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OBJECTIVES: The objective of this study was to engage national experts in geriatric psychiatry and oncology in qualitative interviews to develop consensus regarding how older adult cancer survivors (OACS) experience depressive symptoms, and how best to assess OACs for depression. METHODS: Expert clinicians in geriatric oncology disciplines were interviewed about approaches to assessing depression in OACs. Interviews were audio-recorded and transcribed, and conducted until thematic saturation was achieved. Thematic Content Analysis was utilized to identify key themes. RESULTS: Experts (N = 8) were board certified geriatric psychiatrists and oncologists with specialization in geriatric medicine. Two conceptual domains were identified: Key indicators of depression in OACs (e.g. anhedonia; loss of meaning and purpose; loneliness and social withdrawal) and unique considerations for depression assessment in OACs (e.g. alternative phrasing to "depression," disentangling mood and cancer or treatment-related side effects). CONCLUSIONS: The approaches identified tended to depart from traditional diagnostic criteria for depression. CLINICAL IMPLICATIONS: Results provide additional insight into the limitations of existing depression measures for OACs. The themes and practices identified in the present study suggest that a revised measure of depression for OACs may be useful. Future research will continue to shed light on best practices for depression assessment in OACs.
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OBJECTIVE: To identify the phenomenology of depression in older adults with cancer (OACs) in order to improve the accuracy of depression screening for this population. METHOD: Inclusion criteria were: ≥70 years old, history of cancer, no cognitive impairment or severe psychopathology. Participants completed a demographic questionnaire, a diagnostic interview, and a qualitative interview. Using a Thematic Content Analysis framework, critical themes, passages, and phrases used by patients to describe their perceptions of depression and how it is experienced were identified. Particular attention was paid to divergences between depressed and non-depressed participants. RESULTS: Among 26 OACs (13 depressed, 13 non-depressed), qualitative analyses revealed four major themes indicative of depression (i.e. anhedonia, reduction in social relationships/loneliness, lack of meaning and purpose, lack of usefulness/feeling like a burden) and four minor themes (i.e. attitude towards treatment, mood, regret/guilt, physical symptoms/limitations). Themes of adaptation and acceptance of symptoms also emerged. CONCLUSIONS: Of the eight themes identified, only two overlap with DSM criteria. This supports the need to develop assessment methods of depression in OACs that are less reliant on DSM criteria and distinct from existing measures. This may improve the ability to identify depression in this population.
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Depresión , Neoplasias , Humanos , Anciano , Depresión/psicología , Soledad , Culpa , Neoplasias/complicacionesRESUMEN
INTRODUCTION: The number of older adults with cancer continues to increase. Many national and international organizations have called for the development of training opportunities for healthcare professionals (HCPs) to meet the unique needs of older adults with cancer and their families. MATERIALS AND METHODS: We developed and implemented the Geriatric Oncology Cognition and Communication (Geri-Onc CC) training program for HCPs of all disciplines. This program included a two-day, intensive didactic and experiential training followed by six bi-monthly booster videoconference calls. We describe the format and content of this training, the preliminary results of program evaluation, as well as changes in knowledge, self-efficacy, and attitudes toward older adults pre- to post-training. RESULTS: We describe data from the first six cohorts of HCPs who attended the training (n = 113). Participants rated the training highly favorably and reported that it met their training goals Mean = 4.8 (1-5 Scale). They also demonstrated a significant increase in their knowledge about geriatric oncology [(Pre-Mean = 6.2, standard deviation [SD] = 1.7; Post-Mean 6.8, SD = 1.6), p = 0.03] and self-efficacy in their ability to utilize the knowledge and skills they learned in the course [(Pre-Mean = 3.3, SD = 0.7; Post-Mean 4.5, SD = 0.4), p < 0.001]. There were no significant changes in attitudes toward older adults (p > 0.05), which were already very positive before the training. DISCUSSION: There is a strong need for training in geriatric oncology. We have demonstrated that implementing this training was feasible, highly regarded, and positively impacted knowledge and self-efficacy regarding utilization of the knowledge and skills learned in the training.
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Personal de Salud , Neoplasias , Humanos , Anciano , Comunicación , Neoplasias/terapia , Cognición , Atención a la SaludRESUMEN
Follicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched for EZH2, TNFRSF14, and MEF2B mutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry.
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Linfoma Folicular , Humanos , Linfoma Folicular/genética , Células B de Memoria , Centro Germinal , Linfocitos B , MutaciónRESUMEN
OBJECTIVES: The Cancer and Aging: Reflections for Elders Expressive Writing Intervention (CARE-Express) was developed to enhance coping and minimize psychological distress in older adults with cancer. The aim of the current study is to evaluate the feasibility and initial efficacy of CARE-Express. MATERIALS AND METHODS: Seventy-one distressed older adults (≥70) with cancer were assigned to CARE-Express (n = 41) or the Enhanced Social Work Control (ESWC) arm (n = 30). Participants completed five telephone sessions over seven weeks and were assessed on psychosocial variables at baseline, post-intervention, and four months post study enrollment. Feasibility was assessed by examining rates of eligibility, acceptance, retention, assessment, and fidelity. Initial efficacy was evaluated using standardized effect sizes. RESULTS: Adequate rates of acceptance (29%), eligibility (66%), retention (90%), assessment (70% at post-intervention, 63% at four month follow-up), and fidelity (97%) were observed. At post-intervention, participants receiving CARE-Express reported less depression compared to ESWC (d = 0.69, p = 0.01) and lower demoralization (d = 0.50, p = 0.06). A small/moderate effect was demonstrated for increased total spirituality scores (d = 0.41, p = 0.07), meaning/peace (d = 0.32, p = 0.20) and faith (d = 0.35, p = 0.07). The CARE-Express group reported greater reductions in behavioral disengagement (d = 0.44, p = 0.06), while ESWC demonstrated a small effect for active coping (d = 0.21, p = 0.31). At four months, differential effects of CARE-Express had attenuated, though small/moderate, effects in favor of CARE-Express remained. CONCLUSION: Results support the feasibility of CARE-Express and its potential positive impact on psychological well-being. TRIAL REGISTRATION: Registered at the US National Institutes of Health (ClinicalTrials.gov) #NCT00984321 on September 25, 2009.
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Envejecimiento , Neoplasias , Escritura , Adaptación Psicológica , Anciano , Humanos , Neoplasias/psicología , Neoplasias/terapia , Proyectos PilotoRESUMEN
OBJECTIVE: Blacks have the highest incidence and mortality rates for prostate cancer (PCa) in the U.S. Black PCa patients (PCaP) also report high psychological distress. Identifying culturally specific coping strategies that lower distress among Black PCaP could help improve psychological interventions for this group. African-centered coping (strategies unique to the structure of Black personality and the African-centered worldview) have been identified. We hypothesized that these coping strategies and resilience would be associated with lower psychological distress (anxiety and depression) in Black PCaP. METHODS: Black PCaP (N = 95) completed a survey assessing African-centered coping strategies, resilience, anxiety, and depression. Multiple regression was employed to examine African-centered coping strategies and resilience as predictors of psychological distress. RESULTS: Participants were aged M = 67 ± 9 years and 52% had late-stage PCa. Twenty percent met criteria for clinically significant anxiety, and 17% for depression. African-centered coping strategies were not associated with lower anxiety or depression, while resilience was associated with decreased anxiety (r = -0.45, p < 0.001) and depression (r = -0.54, p < 0.001). Mediation analyses did not support an indirect association among African-centered coping strategies, resilience, and anxiety and depression. CONCLUSIONS: Contrary to hypotheses, African-centered coping strategies were not associated with psychological distress. However, as predicted, greater resilience was associated with lower anxiety and depression. These findings support the relevancy of resilience in Blacks' psychological adjustment to PCa. It might be worthwhile to explore African-centered coping strategies that help Black PCaP cope with distress.
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Neoplasias de la Próstata , Distrés Psicológico , Resiliencia Psicológica , Adaptación Psicológica , Anciano , Ansiedad/psicología , Depresión/psicología , Humanos , Masculino , Neoplasias de la Próstata/psicología , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway frequently is activated in patients with urothelial carcinoma (UC). In the current study, the authors performed a phase 2 study evaluating the efficacy of the pan-isoform class I PI3K inhibitor buparlisib in patients with platinum-refractory metastatic UC. METHODS: Two cohorts were recruited: an initial genetically unselected cohort and a subsequent expansion cohort of patients with PI3K/Akt/mTOR pathway-altered tumors. The primary endpoint was the 2-month progression-free survival rate. A rate of ≥80% was considered promising using a Simon 2-stage minimax design. Secondary endpoints included safety and correlation of markers of PI3K pathway activation with outcome. RESULTS: Six of 13 evaluable patients within the initial cohort demonstrated stable disease and 1 demonstrated a partial response, which was below the cutoff of 9 patients required to proceed to stage 2. Three of the patients with stable disease and the patient with a partial response harbored somatic TSC1 alterations. Four patients subsequently were recruited onto an expansion cohort: 3 patients with TSC1 alterations and 1 patient with a PIK3CA-activating mutation. No patient achieved disease control at 8 weeks and accrual was halted. Of the 19 patients evaluable for toxicity, 17 demonstrated treatment-related toxicities, 2 of whom had to discontinue therapy. CONCLUSIONS: Buparlisib was found to demonstrate modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations; however, this was not a robust predictor of response to buparlisib. The pattern of genetic coalterations likely influences drug sensitivity. Given the modest clinical activity and substantial toxicity of buparlisib, future trials of PI3K inhibitors in patients with UC should focus on isoform-selective PI3K inhibitors in genomically selected patients. LAY SUMMARY: The phosphatidyl 3-inositol kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway frequently is upregulated in patients with metastatic urothelial carcinoma (UC). This trial explored buparlisib, an inhibitor of the pathway, in patients with heavily pretreated metastatic UC. Although the drug was found to have modest efficacy, with 6 patients experiencing stable disease and 1 patient achieving a partial response at 8 weeks on therapy, significant side effects also were observed. Patients with specific genetic alterations responded to treatment. Further studies of PI3K pathway inhibition are warranted using newer agents that have superior toxicity profiles and are more selective inhibitors of the pathway.
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Aminopiridinas/uso terapéutico , Morfolinas/uso terapéutico , Fosfatidilinositol 3-Quinasa/uso terapéutico , Neoplasias Urológicas/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Aminopiridinas/farmacología , Línea Celular Tumoral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morfolinas/farmacología , Metástasis de la Neoplasia , Fosfatidilinositol 3-Quinasa/farmacologíaRESUMEN
OBJECTIVE: Cancer and Aging: Reflections for Elders (CARE) is a novel, telephone-delivered intervention designed to alleviate distress in older cancer patients. This pilot randomized controlled trial tested the feasibility and initial efficacy of CARE, drawing from age-appropriate developmental themes and well-established coping theory. METHOD: Eligible patients were ≥70 years old; ≥6 months post-diagnosis of lung, prostate, breast, lymphoma, or gynecological cancer; on active cancer treatment or within 6 months of ending cancer treatment; and had elevated scores on the Distress Thermometer (≥4) or Hospital Anxiety and Depression Scale (≥6). Participants completed five sessions of psychotherapy over 7 weeks with assessments at study entry, post-intervention, and 2 months post-intervention. Primary outcomes were feasibility and initial efficacy on anxiety and depression; secondary outcomes included demoralization, coping, loneliness, and spiritual well-being. RESULTS: Fifty-nine participants were randomized to either the CARE arm (n = 31) or the enhanced Social Work Control arm (n = 28). The intervention was feasible and tolerable, meeting a priori criteria for rates of eligibility, acceptance, retention, assessment, and treatment fidelity. Upon completion of the intervention, participants in the CARE arm demonstrated lower mean depression scores (d = 0.58 [CI: 0.04-1.12], P = 0.01) and trended towards increased coping-planning (d = 0.30 [CI: -0.83 to 0.24], P = 0.18). Promising trends in anxiety (d = 0.41 [CI: -0.17 to 0.98], P = 0.10) emerged at 2 months post-intervention; effects for coping-planning dissipated. CONCLUSION: These pilot data suggest the CARE intervention is feasibly delivered, potentially impacts important psychosocial variables, and is accessible for older, frail patients with cancer. Future research will evaluate this intervention on a larger scale.
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Ansiedad/terapia , Depresión/terapia , Neoplasias/psicología , Psicoterapia/métodos , Adaptación Psicológica , Anciano , Ansiedad/etiología , Depresión/etiología , Femenino , Humanos , Masculino , Neoplasias/complicaciones , Neoplasias/terapia , Evaluación de Resultado en la Atención de Salud , Educación del Paciente como Asunto/métodos , Proyectos PilotoRESUMEN
BACKGROUND: As the number of older adults in the United States continues to grow, there will be increasing demands on health care providers to address the needs of this population. Cancer is of particular importance, with over half of all cancer survivors older than 65 years. In addition, depression, pain, and fatigue are concerns for older adults with cancer and have been linked to poorer physical outcomes. METHODS: For this retrospective chart review, 1012 eligible participants were identified via a query of the Electronic Medical Record for all patients referred to 1 of 4 Survivorship Clinics at Memorial Sloan Kettering Cancer Center. All patients were between the ages of 30 to 55 (younger adults) and >65 (older adults). Depression was measured using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: The overall rate of depression in this sample of adult cancer survivors was 9.3%. There were no differences in the rates of clinically significant depression (defined as PHQ-9 score ≥10) between younger and older adult cohorts. However, there was a small trend toward higher mean PHQ-9 scores in the younger adult cohort (3.42 vs 2.95; t = 1.763, P = .10). Women reported greater rates of depression and higher pain and fatigue scores. Hispanic/Latino patients also reported significantly greater rates of depression. CONCLUSION: There were no observed differences in depression between older and younger adult cancer survivors. Gender and ethnic discrepancies in depression were observed. Future research should focus on understanding the nature of these differences and targeting interventions for the groups most vulnerable to depression after cancer treatment.
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Supervivientes de Cáncer/estadística & datos numéricos , Depresión/epidemiología , Fatiga/epidemiología , Dolor/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Estados UnidosRESUMEN
OBJECTIVE: To examine the ability of three popular self-report measures of depression to assess depression in a geriatric cancer setting. METHOD: Cancer patients 70 years or older and on active treatment completed the Geriatric Depression Scale-Short Form, the Hospital Anxiety and Depression Scale, and the Center for Epidemiological Studies Depression Scale-Revised, and were interviewed using the depression module of the Structured Clinical Interview for DSM disorders (SCID) as the 'gold standard.' Analyses included calculating internal consistency, ROC curves, and the sensitivity and specificity to detect major depression (MDD) or minor depression (i.e. subthreshold depression). RESULTS: In a sample of 201 cancer patients (85% White; 64% completed college degree or higher), all three of the self-report measures produced adequate internal consistency and predicted depression greater than chance. However, the published cutoff scores for detecting MDD produced inadequate sensitivity, suggesting these scores will miss as many as 33%-83% of geriatric cancer patients who are depressed. Revised cutoff scores were lower than published cutoff scores. CONCLUSION: Although these measures produced good internal consistency and were better than chance at predicting depression in a geriatric cancer sample, the published cutoff scores for these measures did not perform well in predicting MDD nor minor depression. Of the three measures, the CES-D appeared to have the most utility. This data suggests that these popular screening measures may be inadequate for reliably identifying depression in a geriatric cancer population. Researchers and clinicians, therefore, should use caution when selecting depression measures for geriatric cancer patients and consider using the lower cut-off scores presented here.
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Depresión/diagnóstico , Trastorno Depresivo Mayor/diagnóstico , Neoplasias/psicología , Encuestas y Cuestionarios , Anciano , Anciano de 80 o más Años , Depresión/complicaciones , Depresión/psicología , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/psicología , Femenino , Evaluación Geriátrica , Humanos , Masculino , Neoplasias/diagnóstico , Escalas de Valoración Psiquiátrica , Curva ROC , Reproducibilidad de los Resultados , Autoinforme , Sensibilidad y EspecificidadRESUMEN
PURPOSE: The National Cancer Institute has highlighted the need for psychosocial research to focus on Black cancer patients. This applies to Black men with prostate cancer, as there is little systematic research concerning psychological distress in these men. This study was designed to validate the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) in Black men with prostate cancer to help facilitate research within this group. METHODS: At three institutions, Black men with prostate cancer (n = 101) completed the MAX-PC, the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy (FACT) Quality of Life Questionnaire, and the Distress Thermometer. RESULTS: The average age of the 101 men was 66 (SD = 10) and 58 % had early-stage disease. The MAX-PC and its subscales (Prostate Cancer Anxiety, PSA Anxiety, and Fear of Recurrence) produced strong coefficient alphas (0.89, 0.88, 0.71, and 0.77, respectively). Factor analysis supported the three-factor structure of the scale established in earlier findings. The MAX-PC also demonstrated strong validity. MAX-PC total scores correlated highly with the Anxiety subscale of the HADS (r = 0.59, p < 0.01) and the FACT Emotional Well-Being subscale (r = -0.55, p < 0.01). Demonstrating discriminant validity, the correlation with the HADS Depression subscale (r = 0.40, p < 0.01) and the CES-D (r = 0.42, p < 0.01) was lower compared to that with the HADS Anxiety subscale. CONCLUSIONS: The MAX-PC is valid and reliable in Black men with prostate cancer. We hope the validation of this scale in Black men will help facilitate psychosocial research in this group that is disproportionately adversely affected by this cancer.
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Ansiedad/psicología , Neoplasias de la Próstata/psicología , Negro o Afroamericano , Anciano , Humanos , Masculino , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/epidemiología , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
The development of targeted anti-cancer therapies through the study of cancer genomes is intended to increase survival rates and decrease treatment-related toxicity. We treated a transposon-driven, functional genomic mouse model of medulloblastoma with 'humanized' in vivo therapy (microneurosurgical tumour resection followed by multi-fractionated, image-guided radiotherapy). Genetic events in recurrent murine medulloblastoma exhibit a very poor overlap with those in matched murine diagnostic samples (<5%). Whole-genome sequencing of 33 pairs of human diagnostic and post-therapy medulloblastomas demonstrated substantial genetic divergence of the dominant clone after therapy (<12% diagnostic events were retained at recurrence). In both mice and humans, the dominant clone at recurrence arose through clonal selection of a pre-existing minor clone present at diagnosis. Targeted therapy is unlikely to be effective in the absence of the target, therefore our results offer a simple, proximal, and remediable explanation for the failure of prior clinical trials of targeted therapy.
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Neoplasias Cerebelosas/terapia , Células Clonales/efectos de los fármacos , Células Clonales/metabolismo , Meduloblastoma/terapia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Selección Genética/efectos de los fármacos , Animales , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/patología , Neoplasias Cerebelosas/radioterapia , Neoplasias Cerebelosas/cirugía , Células Clonales/patología , Irradiación Craneoespinal , Análisis Mutacional de ADN , Modelos Animales de Enfermedad , Drosophila melanogaster/citología , Drosophila melanogaster/genética , Femenino , Genoma Humano/genética , Humanos , Masculino , Meduloblastoma/genética , Meduloblastoma/patología , Meduloblastoma/radioterapia , Meduloblastoma/cirugía , Ratones , Terapia Molecular Dirigida/métodos , Recurrencia Local de Neoplasia/terapia , Radioterapia Guiada por Imagen , Transducción de Señal , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
An aging population and advances in diagnostics and treatment have resulted in a rapidly growing population of people impacted by cancer. People live longer after a cancer diagnosis and tolerate more aggressive treatments than in the past. Younger patients struggle with diversions from the normal developmental milestones in career and relationships, while older patients deal with the dual challenges of aging and cancer. Cancer's transition from likely death to survival has increased interest in its impact on psychosocial issues and quality of life, rather than just longevity. In this article, the authors review the psychiatric diagnosis and management of the mental health issues most often encountered in oncology. Oncology treatment teams, including oncologists, nurses, social workers, and other ancillary staff, are often on the front lines of addressing psychiatric distress and clinical syndromes when psychiatrists are not easily available. The purpose of this review article is to highlight opportunities for nonpsychiatrists to improve identification and treatment of psychosocial distress and psychiatric syndromes and to request formal psychiatric consultation in appropriate situations. Psychotherapeutic, psychopharmacologic, cognitive, and behavioral-oriented interventions, as well as supportive interventions, are discussed for treating patients who are facing challenges during active cancer treatment, survivorship, and at the end of life. This review is not exhaustive but highlights the more common psychosomatic medicine and palliative care scenarios that impact cancer patient care. The importance of recognizing and addressing burnout and compassion fatigue in multidisciplinary professionals who care for those treated for cancer is also discussed given the secondary impact this can have on patient care.
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Trastornos Mentales/etiología , Neoplasias/complicaciones , Agotamiento Profesional , Terapia Combinada , Humanos , Trastornos Mentales/diagnóstico , Trastornos Mentales/terapia , Neoplasias/psicología , Neoplasias/terapia , Cuidados Paliativos , Grupo de Atención al Paciente , Psicoterapia , Psicotrópicos/uso terapéutico , Calidad de VidaRESUMEN
BACKGROUND: Erectile rehabilitation (ER) following radical prostatectomy (RP) is considered an essential component to help men regain erectile functioning; however, many men have difficulty adhering to this type of program. This qualitative study explored men's experience with ER, erectile dysfunction (ED), and ED treatments to inform a psychological intervention designed to help men adhere to ER post-RP. METHODS: Thirty men, 1-to-3-years post-RP, who took part in an ER program, participated in one of four focus groups. Thematic analysis was used to identify the primary themes. RESULTS: Average age was 59 years (standard deviation = 7); mean time since surgery was 26 months (standard deviation = 6). Six primary themes emerged: (1) frustration with the lack of information about postsurgery ED; (2) negative emotional impact of ED and avoidance of sexual situations; (3) negative emotional experience with penile injections and barriers leading to avoidance; (4) the benefit of focusing on the long-term advantage of ER versus short-term anxiety; (5) using humor to help cope; and (6) the benefit of support from partners and peers. CONCLUSIONS: Men's frustration surrounding ED can lead to avoidance of sexual situations and ED treatments, which negatively impact men's adherence to an ER program. The theoretical construct of acceptance and commitment therapy was used to place the themes into a framework to conceptualize the mechanisms underlying both avoidance and adherence in this population. As such, acceptance and commitment therapy has the potential to serve as a conceptual underpinning of a psychological intervention to help men reduce avoidance to penile injections and adhere to an ER program.
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Disfunción Eréctil/psicología , Disfunción Eréctil/rehabilitación , Prostatectomía/efectos adversos , Adulto , Anciano , Grupos Focales , Objetivos , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente/psicología , Investigación Cualitativa , Conducta Sexual/psicologíaRESUMEN
Human cancers, including breast cancers, comprise clones differing in mutation content. Clones evolve dynamically in space and time following principles of Darwinian evolution, underpinning important emergent features such as drug resistance and metastasis. Human breast cancer xenoengraftment is used as a means of capturing and studying tumour biology, and breast tumour xenografts are generally assumed to be reasonable models of the originating tumours. However, the consequences and reproducibility of engraftment and propagation on the genomic clonal architecture of tumours have not been systematically examined at single-cell resolution. Here we show, using deep-genome and single-cell sequencing methods, the clonal dynamics of initial engraftment and subsequent serial propagation of primary and metastatic human breast cancers in immunodeficient mice. In all 15 cases examined, clonal selection on engraftment was observed in both primary and metastatic breast tumours, varying in degree from extreme selective engraftment of minor (<5% of starting population) clones to moderate, polyclonal engraftment. Furthermore, ongoing clonal dynamics during serial passaging is a feature of tumours experiencing modest initial selection. Through single-cell sequencing, we show that major mutation clusters estimated from tumour population sequencing relate predictably to the most abundant clonal genotypes, even in clonally complex and rapidly evolving cases. Finally, we show that similar clonal expansion patterns can emerge in independent grafts of the same starting tumour population, indicating that genomic aberrations can be reproducible determinants of evolutionary trajectories. Our results show that measurement of genomically defined clonal population dynamics will be highly informative for functional studies using patient-derived breast cancer xenoengraftment.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Células Clonales/metabolismo , Células Clonales/patología , Genoma Humano/genética , Análisis de la Célula Individual , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Neoplasias de la Mama/secundario , Análisis Mutacional de ADN , Genómica , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Ratones , Trasplante de Neoplasias , Factores de Tiempo , Trasplante Heterólogo , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
OBJECTIVE: To review the literature on depression in cancer patients with a particular focus on depression assessment and barriers to mental health treatment in older cancer patients. DESIGN: We conducted a review of the literature on depression and barriers to mental health treatment in older cancer patients. RESULTS: Depression is prevalent in cancer patients. However, little is known about prevalence rates of depression in older adults with cancer, assessing depression in older cancer patients and barriers that impede proper mental health treatment in this sample. CONCLUSION: Improved diagnostic clarity and a better understanding of barriers to mental health treatment can help clarify and facilitate mental health referrals and ultimately improve access to care among older cancer patients in need. Continuing to consider the complexities associated with diagnosing depression in older cancer patients is necessary. Further work may be needed to develop new diagnostic measures for such detection, determine the prevalence of depression among older cancer and ways in which to overcome barriers to mental health care.
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Trastorno Depresivo/terapia , Accesibilidad a los Servicios de Salud/normas , Servicios de Salud Mental/organización & administración , Neoplasias/psicología , Anciano , Trastorno Depresivo/etiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: The relationship between erectile dysfunction (ED) and depressive symptoms is well established. However, this relationship is not well explored in men with prostate cancer. Limited data suggest men with prostate cancer may experience less ED bother than men with ED who do not have prostate cancer, implying that ED and depressive symptoms may not be associated in men with prostate cancer. AIM: To determine if ED is associated with depressive symptoms in men with prostate cancer. MAIN OUTCOME MEASURES: Assessments of quality-of-life (The Functional Assessment of Cancer Therapy [FACT-P]), anxiety/depression (Hospital Anxiety and Depression Scale [HADS]), and erectile function. Erectile function was measured with one question from the FACT-P similar to that used by the Massachusetts Male Aging Study. METHODS: Men with prostate cancer, and naïve of hormone treatment, completed the study questionnaires at a single time point. RESULTS: The average age of the 339 men was 67±10 years. The average time since diagnosis was 3.9±3 years. When answering the question, "I am able to have and maintain an erection" on a 1 to 5 scale (5 representing the best function), the mean score was 2 indicating "a little bit." On univariate analysis, erectile function and depression were associated, r=-0.12, P<0.05. Other variables associated with depression were marital status, r=0.11, P<0.05; anxiety scores, r=0.56, P<0.01; and social support, r=-0.42, P<0.01. On multivariate analysis, erectile function remained a significant predictor of depression, beta=-0.10, P<0.05. CONCLUSIONS: Erectile function was associated with depressive symptoms in both univariate and multivariate analysis, indicating that ED is independently associated with depressive symptoms even though patients were approximately 4 years post diagnosis. These cross-sectional data suggest ED in men with prostate cancer can have lasting psychological effects.