Mental Adjustment, Functional Status, and Depression in Advanced Cancer Patients.

Depressive symptoms are common in individuals with advanced cancer. OBJECTIVES: This study sought to analyze the relationship between physical and functional status and depressive symptoms, and to assess the role of mental adjustment across these variables in people with advanced cancer. METHODS: A prospective, cross-sectional design was adopted. Data were collected from 748 participants with advanced cancer at 15 tertiary hospitals in Spain. Participants completed self-report measures: Brief Symptom Inventory (BSI), Mini-Mental Adjustment to Cancer (Mini-MAC) scale, and the European Organization for Research and Treatment of Cancer (EORTC) questionnaire. RESULTS: Depression was present in 44.3% of the participants and was more common among women, patients <65 years old, non-partnered, and those with recurrent cancer. Results revealed a negative correlation with functional status, and functional status was negatively associated with depressive symptoms. Mental adjustment affected functional status and depression. Patients having a positive attitude displayed fewer depressive symptoms, while the presence of negative attitudes increased depressive symptoms in this population. CONCLUSIONS: Functional status and mental adjustment are key factors in the presence of depressive symptoms among people with advanced cancer. Assessment of functional status and mental adjustment should be considered when planning treatment and rehabilitation in this population.

Perceived Dignity of Advanced Cancer Patients and Its Relationship to Sociodemographic, Clinical, and Psychological Factors.

Objective: Loss of dignity is one of the main reasons for wishing for an early death in patients with incurable diseases such as cancer and is strongly associated with psychological distress and loss of quality of life. The present study aims to analyze the perceived dignity of patients with advanced cancer undergoing systemic treatment and their relationship with sociodemographic, clinical, and psychological factors. Methods: A prospective, cross-sectional, multicenter study was conducted in 15 oncology departments in Spain. Patients with locally advanced, unresectable, or metastatic cancer who were candidates for systemic treatment were included. Participants completed demographic information and Palliative Patients' Dignity Scale, Brief Symptom Inventory, Mental Adjustment to Cancer, Functional Social Support Questionnaire, and Illness Uncertainty. Results: A total of 508 patients were recruited between February 2020 and October 2021. Most were male, aged > 65 years, with digestive tumors (41%), and metastatic disease at diagnosis. Subjects were classified as having low (56%, N = 283) or high (44%, N = 225) perceived dignity. Patients ≥ 65 years, with worse baseline status (ECOG ≥ 1), and worse estimated 18-month survival had lower levels of perceived dignity. People with lower perceived dignity scored higher for anxious preoccupation and hopelessness and lower for positive attitude. They also displayed higher levels of anxiety, depression, and somatic symptoms, greater uncertainty, and less social support. Conclusion: Self-perceived dignity in advancer cancer patients is significantly associated with psychological factors, psychological distress, uncertainty, less social support. Knowledge of these specific interactions is importance for adequate, comprehensive palliative care.

New markers for human ovarian cancer that link platinum resistance to the cancer stem cell phenotype and define new therapeutic combinations and diagnostic tools.

BACKGROUND: Ovarian cancer is the leading cause of gynecologic cancer-related death, due in part to a late diagnosis and a high rate of recurrence. Primary and acquired platinum resistance is related to a low response probability to subsequent lines of treatment and to a poor survival. Therefore, a comprehensive understanding of the mechanisms that drive platinum resistance is urgently needed. METHODS: We used bioinformatics analysis of public databases and RT-qPCR to quantitate the relative gene expression profiles of ovarian tumors. Many of the dysregulated genes were cancer stem cell (CSC) factors, and we analyzed its relation to therapeutic resistance in human primary tumors. We also performed clustering and in vitro analyses of therapy cytotoxicity in tumorspheres. RESULTS: Using bioinformatics analysis, we identified transcriptional targets that are common endpoints of genetic alterations linked to platinum resistance in ovarian tumors. Most of these genes are grouped into 4 main clusters related to the CSC phenotype, including the DNA damage, Notch and C-KIT/MAPK/MEK pathways. The relative expression of these genes, either alone or in combination, is related to prognosis and provide a connection between platinum resistance and the CSC phenotype. However, the expression of the CSC-related markers was heterogeneous in the resistant tumors, most likely because there were different CSC pools. Furthermore, our in vitro results showed that the inhibition of the CSC-related targets lying at the intersection of the DNA damage, Notch and C-KIT/MAPK/MEK pathways sensitize CSC-enriched tumorspheres to platinum therapies, suggesting a new option for the treatment of patients with platinum-resistant ovarian cancer. CONCLUSIONS: The current study presents a new approach to target the physiology of resistant ovarian tumor cells through the identification of core biomarkers. We hypothesize that the identified mutations confer platinum resistance by converging to activate a few pathways and to induce the expression of a few common, measurable and targetable essential genes. These pathways include the DNA damage, Notch and C-KIT/MAPK/MEK pathways. Finally, the combined inhibition of one of these pathways with platinum treatment increases the sensitivity of CSC-enriched tumorspheres to low doses of platinum, suggesting a new treatment for ovarian cancer.