Measuring financial toxicity as a clinically relevant patient-reported outcome: The validation of the COmprehensive Score for financial Toxicity (COST).

BACKGROUND: Cancer and its treatment lead to increased financial distress for patients. To the authors' knowledge, to date, no standardized patient-reported outcome measure has been validated to assess this distress. METHODS: Patients with AJCC Stage IV solid tumors receiving chemotherapy for at least 2 months were recruited. Financial toxicity was measured by the COmprehensive Score for financial Toxicity (COST) measure. The authors collected data regarding patient characteristics, clinical trial participation, health care use, willingness to discuss costs, psychological distress (Brief Profile of Mood States [POMS]), and health-related quality of life (HRQOL) as measured by the Functional Assessment of Cancer Therapy: General (FACT-G) and the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires. Test-retest reliability, internal consistency, and validity of the COST measure were assessed using standard-scale construction techniques. Associations between the resulting factors and other variables were assessed using multivariable analyses. RESULTS: A total of 375 patients with advanced cancer were approached, 233 of whom (62.1%) agreed to participate. The COST measure demonstrated high internal consistency and test-retest reliability. Factor analyses revealed a coherent, single, latent variable (financial toxicity). COST values were found to be correlated with income (correlation coefficient [r] = 0.28; P<.001), psychosocial distress (r = -0.26; P<.001), and HRQOL, as measured by the FACT-G (r = 0.42; P<.001) and by the EORTC QOL instruments (r = 0.33; P<.001). Independent factors found to be associated with financial toxicity were race (P = .04), employment status (P<.001), income (P = .003), number of inpatient admissions (P = .01), and psychological distress (P = .003). Willingness to discuss costs was not found to be associated with the degree of financial distress (P = .49). CONCLUSIONS: The COST measure demonstrated reliability and validity in measuring financial toxicity. Its correlation with HRQOL indicates that financial toxicity is a clinically relevant patient-centered outcome. Cancer 2017;123:476-484. © 2016 American Cancer Society.

What advanced cancer patients with limited treatment options know about clinical research: a qualitative study.

PURPOSE: Discussions between oncologists and advanced cancer patients (ACPs) may touch on the complex issue of clinical trial participation. Numerous initiatives have sought to improve the quality of these potentially difficult conversations. However, we have limited data about what ACPs know about clinical research as they enter such discussions as, to date, such research has focused on the period following informed consent. This study examines ACPs' understanding of clinical research in the treatment period before consent. METHODS: We conducted in-depth interviews with adult ACPs with limited treatment options at four clinics in an academic medical center. So as not to influence patients' perspectives, interviewers probed patients' knowledge of clinical research only if the patient first brought up the topic. Interviews (40-60 min) were audio-recorded, transcribed, and analyzed thematically and via quantitative content analysis by an interdisciplinary team. RESULTS: Of 78 patients recruited, 56 (72%) spontaneously brought up the topic of clinical research during interview and are included in this analysis. Qualitative thematic analysis and quantitative content analysis revealed that patients' knowledge varied in terms of (1) accuracy and (2) specificity (level of detail). ACPs who spoke with high specificity were not always accurate, and ACPs with accurate knowledge included both high- and low-specificity speakers. CONCLUSIONS: ACPs' knowledge of clinical research is variable. Patients who can discuss the technical details of their care may or may not understand the broader purpose and procedures of clinical trials. Understanding this variability is important for improving patient-provider communication about clinical research and supporting efforts to provide individualized care for ACPs.

Psychological morbidities in adolescent and young adult blood cancer patients during curative-intent therapy and early survivorship.

BACKGROUND: Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative-intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients. METHODS: Patients aged 15 to 39 years with acute leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma who were undergoing curative-intent therapy (on-treatment group) or were in remission within 2 years of therapy completion (early survivors) underwent a semistructured interview that incorporated measures of anxiety, depression, and posttraumatic stress (PTS). A subset of providers (n = 15) concomitantly completed a survey for each of the first 30 patients enrolled that evaluated their perception of each subject's anxiety, depression, and PTS. RESULTS: Sixty-one of 77 eligible AYAs participated. The median age at diagnosis was 26 years (range, 15-39 years), 64% were male, and 59% were non-Hispanic white. On-treatment demographics differed significantly from early-survivor demographics only in the median time from diagnosis to interview. Among the 61 evaluable AYAs, 23% met the criteria for anxiety, 28% met the criteria for depression, and 13% met the criteria for PTS; 46% demonstrated PTS symptomatology. Thirty-nine percent were impaired in 1 or more psychological domains. Psychological impairments were as frequent among early survivors as AYAs on treatment. Provider perceptions did not significantly correlate with patient survey results. CONCLUSIONS: AYAs with hematologic malignancies experience substantial psychological morbidities while they are undergoing therapy and during early survivorship, with more than one-third of the patients included in this study meeting the criteria for anxiety, depression, or traumatic stress. This psychological burden may not be accurately identified by their oncology providers.

General internists' preferences and knowledge about the care of adult survivors of childhood cancer: a cross-sectional survey.

BACKGROUND: Adult childhood cancer survivors (CCSs) are at high risk for illness and premature death. Little is known about the physicians who provide their routine medical care. OBJECTIVE: To determine general internists' self-reported attitudes and knowledge about the care of CCSs. DESIGN: Cross-sectional survey. SETTING: Mailed survey delivered between September 2011 and August 2012. PARTICIPANTS: Random sample of 2000 U.S. general internists. MEASUREMENTS: Care preferences, comfort levels with caring for CCSs (7-point Likert scale: 1 = very uncomfortable, 7 = very comfortable), familiarity with available surveillance guidelines (7-point Likert scale: 1 = very unfamiliar, 7 = very familiar), and concordance with Children's Oncology Group Long-Term Follow-Up Guidelines in response to a clinical vignette. RESULTS: The response rate was 61.6% (1110 of 1801). More than half the internists (51.1%) reported caring for at least 1 CCS; 72.0% of these internists never received a treatment summary. On average, internists were "somewhat uncomfortable" caring for survivors of Hodgkin lymphoma, acute lymphoblastic leukemia, and osteosarcoma. Internists reported being "somewhat unfamiliar" with available surveillance guidelines. In response to a clinical vignette about a young adult survivor of Hodgkin lymphoma, 90.6% of respondents did not appropriately recommend yearly breast cancer surveillance, 85.1% did not appropriately recommended cardiac surveillance, and 23.6% did not appropriately recommend yearly thyroid surveillance. Access to surveillance guidelines and treatment summaries were identified as the most useful resources for caring for CCSs. LIMITATION: Findings, based on self-report, may not reflect actual clinical practice. CONCLUSION: Although most general internists report involvement in the care of CCSs, many seem unfamiliar with available surveillance guidelines and would prefer to follow patients in collaboration with a cancer center. PRIMARY FUNDING SOURCE: National Cancer Institute.

The development of a financial toxicity patient-reported outcome in cancer: The COST measure.

BACKGROUND: Considering patients' experience is essential for optimal decision-making. However, despite increasing recognition of the impact of costs on oncology care, there is no patient-reported outcome measure (PROM) that specifically describes the financial distress experienced by patients. METHODS: The content for a comprehensive score for financial toxicity (COST) was developed with a stepwise approach: step 1) a literature review and semistructured, qualitative interviews with patients for content generation; step 2) patients' assessment of the items for importance to their quality of life; step 3) pilot testing assessing interitem (IIC) and item-total (ITC) correlations to identify redundancy (Spearman rho, > 0.7) and statistically unrelated content (P > .05); and step 4) exploratory factor analysis. Sociodemographic data were collected. RESULTS: In total, 155 patients with advanced cancer who were receiving treatment (20 patients in step 1, 35 patients in step 2, and 100 patients in steps 3 and 4) participated in the PROM development. In step 1, the literature was reviewed, and 20 patients generated 147 items, which were reduced to 58 items because of redundancy. In step 2, 35 patients rated the 58 items on importance, and 30 items were retained. In step 3, 46 patients assessed the 30 items, 14 items were excluded because of high IIC, and 3 were excluded because of nonsignificant ITC. In step 4, 2 items were discarded because of poor loadings in a factor analysis of 100 patients, resulting in an 11-item PROM. CONCLUSIONS: The content for a financial toxicity PROM was developed in 155 patients. The provisional COST measure demonstrated face and content validity as well as internal consistency and should be validated in larger samples.

When parents disclose BRCA1/2 test results: their communication and perceptions of offspring response.

BACKGROUND: BRCA1/2 testing is not recommended for children, as risk reduction measures and screening are not generally recommended before 25 years old (YO). Little is known about the prevalence and predictors of parent communication to offspring and how offspring respond to this communication. METHODS: Semi-structured interviews were conducted with parents who had BRCA1/2 testing and at least 1 child <25 YO. Logistic regressions were utilized to evaluate associations with communication. Framework analysis was utilized to analyze open-ended responses. RESULTS: A total of 253 parents completed interviews (61% response rate), reporting on 505 offspring. Twenty-nine percent of parents were BRCA1/2 mutation carriers. Three hundred thirty-four (66%) offspring learned of their parent's test result. Older offspring age (P ≤ .01), offspring gender (female, P = .05), parents' negative test result (P = .03), and parents' education (high school only, P = .02) were associated with communication to offspring. The most frequently reported initial offspring responses were neutral (41%) or relief (28%). Thirteen percent of offspring were reported to experience concern or distress (11%) in response to parental communication of their test results. Distress was more frequently perceived among offspring learning of their parent's BRCA1/2 positive or variant of uncertain significance result. CONCLUSIONS: Many parents communicate their BRCA1/2 test results to young offspring. Parents' perceptions of offspring responses appear to vary by offspring age and parent test result. A better understanding of how young offspring respond to information about hereditary risk for adult cancer could provide opportunities to optimize adaptive psychosocial responses to risk information and performance of health behaviors, in adolescence and throughout an at-risk life span.

Physician preferences and knowledge regarding the care of childhood cancer survivors in Japan: a mailed survey of the Japanese Society of Pediatric Oncology.

OBJECTIVE: Japanese physicians' attitudes regarding the health-care needs of young adult childhood cancer survivors (CCSs) are not well described. Thus, we examined the self-reported preferences and knowledge of pediatric oncologists and surgeons. METHODS: A mailed survey was sent to 858 physician members of the Japanese Society of Pediatric Oncology. We compared the responses of pediatric oncologists and pediatric surgeons. RESULTS: The pediatric oncologists' response rate was 56% (300 out of 533) and that of pediatric surgeons 32% (105 out of 325). The median age of respondents was 46 and 48 years, respectively; 79 and 84% were men. When comfort levels in caring for CCSs were described (i.e. 1 = very uncomfortable; 7 = very comfortable), the mean levels were 4.4 and 3.8 with CCSs ≤ 21 years, 3.6 and 3.6 with 21 years < CCSs ≤ 30 years, and 2.8 and 3.3 with CCSs > 30 years, respectively. In clinical vignette questions, 62% of the pediatric oncologists and 43% of the surgeons answered three or more questions appropriately. Pediatric surgeons reported significantly lower familiarity with long-term follow-up guidelines than pediatric oncologists. Most pediatric oncologists and many surgeons conducted truth-telling of cancer diagnosis to adult CCSs now. They thought that the most important issues are an original long-term follow-up guideline suitable for the Japanese situation and collaborations with adult-based general physicians. CONCLUSIONS: Many Japanese pediatric oncologists are uncomfortable with caring for survivors as they age and have suboptimal knowledge regarding late effects. The change in truth-telling situation and preference for collaboration with adult-based physicians was demonstrated also in Japan.

Utilization of an Electronic Patient-Reported Outcome Platform to Evaluate the Psychosocial and Quality-of-Life Experience Among a Community Sample of Ovarian Cancer Survivors.

PURPOSE: Novel distress screening approaches using electronic patient-reported outcome (ePRO) measurements are critical for the provision of comprehensive quality community cancer care. Using an ePRO platform, the prevalence of psychosocial factors (distress, post-traumatic growth, resilience, and financial stress) affecting quality of life in ovarian cancer survivors (OCSs) was examined. METHODS: A cross-sectional OCS sample from the National Ovarian Cancer Coalition-Illinois Chapter completed web-based clinical, sociodemographic, and psychosocial assessment using well-validated measures: Hospital Anxiety/Depression Scale-anxiety/depression, Post-traumatic Growth Inventory, Brief Resilience Scale, comprehensive score for financial toxicity, and Functional Assessment of Cancer Therapy-Ovarian (FACT-O/health-related quality of life [HRQOL]). Correlational analyses between variables were conducted. RESULTS: Fifty-eight percent (174 of 300) of OCS completed virtual assessment: median age 59 (range 32-83) years, 94.2% White, 60.3% married/in domestic partnership, 59.6% stage III-IV, 48.8% employed full-time/part-time, 55.2% had college/postgraduate education, 71.9% completed primary treatment, and median disease duration 6 (range < 1-34) years. On average, OCS endorsed normal levels of anxiety (mean ± standard deviation = 6.9 ± 3.8), depression (4.1 ± 3.6), mild total distress (10.9 ± 8.9), high post-traumatic growth (72.6 ± 21.5), normal resilience (3.7 ± 0.72), good FACT-O-HRQOL (112.6 ± 22.8), and mild financial stress (26 ± 10). Poor FACT-O emotional well-being was associated with greater participant distress (P < .001). Partial correlational analyses revealed negative correlations between FACT-O-HRQOL and anxiety (r = -0.65, P < .001), depression (r = -0.76, P < .001), and total distress (r = -0.92, P < .001). Yet, high FACT-O-HRQOL was positively correlated with post-traumatic coping (r = 0.27; P = .006) and resilience (r = 0.63; P < .001). CONCLUSION: ePRO assessment is feasible for identification of unique psychosocial factors, for example, financial toxicity and resilience, affecting HRQOL for OCS. Future investigation should explore large-scale, longitudinal ePRO assessment of the OCS psychosocial experience using innovative measures and community-based advocacy populations.

Anxiety Shapes Expectations of Therapeutic Benefit in Phase I Trials for Patients With Advanced Cancer and Spousal Caregivers.

PURPOSE: Advanced cancer patients (ACP) hope to receive significant therapeutic benefit from phase I trials despite terminal disease and presumed symptom burdens. We examined associations between symptom burdens and expectations of therapeutic benefit for ACP and spousal caregivers (SC) during phase I trials. PATIENTS AND METHODS: A prospective cohort of ACP-SC enrolled in phase I trials was assessed at baseline and one month using symptom burden measures evaluating depression, state-trait anxiety, quality of life, global health, post-traumatic coping, and marital adjustment. Interviews evaluated expectations of benefit. RESULTS: Fifty-two phase I ACP and 52 SC (N = 104) were separately assessed and interviewed at baseline and one month. Total population demographics included the following: median age 61 years (28-78), 50% male, 100% married, 90% White, and 46% ≥ college education. At T1, ACP reported symptoms of mild state anxiety, mild trait anxiety, poor global health, and quality of life. SC reported moderate state and mild trait anxiety and good global health with little disability at baseline. State anxiety was a significant predictor of ACP expectations for phase I producing the following therapeutic benefits: stabilization (P = .01), shrinkage (P < .01), and remission (P = .04). Regression analyses also revealed negative associations between SC expectation for stabilization and SC anxiety: state (P = .01) and trait (P = .02). ACP quality of life was also negatively associated with SC expectations for stabilization (P = .02) and shrinkage (P = .01). CONCLUSION: Anxiety, both state and trait, impacts couples' beliefs regarding the likelihood of therapeutic benefit from phase I trial participation.

A Qualitative Analysis of Oncology Patient Awareness of Medication Shortages and Their Preferences for How Shortages Should Be Managed.

PURPOSE: Medication shortages in US hospitals are ongoing, widespread, and frequently involve antineoplastic and supportive medications used in cancer care. The ways shortages are managed and the ways provider-patient communication takes place are heterogeneous, but the related preferences of oncology patients are undefined. This study sought to qualitatively evaluate patient preferences. METHODS: A cross-sectional, semi-structured interview study was conducted from January to June 2019. Participants were adult oncology inpatients who received primary cancer care at the University of Chicago, had undergone treatment within 2 years, and had 1 or more previous hospitalizations during that period. Participants (n = 54) were selected consecutively from alternating hematology and oncology services. The primary outcome was thematic saturation across the domains of awareness of medication shortages, principle preferences regarding decision makers, preferences regarding allocation of therapy drugs, and allocation-related communication. RESULTS: Thematic saturation was reached after 39 participants completed the study procedures (mean age, 59.6 years [standard deviation, 14.5 years]; men made up 61.5% of the study population [mean age, 24 years]; response rate, 72.0%). In all, 18% of participants were aware of institutional medication shortages. Patients preferred having multiple decision makers for allocating medications in the event of a shortage. A majority of patients named oncologists (100%), ethicists (92%), non-oncology physicians (77%), and pharmacists (64%) as their preferred decision makers. Participants favored allocation of drugs based on their efficacy (normalized weighted average, 1.3), and they also favored prioritizing people who were already receiving treatment (1.8), younger patients (2.0), sicker patients (3.1), and those presenting first for treatment (5.3). Most participants preferred preferred disclosure of supportive care medication shortages (74%) and antineoplastic medication shortages (79%) for equivalent substitutions. CONCLUSION: In a tertiary-care center with medication shortages, few oncologic inpatients were aware of shortages. Participants preferred having multiple decision makers involved in principle-driven allocation of scarce medications. Disclosure was preferred when their usual medications needed to be substituted with equivalent alternatives. These preliminary data suggest that preferences do not align with current management practices for medication shortages.

A Cross-Sectional Survey of Medical Trainee Experiences During Medication Shortages.

BACKGROUND: Medication shortages prevent patients from receiving optimal care. Despite the frequency with which medical trainees care for inpatients, no assessment of their experiences in medication shortage management has been performed. OBJECTIVE: We evaluated trainees' experiences managing medication shortages. METHODS: We performed a cross-sectional survey of trainees postgraduate year 2 (PGY-2) and above in medicine, anesthesiology, and emergency medicine departments at 2 academic centers in 2018-2019. Categorical and ordinal assessments evaluated shortage awareness, substitution availability, pharmacy and therapeutics committee-based restrictions, communication, and education. Regressions were performed to determine effect of PGY, department, and institution on responses. RESULTS: A total of 168 of 273 subjects completed the survey (62% response rate). Most (95%, 159 of 168) reported managing medication shortages during training; 51% (86 of 168) described managing clinically relevant shortages daily or weekly. Seventy-seven percent (129 of 168) noted equivalent alternatives were unavailable at least one-quarter of the time, and 43% (72 of 168) reported clinically necessary medications were restricted at least weekly. Fifty-four percent (89 of 168) and 64% (106 of 167) of respondents discussed clinically relevant shortages with supervising physicians or patients "some of the time" or less, respectively. Most respondents (90%, 151 of 168) reported they would benefit from shortage management training, but few (13%, 21 of 168) reported prior training. CONCLUSIONS: Although trainees reported frequent involvement in clinically impactful shortage management, medication shortage communication between trainees and supervising physicians or patients appears sporadic. Medication shortage management training is uncommon but perceived as beneficial.

Before Consent: Qualitative Analysis of Deliberations of Patients With Advanced Cancer About Early-Phase Clinical Trials.

PURPOSE: Patients with advanced cancer and oncologists deliberate about early-phase (EP) trials as they consider whether to pursue EP trial enrollment. We have limited information about those deliberations and how they may facilitate or impede trial initiation. This study describes these deliberations and their relationship to trial initiation. PATIENTS AND METHODS: We collected longitudinal, ethnographic data on deliberations of patients with advanced cancer at two academic medical centers. We used constant comparative and framework analyses to characterize the deliberative process and its relationship to trial initiation. RESULTS: Of 96 patients with advanced cancer, 26% initiated EP enrollment and 19% joined a trial. Constant comparative analysis revealed two foci of deliberation. Setting the stage focused on patient and physician support for EP trial involvement, including patients' interest in research and oncologists' awareness of trials and assessment of patient fit. Securing a seat focused on eligibility for and entrance to a specific trial and involved trial availability, treatment history, disease progression, and enrollment timing. Patients enrolled in a trial only when both stages could be successfully navigated. CONCLUSION: Ethnographic data revealed two foci of deliberation about EP trial enrollment among patients with advanced cancer. Physician support played a consequential role in both stages, but enrollment also reflected factors beyond the control of any specific individual. Insights from this study, combined with other recent studies of trial enrollment, advance our understanding of the complex process of EP trial accrual and may help identify strategies to improve rates of participation.

Learning of your parent's BRCA mutation during adolescence or early adulthood: a study of offspring experiences.

OBJECTIVE: To examine the experience, comprehension and perceptions of learning of a parent's BRCA mutation during adolescence and early adulthood, and explore the impact on offspring's physical and psychosocial well-being. METHODS: Semi-structured interviews were completed with 22 adult offspring who learned of their parent's BRCA mutation prior to age 25 years. Data were summarized using qualitative methods and response proportions. RESULTS: Offspring reports of the content shared varied; discussion of cancer risks and offspring genetic testing were described more frequently than risk modification strategies. The majority of offspring reported a good understanding of the information shared and no negative aspects for learning this information. Some offspring reported changing their health behaviors after learning of the familial mutation; many tobacco users stopped smoking. Offspring interest in genetic counseling surrounding parent disclosure and genetic testing during adulthood were high. CONCLUSIONS: Some offspring understand and respond adaptively to early communication of a genetic risk for cancer, and disclosure may foster improved health behaviors during adolescence and young adulthood. Further research is necessary to evaluate how offspring conceptualize and utilize genetic risk and to identify the biopsychosocial factors predictive of adaptive/maladaptive responses to early disclosure of hereditary risk for adult cancer.

Should genetic testing for BRCA1/2 be permitted for minors? Opinions of BRCA mutation carriers and their adult offspring.

Although professional guidelines recommend against testing minors for adult-onset genetic conditions, the genetic testing of minors for BRCA1/2 alterations has been debated in the literature. To better understand the opinions of BRCA mutation carriers regarding the genetic testing of minors and the cognitive and affective processes underlying these opinions, we interviewed BRCA mutation carriers and their adult offspring who had learned of their parent's BRCA mutation. Semi-structured interviews were conducted with 53 parents and 22 offspring. In response to a closed-ended question, 52% (n = 39) of participants were opposed to the testing of minors. Responses to an open-ended question indicate that many participants (24%, n = 18) feel that testing could be permitted for some minor offspring. Psychological risks and the insufficient maturity of minors were frequent concerns of participants opposed to testing minors. The potential to impact health behaviors was frequently cited as a reason to support the genetic testing of minors. These preliminary results suggest that many BRCA mutation carriers and their adult offspring have concerns about, or are opposed to the genetic testing of minors. However, a significant minority in our study would support testing minors. Greater support for testing among offspring could indicate increasing requests for early genetic diagnosis. Further research is necessary to explore the risks and benefits of providing genetic testing to minors for adult-onset hereditary cancer syndromes in order to inform clinical practice and public policy and to ensure optimal psychosocial and medical outcomes for all members in families at risk for genetically determined disease.

An international pilot study of oncology physicians' opinions and practices on Complementary and Alternative Medicine (CAM).

BACKGROUND: In China and Taiwan, Complementary and Alternative Medicine (CAM) therapies such as traditional Chinese medicine have been an option to cancer patients for centuries, whereas in the United States, CAM has been growing in popularity only in the past few decades. Prior research has indicated that the prevalence of CAM use among cancer patients may exceed 80%. Because of a long cultural history of CAM, we hypothesized that oncologists in China and Taiwan (C/T) would communicate and combine CAM with conventional treatments more often than US oncologists. METHODS: In 2004-2005, a convenience sample of oncologists from the United States, mainland China, and Taiwan were surveyed regarding their opinions and self-reported practice patterns regarding CAM. RESULTS: A total 95 oncologists returned surveys, providing a 38% response rate. Four out of 5 respondents (78%) felt their medical training was inadequate to use CAM. However, 70% reported they would allow CAM use during active cancer treatment, even in the setting of curable disease. Responding C/T oncologists tended to ask patients more frequently (they ask > 25% of patients) about CAM use and recommended CAM more commonly (recommend to > 10%) to patients than surveyed US oncologists, 55% versus 37% (P = .09) and 81% versus 53% (P < .05). Respondents from the United States felt no more prepared for CAM use than C/T respondents, but 70% reported willingness to combine CAM with conventional treatments for curable disease as compared with only 48% (P < .05) of C/T oncologists. CONCLUSIONS: As expected, responding C/T oncologists communicate more often about CAM with patients by asking and recommending CAM. However, contrary to our original hypothesis, C/T oncologists reported a much lower rate of combining CAM with conventional treatment among curable patients than responding US oncologists. Further research is needed to explore, in depth, the reasons for differences in CAM practice patterns among oncologists.

Investigator Disclosure and Advanced Cancer Patient Understanding of Informed Consent and Prognosis in Phase I Clinical Trials.

PURPOSE: Advanced cancer patients (ACPs) who participate in phase I clinical trials often report a less-than-ideal understanding of the required elements of informed consent (IC) and unrealistic expectations for anticancer benefit and prognosis. We examined phase I clinical trial enrollment discussions and their associations with subsequent ACP understanding. METHODS: Clinical encounters about enrollment in phase I trials between 101 ACPs and 29 oncologists (principal investigators [PIs] and fellows) at three US academic medical institutions were recorded. The Roter Interaction Analysis System was used for analysis. ACPs completed follow-up questionnaires to assess IC recall. RESULTS: PIs disclosed the following phase I IC elements to ACPs in encounters: trial purpose in 40%; specific physical risks in 60%; potential specific medical benefits gained by trial participation (eg, disease stabilization) in 48.2%; and alternatives to phase I trial participation in 47.1%, with 1.1% of encounters containing palliative and 2.3% hospice information. PIs provided ACP-specific prognoses in 29.0% of encounters but used precise terms of death in only 4.7% and terminal in 1.2%. A significant association existed between PI disclosure of the trial purpose as dosage/toxicity, and ACPs subsequently correctly recalled trial purpose versus PIs who did not disclose it (85% v 13%; P < .05). CONCLUSION: Many oncologists provide incomplete disclosures about phase I trials to ACPs. When disclosure of certain elements of IC occurs, it seems to be associated with better recall, especially with regard to the research purpose of phase I trials.

Do Patients With Advanced Cancer Have the Ability to Make Informed Decisions for Participation in Phase I Clinical Trials?

Purpose Patients with advanced cancer (ACPs) participating in phase I clinical trials inadequately understand many elements of informed consent (IC); however, the prevalence and impact of cognitive impairment has not been described. Patients and Methods ACPs enrolled onto phase I trials underwent neuropsychological assessment to evaluate cognitive functioning (CF) covering the following domains: memory (Hopkins Verbal Learning Test), executive functioning (Trail Making Test B), language (Boston Naming Test-Short Version and Controlled Oral Word Association Test), attention (Trail Making Test A and Wechsler Adult Intelligenence Scale-IV Digit Span), comprehension (Wechsler Adult Intelligence Scale-IV), and quality of life (Functional Assessment of Cancer Therapy-Cognitive Function). Structured interviews evaluated IC and decisional capacity. Psychological measures included distress (Hospital Anxiety Depression Scale) and depression (Beck Depression Inventory-II). Results One hundred eighteen ACPs on phase I trials were evaluated, with CF ranging from mild impairment to superior performance. Only 45% of ACPs recalled physician disclosure of the phase I trial purpose. The 50% of ACPs who correctly identified the phase I research purpose had greater CF compared with ACPs who did not, as revealed by the mean T scores for memory (37.2 ± 5.6 v 32.5 ± 5.1, respectively; P = .001), attention (29 ± 2.7 v 26.9 ± 2.4, respectively; P < .001), visual attention (35.2 ± 6.6 v 31.5 ± 6.2, respectively; P = .001), and executive function (38.9 ± 7.5 v 34 ± 7.1, respectively; P < .001). Older ACPs (≥ 60 years) were less likely to recall physician disclosure of phase I purpose than younger ACPs (30% v 70%, respectively; P = .02) and had measurable deficits in total memory (34.2 ± 5.0 v 37.3 ± 5.6, respectively; P = .002), attention (24.5 ± 2.6 v 28 ± 2.8, respectively; P < .001), and executive function (32.8 ± 7.3 v 36.4 ± 7.6, respectively; P = .01). Older ACPs, compared with younger ACPs, also had greater depression scores (10.6 ± 9.2 v 8.1 ± 5.2, respectively; P = .03) and lower quality-of-life scores (152 ± 29.6 v 167 ± 20, respectively; P = .03). After adjustment by age, no psychological or neuropsychological variable was further significantly associated with likelihood of purpose identification. Conclusion CF seems to play a role in ACP recall and comprehension of IC for early-phase clinical trials, especially among older ACPs.

Prognostic tumor sequencing panels frequently identify germ line variants associated with hereditary hematopoietic malignancies.

Next-generation sequencing (NGS)-based targeted gene capture panels are used to profile hematopoietic malignancies to guide prognostication and treatment decisions. Because these panels include genes associated with hereditary hematopoietic malignancies (HHMs), we hypothesized that these panels could identify pathogenic germ line variants in malignant cells, thereby identifying patients at risk for HHMs. In total, pathogenic or likely pathogenic variants in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, or TP53 were identified in 74 (21%) of 360 patients. Germ line tissue was available for 24 patients with 25 pathogenic or likely pathogenic variants with variant allele frequencies >0.4. Six (24%) of these 25 variants were of germ line origin. Three DDX41 variants, 2 GATA2 variants, and a TP53 variant previously implicated in Li-Fraumeni syndrome were of germ line origin. No likely pathogenic/pathogenic germ line variants possessed variant allele frequencies <0.4. This study demonstrates that NGS-based prognostic panels may identify individuals at risk for HHMs despite not being designed for this purpose. Furthermore, variants known to cause Li-Fraumeni syndrome as well as known pathogenic variants in genes such as DDX41 and GATA2 are especially likely to be of germ line origin. Thus, tumor-based panels may augment, but should not replace, comprehensive germ line-based testing and counseling.