Communication between Caregivers of Adults with Cancer and Healthcare Professionals: a Review of Communication Experiences, Associated Factors, Outcomes, and Interventions.

PURPOSE OF REVIEW: Family/unpaid caregivers play an important role in cancer care. This review aims to summarize caregiver communication experiences with healthcare professionals (HCPs). RECENT FINDINGS: The Caregiver-Centered Communication model defines five core functions that HCPs should achieve when interacting with caregivers, including fostering relationships, exchanging information, recognizing and responding to caregiver emotions, aiding in decision making, and assisting in patient care management. The literature shows that caregivers have both positive and negative communication experiences with HCPs with respect to these five core functions. Factors at the caregiver (e.g., demographic characteristics, information sources, caregiving duration, health status), patient (e.g., demographic and clinical characteristics), and HCP levels (e.g., time constraints in clinical settings, communication skills) are associated with caregiver-HCP communication quality. Studies further show that these communication experiences may affect caregiver outcomes, including quality of life, mental health, resilience, and satisfaction with cancer care. Moreover, poor quality caregiver-HCP communication is associated with patient readmission to the hospital and unmet care needs. Interventions for caregivers or patient-caregiver dyads have been shown to enhance caregiver confidence and increase their engagement in communication with HCPs. Interventions for HCPs have shown efficacy in improving their communication skills, particularly in involving caregivers in decision-making discussions. Given time constraints during medical visits, we suggest conducting a caregiver assessment by navigators prior to visits to understand their communication needs. Additionally, reimbursing HCPs for time spent communicating with caregivers during visits could be beneficial. More research is needed to better understand how to enhance caregiver-HCP communication quality.

HE4 Overexpression by Ovarian Cancer Promotes a Suppressive Tumor Immune Microenvironment and Enhanced Tumor and Macrophage PD-L1 Expression.

Ovarian cancer is a highly fatal malignancy characterized by early chemotherapy responsiveness but the eventual development of resistance. Immune targeting therapies are changing treatment paradigms for numerous cancer types but have had minimal success in ovarian cancer. Through retrospective patient sample analysis, we have determined that high human epididymis protein 4 (HE4) production correlates with multiple markers of immune suppression in ovarian cancer, including lower CD8+ T cell infiltration, higher PD-L1 expression, and an increase in the peripheral monocyte to lymphocyte ratio. To further understand the impact that HE4 has on the immune microenvironment in ovarian cancer, we injected rats with syngeneic HE4 high- and low-expressing cancer cells and analyzed the differences in their tumor and ascites immune milieu. We found that high tumoral HE4 expression promotes an ascites cytokine profile that is rich in myeloid-recruiting and differentiation factors, with an influx of M2 macrophages and increased arginase 1 production. Additionally, CTL activation is significantly reduced in the ascites fluid, and there is a trend toward lower CTL infiltration of the tumor, whereas NK cell recruitment to the ascites and tumor is also reduced. PD-L1 expression by tumor cells and macrophages is increased by HE4 through a novel posttranscriptional mechanism. Our data have identified HE4 as a mediator of tumor-immune suppression in ovarian cancer, highlighting this molecule as a potential therapeutic target for the treatment of this devastating disease.

The shared uncertainty experience of older adults with advanced cancer and their caregivers.

OBJECTIVE: One primary source of psychological distress in patients with cancer and their caregivers is uncertainty. However, the uncertainty trajectory and its relationship between older adults with advanced cancer and their caregivers have rarely been examined. This study describes the uncertainty trajectory in patient-caregiver dyads, explores the effect of geriatric assessment (GA) intervention on trajectory, and examines the interdependent relationship of uncertainty. METHODS: This secondary analysis used longitudinal data from a national cluster-randomized controlled trial examining a GA intervention compared to usual care. Participants completed the modified 9-item Mishel Uncertainty in Illness Scale at enrollment, 4-6 weeks, 3 months, and 6 months. The dyadic growth model and cross-lagged actor-partner interdependence model were used. RESULTS: A total of 397 dyads (patient age M = 76.81 ± SD5.43; caregiver age M = 66.69 ± SD12.52) were included. Both had a trend of decreased uncertainty over time (b = -0.16, p < 0.01). There was a greater decrease in uncertainty among caregivers in the GA group than those in the usual care group (b = -0.46, p = 0.02). For both patients and caregivers, their past uncertainty was a significant predictor of their own current uncertainty (i.e., actor effect, p < 0.01). The individual's past uncertainty was a significant predictor of the other dyad member's current uncertainty (i.e., partner effect, p < 0.05), indicating an interdependent relationship between patient and caregiver uncertainty over time. CONCLUSIONS: Findings suggest patient and caregiver function as a unit with uncertainty levels affecting each other. Future interventions could build on GA to address uncertainty for older patients with advanced cancer and caregivers.

Patient and caregiver agreement on prognosis estimates for older adults with advanced cancer.

BACKGROUND: Disagreements between patients and caregivers about treatment benefits, care decisions, and patients' health are associated with increased patient depression as well as increased caregiver anxiety, distress, depression, and burden. Understanding the factors associated with disagreement may inform interventions to improve the aforementioned outcomes. METHODS: For this analysis, baseline data were obtained from a cluster-randomized geriatric assessment trial that recruited patients aged ≥70 years who had incurable cancer from community oncology practices (University of Rochester Cancer Center 13070; Supriya G. Mohile, principal investigator). Patient and caregiver dyads were asked to estimate the patient's prognosis. Response options were 0 to 6 months, 7 to 12 months, 1 to 2 years, 2 to 5 years, and >5 years. The dependent variable was categorized as exact agreement (reference), patient-reported longer estimate, or caregiver-reported longer estimate. The authors used generalized estimating equations with multinomial distribution to examine the factors associated with patient-caregiver prognostic estimates. Independent variables were selected using the purposeful selection method. RESULTS: Among 354 dyads (89% of screened patients were enrolled), 26% and 22% of patients and caregivers, respectively, reported a longer estimate. Compared with dyads that were in agreement, patients were more likely to report a longer estimate when they screened positive for polypharmacy (ß = 0.81; P = .001), and caregivers reported greater distress (ß = 0.12; P = .03). Compared with dyads that were in agreement, caregivers were more likely to report a longer estimate when patients screened positive for polypharmacy (ß = 0.82; P = .005) and had lower perceived self-efficacy in interacting with physicians (ß = -0.10; P = .008). CONCLUSIONS: Several patient and caregiver factors were associated with patient-caregiver disagreement about prognostic estimates. Future studies should examine the effects of prognostic disagreement on patient and caregiver outcomes.

The Relationship Between Frailty and Emotional Health in Older Patients with Advanced Cancer.

BACKGROUND: Aging-related deficits that eventually manifest as frailty may be associated with poor emotional health in older patients with advanced cancer. This study aimed to examine the relationship between frailty and emotional health in this population. METHODS: This was a secondary analysis of baseline data from a nationwide cluster randomized trial. Patients were aged ≥70 years with incurable stage III/IV solid tumors or lymphomas, had ≥1 geriatric assessment (GA) domain impairment, and had completed the Geriatric Depression Scale, Generalized Anxiety Disorder-7, and Distress Thermometer. Frailty was assessed using a Deficit Accumulation Index (DAI; range 0-1) based on GA, which did not include emotional health variables (depression and anxiety), and participants were stratified into robust, prefrail, and frail categories. Multivariate logistic regression models examined the association of frailty with emotional health outcomes. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. RESULTS: Five hundred forty-one patients were included (mean age: 77 years; 70-96). DAI ranged from 0.04 to 0.94; 27% of patients were classified as robust, 42% prefrail, and 31% frail. Compared with robust patients, frail patients had an increased risk of screening positive for depression (aOR = 12.8; 95% CI = 6.1-27.0), anxiety (aOR = 6.6; 95% CI = 2.2-19.7), and emotional distress (aOR = 4.62; 95% CI = 2.9-8.3). Prefrail compared with robust patients also had an increased risk of screening positive for depression (aOR = 2.22; 95% CI = 1.0-4.8) and distress (aOR = 1.71; 95% CI = 1.0-2.8). CONCLUSION: In older patients with advanced cancer, frailty is associated with poorer emotional health, which indicates a need for an integrated care approach to treating these patients. IMPLICATIONS FOR PRACTICE: A relationship exists between frailty and poor emotional health in older adults with advanced cancer. Identifying areas of frailty can prompt screening for emotional health and guide delivery of appropriate interventions. Alternatively, attention to emotional health may also improve frailty.

Caregiver-Oncologist Prognostic Concordance, Caregiver Mastery, and Caregiver Psychological Health and Quality of Life.

BACKGROUND: Caregivers of adults with cancer often report a different understanding of the patient's prognosis than the oncologist. We examine the associations of caregiver-oncologist prognostic concordance with caregiver depressive symptoms, distress, and quality of life (QoL). We also explore whether these relationships differed by caregiver environment mastery, an individual's sense of control, and effectiveness in managing life situations. MATERIALS AND METHODS: We used data from a national geriatric assessment cluster-randomized trial (URCC 13070) that recruited patients aged 70 years and older with incurable cancer considering any line of cancer treatment at community oncology practices, their caregivers, and their oncologists. At enrollment, caregivers and oncologists estimated the patient's prognosis (0-6 months, 7-12 months, 1-2 years, 2-5 years, and >5 years; identical responses were concordant). Caregivers completed the Ryff's environmental mastery at enrollment. At 4-6 weeks, caregivers completed the Patient Health Questionnaire-2 (depressive symptoms), distress thermometer, and 12-Item Short-Form Health Survey (quality of life [QoL]). We used generalized estimating equations in models adjusted for covariates. We then assessed the moderation effect of caregiver mastery. RESULTS: Of 411 caregiver-oncologist dyads (mean age = 66.5 years), 369 provided responses and 28% were concordant. Prognostic concordance was associated with greater caregiver depressive symptoms (ß = 0.30; p = .04) but not distress or QoL. A significant moderation effect for caregiver depressive symptoms was found between concordance and mastery (p = .01). Specifically, among caregivers with low mastery (below median), concordance was associated with greater depressive symptoms (ß = 0.68; p = .003). CONCLUSIONS: Caregiver-oncologist prognostic concordance was associated with caregiver depressive symptoms. We found a novel moderating effect of caregiver mastery on the relationship between concordance and caregiver depressive symptoms. IMPLICATIONS FOR PRACTICE: Caregiver-oncologist prognostic concordance is associated with greater caregiver depressive symptoms, particularly in those with low caregiver mastery. When discussing prognosis with caregivers, physicians should be aware that prognostic understanding may affect caregiver psychological health and should assess their depressive symptoms. In addition, while promoting accurate prognostic understanding, physicians should also identify strengths and build resilience among caregivers.

Associations of sleep disturbance with physical function and cognition in older adults with cancer.

PURPOSE: Although sleep disturbances are common in older adults, studies evaluating the prevalence of sleep disturbance and its influence on functional outcomes in older adults with cancer are few. In this study, we examined the prevalence of sleep disturbance and its association with physical function and cognition in older adults with cancer. METHODS: This is a cross-sectional study of patients who were referred and evaluated in the Specialized Oncology Care & Research in the Elderly (SOCARE) clinics at the Universities of Rochester and Chicago from May 2011 to October 2015. All patients underwent a geriatric assessment (GA) as part of their routine evaluation. Our final study cohort included patients who completed a sleep assessment and consented to the study. We collected demographics (age, sex, race, marital status, and education level) and clinical characteristics (depression, comorbidity, cancer type, and stage) from the GA and medical chart reviews. Presence of sleep disturbance was self-reported (yes/no). Physical function was assessed using Instrumental Activities of Daily Living (IADLs), physical activity (PA) survey, falls in the preceding 6 months, and Short Physical Performance Battery (SPPB). Cognition was screened using the Blessed Orientation-Memory-Concentration Test (impairment >4) or Montreal Cognitive Assessment (impairment <26). Bivariate and multivariable analyses were used to examine the associations between sleep disturbance with functional outcomes and cognition. RESULTS: We included 389 older patients. The prevalence of sleep disturbance was 40%. Sixty-eight percent had ≥1 IADL impairment, 76% had PA limitation, 37% had ≥1 fall, 70% had impairment on SPPB, and 47% screened positive for cognitive impairment. On bivariate analyses, sleep disturbance was associated with IADL impairment (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.23-3.13, P = 0.005), and PA limitation (OR 2.43, 95% CI 1.38-4.28, P = 0.002). The associations remained significant on multivariable analyses. Sleep disturbance was not significantly associated with falls, impairment on SPPB, and performance on the cognitive screen. CONCLUSION: Sleep disturbance was associated with IADL impairment and PA limitation. It is important for oncologists to inquire about sleep problems, and these patients should also be screened for functional impairment if sleep disturbance was present.

Older patients' experiences following initial diagnosis of acute myeloid leukemia: A qualitative study.

INTRODUCTION: The onset of symptoms and the diagnosis of acute myeloid leukemia (AML) often occur suddenly and may lead to a range of emotional responses. Understanding patients' experiences and emotional states allows clinicians to tailor care to patients' needs. Previous studies have largely focused on patients' experiences at diagnosis and after remission has been achieved among those who received intensive chemotherapy. In this study, we evaluated experiences of older patients with AML who had received or were receiving treatments of varying intensity, in both outpatient and inpatient settings, and who were at different stages in their treatment course at the time of our interviews. MATERIALS AND METHODS: We conducted a single center qualitative study which aimed to understand factors influencing older patients' treatment decision-making and the findings were previously reported. This analysis specifically explored older patients' experiences at various stages after AML diagnosis. We purposively sampled patients based on treatment intensity and stage of treatment (undergoing induction treatment, post-remission treatment, or post-allogeneic hematopoietic stem cell transplant). We recruited fifteen patients aged ≥60 years with AML. The sample size was determined based on reaching data saturation for the primary study aim. For this analysis, data saturation was reached by the fourteenth manuscript. In-depth semi-structured interviews that had been recorded and transcribed were re-analyzed using inductive thematic analysis to explore patients' experiences. Coding was performed using Atlas.ti. We identified themes with the aim of capturing the most commonly shared experiences. RESULTS: Mean age of the fifteen patients was 72.1 years; all had received one or more treatments including intensive induction therapy (10/15), lower-intensity treatment (7/15), and/or hematopoietic stem cell transplant (3/15). Patients experienced strong negative emotional responses, including shock, that were barriers to processing information and meaningful communication. Patients also shared their perspectives on communication with healthcare professionals (including thoughts on adequacy of information provided) and coping strategies. DISCUSSION: Understanding older patients' experiences, including emotional responses and barriers to communication and decision making, at AML diagnosis and throughout the illness trajectory allows clinicians to address patients' supportive care needs during this difficult period.

Caregiver-oncologist prognostic concordance, caregiving esteem, and caregiver outcomes.

INTRODUCTION: Caregiver-oncologist concordance regarding the patient's prognosis is associated with worse caregiver outcomes (e.g., depressive symptoms), but mechanisms underpinning these associations are unclear. We explored whether caregiving esteem mediates these associations. METHODS: At enrollment, caregivers and oncologists used a 5-point ordinal scale to estimate patient survival; identical responses were considered concordant. At 4-6 weeks, caregivers completed an assessment of the extent to which caregiving imparts self-esteem (Caregiver Reaction Assessment self-esteem subscale; range 0-5; higher score indicates greater esteem). They also completed Patient Health Questionnaire-2 (PHQ-2) for depressive symptoms, Distress Thermometer, and 12-Item Short Form Survey for quality of life (QoL). Mediation analysis with bootstrapping (PROCESS macro by Hayes) was used to estimate the extent to which caregiving mediated the effects of prognostic concordance on caregiver outcomes through caregiving esteem. RESULTS: Prognostic concordance occurred in 28% the caregiver-oncologist dyads; 85% of the discordance were due to caregivers estimating a longer patient's survival. At 4-6 weeks, mean caregiving esteem score was 4.4 (range 1.5-5.0). Lower caregiving esteem mediated the associations of concordance with higher PHQ-2 [indirect effect = 0.12; 95% Confidence Interval (CI) 0.03, 0.27], greater distress (indirect effect =0.25; 95% CI 0.08, 0.48), and poorer QoL (indirect effect = -1.50; 95% CI -3.06, -0.41). Caregiving esteem partially mediated 39%, 64%, and 48% of the associations between caregiver-oncologist concordance and PHQ-2, distress, and SF-12, respectively. CONCLUSIONS: Caregiver-oncologist concordance was associated with lower caregiving esteem. Lower caregiving esteem mediated the negative relationship between caregiver-oncologist concordance and caregiver outcomes.

The orphan G protein-coupled receptor, Gpr161, encodes the vacuolated lens locus and controls neurulation and lens development.

The vacuolated lens (vl) mouse mutant causes congenital cataracts and neural tube defects (NTDs), with the NTDs being caused by abnormal neural fold apposition and fusion. Our positional cloning of vl indicates these phenotypes result from a deletion mutation in an uncharacterized orphan G protein-coupled receptor (GPCR), Gpr161. Gpr161 displays restricted expression to the lateral neural folds, developing lens, retina, limb, and CNS. Characterization of the vl mutation indicates that C-terminal tail of Gpr161 is truncated, leading to multiple effects on the protein, including reduced receptor-mediated endocytosis. We have also mapped three modifier quantitative trait loci (QTL) that affect the incidence of either the vl cataract or NTD phenotypes. Bioinformatic, sequence, genetic, and functional data have determined that Foxe3, a key regulator of lens development, is a gene responsible for the vl cataract-modifying phenotype. These studies have extended our understanding of the vl locus in three significant ways. One, the cloning of the vl locus has identified a previously uncharacterized GPCR-ligand pathway necessary for neural fold fusion and lens development, providing insight into the molecular regulation of these developmental processes. Two, our QTL analysis has established vl as a mouse model for studying the multigenic basis of NTDs and cataracts. Three, we have identified Foxe3 as a genetic modifier that interacts with Gpr161 to regulate lens development.

Treatment decision-making in acute myeloid leukemia: a qualitative study of older adults and community oncologists.

Little is known about the characteristics of patients, physicians, and organizations that influence treatment decisions in older patients with AML. We conducted qualitative interviews with community oncologists and older patients with AML to elicit factors that influence their treatment decision-making. Recruitment was done via purposive sampling and continued until theoretical saturation was reached, resulting in the inclusion of 15 patients and 15 oncologists. Participants' responses were analyzed using directed content analysis. Oncologists and patients considered comorbidities, functional status, emotional health, cognition, and social factors when deciding treatment; most oncologists evaluated these using clinical gestalt. Sixty-seven percent of patients perceived that treatment was their only option and that they had not been offered a choice. In conclusion, treatment decision-making is complex and influenced by patient-related factors. These factors can be assessed as part of a geriatric assessment which can help oncologists better determine fitness and guide treatment decision-making.

Caregiving burden of informal caregivers of older adults with advanced cancer: The effects of rurality and education.

OBJECTIVES: Rural-urban disparities in the experiences of caregivers of older adults with advanced cancer may exist. This study examined factors associated with caregiver mastery and burden and explored whether rural-urban disparities in caregiver outcomes differed by education. MATERIALS AND METHODS: Longitudinal data (baseline, 4-6 weeks, and 3 months) on caregivers of older adults (≥ 70) with advanced cancer were obtained from a multicenter geriatric assessment (GA) trial (ClinicalTrials.gov: NCT02107443). Rurality was determined based on 2010 Rural-Urban Commuting Area codes. Caregivers' education was categorized as ≥ some college vs ≤ high school. Caregiver outcomes included Ryff Environmental Mastery (scored 7-35) and Caregiver Reaction Assessment (including self-esteem, disrupted schedules, financial problems, lack of social support, and health problems; each scored 1-5). Separate linear mixed models with interaction term of education and rurality were performed. RESULTS: Of 414 caregivers, 64 (15.5%) were from rural areas and 263 (63.5%) completed ≥ some college. Rurality was significantly associated with more disrupted schedules (ß = 0.21), financial problems (ß = 0.17), and lack of social support (ß = 0.11). A significant interaction between education and rurality was found, with rurality associated with lower mastery (ß = -1.27) and more disrupted schedule (ß = 0.25), financial problems (ß = 0.33), and lack of social support (ß = 0.32) among caregivers with education ≤ high school. CONCLUSION: Our study identifies subgroups of caregivers who are vulnerable to caregiving burden, specifically those from rural areas and with lower education. Multifaceted interventions are needed to improve caregivers' competency and reduce caregiving burden.

Multimorbidity, Function, and Cognition in Aging.

Multimorbidity is a global health challenge. Here, we define multimorbidity, describe ways multimorbidity is measured, discuss the prevalence of multimorbidity and how it differs across different populations, examine mechanisms of disease and disability, and discuss the effects of multimorbidity on outcomes such as survival and function.

Older adults with cancer and their caregivers - current landscape and future directions for clinical care.

Despite substantial improvements in the outcomes of patients with cancer over the past two decades, older adults (aged ≥65 years) with cancer are a rapidly increasing population and continue to have worse outcomes than their younger counterparts. Managing cancer in this population can be challenging because of competing health and ageing-related conditions that can influence treatment decision-making and affect outcomes. Geriatric screening tools and comprehensive geriatric assessment can help to identify patients who are most at risk of poor outcomes from cancer treatment and to better allocate treatment for these patients. The use of evidence-based management strategies to optimize geriatric conditions can improve communication and satisfaction between physicians, patients and caregivers as well as clinical outcomes in this population. Clinical trials are currently underway to further determine the effect of geriatric assessment combined with management interventions on cancer outcomes as well as the predictive value of geriatric assessment in the context of treatment with contemporary systemic therapies such as immunotherapies and targeted therapies. In this Review, we summarize the unique challenges of treating older adults with cancer and describe the current guidelines as well as investigational studies underway to improve the outcomes of these patients.

Associations of inflammation with frailty in patients with breast cancer aged 50 and over receiving chemotherapy.

PURPOSE: Chronic inflammation is a significant physiologic feature of frailty; however, its role and clinical utility in cancer-related frailty remains unknown. We sought to determine if pre-chemotherapy inflammation is predictive of frailty after chemotherapy in patients with breast cancer. METHODS: Female patients (N = 144; age ≥ 50) with stage I-III breast cancer scheduled to receive chemotherapy and age-matched non-cancer controls (N = 142) were included in this secondary analysis and assessed pre- and post-chemotherapy. Controls were assessed at equivalent time-points. Frailty was assessed using a modified Fried's score (0-4) using self-reported measures of weakness, exhaustion, walking speed, and physical activity. Serum levels of interleukin (IL) 6, and soluble tumor necrosis factor-alpha (sTNFR) I and II were measured. Associations between pre-chemotherapy cytokine and receptors level (median as cutoff) and post-chemotherapy frailty were evaluated using t-tests. RESULTS: Pre-chemotherapy, patients with breast cancer were more frail than non-cancer controls (mean score: 1.17 vs 0.65; p < .01). Patients also became more frail post-chemotherapy (mean score: 1.17 vs 2.08; p < .01). Patients with pre-chemotherapy serum levels of IL-6, sTNFRI, and sTNFRII above the median were more frail after chemotherapy than those with levels below the median [IL-6 (2.31 vs. 1.86; p = .03), sTNFRI (2.30 vs. 1.88; p = .04), and sTNFRII (2.30 vs. 1.88; p = .04)]. No differences were observed in non-cancer controls within the same timeframe. CONCLUSIONS: Both cancer and chemotherapy were associated with frailty. Higher pre-chemotherapy inflammatory cytokine levels were associated with post-chemotherapy frailty. This supports the utility of inflammatory cytokines to identify patients who develop worsening of frailty characteristics with chemotherapy.

Social support for older adults with cancer: Young International Society of Geriatric Oncology review paper.

Older adults with cancer have increasing needs in physical, cognitive, and emotional domains, and they can experience decline in all domains with the diagnosis and treatment of cancer. Social support plays a key role in supporting these patients, mitigating negative effects of diagnosis and treatment of cancer, and improving cancer outcomes. We review the importance of social support in older adults with cancer, describe the different components of social support and how they are measured, discuss current interventions that are available to improve social support in older adults, and describe burdens on caregivers. We also highlight Dr. Arti Hurria's contributions to recognizing the integral role of social support to caring for older adults with cancer.

Associations of Caregiver-Oncologist Discordance in Prognostic Understanding With Caregiver-Reported Therapeutic Alliance and Anxiety.

CONTEXT: Discordance in prognostic understanding between caregivers of adults with advanced cancer and the oncologist may shape caregivers' views of the oncologist and bereavement outcomes. OBJECTIVES: We examined prospective associations of caregiver-oncologist discordance with caregiver-oncologist therapeutic alliance and caregiver anxiety after patient death. METHODS: We conducted a secondary analysis of data collected in a cluster randomized controlled trial from August 2012 to June 2014 in Western New York and California. At enrollment, caregivers and oncologists used a seven-point scale to rate their beliefs about the patient's curability and living two years or more: 100%, about 90%, about 75%, about 50 of 50, about 25%, about 10%, and 0%. Discordance was defined as a difference of two points or more. Outcomes at seven months after patient death included caregiver-oncologist therapeutic alliance (The Human Connection scale, modified into five items) and caregiver anxiety (Generalized Anxiety Disorder-7). We conducted multivariable linear regression models to assess the independent associations of discordance with alliance and anxiety. RESULTS: We included 97 caregivers (mean age 63) and 38 oncologists; 41% of caregiver-oncologist dyads had discordant beliefs about the patient's curability, and 63% of caregiver-oncologist dyads had discordant beliefs about living two years or more. On multivariate analysis, discordance in beliefs about curability was associated with lower anxiety (ß = -2.20; SE 0.77; P = 0.005). Discordance in beliefs about length of life was associated with a weaker alliance (ß = -5.87; SE = 2.56; P = 0.02). CONCLUSION: A better understanding of how caregivers understand and come to terms with poor prognoses will guide interventions to improve cancer care delivery and outcomes of cancer treatment.

PARP inhibitors in older patients with ovarian and breast cancer: Young International Society of Geriatric Oncology review paper.

Breast and ovarian cancer are common malignancies among older adults, causing significant morbidity and mortality. Although most cases of breast and ovarian cancer are sporadic, a significant proportion is caused by mutations in cancer susceptibility genes, most often breast cancer susceptibility genes (BRCA) 1 and 2. Furthermore, some breast and ovarian tumors are phenotypically similar to those with BRCA mutations, a phenomenon known as "BRCAness". BRCA mutations and "BRCAness" lead to defects in DNA repair, which may be a target for therapeutic agents such as Poly ADP-Ribose Polymerase (PARP) inhibitors. PARP inhibitors are novel medications which lead to double-strand breaks resulting in cell death due to synthetic lethality, and which have been shown to be effective in patients with advanced breast and ovarian cancers with or without BRCA mutations. Three different PARP inhibitors (olaparib, niraparib, and rucaparib) have been approved for the treatment of ovarian cancer and one (olaparib) for breast cancer harboring BRCA mutations. Here, we review the currently available evidence regarding the use of PARP inhibitors for the treatment of patients with breast and ovarian cancer, with a particular focus on the inclusion of older adults in clinical trials of these therapies. Additionally, we provide an overview of currently ongoing studies of PARP inhibitors in breast and ovarian cancer, and include recommendations for increasing the evidence-base for using these medications among older patients.

Quantitative trait loci affecting phenotypic variation in the vacuolated lens mouse mutant, a multigenic mouse model of neural tube defects.

The vacuolated lens (vl) mouse mutant arose spontaneously on the C3H/HeSn background and exhibits neural tube defects (NTDs), congenital cataract, and occasionally a white belly spot. We previously reported that 1) the vl phenotypes are due to a mutation in an orphan G protein-coupled receptor (GPCR), Gpr161; 2) the penetrance of the vl NTD and cataract phenotypes are affected by genetic background, allowing three unlinked quantitative trait loci (QTL) to be mapped (modifiers of vacuolated lens, Modvl1-3); and 3) phenotype-based bioinformatics followed by genetic and molecular analysis identified a lens-specific transcription factor that contributes to the cataract-modifying effect of Modvl3. We now extend this analysis in three ways. First, using the Gpr161 mutation to unequivocally identify mutant adults and embryos, we determined that approximately 50% of vl/vl NTD-affected embryos die during development. Second, the MOLF/Ei genetic background suppresses this embryonic lethality but increases the incidence of the adult belly spot phenotype. Additional QTL analysis was performed, and two novel modifiers were mapped [Modvl4, logarithm of odds ratio (LOD) 4.4; Modvl5, LOD 5.0]. Third, phenotype-based bioinformatics identified candidate genes for these modifiers including two GPCRs that cause NTD or skin/pigmentation defects (Modvl4: Frizzled homolog 6; Modvl5: Melanocortin 5 receptor). Because GPCRs form oligomeric complexes, these genes were resequenced and nonsynonymous coding variants were identified. Bioinformatics and protein modeling suggest that these variants may be functional. Our studies further establish vl as a multigenic mouse model for NTDs and identify additional QTL that interact with Gpr161 to regulate neurulation.