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.

Pain Standards for Accredited Healthcare Organizations (ACDON Project): A Mixed Methods Study.

Up to 50% of cancer patients and up to 90% of those in terminal stages experience pain associated with disease progression, poor quality of life, and social impact on caregivers. This study aimed to establish standards for the accreditation of oncological pain management in healthcare organizations. A mixed methods approach was used. First, a pragmatic literature review was conducted. Second, consensus between professionals and patients was reached using the Nominal Group and Delphi technique in a step that involved anesthesiologists, oncologists, family physicians, nurses, psychologists, patient representatives, and caregivers. Third, eight hospitals participated in a pilot assessment of the level of fulfillment of each standard. A total of 37 standards were extracted. The Nominal Group produced additional standards, of which 60 were included in Questionnaire 0 that was used in the Delphi Technique. Two Delphi voting rounds were performed to reach a high level of consensus, and involved 64 and 62 participants with response rates of 90% and 87%, respectively. Finally, 39 standards for the management of cancer pain were agreed upon. In the self-evaluation, the average range of compliance was between 56.4% and 100%. The consensus standards of the ACDON Project might improve the monitoring of cancer pain management. These standards satisfied the demands of professionals and patients and could be used for the accreditation of approaches in cancer pain management.

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.

Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option.

Predictive model of complexity in early palliative care: a cohort of advanced cancer patients (PALCOM study).

PROPOSAL: Model of early palliative care (PC) integrated in oncology is based on shared care from the diagnosis to the end of life and is mainly focused on patients with greater complexity. However, there is no definition or tools to evaluate PC complexity. The objectives of the study were to identify the factors influencing level determination of complexity, propose predictive models, and build a complexity scale of PC. PATIENTS AND METHOD: We performed a prospective, observational, multicenter study in a cohort of advanced cancer patients with an estimated prognosis ≤ 6 months. An ad hoc structured evaluation including socio-demographic and clinical data, symptom burden, functional and cognitive status, psychosocial problems, and existential-ethic dilemmas was recorded systematically. According to this multidimensional evaluation, investigator classified patients as high, medium, or low palliative complexity, associated to need of basic or specialized PC. Logistic regression was used to identify the variables influencing determination of level of PC complexity and explore predictive models. RESULTS: We included 324 patients; 41% were classified as having high PC complexity and 42.9% as medium, both levels being associated with specialized PC. Variables influencing determination of PC complexity were as follows: high symptom burden (OR 3.19 95%CI: 1.72-6.17), difficult pain (OR 2.81 95%CI:1.64-4.9), functional status (OR 0.99 95%CI:0.98-0.9), and social-ethical existential risk factors (OR 3.11 95%CI:1.73-5.77). Logistic analysis of variables allowed construct a complexity model and structured scales (PALCOM 1 and 2) with high predictive value (AUC ROC 76%). CONCLUSION: This study provides a new model and tools to assess complexity in palliative care, which may be very useful to manage referral to specialized PC services, and agree intensity of their intervention in a model of early-shared care integrated in oncology.

Outcome prognostic factors in inoperable malignant bowel obstruction.

PURPOSE: Inoperable malignant bowel obstruction (MBO), a severe complication of peritoneal carcinomatosis, has a low desobstruction rate (30-40 %) and end-of-life decision-making is hampered by the lack of known prognostic factors. This study aimed to explore prognostic factors for desobstruction in MBO. METHODS: All patients with inoperable MBO admitted in our large oncology hospital between 2010 and 2013 were treated following a clinical protocol based on antiemetics, steroids and two antisecretories, octreotide, and hyoscine butylbromide. Two prognostic factor analyses using logistic regressions were performed, one based on data from day 1 of admission and the other on data from day 8. RESULTS: Forty-five patients were included. Frequency of desobstruction was 48.9 %. In the analysis of prognostic factors on day 1, MBO episodes derived from functional physiopathologic mechanisms (vs. mechanic or mixed) were more prone to resolve (p < 0.001 corrected for multiple comparisons). Considering patients alive with persistent obstruction on day 8, a better clinical condition was the variable more associated with desobstruction, but without statistical significance after correction for multiple comparisons. CONCLUSIONS: A functional physiopathologic mechanism of MBO development may be an early prognostic factor for desobstruction. A high proportion of desobstruction was observed, suggesting that the combination of antisecretories with different mechanism of action warrants further investigation.

Clinical evaluation and optimal management of cancer cachexia.

Cancer anorexia-cachexia syndrome (CACS) is a complex metabolic syndrome, different from malnutrition and sarcopenia, which is very common in cancer patients. Treatment for CACS is based on nutritional support and CACS pathophysiology-modulating drugs. The most commonly used are megestrol acetate (MA) and corticosteroids. The efficacy of MA has been confirmed by multiple clinical trials and meta-analyses. Glucocorticoids are also effective but should only be used for short periods and in selected cases. Future strategies should include intensified research into potentially effective drugs (ω-3 fatty acids, thalidomide, cannabinoids, ghrelin, bortezomib, and COX-2 inhibitors), combined treatment and new drugs (anti-IL-6 monoclonal antibodies, melanocortin, ß-2 antagonists, and androgen receptor-modulating analogues). We propose a review based on the literature on the pathophysiology of CACS, the diagnostic criteria and treatment, and future strategies.

Malignant bowel obstruction in advanced cancer patients: epidemiology, management, and factors influencing spontaneous resolution.

Malignant bowel obstruction (MBO) is a frequent complication in advanced cancer patients, especially in those with abdominal tumors. Clinical management of MBO requires a specific and individualized approach that is based on disease prognosis and the objectives of care. The global prevalence of MBO is estimated to be 3% to 15% of cancer patients. Surgery should always be considered for patients in the initial stages of the disease with a preserved general status and a single level of occlusion. Less invasive approaches such as duodenal or colonic stenting should be considered when surgery is contraindicated in obstructions at the single level. The priority of care for inoperable and consolidated MBO is to control symptoms and promote the maximum level of comfort possible. The spontaneous resolution of an inoperable obstructive process is observed in more than one third of patients. The mean survival is of no longer than 4-5 weeks in patients with consolidated MBO. Polymodal medical treatment based on a combination of glucocorticoids, strong opioids, antiemetics, and antisecretory drugs achieves very high symptomatic control. This review focuses on the epidemiological aspects, diagnosis, surgical criteria, medical management, and factors influencing the spontaneous resolution of MBO in advanced cancer patients.

Effectiveness of palliative care services in symptom control of patients with advanced terminal cancer: a spanish, multicenter, prospective, quasi-experimental, pre-post study.

CONTEXT: In implementing the National Strategy of Palliative Care in Spain, there needs to be an evaluation of services, especially of their effectiveness, efficiency, and satisfaction of patients and families. OBJECTIVES: To assess the effectiveness of palliative care services (PCS) in improving symptom control in Spain. METHODS: This multicenter, prospective, quasi-experimental, pre-post intervention study evaluated symptoms, such as pain, breakthrough pain, anorexia, nausea/vomiting, constipation, insomnia, dyspnea at rest and with movement, anxiety, and depression, using patient-reported numeric rating scales on Days 0, 7, and 14 after referral to a PCS. RESULTS: Of the 318 PCSs included in the National Directory for 2004, 105 services in the 17 autonomous regions of Spain were able to report 265 eligible (treatment-naïve) patients. Nonparticipation by some centers was because of excessive workload or because their patients were not treatment-naïve. Median survival was 42 days. Pain severity and number of crises of breakthrough pain significantly improved, as did other indicators of patient satisfaction. Symptom improvement was independent of type of service (in acute bed hospitals, medium-term stay facilities, hospital support teams, home care support teams, and outpatient clinics). CONCLUSION: Our national plan appears to be successful in reducing symptoms irrespective of the type of organization providing the PCS. An area for improvement could be to lessen the workload of individual teams.

Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review.

Until now only intravenous and oral formulations of 5HT(3) receptor antagonists have been available. Recently a new formulation of a 5HT(3) receptor antagonist, transdermal granisetron, has been developed, and approved by the FDA. Three phase I studies to evaluate its pharmacokinetic profile have shown that granisetron administered by a transdermal delivery system is absorbed by passive diffusion and maximal concentration is reached 48 hours after patch application. The patch of 52 cm(2), which contains 34.3 mg of granisetron, releases 3.3 mg of the drug every day and maintains a stable average plasma concentration of 2.2 ng/mL over 6 days, similar to levels obtained with 2 mg of oral granisetron, administered every day during the same period of time. Two randomized as yet unpublished clinical trials (phase II/III) have been conducted to evaluate the antiemetic efficacy of transdermal granisetron in chemotherapy-induced nausea and vomiting, in patients receiving moderately and highly emetogenic chemotherapy, compared with 2 mg of oral granisetron. More than 800 cancer patients were included in the trials. The rate of complete control of acute emesis was 49% for the phase II trial and 60% for the phase III trial. Neither trial showed a statistically significant difference between transdermal and oral granisetron. The control of delayed emesis was observed in 46% of patients, and there were no statistically significant differences between transdermal and oral granisetron. The most common adverse effects in both trials were constipation (<7%) and headache (<1%); there were no statistically significant differences between transdermal and oral granisetron. These data show that transdermal granisetron is effective and safe in controlling acute emesis induced by chemotherapy with both moderate and high emetogenic potential. Efficacy and safety of transdermal granisetron are fully comparable with that of oral granisetron. More clinical trials using regimens of 2 or 3 drugs, including dexamethasone and/or aprepitant, are needed to confirm the place of transdermal granisetron in the control of chemotherapy-induced nausea and vomiting.

Efficacy of granisetron in the antiemetic control of nonsurgical intestinal obstruction in advanced cancer: a phase II clinical trial.

The objective of this study was to assess antiemetic efficacy of granisetron in inoperable intestinal obstruction caused by advanced cancer. The study was open, prospective, and multi-centered. We assessed 24 patients (mean age: 61.3 years; 10 males, 14 females) with intestinal obstruction who were refractory to previous antiemetics. Obstruction involved the upper intestine in six patients, the lower intestine in three, and was at multiple levels in 15. Daily treatment included intravenous granisetron (3mg) and dexamethasone (8 mg); nasogastric drainage was not allowed. Subcutaneous haloperidol was available as rescue therapy. A numeric scale was used to evaluate nausea, pain, asthenia, and anorexia at baseline visit and every 24 hours up to the completion of four days of treatment (final visit). Treatment failure was defined as nausea >4 on the numeric scale, vomiting 2/day or more, and rescue therapy with haloperidol at 5mg/day or more. Of the 24 patients, 23 were evaluable for efficacy. Evaluation pre- vs. post-treatment indicated a significant decrease in the severity of nausea (score 6.9 vs. 0.8; P<0.001), number of episodes of vomiting (5.3 vs. 1.0; P<0.001), and abdominal pain (score 4.4 vs. 1.2; P<0.001). Nausea and vomiting control was achieved in 86.9% of patients. Although there was a trend toward greater efficacy in the lower and multiple levels of obstruction, the differences were not statistically significant owing, probably, to small sample size. We conclude that granisetron may be highly efficacious in the control of emesis resulting from intestinal obstruction caused by metastatic cancer, and can be used effectively in patients refractory to other antiemetics.

Conversion from parenteral to oral methadone.

The described ratio for methadone conversion from oral route (PO) to parenteral route (PAR) is 2:1 and from PAR to PO is 1:2. Frequently, good control of pain with methadone is PR to PO. We use methadone as a function of opioid rotation and not in the context of mortality outcome and we have noted that the traditional ratio produces toxicity problems. We present our experience with patients who we converted from PAR to PO methadone and we recommend a conversion ratio of 0.7 (PO:PAR = 1:0.7), which approximates the bioavailability of the drug administered orally.

Resource consumption and costs of palliative care services in Spain: a multicenter prospective study.

Patients (n=395) with terminal-stage cancer receiving attention from palliative care services (PCSs) were recruited over a period of 15 consecutive days from 171 participating PCS units. Resource consumption and costs were evaluated for 16 weeks of follow-up, and the findings were compared with a study conducted in 1992 so as to assess change over time. The most frequent health care interventions were homecare visits, hospital admissions, and patient-consultant phone calls. PCS provided 67% of all services and consultation interventions in 91% of patients. Compared with the historical data, there was a significant shift from the use of conventional hospital beds toward palliative care beds, a reduced hospital stay (25.5-19.2 days; P=0.002), an increase in the death-at-home option (31%-42%), a lower use of hospital emergency rooms (52%-30.6%; P=0.001), and an increase in programmed care. Compared to the previous resource consumption and expenditure study in 1992, the current PCS policy implies a cost saving of 61%, with greater efficiency and no compromise of patient care.