Personalizing precision medicine: Patients with AML perceptions about treatment decisions.

BACKGROUND: This study aims to explore patients' with acute myeloid leukemia perceptions about precision medicine and their preferences for involvement in this new area of shared decision-making. METHODS: Individual semi-structured interviews were conducted in Finland, Italy and Germany (n = 16). The study population included patients aged 24-79 years. Interviews were analyzed with thematic content analysis. RESULTS: Patient's perceived lack of knowledge as a barrier for their involvement in decision-making. Treatment decisions were often made rapidly based on the patient's intuition and trust for the physician rather than on information, in situations that decrease the patient's decision capacity. The patients emphasized that they are in a desperate situation that makes them willing to accept treatment with low probabilities of being cured. CONCLUSIONS: The study raised important issues regarding patients' understanding of precision medicine and challenges concerning how to involve patients in medical decision-making. Although technical advances were viewed positively, the role of the physician as an expert and person-of-trust cannot be replaced. PRACTICE IMPLICATIONS: Regardless of patients' preferences for involvement in decision-making, information plays a crucial role for patients' perceived involvement in their care. The concepts related to precision medicine are complex and will imply challenges to patient education.

The role of the caregiver in older patients with advanced prostate cancer: results from the ADHERE Prospective Study of the Meet-URO network.

PURPOSE: To assess caregivers' characteristics and influence of the presence or absence of the caregiver on clinical outcomes of older (≥70 years) metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (ABI) or enzalutamide (ENZ). METHODS: Patients from the Meet-URO 5 ADHERE study were assessed with a 5-item caregiver evaluation questionnaire focusing on the presence, age, degree of kinship, working status and qualification of the caregiver. We investigated the association between the presence of a caregiver and the clinical characteristics and outcomes of enrolled patients. RESULTS: No differences were found in the main clinical characteristics between patients with or without a caregiver, except for a lower median G8 score (p = 0.0453) in the caregiver group. A longer radiographic PFS (rPFS) was observed in the group without a caregiver, with a trend towards more prolonged overall survival (OS) in the same group. CONCLUSION: Our work suggests a detrimental effect of caregivers in managing older mCRPC patients treated with ABI or ENZ, especially those identified as frail by the geriatric G8 screening score. Further work is needed to identify and address patients' vulnerability areas, which could have a detrimental effect on prognosis.

Phase III study of the European Organisation for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire.

PURPOSE: The purpose of this study is to develop a European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) questionnaire that captures the full range of physical, mental, and social health-related quality of life (HRQOL) issues relevant to disease-free cancer survivors. In this phase III study, we pretested the provisional core questionnaire (QLQ-SURV111) and aimed to identify essential and optional scales. METHODS: We pretested the QLQ-SURV111 in 492 cancer survivors from 17 countries with one of 11 cancer diagnoses. We applied the EORTC QLG decision rules and employed factor analysis and item response theory (IRT) analysis to assess and, where necessary, modify the hypothesized questionnaire scales. We calculated correlations between the survivorship scales and the QLQ-C30 summary score and carried out a Delphi survey among healthcare professionals, patient representatives, and cancer researchers to distinguish between essential and optional scales. RESULTS: Fifty-four percent of the sample was male, mean age was 60 years, and, on average, time since completion of treatment was 3.8 years. Eleven items were excluded, resulting in the QLQ-SURV100, with 12 functional and 9 symptom scales, a symptom checklist, 4 single items, and 10 conditional items. The essential survivorship scales consist of 73 items. CONCLUSIONS: The QLQ-SURV100 has been developed to assess comprehensively the HRQOL of disease-free cancer survivors. It includes essential and optional scales and will be validated further in an international phase IV study. IMPLICATIONS FOR CANCER SURVIVORS: The availability of this questionnaire will facilitate a standardized and robust assessment of the HRQOL of disease-free cancer survivors.

Inflammatory Biomarkers for Outcome Prediction in Patients With Metastatic Testicular Cancer.

Germ cell tumors are the most common malignant tumors in male young adults. Platinum-based chemotherapy has dramatically improved the outcome of metastatic germ cell tumor patients and overall cure rates now exceed 80%. The choice of medical treatment can be guided by the prognosis estimation which is an important step during the decision-making process. IGCCCG classification plays a pivotal role in the management of advanced disease. However, histological and clinical parameters are the available factors that condition the prognosis, but they do not reflect the tumor's molecular and pathological features and do not predict who will respond to chemotherapy. After first-line chemotherapy 20%-30% of patients relapse and for these patients, the issue of prognostic factors is far more complex. Validated biomarkers and a molecular selection of patients that reflect the pathogenesis are highly needed. The association between cancer-related systemic inflammation, tumorigenesis, and cancer progression has been demonstrated. In the last years, several studies have shown the prognostic utility of immune-inflammation indexes in different tumor types. This review analyzed the prognostic impact of inflammatory markers retrieved from routine blood draws in GCT patients.

A comparison of Dignity Therapy narratives among people with severe mental illness and people with cancer.

OBJECTIVE: To examine Dignity Therapy (DT) narratives in patients with severe mental illness (SMI) and a control group of cancer patients. METHODS: 12 patients with SMI (schizophrenia, bipolar disorders, sever personality disorders) and 12 patients with non-advanced cancer individually participated to DT interviews. DT was tape-recorded, transcribed verbatim and shaped into a narrative through a preliminary editing process. A session was dedicated to the final editing process along with the participant, with a final written legacy (generativity document) provided to the participant. Interpretative Phenomenological Analysis was used to qualitatively analyze the generativity documents. RESULTS: Patients with SMI and patients with cancer presented similar main narrative categories relative to dignity, such as "Meaning making", "Resources", "Legacy", "Dignity"; in addition, inpatients with SMI "Stigma" and inpatients with cancer "Injustice" emerged as separate categories. Patients in both groups strongly appreciated DT as an opportunity to reflect on their life story and legacy. CONCLUSIONS: The study showed that DT is a valuable intervention for people with SMI, grounded in a practical, person-centered approach. All patients found DT as an opportunity to describe their past and present, highlighting changes in the way they relate to themselves and others. These results can guide implementation of DT in mental health settings for people with SMI, as it is for people with cancer.

From Distress Screening to Uptake: An Italian Multicenter Study of Cancer Patients.

INTRODUCTION: Little consideration is given to the referral and uptake of available supportive services after distress screening. However, identifying the reasons for accepting or refusing help is mandatory for implementing a screening policy. The present study explored the practical usefulness of and potential barriers to the application of distress management. METHODS: 406 cancer patients were consecutively selected and asked to complete the Distress Thermometer (DT) and Problem Check List (PL). All patients with a DT score ≥6 were invited for a post-DT telephone interview with a trained psychologist. RESULTS: The 112 patients who refused to take part were more often older, retired, at a more advanced stage of illness, and with no previous experience of psychological intervention with respect to those who accepted. Of the 78 patients with a score ≥6 who were referred to the Psycho-Oncology Service, 65.4% accepted the telephone interview. Twenty-two patients rejected the initial invitation immediately for various reasons including logistic difficulties, physical problems, and feeling embarrassed about opening up to a psychologist. CONCLUSIONS: Our study confirms that screening per sé is insufficient to deal with the problem of distress and that more emphasis should be placed on implementing referral and treatment.

Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review.

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.

Post-traumatic stress symptoms in long-term disease-free cancer survivors and their family caregivers.

BACKGROUND: The experience of cancer is highly stressful and potentially traumatic. We assessed the presence of Post-Traumatic Stress Symptoms (PTSS) in long-term cancer survivors and their caregivers, while examining the association between PTSS and clinical, demographic and psychological variables in the long term. METHODS: In this cross-sectional study 212 survivor-family caregiver dyads completed measures of post-traumatic stress symptoms (PTSS) (Impact of Event Scale), depression and anxiety (Hospital Anxiety Depression Scale). Coping strategies, fatigue, cognitive decline, stressful life events and psychopathological history were also assessed among survivors. Data were analyzed using mixed models, accounting both for individual and dyadic effects. RESULTS: Cancer survivors and their caregivers were assessed after a mean of 6 years after treatment. Twenty per cent of survivors and 35.5% of caregivers had possible posttraumatic stress disorder (PTSD), while 23 patients (11.0%) and 33 caregivers (15.6%) had probable PTSD. Among cancer patients, the severity of post-traumatic symptoms was associated with an anxious coping style, previous psychopathology and depression (p < 0.001), whereas among caregivers it was associated with depression and having a closer relationship with patients (p < 0.001). Patients' depression was associated with caregivers' intrusion symptoms. CONCLUSIONS: High levels of cancer-related PTSS were still present several years after treatment in both survivors and caregivers. Psychopathology may derive from complex interactions among coping, previous disorders and between-person dynamics.

Post-traumatic Stress Symptoms and Serotonin Transporter (5-HTTLPR) Polymorphism in Breast Cancer Patients.

Introduction: Post-traumatic Symptoms (PTSS) and Post-traumatic Stress Disorder (PTSD) have been reported to affect a quite significant proportion of cancer patients. No study has examined the relationship between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cancer, including Gene-Environment interactions between this polymorphism and specific causes of distress, such as cancer related problems (CRP) or life stressful events (SLE). Methods: One hundred and forty five breast cancer outpatients participated in the study and were assessed using the Impact of Event Scale (IES), the Problem List (PL) developed by the National Comprehensive Cancer Network (NCCN) Distress Management Guidelines and the Paykel's Life Events Interview to evaluate the exposure to SLE during the year before the cancer diagnosis. Each patient was genotyped for 5-HTTLPR polymorphism by analyzing genomic DNA obtained from whole blood cells. Gene-Environment interactions were tested through moderation analysis. Results: Twenty-six patients (17.7%) were classified as PTSS cases using the IES. Genotype and phenotype distributions did not differ across individuals with/without PTSS (genotype: χ2 = 1.5; df = 2; p = 0.3; phenotype χ2 = 0.9; df = 1; p = 0.2). For both the genotype and phenotype model, using CRP as a predictor showed significant gene-environment interactions with IES total score (p = 0.020 and p = 0.004, respectively), with individuals carrying the l/l allele showing a greater probability of experiencing PTSS. No interaction was found in relationship to SLE (p = 0.750). Conclusion: This study showed a significant GEI between CRP and PTSS in breast cancer patients, with carriers of the l/l allele showing indicators consistent with greater sensitivity to stress.

Association between Type-D Personality and Affective (Anxiety, Depression, Post-traumatic Stress) Symptoms and Maladaptive Coping in Breast Cancer Patients: A Longitudinal Study.

Background: Type-D (distressed) personality has not been prospectively explored for its association with psychosocial distress symptoms in breast cancer patients. Objective: The objective of the study was to test the hypothesis that Type-D personality can be associated with psychosocial distress variables in cancer over a 2-point period (6 month-follow-up). Aims: The aim of the study was to analyze the role of Type-D personality in relation to anxiety, depression, post-traumatic stress symptoms, general distress, and maladaptive coping among cancer patients. Methods: 145 breast cancer patients were assessed within 6 months from diagnosis (T0) and again 6 months later (T1). The Type-D personality Scale, the Hospital Anxiety and Depression Scale, Depression subscale (HAD-D), the Brief Symptom Inventory (BSI-18) Anxiety subscale, the Distress Thermometer (DT), the Post-traumatic Symptoms (PTS) Impact of Event Scale (IES), and the Mini Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation and Hopelessness scales were individually administered at T0 and T1. Results: One-quarter of cancer patients met the criteria for Type-D personality, which was stable over the follow-up time. The two main constructs of Type-D personality, namely social inhibition (SI) and negative affectivity (NA), were related to anxiety, depression, PTS, BSI-general distress and maladaptive coping (Mini-MAC anxious preoccupation and hopelessness). In regression analysis, Type-D SI was the most significant factor associated with the above-mentioned psychosocial variables, both at T0 and T1. Conclusion: Likewise other medical disorders (especially cardiology), Type-D personality has been confirmed to be a construct significantly related to psychosocial distress conditions and maladaptive coping that are usually part of assessment and intervention in cancer care. More attention to personality issues is important in oncology.

Hostility in cancer patients as an underexplored facet of distress.

OBJECTIVE: In the present study, we aimed to assess hostility and to examine its association with formal psychiatric diagnosis, coping, cancer worries, and quality of life in cancer patients. METHODS: The World Health Organization (WHO) Composite International Diagnostic Interview (CIDI) to make an ICD-10 (International Classification of Disease) psychiatric diagnosis was applied to 516 cancer outpatients. The patients also completed the Brief Symptom Inventory-53 to assess hostility (BSI-HOS), and the Mini-Mental Adjustment to cancer scale (Mini-MAC). A subset of patients completed the Cancer Worries Inventory (CWI), the Openness Scale, and the Quality of Life Index. RESULTS: By analyzing the distribution of the responses 25% of the patients had moderate and 11% high levels of hostility, with about 20% being BSI-HOS "cases." Hostility was higher in patients with a formal ICD-10 psychiatric diagnosis (mainly major depression, other depressive disorders, anxiety disorders) than patients without ICD-10 diagnosis. However, about 25% of ICD-10-non cases also had moderate-to-high hostility levels. Hostility was associated with Mini-MAC hopelessness and anxious preoccupation, poorer quality of life, worries (mainly problems sin interpersonal relationships), and inability to openly discuss these problems within the family. CONCLUSIONS: Hostility and its components should be considered as dimensions to be more carefully explored in screening for distress in cancer clinical settings for its implications in negatively impacting on quality of life, coping and relationships with the family, and possibly the health care system.

Effectiveness of a brief manualized intervention, Managing Cancer and Living Meaningfully (CALM), adapted to the Italian cancer care setting: Study protocol for a single-blinded randomized controlled trial.

Patients with advanced cancer suffer from psychosocial distress that may impair quality of life and that may be ameliorated by psychotherapeutic treatment. We describe here the methodology of a randomized controlled trial (RCT) to assess the effectiveness of a novel, brief, semi-structured psychotherapeutic intervention to reduce distress and increase well-being in patients with advanced or metastatic cancer. The intervention, called Managing Cancer and Living Meaningfully (CALM), was originally developed in Canada and we are now testing its Italian adaptation (CALM-IT). The study is a single-blinded phase III RCT with assessment at baseline, 3 and 6 months with two conditions: CALM-IT versus a nonspecific supportive intervention (SPI). Eligibility criteria include: ≥ 18 years of age; fluency in the Italian language; no cognitive deficit, and diagnosis of advanced or metastatic cancer with an expected survival of 12-18 months. CALM-IT includes up to 12 sessions, delivered over 6 months and covers 4 domains: i) Symptom Management and Communication with Health Care Providers; ii) Changes in Self and Relations with Close Others; iii) Sense of Meaning and Purpose; and iv) the Future and Mortality. The primary outcome is difference in severity of depressive symptoms between treatment arm and the primary endpoint is 6 months. The secondary endpoint is 3 months and secondary outcomes are: generalized anxiety, distress about dying and death, demoralization, spiritual well-being, attachment security, posttraumatic growth, communication with partners, quality of life, and satisfaction with clinical care. If shown to be effective, CALM-IT can be implemented nationally to relieve distress and to promote psychological well-being in patients with advanced cancer.

Immunosenescence in Testicular Cancer Survivors: Potential Implications of Cancer Therapies and Psychological Distress.

Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.

Caregiver Emotional Burden in Testicular Cancer Patients: From Patient to Caregiver Support.

Testicular cancer is the most common tumor in young males aged 15-40 years. The overall cure rate for men with testicular cancer is >90%, so a huge number of these patients will become testicular cancer survivors. These people may feel some stress in the experience of diagnosis, treatment, and consequences that affects the quality of life, and during follow-up, especially when new issues and emotional distresses appear over time, such as late side-effects of treatments and emotional challenges including fear of tumor relapse, fertility and sexuality concerns, and social and workplace issues. The cancer experience has an impact not only on patients, but also on their relatives (e.g., spouses, parents, or siblings), who often have to assume a caregiving role for the duration of and following treatment for cancer. Moreover, the caregiver plays an important role in supporting a man with a testicular cancer, providing physical and emotional care. This review presents a summary of existing knowledge regarding the impact and the burden of testicular cancer on caregivers.

Psychosocial Issues in Long-Term Survivors of Testicular Cancer.

Testicular cancer is the most frequent tumor in young males aged 15-39 years. As cure rates are currently around 90%, the prevalence of survivors is increasing. However, a disease-free condition does not necessarily correspond to a life free of physical and psychosocial health problems. The aim of this review was to explore psychosocial morbidity among testicular cancer survivors. A literature search was conducted in three electronic databases (PubMed, Medline, and Embase). The results of the search on cancer survivors were then combined with those of the search on psychosocial concerns and work performance. Eighty-four publications met the inclusion criteria. Physical, psychological, work-related problems and changing perspectives about work and life in general influenced life and career decisions among testicular cancer survivors. Individual health, sexual relationships and work problems, affect several important aspects of survival and significantly influence the QoL of long-term survivors.

Vitamin D status among long-term survivors of testicular cancer.

A correlation between disturbances in hormone levels and the onset of metabolic disorders has been reported in long-term survivors of testicular cancer (TC).We evaluated serum vitamin D levels and other biological parameters in a consecutive series of 61 long-term (≥3 years) unilateral TC survivors with a median a follow-up of 4 years and in a cohort of healthy males. Deficient vitamin D levels were observed in 10 (17%) of the 58 long-term unilateral TC survivors but were not reported in healthy males (p=.019, Fisher test). Median vitamin D levels were 18.6 ug/L in 58 assessable TC survivors and 23.6 ug/L in 40 healthy males (p=.031). In univariate logistic regression analysis, TC diagnosis was associated with inadequate levels of vitamin D (p=.047). Vitamin D levels were lower when follow-up was > 10 years, albeit this difference was not statistically significant (p=.074). Long-term (especially > 10 years) TC survivors may have difficulty maintaining optimal vitamin D levels. Larger studies are needed to better characterize vitamin D status and possible correlations with premature hormonal aging reported in long-term TC survivors.

Cancer patients' emotional distress, coping styles and perception of doctor-patient interaction in European cancer settings.

OBJECTIVE: As a part of a European study, we cross-culturally examined the rate of emotional distress and maladaptive coping and their association with cancer patients' satisfaction with their interactions with the physician responsible for their care. METHODS: Cancer patients (n = 302) from one Middle European (Austria) and two Southern European (Italy, Spain) countries completed the NCCN Distress Thermometer (DT), the Mini-Mental Adjustment to Cancer (Mini-MAC) Anxious Preoccupation (AP) and Hopelessness (H) sub-scales, and the Physician Patient Satisfaction with Doctors Questionnaire (PSQ). RESULTS: The prevalence of emotional distress (DT caseness) was 60% (26.1% mild, 18.8% moderate, and 14.9% severe distress). Maladaptive coping (Mini-MAC cases) was found in 22.8% (hopeless cases), and 22.5% (anxious preoccupation cases). PSQ-MD was significantly correlated with Mini-MAC/H and Mini-Mac/AP, while PSQ-PS was negatively correlated with Mini-MAC/H. DT cases and those with higher levels of hopelessness reported higher scores on PSQ-MD and lower on PSQ-PS than non-cases. Some differences were found between countries both as far as patients' coping and perception of the interaction with doctors. In hierarchical multiple regression analysis, after adjusting for socio-demographic and medical variables, Mini-MAC/H significantly predicted the scores on PSQ-MD (positive direction) and PSQ-PS (negative direction). SIGNIFICANCE OF RESULTS: The study confirms that about one out of three cancer patients have moderate to high level of emotional distress and about one out of four, clinically significant maladaptive coping. Also, patients showing hopelessness and distress tended to perceive their doctors as both disengaged and less supportive. These results highlights the need for physicians to monitor their patient's level of distress and coping mechanisms and to adjust their own relational and communication style according to patients' psychological condition. Also, cross-cultural issues should be taken into account when exploring psychosocial variables and cancer patients' perception of and satisfaction with the interaction with their doctors.

Expectations of survivors, caregivers and healthcare providers for testicular cancer survivorship and quality of life.

AIMS AND BACKGROUND: We compared expectations of testicular cancer survivors and their caregivers with those of healthcare providers for testicular cancer survivorship care and quality of life to identify experiences and potential expectations in which there was disagreement. METHODS: In a meeting with testicular cancer survivors, their caregivers, and care providers with an interest in testicular cancer, we distributed a structured questionnaire with 24 questions divided into 3 sections: personal information, information on the quality of life of survivors, information on the role of care providers, general practitioners and health-related internet sources in the expectations of survivors. RESULTS: The overall response rate was 91% (29 of 32) for patients and 100% (14 of 14) for caregivers with all questionnaires evaluable, while among 60 care providers, 42 (70%) responded with 41 (68%) evaluable. Between patients/caregivers and care providers, expectations were most incongruent for the role of primary care physicians in testicular cancer follow-up: important/fundamental for 58% of patients/caregivers and 88% of care providers (P = 0.010). Comparing patients/caregivers with care providers in their views of the experience of testicular cancer survivorship, we found several discrepancies: the fear of recurrence was high/very high for 18 of 43 (42%) patients/caregivers and in the perception of 40 of 41 (98%) care providers (P <0.001), and psychological distress was considered as highly relevant by 35% of patients/caregivers and 93% of care providers (P <0.001). CONCLUSIONS: Patients/caregivers and care providers have different perceptions of survivors' experiences and discordant expectations with respect to the roles of primary care providers in testicular cancer survivorship care. Uncertainties about the roles and responsibilities of physicians can lead to deficiencies in care, supporting the need to make survivorship care planning a standard component in cancer management.