlling for age, race, WRAT4 Word Reading score, comorbidity and BMI; two-sided 0.05 p-values were considered statistically significant. RESULTS: There were no group differences in baseline AD-related biomarkers except survivors had higher baseline NfL levels than controls (p = .013). Survivors had lower adjusted longitudinal APE than controls starting from baseline and continuing over time (p = <0.002). However, baseline AD-related biomarker levels were not independently associated with adjusted cognition over time, except controls had lower APE scores with higher GFAP levels (p = .008). CONCLUSION: The results do not support a relationship between baseline AD-related biomarkers and CRCD. Further investigation is warranted to confirm the findings, test effects of longitudinal changes in AD-related biomarkers and examine other mechanisms and factors affecting cognition pre-systemic therapy.

Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.

Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalization. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.

"Pathways": A hope-enhancing intervention for patients undergoing treatment for advanced lung cancer.

OBJECTIVE: Observational data suggest hope is associated with the quality of life and survival of people with cancer. This trial examined the feasibility, acceptability, and preliminary outcomes of "Pathways," a hope intervention for people in treatment for advanced lung cancer. METHODS: Between 2020 and 2022, we conducted a single-arm trial of Pathways among participants who were 3-12 weeks into systemic treatment. Pathways consisted of two individual sessions delivered during infusions and three phone calls in which participants discussed their values, goals, and goal strategies with a nurse or occupational therapist. Participants completed standardized measures of hope and goal interference pre- and post-intervention. Feasibility was defined as ≥60% of eligible patients enrolling, ≥70% of participants completing three or more sessions, ≥70% of participants completing post-assessments, and mean acceptability ratings ≥7 out of 10 on intervention relevance, helpfulness, and convenience. Linear regression fixed effects models with covariates modeled pre-post changes in complete case analysis and multiple imputation models. RESULTS: Fifty two participants enrolled: female (59.6%), non-Hispanic White (84.6%), rural (75.0%), and with low educational attainment (51.9% high school degree or less). Except for enrollment (54%), feasibility and acceptability markers were surpassed (77% adherence, 77% retention, acceptability ratings ≥8/10). There was moderate improvement in hope and goal interference from pre-to post-intervention (d = 0.51, p < 0.05 for hope; d = -0.70, p < 0.005 for goal interference). CONCLUSIONS: Strong feasibility, acceptability, and patient-reported outcome data suggest Pathways is a promising intervention to increase hope and reduce cancer-related goal interference during advanced lung cancer treatment.

Prediction of cognitive decline in older breast cancer survivors: the Thinking and Living with Cancer study.

PURPOSE: Cancer survivors commonly report cognitive declines after cancer therapy. Due to the complex etiology of cancer-related cognitive decline (CRCD), predicting who will be at risk of CRCD remains a clinical challenge. We developed a model to predict breast cancer survivors who would experience CRCD after systematic treatment. METHODS: We used the Thinking and Living with Cancer study, a large ongoing multisite prospective study of older breast cancer survivors with complete assessments pre-systemic therapy, 12 months and 24 months after initiation of systemic therapy. Cognition was measured using neuropsychological testing of attention, processing speed, and executive function (APE). CRCD was defined as a 0.25 SD (of observed changes from baseline to 12 months in matched controls) decline or greater in APE score from baseline to 12 months (transient) or persistent as a decline 0.25 SD or greater sustained to 24 months. We used machine learning approaches to predict CRCD using baseline demographics, tumor characteristics and treatment, genotypes, comorbidity, and self-reported physical, psychosocial, and cognitive function. RESULTS: Thirty-two percent of survivors had transient cognitive decline, and 41% of these women experienced persistent decline. Prediction of CRCD was good: yielding an area under the curve of 0.75 and 0.79 for transient and persistent decline, respectively. Variables most informative in predicting CRCD included apolipoprotein E4 positivity, tumor HER2 positivity, obesity, cardiovascular comorbidities, more prescription medications, and higher baseline APE score. CONCLUSIONS: Our proof-of-concept tool demonstrates our prediction models are potentially useful to predict risk of CRCD. Future research is needed to validate this approach for predicting CRCD in routine practice settings.

Extend the benchmarking indel set by manual review using the individual cell line sequencing data from the Sequencing Quality Control 2 (SEQC2) project.

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

A Social Media-Delivered Melanoma Prevention Program for Young Women Engaged in Frequent UV Tanning: Protocol for a Randomized Controlled Trial.

BACKGROUND: Rates of melanoma have increased dramatically in the United States over the past 25 years, and it has become among the most prevalent cancers for young adult women. Intentional skin tanning leads to a pattern of intense and intermittent UV radiation exposure that is associated with increased risk of melanoma. Frequent tanning is most common among young women and is linked to a variety of sociocultural pressures that negatively impact body image and drive appearance control behaviors. Unfortunately, there are no established interventions designed for frequent tanners. This intervention addresses this gap with unique content informed by body image and acceptance-based interventions. The intervention is delivered using Facebook secret groups, an approach designed to support behavior change and ensure scalability. OBJECTIVE: This study aims to describe the rationale and methodology of a randomized controlled trial of a melanoma prevention program targeting young women engaged in frequent indoor or outdoor UV tanning. METHODS: Participants are women aged 18-25 years who report high-risk tanning (ie, at least 10 indoor tanning sessions in the past 12 months or 10 outdoor sessions in the previous summer). After recruitment and screening, participants completed a baseline survey and were randomly assigned to receive the intervention or an attention-matched control condition. Both conditions were 8-week-long Facebook groups (approximately 25 members each) with daily posting of content. Follow-up surveys are administered at 3, 8, and 18 months after baseline. The primary trial outcome is the combined number of indoor and outdoor tanning sessions reported at the 8-month follow-up. Hypothesized intervention mediators are assessed at the 3-month follow-up. RESULTS: This project was funded by a National Cancer Institute award (R01 CA218068), and the trial procedures were approved by the University of Kentucky Institutional Review Board in February 2020. Trial recruitment and enrollment occurred in 6 waves of data collection, which started in February 2022 and closed in May 2023. The study is closed to enrollment but remains open for follow-ups, and this protocol report was prepared before data analyses. As of February 2024, all participants have completed the 8-month follow-up assessment, and data collection is scheduled to close by the end of 2024 after the collection of the 18-month follow-up. CONCLUSIONS: This trial will contribute unique knowledge to the field of skin cancer prevention, as no fully powered trials have examined the efficacy of an intervention designed for frequent indoor or outdoor tanning. The trial may also contribute evidence of the value in translating principles of body image and acceptance-based interventions into the field of skin cancer prevention and beyond. If successful, the use of the Facebook platform is intended to aid in dissemination as it provides a way to embed the intervention into individuals' everyday routines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03441321; https://clinicaltrials.gov/study/NCT03441321. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56562.

Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies. This timely minireview provides researchers and clinicians with an overview of challenges and opportunities for improving disaster preparedness and response for cancer survivors.

Feasibility and acceptability of C-PRIME: A health promotion intervention for family caregivers of patients with colorectal cancer.

PURPOSE: This study aimed to test the feasibility and acceptability of a digital health promotion intervention for family caregivers of patients with advanced colorectal cancer and explore the intervention's preliminary efficacy for mitigating the impact of caregiving on health and well-being. METHODS: We conducted a single-arm pilot feasibility trial of C-PRIME (Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life), an 8-week digital health-promotion behavioral intervention involving monitoring and visualizing health-promoting behaviors (e.g., objective sleep and physical activity data) and health coaching (NCT05379933). A priori benchmarks were established for feasibility (≥ 50% recruitment and objective data collection; ≥ 75% session engagement, measure completion, and retention) and patient satisfaction (> 3 on a 1-5 scale). Preliminary efficacy was explored with pre- to post-intervention changes in quality of life (QOL), sleep quality, social engagement, and self-efficacy. RESULTS: Participants (N = 13) were M = 52 years old (SD = 14). Rates of recruitment (72%), session attendance (87%), assessment completion (87%), objective data collection (80%), and retention (100%) all indicated feasibility. All participants rated the intervention as acceptable (M = 4.7; SD = 0.8). Most participants showed improvement or maintenance of QOL (15% and 62%), sleep quality (23% and 62%), social engagement (23% and 69%), and general self-efficacy (23% and 62%). CONCLUSION: The C-PRIME digital health promotion intervention demonstrated feasibility and acceptability among family caregivers of patients with advanced colorectal cancer. A fully powered randomized controlled trial is needed to test C-PRIME efficacy, mechanisms, and implementation outcomes, barriers, and facilitators in a divserse sample of family caregivers. TRIAL REGISTRATION: The Caregiver Protocol for Remotely Improving, Monitoring, and Extending Quality of Life (C-PRIME) study was registered on clinicaltrials.gov, NCT05379933, in May 2022.

"I couldn't connect the wires in my brain." Young adult cancer survivors' experience with cognitive functioning.

OBJECTIVE: There is a dearth of literature describing young adult (YA) cancer survivors' experiences with cancer-related cognitive impairment (CRCI). We aimed to elucidate CRCI among YA cancer survivors and identify potentially modifiable risk factors. METHODS: We conducted individual qualitative interviews with YA cancer survivors aged 18-30 years at study enrollment and used applied thematic analysis to identify themes across three topics (i.e., affected cognitive abilities, risk and protective factors influencing the impact of CRCI, and strategies for coping with CRCI). RESULTS: YA cancer survivors (N = 20) were, on average, 23 years old at diagnosis and 26 years old when interviewed. Diverse cancer types and treatments were represented; most participants (85%) had completed cancer treatment. Participants described experiences across three qualitative topics: (1) affected cognitive abilities (i.e., concentration and attention, prospective memory, and long-term memory), (2) Risk factors (i.e., fatigue, sleep problems, mood, stress/distractions, and social isolation) and protective factors (i.e., social support), and (3) coping strategies, including practical strategies that helped build self-efficacy (e.g., writing things down, reducing distractions), beneficial emotion-focused coping strategies (e.g., focus on health, faith/religion), strategies with mixed effects (i.e., apps/games, medications/supplements, and yoga), and "powering through" strategies that exacerbated stress. CONCLUSIONS: YA cancer survivors experience enduring cognitive difficulties after treatment. Specific concerns highlight the importance of attention and executive functioning impairments, long-term memory recall, and sensitivity to distractions. Future work is needed to improve assessment and treatment of CRCI among YA cancer survivors.

Piloting a Patient Tool to Aid Palliative Care Referrals during Advanced Lung Cancer Treatment.

CONTEXT: Patient misperceptions are a strong barrier to early palliative care discussions and referrals during advanced lung cancer treatment. OBJECTIVES: We developed and tested the acceptability of a web-based patient-facing palliative care education and screening tool intended for use in a planned multilevel intervention (i.e., patient, clinician, system-level targets). METHODS: We elicited feedback from advanced lung cancer patients (n = 6), oncology and palliative care clinicians (n = 4), and a clinic administrator (n = 1) on the perceived relevance of the intervention. We then tested the prototype of a patient-facing tool for patient acceptability and preliminary effects on patient palliative care knowledge and motivation. RESULTS: Partners agreed that the intervention-clinician palliative care education and an electronic health record-integrated patient tool-is relevant and their feedback informed development of the patient prototype. Advanced stage lung cancer patients (n = 20; age 60 ± 9.8; 40% male; 70% with a technical degree or less) reviewed and rated the prototype on a five-point scale for acceptability (4.48 ± 0.55), appropriateness (4.37 ± 0.62), and feasibility (4.43 ± 0.59). After using the prototype, 75% were interested in using palliative care and 80% were more motivated to talk to their oncologist about it. Of patients who had or were at risk of having misperceptions about palliative care (e.g., conflating it with hospice), 100% no longer held the misperceptions after using the prototype. CONCLUSION: The palliative care education and screening tool is acceptable to patients and may address misperceptions and motivate palliative care discussions during treatment.

The effect of subscapularis repair in reverse total shoulder arthroplasty depends on the design of the implant: a comparative study with a minimum 2-year follow-up.

INTRODUCTION: The role of the subscapularis (Ssc) tendon does not yet have a well-defined role in RSA. The purpose of the present study was to evaluate if the repair of the Ssc in RSA improves overall clinical and radiographic results and if it has the same results using a medialized design humeral stem compared to a lateralized design. METHODS: Eighty-four consecutive patients undergoing RSA were retrospectively analyzed. Nine patients were lost at FU. Two implants with similar glenosphere design and different stem design (medialized and lateralized) were used. The Ssc was repaired in case of good quality of the fibers and reducibility without tension intraoperatively. Patients were divided into four groups for data analysis depending on whether they had received a medialized or lateralized design and Ssc repair or not. Patients were reviewed at an average follow-up of 40.8 ± 13.1 months. Clinical outcome measures included Active range of motion (ROM), strength, visual analog scale (VAS), Constant-Murley score (CMS), and the American Shoulder and Elbow Surgeons score (ASES). Radiographic evaluation at final follow-up was performed to assess scapular notching, stress shielding, and radiolucent lines. RESULTS: No statistically significant clinical differences (p > 0.05) emerged between Lat/Ssc+ and Lat/Ssc-. Conversely, the patients belonging to the Med/Ssc- group reported statistically worse (p < 0.05) results than the Med/Ssc + group in terms of VAS, ASES and CMS. Statistically worse (p < .05) results in the Med/Ssc- group than in the Med/Ssc + were found also in active ROM achieved in FE, ABD, ER1 and ER2, and in the strength obtained in FE, ABD and ER2. Scapular notching was reported in 3 shoulders (15.7%) in Lat/Ssc+ group and in 7 shoulders (50%) in Lat/Ssc- group, while it was reported in 4 shoulders (14.2%) in Med/Ssc + group and in 6 shoulders (42.8%) in Med/Ssc- group. Stress shielding was observed in 6 cases in Lat/Ssc+ group (31.6%), in 8 cases in Lat/Ssc- group (57.1%), in 3 cases (10.7%) in Med/Ssc + group and 4 cases in Med/Ssc- group (28.6%). CONCLUSIONS: Patients undergoing RSA show clinical improvements at mid-term follow-up with a low rate of complications, regardless of the use of a medialized or a lateralized humeral stem design. Ssc repair is associated with better functional outcomes in the cohort of medialized stem, while it did not yield significant differences in the cohort of lateralized stem. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Comparison; Treatment Study.

Relationships Among Physical Activity, Sleep, and Cancer-related Fatigue: Results From the International ColoCare Study.

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.

Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.

Saddle Nose Deformity in a Patient With Crohn's Disease.

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, frequently presenting with extraintestinal manifestations. Granulomatosis with polyangiitis is a systemic vasculitis primarily affecting the respiratory tract and kidneys. Extraintestinal Crohn's disease and granulomatosis with polyangiitis may have similar clinical presentations and, in rare occurrences, can coexist. This case report highlights the diagnostic and therapeutic complexities of this uncommon overlap syndrome.

Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL128/130/131A and gO. Using high-resolution cryogenic electron microscopy, we revealed the structural basis of the neutralization mechanisms of antibodies targeting various binding sites. Moreover, we identified highly potent antibodies that neutralized a broad spectrum of HCMV strains, including primary clinical isolates, that outperform known antibodies used in clinical trials. Our study provides a deep understanding of the mechanisms of HCMV neutralization and identifies promising antibody candidates to prevent and treat HCMV infection.

Impact of relative dose intensity on pathologic complete response in human epidermal growth factor receptor 2 positive breast cancer patients receiving neoadjuvant TCHP.

PURPOSE: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP. METHODS: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR. RESULTS: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment. CONCLUSIONS: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

Depressive symptom trajectories in older breast cancer survivors: the Thinking and Living with Cancer Study.

PURPOSE: To identify trajectories of depressive symptoms in older breast cancer survivors and demographic, psychosocial, physical health, and cancer-related predictors of these trajectories. METHODS: Recently diagnosed nonmetastatic breast cancer survivors (n = 272), ages 60-98 years, were evaluated for depressive symptoms (Center for Epidemiological Studies Depression Scale, CES-D; scores ≥16 suggestive of clinically significant depressive symptoms). CES-D scores were analyzed in growth-mixture models to determine depression trajectories from baseline (post-surgery, pre-systemic therapy) through 3-year annual follow-up. Multivariable, multinomial logistic regression was used to identify baseline predictors of depression trajectories. RESULTS: Survivors had three distinct trajectories: stable (84.6%), emerging depressive symptoms (10.3%), and recovery from high depressive symptoms at baseline that improved slowly over time (5.1%). Compared to stable survivors, those in the emerging (OR = 1.16; 95% CI = 1.08-1.23) or recovery (OR = 1.26; 95% CI = 1.15-1.38) groups reported greater baseline anxiety. Greater baseline deficit accumulation (frailty composite measure) was associated with emerging depressive symptoms (OR = 3.71; 95% CI = 1.90-7.26). Less social support at baseline (OR = 0.38; 95% CI = 0.15-0.99), but greater improvement in emotional (F = 4.13; p = 0.0006) and tangible (F = 2.86; p = 0.01) social support over time, was associated with recovery from depressive symptoms. CONCLUSIONS: Fifteen percent of older breast cancer survivors experienced emerging or recovery depressive symptom trajectories. Baseline anxiety, deficit accumulation, and lower social support were associated with worse outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Our results emphasize the importance of depression screening throughout the course of cancer care to facilitate early intervention. Factors associated with depressive symptoms, including lower levels of social support proximal to diagnosis, could serve as intervention levers.

Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer.

Importance: Survivors of childhood cancer experience premature aging compared with community controls. The deficit accumulation index (DAI) uses readily available clinical data to measure physiological age in survivors; however, little data exist on how well deficit accumulation represents underlying biological aging among survivors of cancer. Objective: To examine the associations between the DAI and epigenetic age acceleration (EAA) and mean leukocyte telomere length (LTL). Design, Setting, and Participants: This cross-sectional study analyzed data from the St Jude Lifetime Cohort, an assessment of survivors of childhood cancer who were treated at St Jude Children's Research Hospital in Memphis, Tennessee. Data were collected between 2007 and 2016, assayed between 2014 and 2019, and analyzed between 2022 and 2023. Participants were adult survivors who were diagnosed between 1962 and 2012 and who survived 5 years or more from time of diagnosis. The analyses were restricted to survivors with European ancestry, as there were too few survivors with non-European ancestry. Exposures: The DAI included 44 aging-related items, such as chronic health conditions and functional, psychosocial, and mental well-being. Item responses were summed and divided by the total number of items, resulting in a ratio ranging from 0 to 1. These DAI results were categorized based on reported associations with hospitalization and mortality: low, defined as a DAI less than 0.2; medium, defined as a DAI of 0.2 to less than 0.35; and high, defined as a DAI of 0.35 or higher. Main Outcomes and Measures: Genome-wide DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. The EAA was calculated as the residuals from regressing the Levine epigenetic age on chronological age. The mean LTL was estimated using whole-genome sequencing data. Results: This study included 2101 survivors of childhood cancer (1122 males [53.4%]; mean [SD] age, 33.9 [9.1] years; median [IQR] time since diagnosis, 25.1 [18.7-31.9] years) with European ancestry. Compared with survivors in the low DAI group, those in the high DAI group experienced 3.7 more years of EAA (ß = 3.66; 95% CI, 2.47-4.85; P < .001), whereas those in the medium DAI group experienced 1.8 more years of EAA (ß = 1.77; 95% CI, 0.84-2.69; P < .001), independent of treatment exposures. The EAA and DAI association was consistent across 3 common diagnoses (acute lymphoblastic leukemia, Hodgkin lymphoma, and central nervous system tumors) and across chronological age groups. For example, among acute lymphoblastic leukemia survivors, those in the medium DAI group (ß = 2.27; 95% CI, 0.78-3.76; P = .001) experienced greater EAA vs those in the low DAI group. Similarly, among survivors younger than 30 years, the high DAI group experienced 4.9 more years of EAA vs the low DAI group (ß = 4.95; 95% CI, 2.14-7.75; P < .001). There were no associations between mean LTL residual and the DAI. Conclusions and Relevance: This cross-sectional study of survivors of childhood cancer showed that the DAI was associated with EAA, suggesting an underlying biological process to the accumulation of deficits. Both the DAI and EAA were effective at identifying aging phenotypes, and either may be used to measure aging and response to interventions targeting aging pathways.

Associations of Germline Genetic Variants With Depression and Fatigue Among Hematologic Cancer Patients Treated With Allogeneic Hematopoietic Cell Transplantation.

OBJECTIVE: Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT). METHODS: Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05. RESULTS: The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ). CONCLUSIONS: Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.

Trajectories and risk factors of fatigue following colorectal cancer diagnosis.

AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups. METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups. RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05). CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.