Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Impact of systemic cancer treatment on quality of life and mental well-being: a comparative analysis of patients with localized and advanced cancer

Introduction This study investigated the impact of systemic cancer therapy on the quality of life, mental well-being, and life satisfaction of cancer patients. Methods This prospective study was promoted by the Spanish Society of Medical Oncology (SEOM) and enrolled patients with localized, resected, or unresectable advanced cancer from 15 Spanish medical oncology departments. Patients completed surveys on quality of life (EORTC-QoL-QLQ-C30), psychological distress (BSI-18) and life satisfaction (SWLS) before and after systemic cancer treatment. Results The study involved 1807 patients, 944 (52%) having resected, localized cancer, and 863 with unresectable advanced cancer. The mean age was 60 years, and 53% were female. The most common types of localized cancer were colorectal (43%) and breast (38%), while bronchopulmonary (32%), non-colorectal digestive (23%), and colorectal (15%) were the most frequent among those with advanced cancer. Before systemic treatment, patients with advanced cancer had poorer scores than those with localized cancer on physical, role, emotional, cognitive, social limitations, symptoms, psychological distress, and life satisfaction (all p < 0.001), but there were no differences in financial hardship. Patients with localized cancer had greater life satisfaction and better mental well-being than those with advanced cancer before systemic treatment (p < 0.001). After treatment, patients with localized cancer experienced worsening of all scales, symptoms, and mental well-being (p < 0.001), while patients with advanced disease had a minor decline in quality of life. The impact on quality of life was greater on all dimensions except economic hardship and was independent of age, cancer location, and performance status in participants with resected disease after adjuvant chemotherapy (AU)

Coping strategies as mediators of uncertainty and psychological distress in patients with advanced cancer.

PURPOSE: Uncertainty in the context of advanced cancer diagnosis often incurs significant psychological distress. The aims were to evaluate the incidence of psychological distress upon diagnosis of advanced cancer and to analyze whether the relationship between illness uncertainty and psychological distress can be mediated by coping strategies. METHODS: A multicenter, prospective, cross-sectional study was conducted in 15 medical oncology departments across Spain. Individuals with unresectable advanced cancer completed questionnaires on uncertainty (Michel Uncertainty of Illness Scale, coping strategies (Mental Adjustment to Cancer, M-MAC), and psychological distress (Brief Symptom Inventory, BSI-18) after the diagnostic and treatment appointment and before beginning systemic cancer treatment. RESULTS: 841 patients eligible for systemic treatment with palliative intent were included between February 2020 and April 2022. A total of 71.7% had clinically significant levels of psychological distress. Univariate analyses identified that the groups with less psychological distress were male (ηp2  = 0.016), married (ηp2  = 0.006), and had a better performance status (ηp2  = 0.007). The most widely used coping strategies were positive attitude and cognitive avoidance. A positive relationship was found between uncertainty, coping strategies, and psychological distress (p < 0.05). Participants who responded with anxious preoccupation suffered more helplessness and psychological distress, while those who responded with cognitive avoidance displayed greater positive attitude and lesser psychological distress. CONCLUSION: Patients with newly diagnosed unresectable advanced cancer frequently experience psychological distress in the face of uncertainty, potentially influenced by coping strategies like cognitive avoidance.

Clinicians' and Advanced Cancer Patients' Estimates of Treatment Efficacy and Toxicity in Oncologic Treatment.

The purpose of the study was to compare curability expectations between clinicians and patients and examine the influence of sociodemographic and clinical variables on these expectations and satisfaction within the clinician-patient relationship. This prospective study, conducted from February 2020 to May 2023, involved 986 advanced cancer patients. The patients completed questionnaires assessing treatment efficacy and toxicity predictions and the Scale to Assess the Therapeutic Relationship (STAR). Seventy-four percent of advanced cancer patients had an inaccurate perception of treatment curability. Clinicians perceived male patients with lung or digestive cancer without adenocarcinoma at locally advanced stages, with fewer comorbidities and better functional status (ECOG), as having higher curability expectations. Clinicians tended to have more realistic expectations than patients, since they had to consider the presence of treatment's side effects, while patients underestimated the possibility of experiencing these adverse effects. Patients who had more favorable expectations regarding survival and quality of life were found to be more satisfied with the care provided by their oncologists. It is crucial for patients to understand the treatment goals and establish realistic expectations in order to actively participate in decision-making and achieve a better quality of life at the end of life.

Impact of systemic cancer treatment on quality of life and mental well-being: a comparative analysis of patients with localized and advanced cancer.

INTRODUCTION: This study investigated the impact of systemic cancer therapy on the quality of life, mental well-being, and life satisfaction of cancer patients. METHODS: This prospective study was promoted by the Spanish Society of Medical Oncology (SEOM) and enrolled patients with localized, resected, or unresectable advanced cancer from 15 Spanish medical oncology departments. Patients completed surveys on quality of life (EORTC-QoL-QLQ-C30), psychological distress (BSI-18) and life satisfaction (SWLS) before and after systemic cancer treatment. RESULTS: The study involved 1807 patients, 944 (52%) having resected, localized cancer, and 863 with unresectable advanced cancer. The mean age was 60 years, and 53% were female. The most common types of localized cancer were colorectal (43%) and breast (38%), while bronchopulmonary (32%), non-colorectal digestive (23%), and colorectal (15%) were the most frequent among those with advanced cancer. Before systemic treatment, patients with advanced cancer had poorer scores than those with localized cancer on physical, role, emotional, cognitive, social limitations, symptoms, psychological distress, and life satisfaction (all p < 0.001), but there were no differences in financial hardship. Patients with localized cancer had greater life satisfaction and better mental well-being than those with advanced cancer before systemic treatment (p < 0.001). After treatment, patients with localized cancer experienced worsening of all scales, symptoms, and mental well-being (p < 0.001), while patients with advanced disease had a minor decline in quality of life. The impact on quality of life was greater on all dimensions except economic hardship and was independent of age, cancer location, and performance status in participants with resected disease after adjuvant chemotherapy. CONCLUSION: In conclusion, our study highlights that systemic cancer treatment can improve quality of life in patients with advanced cancer, while adjuvant treatments for localized disease may have a negative impact on quality of life and psychological well-being. Therefore, treatment decisions should be carefully evaluated on an individual basis.

The Relationship between Therapeutic Alliance and Quality of Care in Patients with Advanced Cancer in Spain.

The therapeutic alliance is an important factor in successful cancer treatment, particularly for those with advanced cancer. This study aims to determine how the therapeutic alliance relates to prognostic preferences and satisfaction with the physician and medical care among patients with advanced cancer. We conducted a cross-sectional study to explore the therapeutic relationship, trust, satisfaction with healthcare, and prognostic preferences among 946 patients with advanced cancer at 15 tertiary hospitals in Spain. Participants completed questionnaires with self-reported measures. Most were male, aged > 65 years, with bronchopulmonary (29%) or colorectal (16%) tumors and metastatic disease at diagnosis. Results revealed that 84% of patients had a good therapeutic alliance. Collaborative and affective bond was positively associated with a preference to know the prognosis and satisfaction with care and decision. There was no difference in a therapeutic alliance based on clinical or sociodemographic factors. The therapeutic alliance between patient and physician is essential for successful treatment outcomes and better overall satisfaction. Therefore, it is vital for healthcare providers to focus on establishing and maintaining a strong relationship with their patients. To achieve this, transparency and care should be prioritized, as well as respect for the preferences of patients regarding the prognosis of their illness.

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.

Using the emotional functioning in clinical practice to detect psychological distress in patients with advanced thoracic and colorectal cancer.

PURPOSE: Patients with advanced cancer suffer significant decline of their psychological state. A rapid and reliable evaluation of this state is essential to detect and treat it and improve quality of life. The aim was to probe the usefulness of the emotional function (EF) subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EF-EORTC-QLQ-C30) to assess psychological distress in cancer patients. METHODS: This is a multicenter, prospective, observational study involving 15 Spanish hospitals. Patients diagnosed with unresectable advanced thoracic or colorectal cancer were included. Participants completed the Brief Symptom Inventory 18 (BSI-18), the current the gold standard, and the EF-EORTC-QLQ-C30 to assess their psychological distress prior to initiating systemic antineoplastic treatment. Accuracy, sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV) were calculated. RESULTS: The sample comprised 639 patients: 283 with advanced thoracic cancer and 356 with advanced colorectal cancer. According to the BSI scale, 74% and 66% displayed psychological distress with an EF-EORTC-QLQ-C30 accuracy of 79% and 76% in detecting psychological distress in individuals with advanced thoracic and colorectal cancer, respectively. Sensitivity was 79 and 75% and specificity was 79 and 77% with a PPV of 92 and 86% and a NPV of 56 and 61% (scale cut-off point, 75) for patients with advanced thoracic and colorectal cancer, respectively. The mean AUC for thoracic cancer was 0.84 and, for colorectal cancer, it was 0.85. CONCLUSION: This study reveals that the EF-EORTC-QLQ-C30 subscale is a simple and effective tool for detecting psychological distress in people with advanced cancer.

Evolution of RAS Mutations in Cell-Free DNA of Patients with Tissue RAS Wild-Type Metastatic Colorectal Cancer Receiving First-Line Treatment: The PERSEIDA Study.

The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA RAS (KRAS/NRAS) mutational status evolution in first-line, metastatic CRC, RAS wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred and nineteen patients were included (102 received panitumumab and chemotherapy as first-line treatment-panitumumab subpopulation). Fifteen (12.6%) patients presented baseline cfDNA RAS mutations (n = 14 [13.7%], panitumumab subpopulation) (mutant allele fraction ≥0.02 for all results). No patients presented emergent mutations (cfDNA RAS mutations not present at baseline) at 20 weeks. At disease progression, 11 patients (n = 9; panitumumab subpopulation) presented emergent mutations (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], panitumumab subpopulation). In contrast, three (5.2%) patients presenting baseline cfDNA RAS mutations were RAS wild-type at disease progression. No significant associations were observed between overall response rate or progression-free survival and cfDNA RAS mutational status in the total panitumumab subpopulation. Although, in patients with left-sided tumors, a significantly longer progression-free survival was observed in cfDNA RAS wild-type patients compared to those presenting cfDNA RAS mutations at any time. Continuous evaluation of RAS mutations may provide valuable insights on tumor molecular dynamics that can help clinical practice.

Anxiety and depression in patients with advanced cancer during the COVID-19 pandemic.

OBJECTIVE: Cancer patients are at increased risk for psychological difficulties and COVID-19. We sought to analyze anxiety and depression levels during the COVID-19 pandemic and the association between sociodemographic, clinical, and psychological factors in patients with advanced cancer. METHODS: A prospective, multicenter cohort of 401 consecutive patients with newly diagnosed, advanced cancer completed the Brief Symptom Inventory, Michel Uncertainty in Illness Scale, Herth Hope Index, and Cancer Worry Scale between February 2020 and May 2021. Linear regression analyses explored the effects of uncertainty, hopelessness, and cancer worry on anxiety and depression, adjusting for sociodemographic and clinical variables. RESULTS: The incidence of anxiety and depression was 36% and 35%, respectively. Emotional distress was greater among women, patients < 65 years of age, and those with an estimated survival of > 18 months. Linear regression analysis revealed that being female, preoccupation about cancer, and hopelessness were associated with increased levels of anxiety (p < 0.001) and depression (p < 0.001) and younger age was associated with a higher risk of anxiety. No differences in anxiety or depression levels were found in relation to marital status, children, educational level, cancer type, histology, stage, or type of treatment. CONCLUSIONS: Patients with advanced cancer who initiated treatment during the pandemic experienced high levels of depression and anxiety. Early diagnosis and the development of intervention strategies are necessary, especially for specific patient subgroups, such as young women with long survival times.