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.

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Combination therapy with E/P is safe in mUC and select patients with alterations in mTOR or FGFR pathways derive significant clinical benefit.

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Objective Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers’ quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. Method Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. Results Four key themes emerged from interviews: (1) MCP-C validated caregivers’ experience of caregiving; (2) MCP-C helped participants reframe their “caregiving identity” as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers’ openness to discussing death and engaging in advanced care planning discussions with the patient. Significance of results The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

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Objective: In patients with cancer across the illness trajectory, treatment decisions are often influenced by one's perception of their prognosis (i.e., curability of disease, life expectancy, quality of life). However, research on how patients understand their prognosis (i.e., prognostic understanding) has been limited by simplistic measurement tools that fail to capture the complexity of the construct. This study describes the initial development of a measure of prognostic understanding: the Prognostic Understanding Perceptions Scale (PUPS) for use in patients with advanced cancer.Method: An initial pool of 16 candidate items were developed through semistructured interviews with 15 experts (oncology, psycho-oncology and palliative care professionals) and 30 advanced cancer patients. We investigated the dimensionality, internal item structure, item difficulty and item discrimination of the item pool using exploratory factor analysis (EFA), classical test theory (CTT) and item response theory (IRT) analyses. Convergent and divergent validity were based on correlations between PUPS, terminal illness acknowledgement, and self-report measures of depression, anxiety, hopelessness, and death acceptance. Results:The final measure was comprised of nine items encompassing three factors (perceived curability, illness trajectory, treatment options), yielding strong psychometric properties. Conclusion:These results provide preliminarily support for PUPS as a multifaceted measure of prognostic understanding developed for use in patients with advanced cancer. Preliminary findings also highlight the potential utility of the PUPS for clinical settings, as a means of enhancing communication between patients and physicians.