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Application of MRD testing to healthy donor cfDNA samples. Patient specific panels designed for 14 different patients were pooled together and applied to cfDNA collected from four different healthy donors. Reported are the number of sites where ctDNA was detected. We required at least two sites to call a sample MRD+.

Verification of detection power calculation. Comparison between the predicted detection power of 18 replicates and the actual fraction of those replicates that were called MRD+. 18 independent samples from a 1:100k dilution were probed with a 488 SNV panel (see methods). Replicates had their duplex consensus reads downsampled in increments of 10% and detection power was recalculated. Reported are the median and range of predicted detection powers for all replicates at each downsampling.

Early stage breast cancer cohort. (A) Overview of subtype distribution of cohort as well as the timing of blood draws relative to surgery and treatment. (B) REMARK diagram of the early stage breast cancer cohort. (C) Distribution of the number of mutations tracked for each patient.

Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing.Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ER+/HER2− metastatic breast cancer (MBC) sampled within 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples.Results:Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median = 57; range = 2–346). Clinical sensitivity was 81% (n = 13/16) in newly diagnosed MBC, 23% (n = 7/30) at postoperative and 19% (n = 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR = 20.8; 95% confidence interval, 7.3–58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range = 3.4–39.2 months).Conclusions:Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.

Overview schematic of MRD assay. MRD assay workflow from characterizing a primary tumor to determining if a blood draw contains evidence of residual disease.

Validation of tumor fraction confidence interval and effects of biological variability on tumor fraction inference. (A) Confidence intervals inferred from simulated data were aggregated into coverage probability for each condition and compared against theoretical coverage probability of 95% (see Methods). (B) Biological variability of clonal evolution loss was simulated by removing tumor evidence from a fraction of the fingerprint panel. Tumor fraction was calculated for simulated and original samples for comparison.

Patients who experienced local recurrence only after treatment for early stage breast cancer. cfDNA time points for all patients who experienced local recurrence only. End points represent time of last follow up or death.

Supplementary Methods

Supplementary Tables

Digital droplet PCR (ddPCR) testing for single mutation in dilution series. (A) The observed VAFs of HapMap serial dilutions measured by using a ddPCR assay for a single mutation (with three replicates) vs. the expected VAFs; (B) The representative ddPCR raw data and fluorescence intensity thresholds for determining positive or negative droplets.

Technical performance of the MRD Assay. All samples from early stage breast cancer cohort. Includes plasma cfDNA and buffy coat gDNA samples. Samples from the same patient and probed with the same panel are represented independently. (A) On target fraction calculated from Picard CollectHsMetrics and using pct_selected_bases. (B) Coefficient of variation of duplex fragment depth across fingerprint sites. (C) Fold 80 base penalty score for duplex fragment depth across fingerprint sites. (D, E) Error rate comparison between conventional sequencing (requiring Q20 base quality and removing duplicate fragments) and our duplex sequencing with added filters (see methods). (F) Fraction of total duplexes after downsampling raw reads. We considered a sample to be saturated if it still contained at least 95% of its duplexes after downsampling to 80% of its raw reads.

In May 2020, we surveyed 3,291 students enrolled in accredited social work programs in the United States about experiences during the pandemic. More than half reported learning less during online d...

The pre-clinical medical school curriculum provides students with extraordinary experiences in preparation to become physicians. However, it was not originally designed to be delivered remotely. The COVID-19 pandemic promptly threw the medical education process into unforeseen circumstances. A model of student-faculty collaboration created to address new challenges and implement practical solutions rapidly is presented. This model was used effectively to respond to pre-clinical educational interruptions that were imposed by the COVID-19 pandemic and maintain high-quality training. Our experience provides valuable insights and lessons learned that can be applied to the ongoing pandemic response and to future educational challenges.

To determine the impact of a letter-based advance care planning (ACP) healthcare improvement (HI) initiative on rates of ACP conversations and documentation among gynecologic oncology (GO) inpatients. An HI initiative was implemented from January to December 2020 to improve ACP documentation among GO inpatients. Patients admitted to the GO service were given ACP packets with a letter-based ACP worksheet. GO inpatients who were interested in learning more about ACP were visited by medical students trained to lead ACP conversations. ACP documentation rates in the EMR (electronic medical record) pre- and post-intervention were evaluated. Descriptive statistics were calculated. Associations between sociodemographic characteristics and ACP documentation were analyzed using logistic regression. There were 172 patients admitted in 2019 (pre-implementation cohort). Of these, 45/172 patients (26%) had an advance directive (AD) documented in their electronic medical record (EMR). Following the implementation of the ACP HI in 2020, 55/168 patients (33%) had an AD documented in their EMR. This was a 7% absolute increase and 27% relative increase from pre-intervention AD documentation rates. Increasing age was associated with an increased likelihood of having an AD in the chart (p = 0.004). Married women were less likely to have an AD in their chart (p = 0.05). An HI utilizing a letter-based ACP packet given to GO inpatients improved AD documentation in the EMR. This HI offers a unique method for introducing ACP to patients. More work is needed to improve the occurrence and documentation of ACP conversations.

Background The global prevalence of cancer is rapidly increasing and will increase the acute care needs of patients with cancer, including emergency department (ED) care. Patients with cancer present to the ED across the cancer care continuum from diagnosis through treatment, survivorship, and end-of-life. This article describes the characteristics and determinants of ED visits, as well as challenges in the effort to define preventable ED visits in this population. Findings The most recent population-based estimates suggest 4% of all ED visits are cancer-related and roughly two thirds of these ED visits result in hospitalization—a 4-fold higher ED hospitalization rate than the general population. Approximately 44% of cancer patients visit the ED within 1 year of diagnosis, and more often have repeat ED visits within a short time frame, though there is substantial variability across cancer types. Similar patterns of cancer-related ED use are observed internationally across a range of different national payment and health system settings. ED use for patients with cancer likely reflects a complex interaction of individual and contextual factors—including provider behavior, health system characteristics, and health policies—that warrants greater attention in the literature. Conclusions Given the amount and complexity of cancer care delivered in the emergency setting, future research is recommended to examine specific symptoms associated with cancer-related ED visits, the contextual determinants of ED use, and definitions of preventable ED use specific to patients with cancer.

Introduction In the United States, there are 5.5 million military caregivers, defined as family members, friends, or other acquaintances who provide essential care and support to current or former military service members. This study describes the prevalence and predictors of unmet information and support needs in this unique group of caregivers. Until recently, little research has focused on military caregivers. In 2014, a comprehensive RAND report underscored the specific challenges experienced by military caregivers including greater physical, financial, and emotional strain when compared with civilian caregivers. Of note, compared to civilian caregivers, military caregivers provide care and support for care recipients who are more likely to have complex illness. While this recent research improved our understanding of the increased burden associated with military caregiving, it also identified gaps for future work, including the need for additional studies to better understand unmet information and support needs to inform future interventions. The current study was designed to address this gap. Materials and Methods We examined data collected in the Caregiving in the U.S. Survey, a cross-sectional online survey fielded in 2014, by the National Alliance for Caregiving and the American Association of Retired Persons (AARP) for primary caregivers who had been in the role for at least six months. Four outcomes representing unmet caregiver needs were examined measuring caregiver report of needing more help or information to: (1) keep the care recipient safe at home; (2) manage challenging behaviors such as wandering; (3) manage their own emotional and physical stress; and (4) make end-of-life decisions. Survey-weighted logistic regression was used to test associations between military caregiver status (military/civilian) and unmet needs while controlling for key socio-demographic, caregiving and care recipient health variables, with nationally generalizable results. Results Compared to their civilian counterparts, military caregivers had significantly higher odds of reporting need for information or support to make end-of-life decisions (OR = 2.22; 95% CI: 1.24, 3.97; p = 0.01) and marginally higher odds of reporting need for more information or support to manage physical and emotional stress (OR = 1.64; 95% CI: 0.93, 2.88; p = 0.08). In contrast, military caregivers had significantly lower odds of reporting need for more information or support to keep the care recipient safe compared to civilian caregivers (OR = 0.54; 95% CI: 0.30, 0.95; p = 0.03). Reports of unmet needs related to managing challenging behaviors were similar between military and civilian caregivers. Conclusions Needs for information and support differ for civilian and military caregivers and may reflect direct or indirect impacts on caregivers arising from differences in TRICARE and Veterans Affairs health insurance coverage and related benefits, services and systems or access to resources that address the unique needs of military populations. Future research is needed to better understand the unique concerns of military caregivers and inform interventions that support end-of-life care decision-making for military service members and their caregivers.

We examine the relationships between fear of cancer recurrence (FCR), physical activity, smoking status, and engagement in healthier habits in a US population-based sample of post-treatment cancer survivors. We used data from the 2011 Medical Expenditure Panel Survey (MEPS) Experience with Cancer Survivorship Supplement. Multivariable logistic regression was used to test the relationship of FCR to physical activity, smoking status, and engagement in healthier habits. In all analyses, MEPS survey weights were applied to account for the survey design. Compared with those reporting no FCR, survivors reporting high FCR had significantly lower odds of reporting that they were not currently smokers (odds ratio [OR] = 0.46; 95% CI 0.24, 0.91) and those with any level of FCR had significantly higher odds of reporting healthier habits since diagnosis relative to those with no FCR (low FCR OR = 1.97; 95% CI 1.36, 2.85; high FCR OR = 2.40; 95% CI 1.33, 4.32). FCR was not associated with the odds of reporting physical activity. Findings from this large population-based survey suggest that some of survivors’ lifestyle factors may be related to their level of FCR. Understanding the effects of FCR on lifestyle factors may help survivors, survivorship care providers, and policy makers better understand important differences among cancer survivors and personalize interventions in clinical care.

Intratumor heterogeneity is an important mediator of poor outcomes in many cancers, including breast cancer. Genetic subclones frequently contribute to this heterogeneity; however, their growth dynamics and interactions remain poorly understood. PIK3CA and HER2 alterations are known to coexist in breast and other cancers. Herein, we present data that describe the ability of oncogenic PIK3CA mutant cells to induce the proliferation of quiescent HER2 mutant cells through a cell contact–mediated mechanism. Interestingly, the HER2 cells proliferated to become the major subclone over PIK3CA counterparts both in vitro and in vivo. Furthermore, this phenotype was observed in both hormone receptor–positive and –negative cell lines, and was dependent on the expression of fibronectin from mutant PIK3CA cells. Analysis of human tumors demonstrated similar HER2:PIK3CA clonal dynamics and fibronectin expression. Our study provides insight into nonrandom subclonal architecture of heterogenous tumors, which may aid the understanding of tumor evolution and inform future strategies for personalized medicine.

Problem statement The use of evidence-informed symptom guides has not been widely adopted in telephonic support. Design This is a descriptive study of nurse-led support using evidence-based symptom guides during telephone outreach. Data sources Documentation quantified telephone encounters by frequency, length, and type of patient-reported symptoms. Nurse interviews examined perceptions of their role and the use of symptom guides. Analysis Quantitative data were summarized using univariate descriptive statistics, and interviews were analyzed using directed descriptive content analysis. Findings Symptom guides were viewed as trusted evidence-based resources, suitable to address common treatment-related symptoms. A threshold effect was a reported barrier of the guides, such that the benefit diminished over time for managing recurring symptoms. Implications for practice Telephone outreach using evidence-based symptom guides can contribute to early symptom identification while engaging patients in decision making. Understanding nurse activities aids in developing an economical and high-quality model for symptom support, as well as in encouraging nurses to practice at the highest level of preparation.

In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10−5. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care. A new approach for whole-genome sequencing of plasma circulating tumor DNA allows for dynamic monitoring of disease burden and ultra-sensitive detection of minimal residual disease.

Assaying for large numbers of low-frequency mutations requires sequencing at extremely high depth and accuracy. Increasing sequencing depth aids the detection of low-frequency mutations yet limits the number of loci that can be simultaneously probed. Here we report a method for the accurate tracking of thousands of distinct mutations that requires substantially fewer reads per locus than conventional hybrid-capture duplex sequencing. The method, which we named MAESTRO (for minor-allele-enriched sequencing through recognition oligonucleotides), combines massively parallel mutation enrichment with duplex sequencing to track up to 10,000 low-frequency mutations, with up to 100-fold fewer reads per locus. We show that MAESTRO can be used to test for chimaerism by tracking donor-exclusive single-nucleotide polymorphisms in sheared genomic DNA from human cell lines, to validate whole-exome sequencing and whole-genome sequencing for the detection of mutations in breast-tumour samples from 16 patients, and to monitor the patients for minimal residual disease via the analysis of cell-free DNA from liquid biopsies. MAESTRO improves the breadth, depth, accuracy and efficiency of mutation testing by sequencing.

Purpose:Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test for tracking hundreds of patient-specific mutations to detect MRD with a 1,000-fold lower error rate than conventional sequencing.Experimental Design:We compared the sensitivity of our approach to digital droplet PCR (ddPCR) in a dilution series, then retrospectively identified two cohorts of patients who had undergone prospective plasma sampling and clinical data collection: 16 patients with ER+/HER2− metastatic breast cancer (MBC) sampled within 6 months following metastatic diagnosis and 142 patients with stage 0 to III breast cancer who received curative-intent treatment with most sampled at surgery and 1 year postoperative. We performed whole-exome sequencing of tumors and designed individualized MRD tests, which we applied to serial cfDNA samples.Results:Our approach was 100-fold more sensitive than ddPCR when tracking 488 mutations, but most patients had fewer identifiable tumor mutations to track in cfDNA (median = 57; range = 2–346). Clinical sensitivity was 81% (n = 13/16) in newly diagnosed MBC, 23% (n = 7/30) at postoperative and 19% (n = 6/32) at 1 year in early-stage disease, and highest in patients with the most tumor mutations available to track. MRD detection at 1 year was strongly associated with distant recurrence [HR = 20.8; 95% confidence interval, 7.3–58.9]. Median lead time from first positive sample to recurrence was 18.9 months (range = 3.4–39.2 months).Conclusions:Tracking large numbers of individualized tumor mutations in cfDNA can improve MRD detection, but its sensitivity is driven by the number of tumor mutations available to track.

Background and Objectives Although most people have some experience as caregivers, the nature and context of care are highly variable. Caregiving, socioeconomic factors, and health are all interrelated. For these reasons, caregiver interventions must consider these factors. This review examines the degree to which caregiver intervention research has reported and considered social determinants of health. Research Design and Methods We examined published systematic reviews and meta-analyses of interventions for older adults with age-related chronic conditions using the PRISMA and AMSTAR 2 checklists. From 2,707 papers meeting search criteria, we identified 197 potentially relevant systematic reviews, and selected 33 for the final analysis. Results We found scant information on the inclusion of social determinants; the papers lacked specificity regarding race/ethnicity, gender, sexual identity, socioeconomic status, and geographic location. The majority of studies focused on dementia, with other conditions common in later life vastly underrepresented. Discussion and Implications Significant gaps in evidence persist, particularly for interventions targeting diverse conditions and populations. To advance health equity and improve the effectiveness of interventions, research should address caregiver heterogeneity and improve assessment, support, and instruction for diverse populations. Research must identify aspects of heterogeneity that matter in intervention design, while recognizing opportunities for common elements and strategies.

BACKGROUND Cancer care coordination addresses the fragmented and inefficient care of individuals with complex care needs. The complexity of care coordination can be aided by innovative technology. Few examples of information technology-enabled care coordination exist beyond the conventional telephone follow-up. For this study, we implemented a custom-designed app, the Personal Health Network (PHN)—a Health Insurance Portability and Accountability Act-compliant social network built around a patient to enable patient-centered health and health care activities in collaboration with clinicians, care team members, caregivers, and others designated by the patient. The app facilitates a care coordination intervention for patients undergoing chemotherapy. OBJECTIVE This study aimed to understand patient experiences with PHN technology and assess their perspectives on the usability and usefulness of PHNs with care coordination during chemotherapy. METHODS A two-arm randomized clinical trial was conducted to compare the PHN and care coordination with care coordination alone over a 6-month period beginning with the initiation of chemotherapy. A semistructured interview guide was constructed based on a theoretical framework of technology acceptance addressing usefulness, usability, and the context of use of the technology within the participant’s life and health care setting. All participants in the intervention arm were interviewed on completion of the study. Interviews were recorded and transcribed verbatim. A summative thematic analysis was completed for the transcribed interviews. Features of the app were also evaluated. RESULTS A total of 27 interviews were completed. The resulting themes included the care coordinator as a partner in care, learning while sick, comparison of other technology to make sense of the PHN, communication, learning, usability, and usefulness. Users expressed that the nurse care coordinators were beneficial to them because they helped them stay connected to the care team and answered their questions. They shared that the mobile app gave them access to the health information they were seeking. Users expressed that the mobile app would be more useful if it was fully integrated with the electronic health record. CONCLUSIONS The findings highlight the value of care coordination from the perspectives of cancer patients undergoing chemotherapy and the important role of technology, such as the PHN, in enhancing this process by facilitating better communication and access to information regarding their illness.

Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM., Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) enables characterization of a patient’s cancer. Here, the authors analyse CTCs, cfDNA, and tumor biopsies from multiple myeloma patients to show these approaches are complementary for mutation detection, together enabling a greater fraction of patient tumors to be profiled.

Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number alterations (SCNAs), yet little is known regarding SCNAs in metastatic TNBC. We sought to evaluate SCNAs in metastatic TNBC exclusively via cfDNA and determine if cfDNA tumor fraction is associated with overall survival in metastatic TNBC. Patients and Methods In this retrospective cohort study, we identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who received prior chemotherapy in the (neo)adjuvant or metastatic setting. We performed low-coverage genome-wide sequencing of cfDNA from plasma. Results Without prior knowledge of tumor mutations, we determined tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and primary TNBCs in publicly available data sets The Cancer Genome Atlas and METABRIC, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. Prespecified cfDNA tumor fraction threshold of ≥ 10% was associated with significantly worse metastatic survival (median, 6.4 v 15.9 months) and remained significant independent of clinicopathologic factors (hazard ratio, 2.14; 95% CI, 1.4 to 3.8; P < .001). Conclusion We present the largest genomic characterization of metastatic TNBC to our knowledge, exclusively from cfDNA. Evaluation of cfDNA tumor fraction was feasible for nearly all patients, and tumor fraction ≥ 10% is associated with significantly worse survival in this large metastatic TNBC cohort. Specific SCNAs are enriched and prognostic in metastatic TNBC, with implications for metastasis, resistance, and novel therapeutic approaches.

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing., Identifying the mutational landscape of tumours from cell-free DNA in the blood could help diagnostics in cancer. Here, the authors present ichorCNA, software that quantifies tumour content in cell free DNA, and they demonstrate that cell-free DNA whole-exome sequencing is concordant with metastatic tumour whole-exome sequencing.

OBJECTIVE The objective of the study is to understand potential differences in psychosocial outcomes from active treatment to survivorship. METHODS Using the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement (n = 1360), we examined and compared psychosocial outcomes among respondents in active treatment with survivors by year(s) since treatment ended. Survey-weighted regression models were used to test associations between year(s) since treatment and depressive symptoms (Patient Health Questionnaire-2), psychological distress (K6), and cancer-specific worry related to recurrence. RESULTS Unadjusted estimates showed no significant differences in depressive symptoms or psychological distress between those in active treatment and cancer survivors at any time posttreatment. In contrast, the prevalence of cancer-specific worry was lowest among survivors more than 5 years since treatment (10%), slightly higher among those with less than 1 year since treatment (15%), and highest among those in active treatment (32%). In models controlled for sociodemographic and health-related covariates, the year(s) since treatment ended was inversely associated with the odds of cancer-specific worry but was not associated with depressive symptoms or psychological distress. CONCLUSIONS In this population-based sample, worry about cancer recurrence may diminish with years since treatment ended, while depressive symptoms and distress are persistent across the trajectory. These findings highlight unmet psychosocial needs among cancer survivors and demonstrate the importance of targeted interventions across the survivorship continuum.

Prior studies reveal gaps in cancer survivors' discussions with health care providers about follow-up care and receipt of care plans; however, whether survivorship care planning may vary by cancer type is not known. We surveyed 615 survivors of breast, colorectal, prostate, lung cancer, and melanoma enrolled in three health plans to examine cancer survivors' self-reported discussions of follow-up care, including the need for surveillance, late and long-term effects, emotional needs, and health behaviors. We assessed whether cancer survivors received a written treatment summary and post-treatment care instructions. Most (92%) survivors reported having a discussion about the need for surveillance; 75%, late and long-term effects; 69%, lifestyle and health behaviors; and 53%, emotional and social needs. Most (88%) reported receiving post-treatment care instructions and 47%, a treatment summary. While there was little difference among survivors' receipt of surveillance or health behavior recommendations by cancer type (p = 0.85 and p = 0.66, respectively), discussions of late and long-term effects occurred among 82% of prostate, 78% of breast, 73% of melanoma, 72% of colorectal, and 67% of lung survivors (p = 0.06). Approximately half of survivors reported discussions of emotional needs, with modest differences by cancer type (p = 0.08). Our findings indicate that most patient-provider discussions cover information on surveillance, with less emphasis on late and long-term effects, lifestyle and health behaviors, and substantially less focusing on emotional and social needs. No or modest differences in discussions occurred by cancer type. Whether tailoring information to individual cancer survivor needs is beneficial should be examined.

147 Background: Fear of cancer recurrence (FCR) and related constructs are experienced by many cancer survivors and are consistently identified as important areas of need. This study adds to sparse literature on this topic by describing the prevalence of FCR and testing its associations with mental health status measures in a US sample of cancer survivors. Methods: Using the Medical Expenditure Panel Survey (MEPS) Experiences with Cancer Survivorship Supplement (n = 1,032), we examined socio-demographic, health and mental health characteristics of cancer survivors by their level of fear of cancer recurrence (none, low, high). Survey-weighted population-based estimates describe the prevalence of key variables. Multinomial logistic regression was used to test associations between validated measures of mental health status and individual characteristics, and levels of FCR in models unadjusted and controlling for socio-demographic and health characteristics. MEPS survey weights were applied in all analyses to account for the survey design. Results: Overall, 34% of cancer survivors reported no FCR, 54% reported low FCR, and 11% reported high FCR. Cancer survivors were at increased risk of reporting high FCR relative to no FCR if they had a low 12-item Short Form Health Survey (SF-12) Mental Component Summary (MCS) score (≤48) compared to high scores (odds ratio = 2.89; 95% confidence interval (CI) = 1.58, 5.32). Reporting depressive symptoms or psychological distress did not significantly increase the risk of reporting high or low FCR relative to no FCR. Conclusions: This study is the first to provide US population-based estimates of associations between FCR and individual, health and mental characteristics. Our results also provide valuable information on which survivors are most at-risk for FCR, and add to a new and growing literature supporting FCR as a multidimensional construct distinct from depression and distress. Future research is needed to more clearly differentiate FCR from other constructs, specifically anxiety disorders, and to identify clinically significant levels of FCR to better target survivors with the highest needs.

We examine the relationships between fear of cancer recurrence (FCR), physical activity, smoking status, and engagement in healthier habits in a US population-based sample of post-treatment cancer survivors. We used data from the 2011 Medical Expenditure Panel Survey (MEPS) Experience with Cancer Survivorship Supplement. Multivariable logistic regression was used to test the relationship of FCR to physical activity, smoking status, and engagement in healthier habits. In all analyses, MEPS survey weights were applied to account for the survey design. Compared with those reporting no FCR, survivors reporting high FCR had significantly lower odds of reporting that they were not currently smokers (odds ratio [OR] = 0.46; 95% CI 0.24, 0.91) and those with any level of FCR had significantly higher odds of reporting healthier habits since diagnosis relative to those with no FCR (low FCR OR = 1.97; 95% CI 1.36, 2.85; high FCR OR = 2.40; 95% CI 1.33, 4.32). FCR was not associated with the odds of reporting physical activity. Findings from this large population-based survey suggest that some of survivors' lifestyle factors may be related to their level of FCR. Understanding the effects of FCR on lifestyle factors may help survivors, survivorship care providers, and policy makers better understand important differences among cancer survivors and personalize interventions in clinical care.

Background Cancer care coordination addresses the fragmented and inefficient care of individuals with complex care needs. The complexity of care coordination can be aided by innovative technology. Few examples of information technology-enabled care coordination exist beyond the conventional telephone follow-up. For this study, we implemented a custom-designed app, the Personal Health Network (PHN)—a Health Insurance Portability and Accountability Act-compliant social network built around a patient to enable patient-centered health and health care activities in collaboration with clinicians, care team members, caregivers, and others designated by the patient. The app facilitates a care coordination intervention for patients undergoing chemotherapy. Objective This study aimed to understand patient experiences with PHN technology and assess their perspectives on the usability and usefulness of PHNs with care coordination during chemotherapy. Methods A two-arm randomized clinical trial was conducted to compare the PHN and care coordination with care coordination alone over a 6-month period beginning with the initiation of chemotherapy. A semistructured interview guide was constructed based on a theoretical framework of technology acceptance addressing usefulness, usability, and the context of use of the technology within the participant’s life and health care setting. All participants in the intervention arm were interviewed on completion of the study. Interviews were recorded and transcribed verbatim. A summative thematic analysis was completed for the transcribed interviews. Features of the app were also evaluated. Results A total of 27 interviews were completed. The resulting themes included the care coordinator as a partner in care, learning while sick, comparison of other technology to make sense of the PHN, communication, learning, usability, and usefulness. Users expressed that the nurse care coordinators were beneficial to them because they helped them stay connected to the care team and answered their questions. They shared that the mobile app gave them access to the health information they were seeking. Users expressed that the mobile app would be more useful if it was fully integrated with the electronic health record. Conclusions The findings highlight the value of care coordination from the perspectives of cancer patients undergoing chemotherapy and the important role of technology, such as the PHN, in enhancing this process by facilitating better communication and access to information regarding their illness.

Background: Breast cancer (BC) may recur years to decades after initial treatment, leading to incurable, metastatic disease. Prior studies have shown blood biopsy can detect minimal residual disease (MRD), but not in all patients and often with very short lead time. Most efforts thus far have focused on tracking one or a few mutations via ctDNA, which may limit sensitivity. Here we sought to maximize the detection sensitivity of blood biopsies by tracking up to hundreds of individualized tumor mutations in cell-free DNA (cfDNA). Doing so enables us to break the detection ceiling imposed by the limited copies of each gene in the cell-free DNA in a blood draw. Methods: cfDNA was extracted from archival plasma samples (n=271) from 142 patients with stage 0-III BC enrolled prospectively onto two IRB-approved studies. We applied whole-exome sequencing (WES) to define up to several hundred mutations from each patient’s tumor. To limit potential errors, we employed strict criteria to select somatic SNVs to track using duplex sequencing in cfDNA. We required detection of ≥ 2 mutations for a cfDNA sample to be MRD+ and excluded any mutations also found in a patient’s own germline DNA. Results: We identified 142 patients treated for stage 0-III BC, who had postoperative blood and plasma samples available, and were monitored for distant recurrences for up to thirteen years. All patients had biopsy-proven BC, with 86 (61%) having HR+/HER2- BC, 31 (22%) having HR-/HER2-, or “triple negative” BC (TNBC), and 25 (18%) having HER2-positive disease. Three (2%) patients had stage 0 disease, 32 (23%) had stage I, 68 (42%) had stage II, and 39 (27%) had stage III BC at diagnosis. Archived plasma samples were collected post-operatively, at year 1, and at year 4. We created individualized assays targeting a median of 57 mutations (range 2 - 346) per patient. Reasoning that MRD status after completion of all local therapy and chemotherapy might best predict for distant recurrence, we conducted a landmark analysis at one year following surgery, and found all patients (n=6/6) with detectable MRD experienced recurrence (HR=21.2 (7.43-60.35)) in a median of 6.7 (range 3.4 - 15.8) months. Median lead time including all timepoints from first positive blood sample to recurrence was 18.9 (range: 3.4 - 39.2) months. Finally, in a multivariate model, MRD remained highly statistically significant independent of stage, subtype, and age at diagnosis. Conclusions: We present a novel approach to MRD tracking based on the premise that tracking many - rather than one or a handful of - mutations inherently increases sensitivity and that assay personalization maximizes sensitivity in a disease without multiple, recurrent mutations. To our knowledge, the lead time we show here is significantly longer than that seen in prior investigations, and if confirmed, could offer an opportunity to treat MRD long before the development of clinically apparent metastatic disease. Prospective studies are needed to determine whether earlier detection of MRD is clinically meaningful for patients. Citation Format: Heather A Parsons, Justin Rhoades, Sarah C. Reed, Greg Gydush, Priyanka Ram, Pedro Exman, Kan Xiong, Christopher Lo, Tianyu Li, Mark Fleharty, Greg Kirkner, Denisse Rotem, Ofir Cohen, Melissa Hughes, Shoshanna Rosenberg, Laura Collins, Kathy Miller, Brendan Blumenstiel, Carrie Cibulskis, Donna Neuberg, Samuel S. Freeman, Niall Lennon, Nikhil Wagle, Gavin Ha, Daniel G. Stover, Atish D. Choudhury, Gad Getz, Matthew Meyerson, Nancy U. Lin, Ian E. Krop, J. Christopher Love, G. Mike Makrigiorgos, Ann Partridge, Erika Mayer, Todd R. Golub, Viktor A. Adalsteinsson. Ultrasensitive detection of minimal residual disease in patients treated for breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-01-03.

Tumor content in circulating cell-free DNA (cfDNA) is a promising biomarker, but longitudinal dynamics of tumor-derived and non-tumor-derived cfDNA through multiple courses of therapy have not been well described.CfDNA from 663 plasma samples from 140 patients with castration-resistant prostate cancer (CRPC) was subject to sparse whole genome sequencing. Tumor fraction (TFx) estimated using the computational tool ichorCNA was correlated with clinical features and responses to therapy.TFx associated with the number of bone metastases (median TFx = 0.014 with no bone metastases, 0.047 with 1-3 bone metastases, 0.190 for 4+ bone metastases; P0.0001) and with visceral metastases (P0.0001). In multivariable analysis, TFx remained associated with metastasis location (P = 0.042); TFx was positively correlated with alkaline phosphatase (P = 0.0227) and negatively correlated with hemoglobin (Hgb) (P0.001), but it was not correlated with prostate specific antigen (PSA) (P = 0.75). Tumor-derived and non-tumor-derived cfDNA track together and do not increase with generalized tissue damage from chemotherapy or radiation at the time scales examined. All new treatments that led to ≥30% PSA decline at 6 weeks were associated with TFx decline when baseline TFx was7%; however, TFx in patients being subsequently maintained on secondary hormonal therapy was quite dynamic.TFx correlates with clinical features associated with overall survival in CRPC, and TFx decline is a promising biomarker for initial therapeutic response.Dana-Farber/Harvard Cancer Center (DF/HCC) protocol no. 18-135.Wong Family Award in Translational Oncology, Dana Farber Cancer Institute Medical Oncology grant, Gerstner Family Foundation, Janssen Pharmaceuticals Inc., and Koch Institute Support (core) grant P30-CA14051 from the National Cancer Institute (NCI).

Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy. Significance: We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. Cancer Discov; 8(1); 37–48. ©2017 AACR. See related commentary by Sundar and Tan, p. 14. See related article by Janjigian et al., p. 49. This article is highlighted in the In This Issue feature, p. 1

The physical and psychological effects of a cancer diagnosis and treatment on an individual may be significant and require appropriate monitoring and management. Furthermore, attention to preventive care and comorbid medical conditions is critical. Innovative approaches are needed to provide quality care to this growing population.We reviewed the literature evaluating shared medical appointments (SMAs) in noncancer and cancer care settings. Supported by a conceptual framework and adhering to the goals of patient-centered communication, we propose how SMAs may be used in clinical practice to enhance survivorship care.The literature suggests that SMAs are an effective model in noncancer settings, showing improved blood pressure and health-related quality of life, among others. Although evidence for SMAs in cancer care is limited, there is significant potential for improved patient outcomes and costs. In particular, SMAs may provide an opportunity to address medical and psychological needs while creating a structure for enhanced communication.SMAs may offer an innovative care model for cancer survivors and their providers. Implementation and evaluation of SMAs in the care of cancer survivors is warranted.

Author(s): Lash, Rebecca S; Bell, Janice F; Reed, Sarah C; Poghosyan, Hermine; Rodgers, James; Kim, Katherine K; Bold, Richard J; Joseph, Jill G | Abstract: BackgroundRecent reports call for reductions in costly and potentially avoidable services such as emergency department (ED) visits. Providing high-quality and safe care for oncology patients remains challenging for ED providers given the diversity of patients seeking care and the unpredictable clinical environment. While ED use by oncology patients is appropriate for acute health concerns, some ED visits may be preventable with well-coordinated care and adequate symptom management.ObjectiveThe aim of this study was to summarize available evidence regarding the incidence, predictors of, and reasons for ED visits among oncology patients.MethodsKeyword/MeSH term searches were conducted using 4 online databases. Inclusion criteria were publication date between April 1, 2003, and December 5, 2014; sample size of 50 or more; and report of the incidence or predictors of ED use among oncology patients.ResultsThe 15 studies that met criteria varied in study aim, design, and time frames for calculating ED utilization rates. The incidence of ED visits among oncology patients ranged from 1% to 83%. The 30-day standardized visit rate incidence ranged from 1% to 12%. Collectively, the studies lack population-based estimates for all cancers combined.ConclusionsThe studies included in this review suggest that rates of ED use among cancer patients exceed those of the general population. However, the extent of ED use by oncology patients and the reasons for ED visits remain understudied.Implications for practiceNurses are involved in the treatment of cancer, patient education, and symptom management. Nurses are well positioned to develop patient-centered treatment and care coordination plans to improve quality of care and reduce ED visits.

To review the existing literature on readmission rates, predictors, and reasons for readmission among adults with cancer. .U.S.-based empirical studies reporting readmission rates from January 2005 to December 2015 were identified using four online library databases-PubMed, CINAHL®, EconLit, and the online bibliography of the National Cancer Institute's Surveillance Epidemiology and End Results Program. Some articles were identified by the authors outside the database and bibliography searches. .Of the 1,219 abstracts and 271 full-text articles screened, 56 studies met inclusion criteria. The highest readmission rates were observed in patients with bladder, pancreatic, ovarian, or liver cancer. Significant predictors of readmission included comorbidities, older age, advanced disease, and index length of hospital stay. Common reasons for readmission included gastrointestinal and surgical complications, infection, and dehydration. .Clinical efforts to reduce the substantial readmission rates among adults with cancer may target high-rate conditions, infection prevention, proactive management of nausea and vomiting, and nurse-led care coordination interventions for older adult patients with multiple comorbid conditions and advanced cancer. .Commonly reported reasons for readmission were nursing-sensitive patient outcomes (NSPOs), amenable to nursing intervention in oncology settings. These findings underscore the important role oncology nurses play in readmission prevention by implementing evidence-based interventions to address NSPOs and testing their impact in future research.

To examine associations between parental military service and school-based weapon carrying, school-based physical fighting and gang membership among youth. We used cross-sectional data from the 2008 Washington State Healthy Youth Survey collected in 8th, 10th, and 12th grades of public schools (n = 9,987). Parental military service was categorized as none (reference group), without combat zone deployment, or deployed to a combat zone. Multivariable logistic regression was used to test associations between parental military service and three outcomes: school-based weapon carrying, school-based physical fighting and gang membership. Standard errors were adjusted for the complex survey design. In 8th grade, parental deployment was associated with higher odds of reporting gang membership (OR = 1.8) among girls, and higher odds of physical fighting (OR = 1.6), and gang membership (OR = 1.9) among boys. In 10th/12th grade, parental deployment was associated with higher odds of reporting physical fighting (OR = 2.0) and gang membership (OR = 2.2) among girls, and physical fighting (OR = 2.0), carrying a weapon (OR = 2.3) among boys. Parental military deployment is associated with increased odds of reporting engagement in school-based physical fighting, school-based weapon carrying, and gang membership, particularly among older youth. Military, school, and public health professionals have a unique, collaborative opportunity to develop school- and community-based interventions to prevent violence-related behaviors among youth and, ultimately, improve the health and safety of youth in military families. Ideally, such programs would target families and youth before they enter eighth grade.