Prevalence of ethical dilemmas in advanced cancer patients (secondary analysis of the PALCOM study).

PURPOSE: The main aim of this study was to determine the prevalence of ethical dilemmas in the end-of-life process in advanced cancer patients. METHODS: We carried out a multicenter, cross-sectional, observational, prospective study in a cohort of cancer patients whose life expectancy was ≤ 6 months. We recorded sociodemographic characteristics, diagnosis of cancer, symptom burden, cognitive and functional status, emotional impact, and sociofamilial risk factors. The main outcome measure was the detection of ethical dilemmas, based on the following definition: conflict in decision-making during the end-of-life process that involves the need to choose between morally acceptable opposing options, where none is clearly preferable to another. RESULTS: We included 324 patients (mean age, 69 years; 58% men). We identified 117 dilemmas in 90 patients (27.8%). The dilemmas detected were as follows: (a) conflicts of information (adaptive denial, conspiracy of silence, information exceeding patient's desired limit), 15.7%; (b) discrepancies in proportionality (discussion on futility, rejection of treatment, withdrawal of life support measures), 16.7%; (c) unrealistic expectations about the outcome of clinical trials, 2.5%; and (d) request for euthanasia or medically assisted suicide, 1.2%. We observed a greater prevalence of ethical dilemmas in men, in patients receiving active cancer treatment, and in patients with emotional distress (p < 0.05). CONCLUSIONS: The prevalence of ethical dilemmas during the end-of-life process in cancer patients is relevant. Most dilemmas were associated directly or indirectly with respect for patient autonomy. In this context, the communication skills of the health professionals and advanced care planning take on a key role.

Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy.

BACKGROUND: Predicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC). METHODS: Gene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used. RESULTS: Basal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7%, 30.6%, 18.2%, and 10.3% of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2-positive disease, and in TNBC. The pCR rate of Basal-like disease was >35% across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5% (92.8-100.0%) was observed in these neoadjuvant-treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4% of Luminal A tumors with clinically node-negative disease). CONCLUSIONS: Intrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any).

Evolution of Complexity of Palliative Care Needs and Patient Profiles According to the PALCOM Scale (Part Two): Pooled Analysis of the Cohorts for the Development and Validation of the PALCOM Scale in Advanced Cancer Patients.

INTRODUCTION: Identifying the complexity of palliative care needs is a key aspect of referral to specialized multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains developed in 2018 and validated in 2023 to identify the level of complexity in patients with advanced cancer. (1) Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and the survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. (2) Method: An observational, prospective, multicenter study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were as follows: (a) instability ratio (IR), defined as the probability of level change or death; (b) emergency department visits; (c) days of hospitalization; (d) hospital death; (e) survival. All the variables were analyzed monthly according to the level of complexity assigned at the baseline visit. (3) Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p < 0.001). No significant differences in mean monthly emergency department visits (0.2 visits/ patient/month) were observed between the different levels of complexity. The mean number of days spent in hospital per month was 1.5 in the low complexity group, 1.8 in the medium complexity group and 3.2 in the high complexity group (p < 0.001). The likelihood of in-hospital death was significantly higher in the high complexity group (29%) compared to the medium (16%) and low (8%) complexity groups (p < 0.001). Six-month survival was significantly lower in the high complexity group (24%) compared to the medium (37%) and low (57%) complexity groups (p < 0.001). CONCLUSION: According to the PALCOM scale, more complex cases are associated with greater instability and use of hospital resources and lower survival. The data also confirm that the PALCOM scale is a consistent and useful tool for describing complexity profiles, targeting referrals to the EPC and managing the intensity of shared care.

Characterisation and Outcomes of Patients with Solid Organ Malignancies Admitted to the Intensive Care Unit: Mortality and Impact on Functional Status and Oncological Treatment.

BACKGROUND: Despite the increasing number of ICU admissions among patients with solid tumours, there is a lack of tools with which to identify patients who may benefit from critical support. We aim to characterize the clinical profile and outcomes of patients with solid malignancies admitted to the ICU. METHODS: Retrospective observational study of patients with cancer non-electively admitted to the ICU of the Hospital Clinic of Barcelona (Spain) between January 2019 and December 2019. Data regarding patient and neoplasm characteristics, ICU admission features and outcomes were collected from medical records. RESULTS: 97 ICU admissions of 84 patients were analysed. Lung cancer (22.6%) was the most frequent neoplasm. Most of the patients had metastatic disease (79.5%) and were receiving oncological treatment (75%). The main reason for ICU admission was respiratory failure (38%). Intra-ICU and in-hospital mortality rates were 9.4% and 24%, respectively. Mortality rates at 1, 3 and 6 months were 19.6%, 36.1% and 53.6%. Liver metastasis, gastrointestinal cancer, hypoalbuminemia, elevated basal C-reactive protein, ECOG-PS greater than 2 at ICU admission, admission from ward and an APACHE II score over 14 were related to higher mortality. Functional status was severely affected at discharge, and oncological treatment was definitively discontinued in 40% of the patients. CONCLUSION: Medium-term mortality and functional deterioration of patients with solid cancers non-electively admitted to the ICU are high. Surrogate markers of cachexia, liver metastasis and poor ECOG-PS at ICU admission are risk factors for mortality.

Epidemiology and risk factors for recurrence in biliary source bloodstream infection episodes in oncological patients.

We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008-2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906-7.503), biliary prosthesis (OR 2.232, 95% CI 1.157-4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338-8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389-5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

Validation Study of the PALCOM Scale of Complexity of Palliative Care Needs: A Cohort Study in Advanced Cancer Patients.

BACKGROUND: In a patient-centred model of care, referral to early palliative care (EPC) depends on both the prognosis and the complexity of care needs. The PALCOM scale is a 5-domain multidimensional assessment tool developed to identify the level of complexity of palliative care needs of cancer patients. The aim of this study was to validate the PALCOM scale. PATIENT AND METHODS: We conducted a prospective cohort study of cancer patients to compare the PALCOM scale and expert empirical assessment (EA) of the complexity of palliative care needs. The EA had to categorise patients according to their complexity, considering that medium to high levels required priority attention from specialist EPC teams, while those with low levels could be managed by non-specialist teams. Systematically collected multidimensional variables were recorded in an electronic report form and stratified by level of complexity and rating system (PALCOM scale versus EA). The correlation rank (Kendall's tau test) and accuracy test (F1-score) between the two rating systems were analysed. ROC curve analysis was used to determine the predictive power of the PALCOM scale. RESULTS: A total of 283 advanced cancer patients were included. There were no significant differences in the frequency of the levels of complexity between the EA and the PALCOM scale (low 22.3-23.7%; medium 57.2-59.0%; high 20.5-17.3%). The prevalence of high symptom burden, severe pain, functional impairment, socio-familial risk, existential/spiritual problems, 6-month mortality and in-hospital death was significantly higher (p < 0.001) at the high complexity levels in both scoring systems. Comparative analysis showed a high correlation rank and accuracy between the two scoring systems (Kendall's tau test 0.81, F1 score 0.84). The predictive ability of the PALCOM scale was confirmed by an area under the curve in the ROC analysis of 0.907 for high and 0.902 for low complexity. CONCLUSIONS: In a patient-centred care model, the identification of complexity is a key point to appropriate referral and management of shared care with EPC teams. The PALCOM scale is a high precision tool for determining the level of complexity of palliative care needs.

Severe Immune-Related Adverse Events: A Case Series of Patients Needing Hospital Admission in a Spanish Oncology Referral Center and Review of the Literature.

Immune checkpoint inhibitors (ICI) have revolutionized the landscape of cancer treatment. Although several studies have shown that ICIs have a better safety profile than chemotherapy, some patients develop immune-related adverse events (irAEs), which require specialized and multidisciplinary management. Since ICI indications are rapidly increasing, it is crucial that clinicians involved in cancer care learn to identify irAEs and manage them properly. Here, we report a case series of 23 patients with severe irAEs requiring hospitalization over a period of 12 months and seize the opportunity to review and update different general features related to irAEs along with the management of the most frequent severe irAEs in our series.

COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry.

BACKGROUND: Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post-COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae. METHODS: OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided. RESULTS: Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR = 0.57, 95% CI: 0.36 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found. CONCLUSIONS: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development.

Palliative Care in Diffuse Interstitial Lund Disease: Results of a Spanish Survey. / Cuidados paliativos en la enfermedad pulmonar intersticial difusa: resultados de una encuesta de ámbito nacional.

INTRODUCTION: Interstitial lung diseases (ILD) and, in particular, idiopathic pulmonary fibrosis, may have a significant impact on patient survival. Recent studies highlight the need for palliative care (PC) in the management of ILD patients. The aim of this study was to determine the current situation of PC in patients in Spain. METHODS: A 36-question survey addressing the main aspects of PC in ILD patients was designed. The survey was sent via email to all members of the Spanish Society of Pulmonology and Thoracic Surgery. Participation was voluntary. RESULTS: One hundred and sixty-four participants responded to the survey. Ninety-eight percent said they were interested in PC, 46% had received specific training, and 44% reported being responsible for PC in their ILD patients. Symptom control and end-of-life stage were the most frequent reasons for referral to PC teams. Regarding end-of-life, 78% reported consensual agreement with patients on the limitation of therapeutic efforts, 35% helped prepare an end-of-life advance directive, and 22% agreed on the place of death. CONCLUSION: Despite the well-known need for PC in patients with ILD and the notable interest of the survey participants in this subject, there are clear formative and organizational gaps that should be addressed to improve care in this area in ILD patients in Spain.

Limitations in predicting PAM50 intrinsic subtype and risk of relapse score with Ki67 in estrogen receptor-positive HER2-negative breast cancer.

PAM50/Prosigna gene expression-based assay identifies three categorical risk of relapse groups (ROR-low, ROR-intermediate and ROR-high) in post-menopausal patients with estrogen receptor estrogen receptor-positive (ER+)/ HER2-negative (HER2-) early breast cancer. Low risk patients might not need adjuvant chemotherapy since their risk of distant relapse at 10-years is below 10% with endocrine therapy only. In this study, 517 consecutive patients with ER+/HER2- and node-negative disease were evaluated for Ki67 and Prosigna. Most of Luminal A tumors (65.6%) and ROR-low tumors (70.9%) had low Ki67 values (0-10%); however, the percentage of patients with ROR-medium or ROR-high disease within the Ki67 0-10% group was 42.7% (with tumor sizes ≤2 cm) and 33.9% (with tumor sizes > 2 cm). Finally, we found that the optimal Ki67 cutoff for identifying Luminal A or ROR-low tumors was 14%. Ki67 as a surrogate biomarker in identifying Prosigna low-risk outcome patients or Luminal A disease in the clinical setting is unreliable. In the absence of a well-validated prognostic gene expression-based assay, the optimal Ki67 cutoff for identifying low-risk outcome patients or Luminal A disease remains at 14%.

Life-threatening colitis and complete response with ipilimumab in a patient with metastatic BRAF-mutant melanoma and rheumatoid arthritis.

Immune checkpoint inhibitors, such as ipilimumab (an anti-CTLA4 antibody), have become a commonly used therapy in cancer. To date, safety data of patients with underlying autoimmune disease is limited. We present a case of a patient with rheumatoid arthritis who was diagnosed of a BRAF-mutant metastatic melanoma. The patient was treated with ipilimumab and presented with high-grade colitis requiring immunosuppressors. Despite of the immune-related adverse event, no exacerbation of the rheumatoid arthritis was observed and the patient achieved a complete response. This case report contributes to the scarce literature on the use of immune checkpoint inhibitors in patients with an underlying autoimmune condition.

Clinical implications of the intrinsic molecular subtypes of breast cancer.

Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

Cuidados paliativos en la enfermedad pulmonar intersticial difusa: resultados de una encuesta de ámbito nacional / Palliative Care in Diffuse Interstitial Lund Disease: Results of a Spanish Survey

Introducción: Las enfermedades pulmonares intersticiales difusas (EPID) y, concretamente, la fibrosis pulmonar idiopática, pueden tener un elevado impacto en la supervivencia de los pacientes. Recientes estudios destacan la necesidad de implementar los cuidados paliativos (CP) en el manejo del enfermo con EPID. El objetivo del estudio fue conocer la situación actual de los CP en nuestro país. Métodos: Se diseñó una encuesta de 36 preguntas, que abordaba los principales aspectos de los CP en el paciente con EPID. Esta encuesta fue remitida a través de correo electrónico a todos los miembros de la Sociedad Española de Neumología y Cirugía Torácica, cuya participación fue voluntaria. Resultados: Cientosesenta y cuatro participantes respondieron a la encuesta. El 98% manifestó tener interés en los CP, 46% habían recibido formación específica. El 44% refirió ser el responsable de los CP en sus pacientes EPID. El control de síntomas y la fase final de vida fueron los motivos más frecuentes de derivación a los equipos de CP. Referente a la fase final de vida el 78% refirió consensuar con los pacientes la limitación del esfuerzo terapéutico, el 35% realizar un documento de voluntades anticipadas y el 22% consensuar el lugar de fallecimiento. Conclusión: A pesar de la conocida necesidad del CP en los pacientes con EPID y el notable interés de los participantes de la encuesta en este tema, existen claras lagunas formativas y organizativas, que deberían ser contempladas para mejorar la atención sobre esta área de salud en los pacientes con EPID de nuestro país (AU)

Introduction: Interstitial lung diseases (ILD) and, in particular, idiopathic pulmonary fibrosis, may have a significant impact on patient survival. Recent studies highlight the need for palliative care (PC) in the management of ILD patients. The aim of this study was to determine the current situation of PC in patients in Spain. Methods: A 36-question survey addressing the main aspects of PC in ILD patients was designed. The survey was sent via email to all members of the Spanish Society of Pulmonology and Thoracic Surgery. Participation was voluntary. Results: One hundred and sixty-four participants responded to the survey. Ninety-eight percent said they were interested in PC, 46% had received specific training, and 44% reported being responsible for PC in their ILD patients. Symptom control and end-of-life stage were the most frequent reasons for referral to PC teams. Regarding end-of-life, 78% reported consensual agreement with patients on the limitation of therapeutic efforts, 35% helped prepare an end-of-life advance directive, and 22% agreed on the place of death. Conclusion: Despite the well-known need for PC in patients with ILD and the notable interest of the survey participants in this subject, there are clear formative and organizational gaps that should be addressed to improve care in this area in ILD patients in Spain (AU)