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Background: Although early palliative care is linked to improved health-related quality of life, satisfaction with care, and symptom management, the clinical strategies that nurses use to actively initiate this care are unknown., Objectives: The aims of this study were to conceptualize the clinical strategies that outpatient oncology nurses use to introduce early palliative care and to determine how these strategies align with the framework of practice., Methods: A constructivist-informed grounded theory study was conducted in a tertiary cancer care center in Toronto, Canada. Twenty nurses (6 staff nurses, 10 nurse practitioners, and 4 advanced practice nurses) from multiple outpatient oncology clinics (ie, breast, pancreatic, hematology) completed semistructured interviews. Analysis occurred concurrently with data collection and used constant comparison until theoretical saturation was reached., Results: The overarching core category, pulling it all together , outlines the strategies used by oncology nurses to support timely palliative care referral, drawing on the coordinating, collaborating, relational, and advocacy dimensions of practice. The core category incorporated 3 subcategories: (1) catalyzing and facilitating synergy among disciplines and settings , (2) promoting and considering palliative care within patients' personal narratives , and (3) widening the focus from disease-focused treatment to living well with cancer ., Conclusion: Outpatient oncology nurses enact unique clinical strategies, which are aligned with the nursing framework and reflected multiple dimensions of practice, to introduce early palliative care., Implications for Practice: Our findings have clinical, educational, and policy implications for fostering the conditions in which nurses are supported to maximize their full potential in the introduction of early palliative care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The understanding of T-cell lymphoma (TCL) pathobiology has grown substantially due to gene expression profiling and high-throughput next-generation sequencing (NGS). However, real-world data on mutational profiles of mature T-cell lymphomas (TCLs) are limited, and their impact on clinical decision making has not been reported., Methods: A single-institution study of biopsies from patients with histopathologically confirmed T-cell lymphomas and available NGS data between January 1, 2021, to July 1, 2023, was performed. Reported variants were classified as disease-associated or pathogenic variants (DAV), or variants of unknown significance (VUS). Individual physicians were surveyed via email regarding the impact of NGS results on next steps in patient care., Results: About 94% of patients (n = 93) had ≥ 1 variants identified; at least 1 pathogenic variant or likely pathogenic variant was identified in 71% of patients (n = 70). Variants were detected in 90 unique genes with 41% (37/90) having disease-associated variants (DAV). The genes with mutations most frequently resulting in disease-associated variants in this study were TET2, RHOA, DNMT3A and TP53, IDH2, and PLCG1. NGS results were integral to clinical management in 19% of patients per physician survey., Conclusion: This work gives insight into the real-world utility of NGS regarding clinical decision making for patients with T-cell lymphoma. Given the impact of NGS on prognostication, evaluation of therapeutic options, as well as cessation of potentially unhelpful treatments, these findings support the role of NGS as an important part in the management of T-cell lymphomas., Competing Interests: Disclosure SKB reports the following potential COIs: Acrotech (advisory board, non-CME education), BMS (advisory board), Daiichi Sankyo (advisory board), Kyowa Kirin (advisory board, non-CME education). Janssen (data Safety monitoring board). All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Alterations in forkhead box A1 (FOXA1), a pioneer transcription factor, are associated with poor prognosis in breast cancer and prostate cancer. We characterized FOXA1 genomic alterations and their clinical impacts in a large pan-cancer cohort from the American Association for Cancer Research Genomics, Evidence, Neoplasia, Information, Exchange database., Methods: FOXA1 alterations were characterized across more than 87 000 samples from more than 30 cancer types for primary and metastatic tumors alongside patient characteristics and clinical outcomes. FOXA1 alterations were queried in the Memorial Sloan Kettering - Metastatic Events and Tropisms (MSK-MET) cohort (a GENIE subset), allowing definition of hazard ratios (HRs) and survival estimates based on Cox proportional hazard models., Results: FOXA1 was altered in 1869 (2.1%) samples, with distinct patterns across different cancers: prostate cancer enriched with indel-inframe alterations, breast cancer with missense mutations, and lung cancers with copy number amplifications. Of 74 715 samples with FOXA1 copy number profiles, amplification was detected in 834 (1.1%). Amplification was most common in non-small cell lung cancer (NSCLC; 3% in primary; 6% in metastatic) and small cell lung cancer (4.1% primary; 3.5% metastatic), followed by breast cancer (2% primary; 1.6% metastatic) and prostate cancer (2.2% primary; 1.6% metastatic). Copy number amplifications were associated with decreased overall survival in NSCLC (HR = 1.45, 95% confidence interval [CI] = 1.06 to 1.99; P = .02), breast cancer (HR = 3.04, 95% CI = 1.89 to 4.89; P = 4e-6), and prostate cancer (HR = 1.94, 95% CI = 1.03 to 3.68; P = .04). Amplifications were associated with widespread metastases in NSCLC, breast cancer, and prostate cancer., Conclusions: FOXA1 demonstrates distinct alteration profiles across cancer sites. Our findings suggest an association between FOXA1 amplification and enhanced metastatic potential and decreased survival, highlighting prognostic and therapeutic potential in breast cancer, prostate cancer, and NSCLC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The study objective was to describe the course and outcomes of children under 18 years of age, with left-to-right shunts and pulmonary arterial hypertension undergoing 1 of 2 management approaches: pulmonary arterial hypertension treatment before left-to-right shunt repair (Treat First) and left-to-right shunt repair first with or without subsequent pulmonary arterial hypertension treatment (Repair First)., Methods: We performed a retrospective single-center study, conducted from September 2015 to September 2021, of children with left-to-right shunts and pulmonary arterial hypertension (defined as indexed pulmonary vascular resistance ≥ 4 Wood units [WU]∗m 2 ) but without Eisenmenger physiology. Patient characteristics, longitudinal hemodynamics data, pulmonary arterial hypertension management, left-to-right shunt repair, and outcomes were reviewed., Results: Of 768 patients evaluated for left-to-right shunt closure, 51 (6.8%) had left-to-right shunts associated with pulmonary arterial hypertension (median age 1.1 [0.37-5] years, median indexed pulmonary vascular resistance 6 [5.2-8.7] WU∗m 2 ). In the "Treat First" group (n = 33, 65%), 27 patients (82%) underwent left-to-right shunt closure and 6 patients (18%) did not respond to pulmonary arterial hypertension therapy and did not undergo left-to-right shunt closure. In the "Repair First" group (n = 18, 35%), 12 patients (67%) received pulmonary arterial hypertension therapy and 6 patients (33%) did not. Mortality rates were 6% in the "Treat First" group and 11% in "Repair First" group with follow-ups of 3.4 and 2.5 years, respectively. After left-to-right shunt closure, there was no significant change in indexed pulmonary vascular resistance over a median follow-up of 2 years after surgery (P = .77)., Conclusions: In children with left-to-right shunts and associated pulmonary arterial hypertension, treatment with pulmonary arterial hypertension-targeted therapy before defect repair does not appear to endanger the subjects and may have some benefit. The response to pulmonary arterial hypertension-targeted therapy before shunt closure persists 2 to 3 years postclosure, providing valuable insights into the long-term management of these patients., Competing Interests: Conflict of Interest Statement D.F.T.: royalties or licenses from McGraw Hill. R.L.K.: payment for expert testimony University of Michigan. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study is to present a cross-sectional analysis of cancer burden in the South Asian Association for Regional Cooperation (SAARC) region and explain unique characteristics of its cancer burden as compared with the rest of the world., Methods and Analysis: Using publicly available data from the Global Cancer Observatory (GCO) and the World Bank, we collected cancer statistics and population statistics for Afghanistan, Bangladesh, Bhutan, India, the Maldives, Nepal, Pakistan, and Sri Lanka from 2017 to 2022., Results: The number of newly diagnosed cases in the region was 1 846 963, representing 9.3% of the incidence worldwide. As defined by the GCO, the crude incidence rate (CIR) (per 100 000) of cancer in SAARC was 97.3 compared with the worldwide rate of 235.5. The crude mortality rate (per 100 000) in SAARC was 63.4, compared with 123.6 globally. However, the mortality to incidence ratio (MIR) (per 100 000) was 0.65, compared with 0.49 globally., Conclusion: Our research highlights SAARC's unique cancer landscape with low incidence (CIR) and mortality (CMR) but elevated MIR compared with global figures. These findings underscore the need for a united, contextually relevant approach to addressing the burden of cancer in SAARC. In particular, investment in collaborative, tailored cancer care programmes will build the SAARC region's capacity to address the growing cancer challenge., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Palliative care plays essential roles in cancer care. However, differences in receipt among individuals identifying as Asian American, Native Hawaiian, and Other Pacific Islanders (AA&NHPI) with cancer are not well-characterized, especially when these diverse groups are disaggregated. We characterized disparities in receipt of palliative care among AA&NHPI patients with AJCC Stage IV prostate, breast, or lung cancer., Methods: We performed multivariable logistic regressions were performed in this retrospective cohort analysis, using deidentified data from the National Cancer Database (NCDB) of patients diagnosed with AJCC analytic group stage IV breast, lung, or prostate cancer (2004-2018) who were White or of Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. We conducted multivariable logistic regression analyses in a retrospective cohort study using deidentified data from the National Cancer Database (NCDB). The study included patients diagnosed with AJCC analytic group Stage IV breast, lung, or prostate cancer between 2004 and 2018, who were White or identified as Asian Indian/Pakistani, Chinese, Filipino, Hawaiian, Hmong, Japanese, Kampuchean, Korean, Laotian, Other Pacific Islander, Thai, or Vietnamese descent. Adjusted odds ratios and 95% confidence intervals of receiving palliative care were measured when comparing White vs. AA&NHPI patients as one cohort and White vs. disaggregated AA&NHPI patients, adjusting for clinical, socioeconomic, and demographic covariates., Results: Among 775,289 individuals diagnosed with cancer (median age: 68 years), no significant differences in palliative care receipt were observed between White patients and aggregated AA&NHPI patients among patients with prostate, breast, or lung cancer. However, disaggregated analyses revealed reduced palliative care receipt for breast cancer patients of Asian Indian/Pakistani descent (AOR 0.75, 95% CI, 0.60-0.94, P = 0.011) and for lung cancer patients of Chinese, Vietnamese, Thai, and Asian Indian/Pakistani descent compared to White patients (Chinese AOR 0.88, [0.81-0.94], P = 0.001; Vietnamese AOR 0.89, [0.80 to 0.99], P = 0.032; Thai AOR 0.64, [0.44-0.92], P = 0.016; Asian Indian/Pakistani AOR 0.83, [0.74-0.93], P = 0.001). Palliative care was greater for patients of Japanese and Hawaiian descent with prostate cancer (Japanese AOR 1.92, [1.32-2.75], P = 0.001; Hawaiian AOR 2.09, [1.20-3.66], P = 0.009), breast cancer (Japanese AOR 1.72, [1.21-2.43], P = 0.001; Hawaiian AOR 1.70, [1.08-2.67], P = 0.021), and lung cancer (Japanese AOR 1.92, [1.70-2.17], P < 0.001; Hawaiian AOR 2.95, [2.5-3.5], P < 0.001), as well as patients of Other Pacific Islander descent with lung cancer (AOR 1.62, [1.34-1.96], P < 0.001)., Conclusions and Relevance: Our findings demonstrate disparities in receipt of palliative care upon disaggregation of diverse AA&NHPI groups, the need for disaggregated research and targeted interventions that address the unique cultural, socioeconomic, and healthcare system barriers to palliative care receipt., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: ECD is funded in part through the NIH/NCI Support Grant P30 CA008748. SS, SRR, and NS declare no competing interests.

Purpose: Although early palliative care is recommended, resource limitations prevent its routine implementation. We report on the preliminary findings of a mixed methods study involving a randomized controlled trial (RCT) of Symptom screening with Targeted Early Palliative care (STEP) and qualitative interviews., Methods: Adults with advanced solid tumors and an oncologist-estimated prognosis of 6-36 months were randomized to STEP or symptom screening alone. STEP involved symptom screening at each outpatient oncology visit; moderate to severe scores triggered an email to a palliative care nurse, who offered referral to in-person outpatient palliative care. Patient-reported outcomes of quality of life (FACT-G7; primary outcome), depression (PHQ-9), symptom control (ESAS-r-CS), and satisfaction with care (FAMCARE P-16) were measured at baseline and 2, 4, and 6 months. Semi-structured interviews were conducted with a subset of participants., Results: From Aug/2019 to Mar/2020 (trial halted due to COVID-19 pandemic), 69 participants were randomized to STEP (n = 33) or usual care (n = 36). At 6 months, 45% of STEP arm patients and 17% of screening alone participants had received palliative care (p = 0.009). Nonsignificant differences for all outcomes favored STEP: difference in change scores for FACT-G7 = 1.67 (95% CI: -1.43, 4.77); ESAS-r-CS = -5.51 (-14.29, 3.27); FAMCARE P-16 = 4.10 (-0.31, 8.51); PHQ-9 = -2.41 (-5.02, 0.20). Sixteen patients completed qualitative interviews, describing symptom screening as helpful to initiate communication; triggered referral as initially jarring but ultimately beneficial; and referral to palliative care as timely., Conclusion: Despite lack of power for this halted trial, preliminary results favored STEP and qualitative results demonstrated acceptability. Findings will inform an RCT of combined in-person and virtual STEP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: PN declares consulting fee from Boston Scientific, Janssen, Blue Earth, Astellas, Bayer, Novartis, Theranano, Included Health, AIQ, Grand Rounds Urology, unrelated to the topic of this work, and stocks from Nanocan, Reversal Therapeutics, Strategen Bio, Telerad Oncology. All other authors have no relevant conflicts-of-interest to declare.

Purpose: Hispanic and Latinx people in the United States are the fastest-growing ethnic group. However, previous studies in non-small-cell lung cancer (NSCLC) often analyze these diverse communities in aggregate. We aimed to identify differences in NSCLC stage at diagnosis in the US population, focusing on disaggregated Hispanic/Latinx individuals., Methods: Data from the National Cancer Database from 2004 to 2018 identified patients with primary NSCLC. Individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression adjusting for age, facility type, income, educational attainment, comorbidity index, insurance, and year of diagnosis was used to create adjusted odds ratios (aORs), with higher odds representing diagnosis at later-stage NSCLC., Results: Of 1,565,159 patients with NSCLC, 46,616 were Hispanic/Latinx (3.0%). When analyzed in the setting of race and ethnicity, Hispanic patients were more likely to be diagnosed with metastatic disease compared with non-Hispanic White (NHW) patients: 47.0% for Hispanic Black, 46.0% Hispanic White, and 44.3% of Hispanic other patients versus 39.1% of non-Hispanic White patients ( P < .001 for all). By country of origin, 51.4% of Mexican, 41.7% of Puerto Rican, 44.6% of Cuban, 50.8% of South or Central American, 48.4% of Dominican, and 45.6% of other Hispanic patients were diagnosed with metastatic disease, compared with 39.1% of NHWs. Conversely, 20.2% of Mexican, 26.9% of Puerto Rican, 24.2% of Cuban, 22.5% of South or Central American, 23.7% of Dominican, and 24.5% of other Hispanic patients were diagnosed with stage I disease, compared with 30.0% of NHWs. All Hispanic groups were more likely to present with later-stage NSCLC than NHW patients (greatest odds for Mexican patients, aOR, 1.44; P < .001)., Conclusion: Hispanic/Latinx patients with non-small-cell lung cancer were more likely to be diagnosed with advanced disease compared with NHWs. Disparities persisted upon disaggregation by both race and country of origin, with over half of Mexican patients with metastatic disease at diagnosis. Disparities among Hispanic/Latinx groups by race and by country of origin highlight the shortcomings of treating these groups as a monolith and underscore the need for disaggregated research and targeted interventions.

Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) represent the fastest-growing group in the United States. While described in aggregate, great variations exist within the community. We aimed to determine whether there were differences in stage at presentation and treatment status among AANHPI women with non-small cell lung cancer (NSCLC)., Methods: Between 2004 and 2016, we identified 522 361 female patients with newly diagnosed NSCLC from the National Cancer Database. Multivariable logistic regression models were used to define adjusted odds ratios (aORs) of presenting with stage IV disease and not receiving treatment., Results: AANHPI women were more likely to present with stage IV disease compared to White (54.32% vs. 40.28%, p < 0.001). Aside from Hawaiian, Pakistani, and Hmong women, all other ethnic groups had greater odds of presenting with stage IV disease than White women. AANHPI women <65 years were more likely to present with stage IV disease (p = 0.030). Only Vietnamese women showed a significant difference (aOR = 1.30 [1.06-1.58], p = 0.010) for likelihood of receiving treatment compared to White., Conclusions: Differences in stage at presentation and treatment status in women with NSCLC were observed among AANHPI ethnic groups when populations were disaggregated., (© 2023 Wiley Periodicals LLC.)

Purpose: We investigated relationships between domains of quality of dying and death in patients with advanced cancer and their caregivers' bereavement outcomes and the moderating effect of patient age at death., Methods: Bereaved caregivers of deceased patients with advanced cancer who had participated in an early palliative care trial completed measures of grief (Texas Revised Inventory of Grief [TRIG]), complicated grief (Prolonged Grief Inventory [PG-13]), and depression (Center for Epidemiologic Studies-Depression [CESD-10]). They also completed the Quality of Dying and Death measure (QODD), which assesses patients' symptom control, preparation for death, connectedness with loved ones, and sense of peace with death., Results: A total of 157 bereaved caregivers completed the study. When patient age × QODD subscale interactions were included, greater death preparation was related to less grief at patient death (past TRIG: β =  - .25, p = .04), less current grief (present TRIG: β =  - .26, p = .03), less complicated grief (PG-13: β =  - .37, p = .001), and less depression (CESD-10: β =  - .35, p = .005). Greater symptom control was related to less current grief (present TRIG: β =  - .27, p = .02), less complicated grief (PG-13: β =  - .24, p = .03), and less depression (CESD-10: β =  - .29, p = .01). Significant patient age × connectedness interaction effects for current grief (present TRIG: β = .30, p = .02) and complicated grief (PG-13: β = .29, p = .007) indicated that, with less connectedness, younger patient age at death was associated with greater caregiver grief., Conclusion: Better end-of-life death preparation and symptom control for patients with cancer may attenuate later caregiver grief and depression. Less connectedness between younger patients and their families may adversely affect caregiver grief., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Although breast cancer (BC) risk increases with age, BC in younger women is more aggressive with higher mortality compared with older women. We characterize the genomic landscape of BCs in younger women., Methods: Clinicopathologic, molecular, and genomic differences across age groups (< 40 years, 40-60 years, > 60 years) in female BC patients were investigated in two large cohorts [AACR-GENIE8.1 (n = 11,594) and METABRIC (n = 2509)]. Cox-proportional regression analyzed the prognostic impact of age groups for disease-specific survival (DSS) and recurrence-free survival (RFS) in METABRIC and progression-free survival (PFS) in GENIE cohorts. Chi-squared test was used to assess statistical associations between genomic alterations and age groups., Results: Survival analysis showed that women < 40 years had shorter DSS [hazard ratio (HR): 1.52, p = 0.005], RFS (HR: 1.4, p = 0.006), and PFS (HR: 1.82, p = 0.0003) compared with women 40-60 years, and shorter RFS (HR: 1.5, p = 0.001) and PFS (HR: 2.95, p < 0.0001) compared with women > 60 years. Molecular subtypes in the METABRIC cohort showed women < 40 years were enriched with basal, and HER2+ subtypes, and less enriched with luminal A and B subtype (p < 0.0001). Characterization of genomic alterations in both cohorts demonstrated that BCs in women < 40 years were more enriched with TP53 mutations (FDR < 0.0001), BRCA1 mutations (FDR = 0.01), ERBB2 amplifications (FDR < 0.001), CDK12 amplifications (FDR < 0.001), and PPM1D amplifications (FDR < 0.001). In contrast, BCs in older women (> 60 years) were more enriched with PIK3CA, KMT2C, and CDH1 mutations (FDR < 0.0001)., Conclusions: BCs in young women are associated with shorter survival and more aggressive genomic features, including mutations in TP53 and BRCA1, and amplifications in ERBB2 and CDK12. These findings have the potential to impact clinical trial design and treatment., (© 2023. Society of Surgical Oncology.)

Objective: Early palliative care (EPC) in the outpatient setting improves quality of life for patients with advanced cancer, but its impact on quality of dying and death (QODD) and on quality of life at the end of life (QOL-EOL) has not been examined. Our study investigated the impact of EPC on patients' QODD and QOL-EOL and the moderating role of receiving inpatient or home palliative care., Method: Bereaved family caregivers who had provided care for patients participating in a cluster-randomised trial of EPC completed a validated QODD scale and indicated whether patients had received additional home palliative care or care in an inpatient palliative care unit (PCU). We examined the effects of EPC, inpatient or home palliative care, and their interactions on the QODD total score and on QOL-EOL (last 7 days of life)., Results: A total of 157 caregivers participated. Receipt of EPC showed no association with QODD total score. However, when additional palliative care was included in the model, intervention patients demonstrated better QOL-EOL than controls (p=0.02). Further, the intervention by PCU interaction was significant (p=0.02): those receiving both EPC and palliative care in a PCU had better QOL-EOL than those receiving only palliative care in a PCU (mean difference=27.10, p=0.002) or only EPC (mean difference=20.59, p=0.02)., Conclusion: Although there was no association with QODD, EPC was associated with improved QOL-EOL, particularly for those who also received inpatient care in a PCU. This suggests a long-term benefit from early interdisciplinary palliative care on care throughout the illness., Trial Registration Number: ClinicalTrials.gov Registry (#NCT01248624)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aneuploidy, or an incorrect chromosome number, is ubiquitous among cancers. Whole-genome duplication, resulting in tetraploidy, often occurs during the evolution of aneuploid tumors. Cancers that evolve through a tetraploid intermediate tend to be highly aneuploid and are associated with poor patient prognosis. The identification and enrichment of tetraploid cells from mixed populations is necessary to understand the role these cells play in cancer progression. Dielectrophoresis (DEP), a label-free electrokinetic technique, can distinguish cells based on their intracellular properties when stimulated above 10 MHz, but DEP has not been shown to distinguish tetraploid and/or aneuploid cancer cells from mixed tumor cell populations. Here, we used high-frequency DEP to distinguish cell subpopulations that differ in ploidy and nuclear size under flow conditions. We used impedance analysis to quantify the level of voltage decay at high frequencies and its impact on the DEP force acting on the cell. High-frequency DEP distinguished diploid cells from tetraploid clones due to their size and intracellular composition at frequencies above 40 MHz. Our findings demonstrate that high-frequency DEP can be a useful tool for identifying and distinguishing subpopulations with nuclear differences to determine their roles in disease progression.

Background: Mental health disorders are ranked globally as the single largest contributor to non-fatal ill-health. Social support can be a means of reducing and managing depression. However, depression can also impact on a person's level of social support., Objective: As men typically have fewer sources of social support than females, this study investigated the bi-directional associations between depressive symptoms and perceived levels of social support among Australian males, aged 18-63., Methods: Three waves of panel data from Ten to Men : The Australian Longitudinal Study on Male Health collected over 7 years (2013-2020) were used. A random intercept cross-lagged panel analysis with 5112 participants was undertaken. Mediating effects and indirect and total effects for lagged and cross-lagged pathways were also examined., Results: Over time, greater social support was found to be associated with lower depression levels, and simultaneously greater levels of depression was found to be associated with lower levels of social support. Standardised cross-lagged effects between waves were mostly similar (β = 0.10). However, mediation analyses identified that only the total effect size of the association for depression at wave 1 predicting social support at wave 3 (β = -0.29) was significant. Mediated effects of social support at wave 1 predicting depression at wave 3 were not significant., Limitations: These include the number of years between each wave, and data were collected during the COVID pandemic., Conclusion: The study provides robust longitudinal evidence supporting the notion that social support and depression are both a cause and consequence of the other. However, the long-term effects of depression reducing social support were longer lasting than the effects of social support reducing depression.

Context: Early palliative care (EPC) is widely recommended but its implementation may be challenging., Objectives: We conducted a qualitative analysis of Canadian palliative care physicians' opinions about conditions necessary to provide EPC., Methods: A survey assessing attitudes and opinions regarding EPC was distributed to physicians providing primary or specialized palliative care, as identified by the Canadian Society of Palliative Care Physicians. The survey included an optional final section for respondents' general comments; we screened these for relevance to our study aims and conducted a thematic analysis of relevant comments., Results: Of 531 completed surveys, 129 (24%) respondents provided written comments, of whom 104 mentioned conditions they felt to be necessary to provide EPC. Four key themes were identified: 1) Clear delineation of roles of primary and specialized palliative care physicians-all physicians should be empowered to provide primary palliative care, with specialists providing additional support; 2) Shared care with needs-dependent referral-primary and specialized palliative care physicians should work collaboratively, with referral to specialized palliative care based on need rather than on prognosis; 3) Adequate resources to support primary palliative care-education, financial incentives, and collaboration with interdisciplinary team members such as nurses and specialized providers were specifically mentioned; 4) Addressing the misconception that palliative care equals end-of-life care-there was particular emphasis on education of both healthcare providers and the public., Conclusion: Changes are necessary at the level of palliative care referral systems, providers, resources, and policy to enable implementation of EPC., (Copyright © 2023 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Reporting racial/ethnic disparities in aggregate obscures within-group heterogeneity. We sought to identify disparities in diagnosis and treatment in Hispanic subpopulations with metastatic prostate cancer (mPCa)., Methods: We disaggregated men with prostate adenocarcinoma from the National Cancer Database from 2004 to 2017 by racial subgroup and Hispanic background. We assessed (1) presenting with mPCa, (2) receiving any treatment, and (3) receiving delayed treatment beyond 90 days. Logistic regression and adjusted odds ratios (aOR) were reported., Results: Hispanic men had greater odds of presenting with mPCa (aOR, 1.54; 95% CI, 1.50 to 1.58; P < .001) compared with non-Hispanic White (NHW) men. All Hispanic racial subgroups were more likely to present with mPCa, with the highest risk in Hispanic Black (HB) men (aOR, 1.68; 95% CI, 1.46 to 1.93; P < .01). Men from all Hispanic backgrounds had higher odds of presenting with mPCa, especially Mexican men (aOR, 1.99; 95% CI, 1.86 to 2.12; P < .01). Hispanic men were less likely to receive any treatment (aOR, 0.60; 95% CI, 0.53 to 0.67; P < .001), and this effect was particularly strong for Hispanic White patients (aOR, 0.58; 95% CI, 0.52 to 0.66; P < .001) and Dominican men (aOR, 0.52; 95% CI, 0.28 to 0.98; P = .044). Hispanic men were more likely to experience treatment delays compared with NHW men (aOR, 1.38; 95% CI, 1.26 to 1.52; P < .001) and in particular HB (aOR, 1.83; 95% CI, 1.22 to 2.75; P = .002) and South/Central American men (aOR, 1.48; 95% CI, 1.07 to 2.04; P = .018)., Conclusion: Differences exist in stage at presentation, treatment receipt, and delays in treatment on disaggregation by racial subgroup and Hispanic heritage. We need to study the potential mechanisms of the observed variations to help develop targeted interventions.

Background: Assessing quality of life is essential for individuals with advanced cancer, but lengthy assessments can be burdensome. The authors investigated the psychometric characteristics of the FACT-G7, a 7-item quality-of-life measure derived from the Functional Assessment of Cancer Therapy-General (FACT-G) scale, in advanced cancer., Methods: Data were obtained from outpatients with advanced cancer who were enrolled in a randomized controlled trial of early palliative care. At baseline, 228 intervention participants and 233 control participants (N = 461) completed the FACT-G and measures of symptom severity, quality of life near the end of life, problematic medical communication, and satisfaction with care. Follow-up measures were administered monthly for 4 months., Results: The FACT-G7 showed good internal consistency (Cronbach α = .72-.80), and its single-factor structure was supported. It correlated strongly with the FACT-G total, physical, and functional indices and with symptom severity (absolute r = 0.73-0.92); more moderately with the FACT-G emotional index and with symptom impact and preparation for the end of life (r = .40-.71); and least with the FACT-G social/family index and with relationship with health care provider, life completion, problematic medical communication, and care satisfaction measures (absolute r = .26-.44). Eastern Cooperative Oncology Group performance status groups differed on FACT-G7 scores, as expected (all P < .001). Improvements in FACT-G7 scores in the intervention group compared with the control group at 3-month (P = .049) and 4-month (P = .034) follow-up supported responsiveness to change and somewhat greater sensitivity than the FACT-G scores., Conclusions: The FACT-G7 is a valid, brief measure particularly of the physical and functional facets of quality of life. It may enable rapid quality-of-life assessments in patients with advanced cancer., (© 2020 American Cancer Society.)

Background: Despite great heterogeneity amongst Hispanic groups, prostate cancer studies often report Hispanic patients in aggregate. We sought to identify differences in prostate cancer risk group at presentation and treatment status among Hispanic subgroup populations., Methods: Patients with localized prostate adenocarcinoma diagnosed from 2004-2017 were identified in the National Cancer Database (NCDB) and disaggregated by racial subgroup and Hispanic country of origin. Ordinal logistic regression defined adjusted odds ratios (AORs) with 95% CI of (1) presenting at progressively higher risk group and (2) receiving treatment with intermediate-unfavorable or high-risk disease., Results: In our sample (n = 895,087), Hispanic men had greater odds of presenting with higher-risk localized prostate cancer compared with non-Hispanic White men (AOR = 1.18 95% CI 1.16-1.21, p < 0.001). Additionally, Hispanic Black men were less likely to present with higher-risk disease than non-Hispanic Black men. Disparities also existed when disaggregated by country of origin, particularly for Mexican men. Amongst men with unfavorable-risk disease, Hispanic men were less likely to receive treatment than non-Hispanic White men (95% CI 0.57-0.67, p < 0.001). The odds of Hispanic Black patients receiving treatment was 2.00 times the odds (95% CI 1.17-3.41 p = 0.011) of non-Hispanic Black patients receiving treatment. Upon disaggregation by country of origin, disparities persisted, particularly for Mexican men., Conclusion: We found marked heterogeneity when risk group at presentation and treatment for higher-risk disease were disaggregated by racial subgroup and country of origin. Our findings support further collection of disaggregated data in Hispanic communities and study of potential mechanisms underlying the observed differences., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Emerging evidence suggests that metastasis is better described as a spectrum of disease rather than a binary state. A greater understanding of the genomic features that determine extent and location of metastatic spread may inform risk stratification and monitoring. Here, we identify genomic alterations from primary prostate carcinomas that are predictive of wide-spread metastatic potential., Methods: Genomic and clinical data from 1,312 patients with primary prostate carcinoma were extracted from the MSK-MET cohort through cBioPortal. Metastatic site counts and overall survival (OS) data were publicly available and used as the primary outcomes. Primary tumor samples were profiled using the MSK-IMPACT targeted sequencing platform. We focused on 58 genes frequently altered in prostate cancer. Cox proportional hazard analyses defined hazard ratios (HRs) and 95% confidence intervals (CIs) for overall mortality in patients with different metastatic outcomes., Results: Out of the 1,312 patients in our cohort, 939 (71%) developed metastases, of whom 113 (8.6%) had metastases to 5 or more distinct anatomical sites (defining wide-spread metastases, WSM). Bone was the most common site of metastasis (36%), and 80% of patients with liver metastases had 4 or more additional sites of metastasis. Among patients with metastasis, increasing number of metastatic sites was associated with increased risk of death (HR: 1.8, 95%CI: 1.63-1.99, P < 0.001). Alterations in the following genes were enriched in tumors from patients with WSM vs. others: TP53 (40% vs. 20%, P < 0.0001), FOXA1-amplification (8% vs. 3%, P = 0.02), AR-amplification (4.4% vs. 1%, P = 0.01), RB1-deletion (5.3% vs. 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs. 0.7%, P = 0.01). Univariable survival analysis showed all these alterations were predictive of OS (P < 0.05). On multivariable analysis, only TP53 mutations, and FOXA1 and AR amplifications were independent prognostic factors. FOXA1 (n = 37) and AR (n = 13) amplifications were mutually exclusive and patients with these experienced very poor OS (HR: 3.57, 95%CI:2.26-5.6, P < 0.001]., Conclusions: We identified genomic alterations (TP53 mutations, FOXA1/AR amplification, RB1/BRCA2 deletion) from primary prostate carcinomas that are predictive of wide-spread metastases and poor outcome., Competing Interests: Conflict of Interest Dr. Paul L Nguyen reports grants and personal fees from Bayer, Janssen, and Astellas and personal fees from Boston Scientific, Dendreon, Ferring, COTA, Myovant Sciences, Blue Earth Diagnostics, and Augmenix outside the submitted work. All other authors have no relevant conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Despite guidelines recommending narrow-spectrum perioperative antibiotics (NSPA) as prophylaxis for most children undergoing congenital heart disease (CHD) surgery, broad-spectrum perioperative antibiotics (BSPA) are variably used, and their impact on postoperative outcomes is poorly understood., Methods: We used administrative data from U.S. hospitals participating in the Vizient Clinical Data Base. Admissions from 2011 to 2018 containing a qualifying CHD surgery in children 0-17 years old were evaluated for exposure to BSPA versus NSPA. Propensity score-adjusted models were used to compare postoperative length of hospital stay (PLOS) by exposure group, while adjusting for confounders. Secondary outcomes included subsequent antimicrobial treatment and in-hospital mortality., Results: Among 18 088 eligible encounters from 24 U.S. hospitals, BSPA were given in 21.4% of CHD surgeries, with mean BSPA use varying from 1.7% to 96.1% between centers. PLOS was longer for BSPA-exposed cases (adjusted hazard ratio 0.79; 95% confidence interval [CI]: 0.71-0.89, P < .0001). BSPA was associated with higher adjusted odds of subsequent antimicrobial treatment (odds ratio [OR] 1.24; 95% CI: 1.06-1.48), and there was no significant difference in adjusted mortality between exposure groups (OR 2.06; 95% CI: 1.0-4.31; P = .05). Analyses of subgroups with the most BSPA exposure, including high-complexity procedures and delayed sternal closure, also did not find (but could not exclude) a measurable benefit from BSPA on PLOS., Conclusions: BSPA use was common in high-risk populations, and varied substantially between centers. Standardizing perioperative antibiotic practices between centers may reduce unnecessary broad-spectrum antibiotic exposure and improve clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Family physicians' (FPs) long-term relationships with their oncology patients position them ideally to provide primary palliative care, yet their involvement is variable. We examined perceptions of FP involvement among outpatients receiving palliative care at a cancer center and identified factors associated with this involvement., Methods: Patients with advanced cancer attending an oncology palliative care clinic (OPCC) completed a 25-item survey. Eligible patients had seen an FP within 5 years. Binary multivariable logistic regression analyses were conducted to identify factors associated with (1) having seen an FP for palliative care within 6 months, and (2) having a scheduled/planned FP appointment., Results: Of 258 patients, 35.2% (89/253) had seen an FP for palliative care within the preceding 6 months, and 51.2% (130/254) had a scheduled/planned FP appointment. Shorter travel time to FP (odds ratio [OR] = 0.67, 95% confidence interval [CI] = 0.48-0.93, p = 0.02), the FP having a 24-h support service (OR = 1.96, 95% CI = 1.02-3.76, p = 0.04), and a positive perception of FP's care (OR = 1.05, 95% CI = 1.01-1.09, p = 0.01) were associated with having seen the FP for palliative care. English as a first language (OR = 2.90, 95% CI = 1.04-8.11, p = 0.04) and greater ease contacting FP after hours (OR = 1.33, 95% CI = 1.08-1.64, p = 0.008) were positively associated, and female sex of patient (OR = 0.51, 95% CI = 0.30-0.87, p = 0.01) and travel time to FP (OR = 0.66, 95% CI = 0.47-0.93, p = 0.02) negatively associated with having a scheduled/planned FP appointment. Number of OPCC visits was not associated with either outcome., Conclusion: Most patients had not seen an FP for palliative care. Accessibility, availability, and equity are important factors to consider when planning interventions to encourage and facilitate access to FPs for palliative care., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Competing Interests: The authors declare no conflicts of interest.

Introduction: Understanding if divergent molecular profiles of DNA damage and repair (DDR) pathway activity, a biomarker of disease progression, exist in prostate tumors with favorable-risk features is an unmet need, which this study aim to unearth., Materials and Methods: This was a multicenter registry genome-wide expression profiling study of prospectively collected radical prostatectomy (RP) tumor samples from 2014 to 2016. DDR activity was calculated from average expression of 372 DDR genes. Consensus hierarchical clustering was used to arrive at a robust clustering solution based on DDR gene expression patterns. Genome-wide differential expression between clusters was performed, and outcomes were evaluated across expression patterns., Results: Of 5239 patients from the prospective registry, 376 had favorable-risk disease (Grade group [GG] 1 to 2, PSA prior to RP <10ng/ml, pT2 or less). DDR activity score was correlated with prognostic genomic signatures that predict for metastatic risk (r = 0.37, P < 2e -16 ) and high grade groups (P < .001). High DDR activity (top-quartile) was observed in 28% of patients with favorable-risk disease. In favorable-risk disease, 3 distinct clusters with varied DDR activity emerged with consensus clustering. Cluster I (compared with cluster II-III and GG3-GG5 disease) had the highest expression of all DDR sub-pathways, MYC, PAPR1, AR, and AR activity (P < .001 for all). Furthermore, cluster I was associated with poorer metastasis-free survival (MFS) and Overall survival (OS) compared with other clusters (MFS; HR: 2.43, 95%CI, [1.22-4.83], P = .01; OS; HR: 2.77, 95%CI, [1.18-6.5], P = .01)., Conclusions: Cluster I is a novel subgroup of favorable-risk disease with high DDR activity, AR activity, PARP1 and chr8q/MYC expression, and poorer MFS and OS., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Patient-reported outcome measures (PROMs) are not routinely used in clinical care by pediatric liver transplant (LT) teams. The Starzl Network for Excellence in Pediatric Transplantation (SNEPT) assessed feasibility of using a disease-specific Quality of Life (QoL) questionnaire in the ambulatory setting at 10 SNEPT sites., Methods: A mixed methods feasibility project assessing administration processes, barriers, and user experiences with the Pediatric Liver Transplant Quality of Life (PeLTQL) tool. Iterative processes sought stakeholder feedback across four phases (Pilot, Extended Pilot, Development of a Mobile App PeLTQL version, and Pilot App use)., Results: A total of 149 patient-parent dyads completed the PeLTQL during LT clinic follow-up. Clinicians, parents, and patients evaluated and reported on feasibility of operationalization. Only two of 10 SNEPT sites continued PeLTQL administration after the initial two pilot phases. Reasons include limited clinical time and available personnel aggravated by the COVID-19 pandemic. In response, a mobile application version of the PeLTQL was initiated. Providing PeLTQL responses electronically was "very easy" or "easy" as reported by 96% (22/23) parents., Conclusions: Administration of a PROM into post-pediatric LT clinical care was feasible, but ongoing utilization stalled. Use of a mobile app towards facilitating completion of the PeLTQL outside of clinic hours may address the time and work-flow barriers identified., (© 2022 Wiley Periodicals LLC.)

Objective: Chromosome 8q arm (chr8q) is the most amplified chromosomal segment in advanced metastatic castration-resistant prostate cancer after chXq12. These regions harbor important oncogenes driving prostate cancer progression, including MYC that plays a role in various hallmarks of cancer, including cell cycle progression and immune surveillance. Herein we characterize the co-expression patterns of chr8q genes and their clinical utility in more than 7,000 radical prostatectomy samples., Materials and Methods: Copy Number alterations of 336 genes on chr8q21 to chr8q24 were extracted from 2 primary prostate cancer cohorts (TCGA, n = 492; MSK-primary, n = 856) and 3 metastatic prostate cancer cohorts (MSK-met, N = 432; MSK-mCSPC, N = 424; SU2CPNAS, n = 444) from cBioPortal. Expression data for the 336 genes was extracted from 6,135 radical prostatectomy samples from Decipher GRID registry. For survival analysis, patients were grouped into top 10% and top 25% by band expression and were compared with the remaining cohort. Hazard ratios were calculated using Cox proportional hazards models., Results: Genes on chr8q were highly co-amplified and co-expressed. Copy number alterations and overexpression of chr8q genes in primary disease were associated with higher Gleason scores, increased risk of metastases, and increased prostate cancer specific mortality. Additionally, our data demonstrated high expression of MYC alone was not associated with differences in metastases free survival while high expression of other chr8q bands was associated with decreased metastases free survival. By combining chr8q data with an established genomic classifier like Decipher, we were able to develop a new model that was better at predicting metastases than Decipher alone., Conclusions: Our findings highlight the clinical utility of chr8q data, which can be used to improve prognostication and risk prediction in localized prostate cancer., Competing Interests: Conflicts of interest No conflicts of interest relevant to this submission reported., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Objectives: Medical assistance in dying (MAiD) is legal in an increasing number of countries, but there are concerns that its availability may compromise access to palliative care. We assessed public interest in MAiD, palliative care, both, or neither, and examined characteristics associated with this interest., Methods: We surveyed a representative sample of the adult Canadian public, accessed through a panel from May to June 2019. Weighted generalised multinomial logistic regression analyses were used to determine characteristics associated with interest in referral to palliative care, MAiD, or both, in the event of diagnosis with a serious illness., Results: Of 1362 participants who had heard of palliative care, 611 (44.8% weighted (95% CI 42.1% to 47.5%)) would be interested in both MAiD and palliative care, 322 (23.9% (95% CI 21.5% to 26.2%)) palliative care alone, 171 (12.3% (95% CI 10.5% to 14.1%)) MAiD alone and 258 (19.0% (95% CI 16.9% to 21.2%)) neither. In weighted multinomial logistic regression analyses, interest in both MAiD and palliative care (compared with neither) was associated with better knowledge of the definition of palliative care, older age, female gender, higher education and less religiosity; interest in palliative care alone was associated with better knowledge of the definition of palliative care, older age, female gender and being married/common law; interest in MAiD alone was associated with less religiosity (all p<0.05)., Conclusions: There is substantial public interest in potential referral to both MAiD and palliative care. Simultaneous availability of palliative care should be ensured in jurisdictions where MAiD is legal, and education about palliative care should be a public health priority., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although the United States (US) Hispanic population consists of diverse communities, prior breast cancer studies often analyze this group in aggregate. Our aim was to identify differences in breast cancer stage at presentation in the US population, with a particular focus on Hispanic subgroups., Methods: Data from the National Cancer Database (NCDB) from 2004 to 2017 were used to select women with primary breast cancer; individuals were disaggregated by racial and ethnic subgroup and Hispanic country of origin. Ordinal logistic regression was used to create adjusted odds ratios (aORs) with 95% confidence intervals (CIs), with higher odds representing presentation at later-stage breast cancer. Subgroup analysis was conducted based on tumor receptor status., Results: Overall, among 2,282,691 women (5.2% Hispanic), Hispanic women were more likely to live in low-income and low-educational attainment neighborhoods, and were also more likely to be uninsured. Hispanic women were also more likely to present at later-stage primary breast cancer when compared with non-Hispanic White women (aOR 1.19, 95% CI 1.18-1.21; p < 0.01). Stage disparities were demonstrated when populations were disaggregated by country of origin, particularly for Mexican women (aOR 1.55, 95% CI 1.51-1.60; p < 0.01). Disparities worsened among both racial and country of origin subgroups in women with triple-negative disease., Conclusion: Later breast cancer stage at presentation was observed among Hispanic populations when disaggregated by racial subgroup and country of origin. Socioeconomic disparities, as well as uncaptured disparities in access and/or differential care, may drive these observed differences. Future studies with disaggregated data are needed to characterize outcomes in Hispanic communities and develop targeted interventions., (© 2022. Society of Surgical Oncology.)