Associations Between Family-Assessed Quality-of-Dying-and-Death Latent Classes and Bereavement Outcomes for Family Surrogates of ICU Decedents.

OBJECTIVES: To examine associations between family surrogates' bereavement outcomes and four previously determined quality of dying and death (QODD) latent classes (high, moderate, poor-to-uncertain, and worst). DESIGN: Prospective, longitudinal, observational study. SETTING: Medical ICUs at two academically affiliated medical centers in Taiwan. PATIENTS/PARTICIPANTS: Three hundred nine family surrogates responsible for decision-making for critically ill patients at high risk of death (Acute Physiology and Chronic Health Evaluation II scores > 20) from a disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by the depression and anxiety subscales of the Hospital Anxiety and Depression Scale, the Impact of Event Scale-Revised, 11 items of the Prolonged Grief Disorder (PGD) scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey at 1, 3, 6, 13, 18, and 24 months post-loss. We simultaneously examined associations of four QODD latent classes with physical and mental health-related quality of life (HRQOL) and symptoms of anxiety, depression, post-traumatic stress disorder (PTSD), and PGD assessed over 24 bereavement months using multivariate hierarchical linear modeling. Surrogates' distinct QODD latent classes assessed at 1-month post-loss were significantly associated with bereavement outcomes, except for physical HRQOL and PGD symptoms. Significantly more depressive symptoms and worse mental HRQOL (ß [95% CI]) were reported by bereaved surrogates in the moderate (1.958 [1.144-2.772], -2.245 [-3.961 to -0.529]), poor-to-uncertain (2.224 [1.438-3.010], -7.026 [-8.683 to -5.369]), and worst (2.081 [1.215-2.964], -4.268 [-6.096 to -2.440]) QODD classes than those in the high QODD class. Bereaved surrogates in the moderate (2.095 [1.392-2.798]) and poor-to-uncertain (0.801 [0.123-1.480]) QODD classes reported more anxiety symptoms, whereas those in the poor-to-uncertain QODD class suffered more PTSD symptoms (2.889 [1.005-4.774]) than those in the high QODD class. CONCLUSIONS: The four distinct QODD latent classes were significantly associated with ICU family surrogates' bereavement outcomes, suggesting targets to improve end-of-life care quality in ICUs.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Serum Cytokines Correlate with Pretreatment Body Mass Index-adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery.

Serum Cytokines Correlate with Pretreatment Body Mass Index-Adjusted Body Weight Loss Grading and Cancer Progression in Patients with Stage III Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Chemoradiotherapy Followed by Surgery. Circulating cytokines have been linked to the development of esophageal squamous cell carcinoma (ESCC) and its associated malnutrition process. Nonetheless, given the varied disease stages and treatment modalities in previous studies, the clinical relevance of their findings is limited. We retrospectively studied 52 patients with stage III ESCC who underwent neoadjuvant chemoradiotherapy and curative-intent surgery. We investigated the association of clinicopathological features, pretreatment laboratory data, and pretreatment inflammatory status, as indicated by the levels of albumin, C-reactive protein, and 10 circulating cytokines, namely tumor necrosis factor-alpha (TNF-α), interferon-gamma, interleukin-1-beta (IL-1ß), IL-4, IL-6, IL-8, IL-12, IL-13, IL-17A, and IL-23, with malnutrition, as shown by body mass index-adjusted body weight loss (BMI-BWL) grading, cancer progression. Half the patients showed severe malnutrition and high BMI-BWL grades (3 and 4). Multivariate analysis revealed an independent association between the levels of three cytokines (TNF-α, ≤ 5.8 pg/ml; IL-1ß, > 0.4 pg/ml; IL-6, ≤ 12.4 pg/ml) and high BMI-BWL grades and between IL-4 levels > 22.5 pg/ml and cancer progression. All 10 cytokines were closely correlated with each other. In conclusion, TNF-α, IL-1ß, and IL-6 were independent markers of malnutrition status and IL-4 was a prognostic factor for cancer progression in this patient population.

Frailty is an independent factor for health-related quality of life in patients with head and neck cancer receiving definitive concurrent chemoradiotherapy.

PURPOSE: Health-related quality of life (HRQoL) is associated with treatment-related complications and poor survival in patients with head and neck cancer (HNC). We investigated the effects of frailty on HRQoL in patients with HNC receiving definitive concurrent chemoradiotherapy (CCRT). METHODS: A total of 461 consecutive patients with locally advanced HNC who received CCRT between 2017 and 2018 at three medical centers in Taiwan were included. Frailty and HRQoL were assessed using the Comprehensive Geriatric Assessment and QLQ-H&N35 before CCRT. The sum score was calculated based on the first 30 questions of QLQ-H&N35. Multivariate analysis was performed to evaluate the impact of frailty on HRQoL. RESULTS: The overall sum score was 39 (34-49). The sum scores of patients with impairments in 0, 1, 2, 3, and ≥ 4 frailty domains were 34 (32-38), 40 (34-47), 46 (36-55), 48 (41-64), and 56 (50-60), respectively. Patients with impairments in more frailty domains had a higher symptom burden (p for trend < 0.001). Frail patients tended to experience symptoms across all QLQ-H&N35 subscales. Sex, body mass index, tumor type, tumor stage, Eastern Cooperative Oncology Group performance status, and frailty were determinants of HRQoL in the univariate analysis. Frailty was an independent determinant of HRQoL in the multivariate analysis. CONCLUSION: Routine frailty assessment may serve as a surrogate for the selection of patients with HNC with poor HRQoL before CCRT. Further studies are needed to determine whether appropriate interventions in frail patients would improve their HRQoL during CCRT.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

Factors of preparedness for loss from cancer among Taiwanese family caregivers.

This cohort study investigated factors associated with 336 Taiwanese family caregivers' emotional and cognitive preparedness for death of a loved one with terminal cancer. Caregivers' death-preparedness states (no-death-preparedness [as reference], cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) were previously identified. Associations of factors with these states were determined by a hierarchical generalized linear model. Financial hardship decreased caregivers' likelihood for the emotional-death-preparedness-only and sufficient-death-preparedness states. Physician prognostic disclosure increased membership in the cognitive-death-preparedness-only and sufficient-death-preparedness states. The better the quality of the patient-caregiver relationship, the higher the odds for the emotional-death-preparedness-only and sufficient-death-preparedness states, whereas the greater the tendency for caregivers to communicate end-of-life issues with their loved one, the lower the odds for emotional-death-preparedness-only state membership. Stronger coping capacity increased membership in the emotional-death-preparedness-only state, but perceived social support was not associated with state membership. Providing effective interventions tailored to at-risk family caregivers' specific needs may facilitate their death preparedness.

Clinical characteristics and genetic HLA marker for patients with oxaliplatin-induced adverse drug reactions.

BACKGROUND: Oxaliplatin is commonly used to treat gastrointestinal malignancies. However, its applications are limited due to potential adverse drug reactions (ADRs), particularly severe anaphylactic shock. There is no method to predict or prevent ADRs caused by oxaliplatin. Therefore, we aimed to investigate the genetic HLA predisposition and immune mechanism of oxaliplatin-induced ADRs. METHODS: A retrospective review was performed for 154 patients with ADRs induced by oxaliplatin during 2016-2021 recorded in our ADR notification system. HLA genotyping was conducted for 47 patients with oxaliplatin-induced ADRs, 1100 general population controls, and 34 oxaliplatin-tolerant controls in 2019-2023. The in vitro basophil activation test (BAT) was performed and oxaliplatin-specific IgE levels were determined. RESULTS: The incidence of oxaliplatin-induced ADRs and anaphylactic shock in our cohort was 7.1% and 0.15%, respectively. Of the 154 patients, 67.5% suffered rash/eruption; 26.0% of the patients who could not undergo oxaliplatin rechallenge were considered to show oxaliplatin-induced immune-mediated hypersensitivity reactions (HRs). The genetic study found that the HLA-DRB∗12:01 allele was associated with oxaliplatin-induced HRs compared to the general population controls (sensitivity = 42.9%; odds ratio [OR] = 3.4; 95% CI = 1.4-8.2; P = 0.008) and tolerant controls (OR = 12; 95% CI = 2.3-63.7; P = 0.001). The in vitro BAT showed higher activation of CD63+ basophils in patients with oxaliplatin-induced HRs compared to the tolerant controls (P < 0.05). Only four patients (8.5%) with oxaliplatin-induced ADRs were positive for oxaliplatin-specific IgE. CONCLUSIONS: This study found that 26.0% of patients with oxaliplatin-induced ADRs could not undergo oxaliplatin rechallenge. HLA-DRB∗12:01 is regarded as a genetic marker for oxaliplatin-induced hypersensitivity.

Evaluating the cancer aging and research group model in predicting immunochemotherapy toxicity among elderly patients with diffuse large B-cell lymphoma.

BACKGROUND: The management of diffuse large B-cell lymphoma (DLBCL) in elderly patients is complicated by an increased risk of treatment-related toxicity associated with aging. This study aimed to validate the effectiveness of the Cancer Aging and Research Group (CARG) model in elderly patients with DLBCL receiving rituximab-based chemotherapy. METHODS: In this prospective study, elderly DLBCL patients (aged 65 years or older) receiving rituximab-based chemotherapy were consecutively assessed between August 2016 and December 2021 at one medical center in Taiwan using the CARG model to predict treatment-related toxicity. Patients were categorized into low-, medium-, and high-risk groups based on their CARG scores. Comparisons were made regarding toxicities and survival rates among these groups. RESULTS: Ninety-one patients, with a median age of 70 years (range 65-96), were included. A substantial 81 % (74 patients) experienced grade 3-5 toxicity. The overall 2-year survival rate was 63.8 % after a median follow-up of 28 months (range, 2-46). The risk of grade 3-5 toxicity was 83 %, 78 %, and 87 %, respectively, among the low-, medium-, and high-risk groups (p = 0.60). The receiver operating characteristic (ROC) curve for CARG was 0.521 (95 % CI, 0.376-0.666), which was significantly lower than that for the Eastern Cancer Oncology Group score (ROC = 0.701, 95 % CI, 0.571-0.831). Similarly, compared with those of low-risk patients, hazard ratios for overall survival were 9.22 (95 % CI, 1.23-69.1; p = 0.031) and 14.6 (95 % CI, 1.90-112; p = 0.010) for medium- and high-risk patients, respectively. CONCLUSION: While CARG exhibited limitations in predicting treatment-related toxicity in elderly DLBCL patients, it demonstrated potential efficacy in predicting survival outcomes.

Integrating Frailty Assessment to Enhance Care in Cancer Patients with Borderline Eastern Cooperative Oncology Group Performance Status.

BACKGROUND: The (ECOG) performance status (PS) is commonly used to evaluate the functional ability of patients undergoing antitumor therapy. An ECOG PS of 2, indicating patients capable of self-care but restricted strenuous activity, can complicate treatment decisions owing to concerns regarding treatment-related toxicity. We investigated whether frailty assessment could help discriminate treatment tolerance and survival outcomes in patients with an ECOG PS of 2. METHODS: We prospectively included 45 consecutive patients, aged ≥65 years, with an ECOG PS of 2, and newly diagnosed solid cancer scheduled for chemotherapy. Frailty was assessed using an eight-indicator geriatric assessment. The primary outcome was overall survival (OS) based on frailty status; secondary outcomes included treatment tolerance and toxicity. RESULTS: The median patient age was 73 years (range 65-94), and 71% had stage IV disease. Predominant frailty-related deficits were functional decline (96%), malnutrition (78%), and polypharmacy (51%). The median OS was 12.6 months (95% confidence interval [CI]: 6.8-18.4). Patients with 4-6 deficits had significantly lower OS than those with 1-3 deficits (9.9 months vs. 20.0 months, adjusted hazard ratio 2.51, 95% CI: 1.16-5.44, P = .020). Frailty significantly correlated with reduced 12-week chemotherapy competence (52% vs. 85%, adjusted odds ratio [OR] .14, 95% CI: .03-.70, P = .016) and enhanced risk of unexpected hospitalization (60% vs. 20%, adjusted OR 6.80, 95% CI: 1.64-28.1, P = .008). CONCLUSION: Our findings highlight the multifaceted nature of patients with an ECOG PS of 2 and emphasize the importance of frailty assessment for treatment outcomes.

Factors Associated With Quality-of-Dying-and-Death Classes Among Critically Ill Patients.

Importance: Improving end-of-life care in the intensive care unit (ICU) is a priority, but clinically modifiable factors of quality of dying and death (QODD) are seldom identified. Objectives: To comprehensively identify factors associated with QODD classes of dying ICU patients, emphasizing clinically modifiable factors based on the integrative framework of factors associated with for bereavement outcomes. Design, Setting, and Participants: This observational cohort study was conducted at medical ICUs of 2 Taiwanese medical centers from January 2018 to March 2020 with follow-up through December 2022. Eligible participants included primary family surrogates responsible for decision making for critically ill ICU patients at high risk of death (Acute Physiology and Chronic Health Evaluation II score >20) but who survived more than 3 days after ICU admission. Data analysis was conducted from July to September 2023. Main Outcomes and Measures: QODD was measured by the 23-item ICU-QODD questionnaire. Factors associated with patient membership in 4 previously determined QODD classes (high, moderate, poor to uncertain, and worst) were examined using a 3-step approach for latent class modeling with the high QODD class as the reference category. Results: A total of 309 family surrogates (mean [SD] age, 49.83 [12.55] years; 184 women [59.5%] and 125 men [40.5%]) were included in the study. Of all surrogates, 91 (29.4%) were the patients' spouse and 66 (53.7%) were the patients' adult child. Patient demographics were not associated with QODD class. Two family demographics (age and gender), relationship with the patient (spousal or adult-child), and length of ICU stay were associated with QODD classes. Patients of surrogates perceiving greater social support were less likely to be in the poor to uncertain (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94) and worst (aOR, 0.92; 95% CI, 0.87-0.96) QODD classes. Family meetings were associated with the poor to uncertain QODD class (aOR, 8.61; 95% CI, 2.49-29.74) and worst QODD class (aOR, 7.28; 95% CI, 1.37-38.71). Death with cardiopulmonary resuscitation was associated with the worst QODD class (aOR, 7.51; 95% CI, 1.12-50.25). Family presence at patient death was uniformly negatively associated with the moderate QODD class (aOR, 0.16; 95% CI, 0.05-0.54), poor to uncertain QODD class (aOR, 0.21; 95% CI, 0.05-0.82), and worst QODD class (aOR, 0.08; 95% CI, 0.02-0.38). Higher family satisfaction with ICU care was negatively associated with the poor to uncertain QODD class (aOR, 0.93; 95% CI, 0.87-0.98) and worst QODD class (aOR, 0.86; 95% CI, 0.81-0.92). Conclusions and Relevance: In this cohort study of critically ill patients and their family surrogates, modifiable end-of-life ICU-care characteristics played a more significant role in associations with patient QODD class than did immutable family demographics, preexisting family health conditions, patient demographics, and patient clinical characteristics, thereby illuminating actionable opportunities to improve end-of-life ICU care.

Systemic treatments in pancreatic cancer: Taiwan pancreas society recommendation.

Pancreatic cancer is a highly aggressive malignancy with a poor prognosis. Over the past decade, significant therapeutic advancements have improved the survival rates of patients with pancreatic cancer. One of the primary factors contributing to these positive outcomes is the evolution of chemotherapy, from monotherapy to doublet or triplet regimens, and the integration of multimodal approaches. Additionally, targeted agents tailored to patients with specific genetic alterations and the development of cell therapies show promise in benefiting certain subpopulations. This article focuses on examining pivotal studies that explore the role of chemotherapy in neoadjuvant, adjuvant, maintenance, and salvage settings; highlights interesting findings related to cell therapy; and provides an overview of ongoing trials concerning metastatic settings. This review primarily aimed to offer recommendations based on therapeutic evidence, recent advancements in new treatment combinations, and the most innovative approaches. A unique aspect of this review is the inclusion of published papers on clinical trials and real-world data in Taiwan, thus adding a valuable perspective to the overall analysis.

Efficacy of first-line combination therapies versus gemcitabine monotherapy for advanced pancreatic cancer: a systematic review and network meta-analysis.

Various first-line gemcitabine-based or fluorouracil-based combination regimens were approved in patients with advanced pancreatic cancer. Recent randomized clinical trials (RCTs) have investigated chemotherapy backbones in combination with novel investigational drugs, including chemotherapy agents or targeted drugs. However, the comparative efficacy of these different combination therapies remains limited. This systematic review and network meta-analysis aimed to assess the efficacy of first-line combination therapies for advanced pancreatic cancer. The study included 46 RCTs with 10,499 patients and 47 distinct regimens, using data sources from MEDLINE, EMBASE, Cochrane Clinical Trials, and ClinicalTrials.gov from January 1, 2010 to April 23, 2024. The primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included overall response rate (ORR) and disease control rate (DCR). The analysis revealed that gemcitabine+nab-paclitaxel (GA), GA with platinum and fluorouracil (GA+Plat+FU), gemcitabine with fluorouracil (G+FU), G+Plt+FU, and FOLFIRINOX were associated with superior OS and PFS compared to gemcitabine monotherapy. Triplet or quadruplet polychemotherapy combinations, such as GA+Plat+FU, G+Plt+FU, and FOLFIRINOX, demonstrated better OS benefit with hazard ratios of 0.42 (95% CI, 0.26-0.68), 0.41 (95% CI, 0.24-0.71), and 0.58 (95% CI, 0.48-0.71), respectively, compared to doublet regimens like GA and G+FU, which had hazard ratios of 0.70 (95% CI, 0.59-0.82) and 0.82 (95% CI, 0.72-0.95), respectively. Notably, no targeted drugs, monoclonal antibodies, or other medications showed improved survival when added to chemotherapy backbones. These findings support the use of gemcitabine-based or fluorouracil-based triplet or quadruplet regimens for better survival outcomes in patients with advanced pancreatic cancer. Further research is warranted to explore the potential benefits of adding chemotherapy agents, such as fluorouracil, to the GA doublet regimen.

All-cause and immune checkpoint inhibitor-associated acute kidney injury in immune checkpoint inhibitor users: a meta-analysis of occurrence rate, risk factors and mortality.

Background: Immune checkpoint inhibitors (ICIs) have been associated with acute kidney injury (AKI). However, the occurrence rate of ICI-related AKI has not been systematically examined. Additionally, exposure to proton pump inhibitors (PPIs) and non-steroidal anti-inflammatory drugs (NSAIDs) were considered as risk factors for AKI, but with inconclusive results in ICI-related AKI. Our aim was to analyse the occurrence rate of all-cause AKI and ICI-related AKI and the occurrence rates of severe AKI and dialysis-requiring AKI, and to determine whether exposure to PPIs and NSAIDs poses a risk for all-cause and ICI-related AKI. Methods: This study population was adult ICI recipients. A systematic review was conducted by searching MEDLINE, Embase and PubMed through October 2023. We included prospective trials and observational studies that reported any of the following outcomes: the occurrence rate of all-cause or ICI-related AKI, the relationship between PPI or NSAID exposure and AKI development or the mortality rate in the AKI or non-AKI group. Proportional meta-analysis and pairwise meta-analysis were performed. The evidence certainty was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Results: A total of 120 studies comprising 46 417 patients were included. The occurrence rates of all-cause AKI were 7.4% (14.6% from retrospective studies and 1.2% from prospective clinical trials). The occurrence rate of ICI-related AKI was 3.2%. The use of PPIs was associated with an odds ratio (OR) of 1.77 [95% confidence interval (CI) 1.43-2.18] for all-cause AKI and an OR of 2.42 (95% CI 1.96-2.97) for ICI-related AKI. The use of NSAIDs was associated with an OR of 1.77 (95% CI 1.10-2.83) for all-cause AKI and an OR of 2.57 (95% CI 1.68-3.93) for ICI-related AKI. Conclusions: Our analysis revealed that approximately 1 in 13 adult ICI recipients may experience all-cause AKI, while 1 in 33 adult ICI recipients may experience ICI-related AKI. Exposure to PPIs and NSAIDs was associated with an increased OR risk for AKI in the current meta-analysis.