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.

Long-term use and risk of major adverse cardiac events: Comparing enzalutamide and abiraterone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database in Taiwan to compare long-term effectiveness and risk of major adverse cardiac events (MACE) in chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide (ENZ) or abiraterone (AA). Patients aged 20 years and older and newly receiving androgen receptor targeted therapies ENZ or AA from September 2016 to December 2019 were included. We followed patients from initiation of therapies to the occurrence of outcomes (prostate-specific antigen (PSA) response rate, PSA progression free survival (PFS), overall survival (OS), and MACE), death, the last clinical visit, or December 31, 2020. We performed multivariable Cox proportional hazard models to compare ENZ and AA groups for the measured outcomes. A total of 363 patients treated with either ENZ (n = 157) or AA (n = 206) were identified. The analysis found a significantly higher proportion of patients with a PSA response rate higher than 50% among those receiving ENZ than among those receiving AA (ENZ vs AA: 75.80% vs 63.59%, P = .01). However, there was no significant difference in PSA PFS (adjusted hazard ratio: 0.86; 95% CI 0.63-1.17) and OS (0.68: 0.41-1.14) between the use of ENZ and AA in chemotherapy-naïve mCRPC patients. Regarding the cardiovascular (CV) safety outcome, there was a significantly lower risk of MACE in patients receiving ENZ, compared to patients receiving AA (0.20: 0.07-0.55). The findings suggest that enzalutamide may be more efficacious for PSA response and suitable for chemotherapy-naïve mCRPC patients with high CV risk profile.

The prognostic significance of histologic variant on survival outcomes in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitor therapy.

BACKGROUND: While the treatment guidelines have been established for pure urothelial carcinoma (pUC), patients with variant type urothelial carcinoma (vUC) face limited effective treatment options. The effectiveness of immune checkpoint inhibitors (ICI) in patients with vUC remains uncertain and necessitates additional research. METHOD: We conducted a retrospective, multicenter study to explore the effectiveness of ICI in patients with pUC or vUC in Taiwan. We evaluated the overall response rate (ORR) through univariate logistic regression analysis and examined the overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analysis. Additionally, we employed univariate and multivariate Cox proportional hazards models to analyze the data. RESULT: A total of 142 patients (116 pUC, 26 vUC) were included in our final analysis. The ORR was marginally higher in patients with pUC compared to those with vUC (34.5% vs. 23.1%, p = 0.26). Among all patients, 12.9% with pUC achieved a complete response (CR) after ICI treatment, while no vUC cases achieved CR (p = 0.05). There were no significant differences in PFS (median 3.6 months vs. 4.1 months, p = 0.34) or OS (median 16.3 months vs. 11.0 months, p = 0.24) when comparing patients with pUC or vUC. In the subgroup analysis, patients with pUC who underwent first-line ICI treatment exhibited significantly improved OS compared to those with vUC (24.6 months vs. 9.1 months, p = 0.004). CONCLUSION: The use of ICI as monotherapy is a feasible and effective treatment approach for patients with metastatic vUC.

Associations Between Surrogates' Decisional Regret Trajectories and Bereavement Outcomes.

BACKGROUND: Family surrogates experience heterogeneous decisional regret and negative long-lasting postdecision impacts. Cross-sectional findings on the associations between decisional regret and surrogates' bereavement outcomes are conflicting and cannot illustrate the directional and dynamic evolution of these associations. In this study, we sought to longitudinally examine the associations between 4 previously identified decisional-regret trajectories and bereavement outcomes among family surrogates of terminally ill patients with cancer. PATIENTS AND METHODS: This prospective, longitudinal, observational study included 377 family surrogates. Decisional regret was measured using the 5-item Decision Regret Scale, and 4 decisional regret trajectories were identified: resilient, delayed-recovery, late-emerging, and increasing-prolonged. Associations between bereavement outcomes (depressive symptoms, prolonged grief symptoms, and physical and mental health-related quality of life [HRQoL]) and decisional-regret trajectories were examined simultaneously by multivariate hierarchical linear modeling using the resilient trajectory as a reference. RESULTS: Surrogates in the delayed-recovery, late-emerging, and increasing-prolonged trajectories experienced significantly higher symptoms of prolonged grief (ß [95% CI], 1.815 [0.782 to 2.848]; 2.312 [0.834 to 3.790]; and 7.806 [2.681 to 12.931], respectively) and poorer physical HRQoL (-1.615 [-2.844 to -0.386]; -1.634 [-3.226 to -0.042]; and -4.749 [-9.380 to -0.118], respectively) compared with those in the resilient trajectory. Membership in the late-emerging and increasing-prolonged trajectories was associated with higher symptoms of depression (ß [95% CI], 2.942 [1.045 to 4.839] and 8.766 [2.864 to 14.668], respectively), whereas only surrogates in the increasing-prolonged decisional-regret trajectory reported significantly worse mental HRQoL (-4.823 [-8.216 to -1.430]) than those in the resilient trajectory. CONCLUSIONS: Surrogates who experienced delayed-recovery, unresolved, or late-emerging decisional regret may carry ceaseless doubt, guilt, or self-blame for patient suffering, leading to profound symptoms of prolonged grief, depressive symptoms, and worse HRQoL over their first 2 bereavement years.

Factors associated with cancer patients' distinct death-preparedness states.

BACKGROUND/OBJECTIVE: Facilitating death preparedness is important for improving cancer patients' quality of death and dying. We aimed to identify factors associated with the four death-preparedness states (no-preparedness, cognitive-only, emotional-only, and sufficient-preparedness) focusing on modifiable factors. METHODS: In this cohort study, we identified factors associated with 314 Taiwanese cancer patients' death-preparedness states from time-invariant socio-demographics and lagged time-varying modifiable variables, including disease burden, physician prognostic disclosure, patient-family communication on end-of-life (EOL) issues, and perceived social support using hierarchical generalized linear modeling. RESULTS: Patients who were male, older, without financial hardship to make ends meet, and suffered lower symptom distress were more likely to be in the emotional-only and sufficient-preparedness states than the no-death-preparedness-state. Younger age (adjusted odds ratio [95% confidence interval] = 0.95 [0.91, 0.99] per year increase in age) and greater functional dependency (1.05 [1.00, 1.11]) were associated with being in the cognitive-only state. Physician prognostic disclosure increased the likelihood of being in the cognitive-only (51.51 [14.01, 189.36]) and sufficient-preparedness (47.42 [10.93, 205.79]) states, whereas higher patient-family communication on EOL issues reduced likelihood for the emotional-only state (0.38 [0.21, 0.69]). Higher perceived social support reduced the likelihood of cognitive-only (0.94 [0.91, 0.98]) but increased the chance of emotional-only (1.09 [1.05, 1.14]) state membership. CONCLUSIONS: Death-preparedness states are associated with patients' socio-demographics, disease burden, physician prognostic disclosure, patient-family communication on EOL issues, and perceived social support. Providing accurate prognostic disclosure, adequately managing symptom distress, supporting those with higher functional dependence, promoting empathetic patient-family communication on EOL issues, and enhancing perceived social support may facilitate death preparedness.

Associations of surrogates' death-preparedness states with decisional conflict and heightened decisional regret over cancer patients' last 6 months of life.

OBJECTIVE: Preparing family surrogates for patient death and end-of-life (EOL) decision making may reduce surrogate decisional conflict and regret. Preparedness for patient death involves cognitive and emotional preparedness. We assessed the associations of surrogates' death-preparedness states (that integrate both cognitive and emotional preparedness for patient death) with surrogates' decisional conflict and regret. METHODS: Associations of 173 surrogates' death-preparedness states (no, cognitive-only, emotional-only, and sufficient preparedness states) with decisional conflict (measured by the Decision Conflict Scale) and heightened decisional regret (Decision Regret Scale scores >25) were evaluated using hierarchical linear modeling and hierarchical generalized linear modeling, respectively, during a longitudinal observational study at a medical center over cancer patients' last 6 months. RESULTS: Surrogates reported high decisional conflict (mean [standard deviation] = 41.48 [6.05]), and 52.7% of assessments exceeded the threshold for heightened decisional regret. Surrogates in the cognitive-only preparedness state reported a significantly higher level of decisional conflict (ß = 3.010 [95% CI = 1.124, 4.896]) than those in the sufficient preparedness state. Surrogates in the no (adjusted odds ratio [AOR] [95% CI] = 0.293 [0.113, 0.733]) and emotional-only (AOR [95% CI] = 0.359 [0.149, 0.866]) preparedness states were less likely to suffer heightened decisional regret than those in the sufficient preparedness state. CONCLUSIONS: Surrogates' decisional conflict and heightened decisional regret are associated with their death-preparedness states. Improving emotional preparedness for the patient's death among surrogates in the cognitive-only preparedness state and meeting the specific needs of those in the no, emotional-only, and sufficient preparedness states are actionable high-quality EOL-care interventions that may lessen decisional conflict and decisional regret.

Associations of death-preparedness states with bereavement outcomes for family caregivers of terminally ill cancer patients.

OBJECTIVE: Death preparedness involves cognitive prognostic awareness and emotional acceptance of a relative's death. Effects of retrospectively assessed cognitive prognostic awareness and emotional preparedness for patient death have been individually investigated among bereaved family caregivers. We aimed to prospectively examine associations of caregivers' death-preparedness states, determined by conjoint cognitive prognostic awareness and emotional preparedness for death, with bereavement outcomes. METHODS: Associations of caregivers' death-preparedness states (no-death-preparedness, cognitive-death-preparedness-only, emotional-death-preparedness-only, and sufficient-death-preparedness states) at last preloss assessment with bereavement outcomes over the first two bereavement years were evaluated among 332 caregivers of advanced cancer patients using hierarchical linear models with the logit-transformed posterior probability for each death-preparedness state. RESULTS: Caregivers with a higher logit-transformed posterior probability for sufficient death-preparedness state reported less prolonged-grief symptoms, lower likelihoods of severe depressive symptoms and heightened decisional regret, and better mental health-related quality of life (HRQOL). Caregivers with a higher logit-transformed posterior probability for no-death-preparedness state reported less prolonged-grief symptoms, a lower likelihood of severe depressive symptoms, and better mental HRQOL. A higher logit-transformed posterior probability for cognitive-death-preparedness-only state was associated with bereaved caregivers' higher likelihood of heightened decisional regret, whereas that for emotional-death-preparedness-only state was not associated with caregivers' bereavement outcomes. CONCLUSIONS: Caregivers' bereavement outcomes were associated with their preloss death-preparedness states, except for physical health-related QOL. Interventions focused on not only cultivating caregivers' accurate prognostic awareness but also adequately preparing them emotionally for their relative's forthcoming death are actionable opportunities for high-quality end-of-life care and are urgently warranted to facilitate caregivers' bereavement adjustment.

Modifiable factors of depressive-symptom trajectories from caregiving through bereavement.

BACKGROUND/PURPOSE: The purpose of this secondary-analysis study was to identify never-before-examined factors associated with distinct depressive-symptom trajectories among family caregivers from end-of-life caregiving through the first 2 bereavement years. PARTICIPANTS/METHODS: Participants (N=661) were family caregivers who provided end-of-life caregiving for terminally ill cancer patients. Multinomial logistic regressions were conducted to identify modifiable factors associated with caregivers' seven previously identified depressive-symptom trajectories: minimal-impact resilience, recovery, preloss-depressive-only, delayed symptomatic, relief, prolonged symptomatic, and chronically persistent distressed. Drawing from the stress-appraisal-coping model, modifiable time-varying factors associated with distinct depressive-symptom trajectories were examined in three domains: (1) stressors, (2) stress appraisal, and (3) available resources (internal coping capacity and external social support). RESULTS: Profound objective caregiving demands were associated with caregivers' increased likelihood of belonging to more distressing depressive-symptom trajectories than to the minimal-impact-resilience trajectory. But, stronger negative appraisal of end-of-life caregiving increased odds of caregiver membership in preloss-depressive-only and relief trajectories over the recovery, delayed, and prolonged-symptomatic trajectories. Stronger internal coping capacity and perceived social support buffered the tremendous stress of end-of-life caregiving and permanent loss of a relative, as evidenced by higher odds of being in the minimal-impact-resilience and recovery trajectories. CONCLUSION: Family caregivers' distinct depressive-symptom trajectories were linked to their preloss caregiving demands, appraisal of negative caregiving impact, personal coping capacity, and perceived social support. Our results highlight actionable opportunities to improve end-of-life-care quality by boosting family caregivers' coping capacity and enhancing their social support to help them adequately manage daily caregiving loads/burdens thus relieving the emotional toll before patient death and throughout bereavement.

Gonadotropin-releasing hormone antagonist associated with lower cardiovascular risk compared with gonadotropin-releasing hormone agonist in prostate cancer: A nationwide cohort and in vitro study.

BACKGROUND: We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score-matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional-hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase-9 (MMP-9) expression and invasion ability in THP-1 differentiated macrophages. RESULTS: GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90) than GnRHa therapy, with a mean follow-up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06-0.70) and all-cause mortality (HR, 0.77; 95% CI, 0.61-0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP-9 activity and the invasive ability of THP-1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively. CONCLUSION: GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.

Purely laparoscopic feeding jejunostomy: a procedure which deserves more attention.

BACKGROUND: Laparoscopic procedure has inherent merits of smaller incisions, better cosmesis, less postoperative pain, and earlier recovery. In the current study, we presented our method of purely laparoscopic feeding jejunostomy and compared its results with that of conventional open approach. METHODS: We retrospectively reviewed our patients from 2012 to 2019 who had received either laparoscopic jejunostomy (LJ, n = 29) or open ones (OJ, n = 94) in Chang Gung Memorial Hospital, Linkou. Peri-operative data and postoperative outcomes were analyzed. RESULTS: In the current study, we employed 3-0 Vicryl, instead of V-loc barbed sutures, for laparoscopic jejunostomy. The mean operative duration of LJ group was about 30 min longer than the OJ group (159 ± 57.2 mins vs 128 ± 34.6 mins; P = 0.001). There were no intraoperative complications reported in both groups. The patients in the LJ group suffered significantly less postoperative pain than in the OJ group (mean NRS 2.03 ± 0.9 vs. 2.79 ± 1.2; P = 0.002). The majority of patients in both groups received early enteral nutrition (< 48 h) after the operation (86.2% vs. 74.5%; P = 0.143). CONCLUSIONS: Our study demonstrated that purely laparoscopic feeding jejunostomy is a safe and feasible procedure with less postoperative pain and excellent postoperative outcome. It also provides surgeons opportunities to enhance intracorporeal suture techniques.

Trajectory and predictors of quality of life during the dying process: roles of perceived sense of burden to others and posttraumatic growth.

PURPOSE: Quality of life (QOL) at end of life (EOL) is related to important themes, e.g., "sense of burden to others" and "perceived posttraumatic growth," which have never been investigated concurrently. The purposes of this study were: (1) to describe the trajectory of QOL during the dying process and (2) to identify determinants of QOL, including the roles of perceived sense of burden to others and posttraumatic growth. METHODS: A convenience sample of 313 terminally ill cancer patients was surveyed and longitudinally followed until death. QOL was measured by a modified McGill quality of life scale, and determinants were evaluated by a multiple linear regression model with the generalized estimating equation. RESULTS: Terminally ill Taiwanese cancer patients' QOL decreased substantially as their death approached. However, after controlling for confounders, patients' QOL did not change significantly in the last months of their life. QOL was significantly better for female and non-middle-aged patients with a religious affiliation of Buddhism/Taoism. Poorer QOL tended to be experienced by patients with greater physical symptom distress, anxiety, and depression. Patient QOL increased with greater tangible support, but decreased with greater emotional and affectionate social support. QOL was diminished by a greater degree of perceived burden to others but improved with greater perceived posttraumatic growth. CONCLUSIONS: Deteriorating QOL as death approaches may not be inevitable. Optimal QOL at EOL may be achieved by interventions designed to adequately manage physical and psychological symptoms, enhance social support, lighten perceived sense of burden to others, and facilitate experiences of posttraumatic growth.

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy.

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

Factors Associated With Family Surrogate Decisional-Regret Trajectories.

CONTEXT/OBJECTIVES: The scarce research on factors associated with surrogate decisional regret overlooks longitudinal, heterogenous decisional-regret experiences and fractionally examines factors from the three decision-process framework stages: decision antecedents, decision-making process, and decision outcomes. This study aimed to fill these knowledge gaps by focusing on factors modifiable by high-quality end-of-life (EOL) care. METHODS: This observational study used a prior cohort of 377 family surrogates of terminal-cancer patients to examine factors associated with their membership in the four preidentified distinct decisional-regret trajectories: resilient, delayed-recovery, late-emerging, and increasing-prolonged trajectories from EOL-care decision making through the first two bereavement years by multinomial logistic regression modeling using the resilient trajectory as reference. RESULTS: Decision antecedent factors: Financial sufficiency and heavier caregiving burden increased odds for the delayed-recovery trajectory. Spousal loss, higher perceived social support during an EOL-care decision, and more postloss depressive symptoms increased odds for the late-emerging trajectory. More pre- and postloss depressive symptoms increased odds for the increasing-prolonged trajectory. Decision-making process factors: Making an anticancer treatment decision and higher decision conflict increased odds for the delayed-recovery and increasing-prolonged trajectories. Making a life-sustaining-treatment decision increased membership in the three more profound trajectories. Decision outcome factors: Greater surrogate appraisal of quality of dying and death lowered odds for the three more profound trajectories. Patient receipt of anticancer or life-sustaining treatments increased odds for the late-emerging trajectory. CONCLUSION: Surrogate membership in decisional-regret trajectories was associated with decision antecedent, decision-making process, and decision outcome factors. Effective interventions should target identified modifiable factors to address surrogate decisional regret.

The impact of body mass index on survival endpoints among patients with metastatic urothelial carcinoma undergoing treatment with immune checkpoint inhibitors: A real-world multicenter analysis.

BACKGROUND: Studies on the correlation between high body mass index (BMI) and extended survival among patients receiving immune checkpoint inhibitors (ICIs) have been made, although findings have shown variability. Our research explored the phenomenon of the "obesity paradox" in patients with metastatic urothelial carcinoma (mUC) undergoing treatment with ICIs. MATERIALS AND METHODS: We conducted a retrospective analysis of patients diagnosed with mUC who received a minimum of one cycle of ICI treatment at two medical centers in Taiwan from September 2015 to January 2023. Features of patients' clinicopathologic factors, including age, sex, primary or metastatic location, treatment line, and BMI were examined. The primary outcome were overall survival (OS) and progression-free survival (PFS), which were assessed utilizing the Kaplan-Meier method. We employed the Cox-regression model to adjust for multiple covariates. RESULTS: A total of 215 patients were included, with 128 (59.5%) being male, and the median age was 70 years. In the obese group (BMI ≥25 kg/m2 ), patients demonstrated significantly better median OS compared to the non-obese group (BMI <25 kg/m2 ) (21.9 vs. 8.3 months; p = 0.021). However, there was no significant difference in median PFS between the high and low BMI groups (4.7 vs. 2.8 months; p = 0.16). Post-hoc subgroup revealed a survival benefit from ICI treatment in male patients within the BMI ≥25 kg/m2 group (HR 0.49, 95% CI 0.30-0.81, p = 0.005). CONCLUSION: Based on real-world data from the Asia-Pacific region, there appears to be a correlation between obesity and prolonged OS in patients receiving ICI treatment for mUC.

Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer.

Activated T regulatory (T(reg)) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T(reg) cells and the progression of human colon cancer. We designed a cross-sectional study of CD4(+) Foxp3(+) T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of T(reg) cells with colon cancer stage. The phenotypes, cytokine-release patterns and suppression ability of these T(reg) cells were analyzed. We found that T(reg) cells increased significantly in both peripheral blood and cancer tissue. In addition, the T(reg) cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T(reg) cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T(reg) cells (Foxp3(hi) CD45RA(-)) and nonsuppressive T(reg) cells (Foxp3(lo) CD45RA(-)), but not resting T(reg) cells (Foxp3(low) CD45RA(+)), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T(reg) cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T-cell antigen-4. Activated T(reg) cells, however, secreted significantly lower levels of effector cytokines (interleukin-2, tumor necrosis factor-α and interferon-γ) than did resting T(reg) cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T(reg) cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T(reg) cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.

Impact of palliative care consultative service on disease awareness for patients with terminal cancer.

PURPOSE: Awareness of the status of disease among terminally ill cancer patients is an important part of the end-of-life care. We have evaluated how palliative care consultative service (PCCS) affects patient disease awareness and determined who may benefit from such services in Taiwan. METHODS: In total, 2,887 terminally ill cancer patients consecutively received PCCS between January 2006 and December 2010 at a single medical center in Taiwan, after which they were evaluated for disease awareness. At the beginning of PCCS, 31 % of patients (n = 895) were unaware of their disease status. The characteristics of these 895 patients were analyzed retrospectively to determine variables pertinent to patient disease awareness after PCCS. RESULTS: In total, 485 (50 %) of the 895 patients became aware of their disease at the end of PCCS. Factors significantly associated with higher disease awareness included a longer interval between the date of hospital admission and that of PCCS referral (>4 weeks versus ≤2 weeks), a longer duration of PCCS (>14 days versus ≤7 days), the male gender, divorced marital status (versus married), and family awareness (versus lack of family awareness). Lower disease awareness was associated with older age (age > 75 years versus age = 18-65 years), referral from non-oncology departments, and primary cancer localization (lung, colon-rectum, or urological versus liver). CONCLUSIONS: Disease awareness is affected by multiple factors related to the patients, their families, and the clinicians. The promotion of PCCS increased disease awareness among terminally ill cancer patients in Taiwan.

A cost-effectiveness analysis of avelumab plus best supportive care versus best supportive care alone as first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma in Taiwan.

BACKGROUND: Patients with locally advanced or metastatic urothelial carcinoma have limited treatment options and a poor prognosis. The JAVELIN Bladder 100 trial showed that avelumab as first-line maintenance plus best supportive care significantly prolonged overall survival and progression-free survival versus best supportive care alone in patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line platinum-containing chemotherapy. AIMS: We assessed whether avelumab plus best supportive care is a cost-effective treatment option versus best supportive care alone in this patient group in Taiwan. METHODS AND RESULTS: A partitioned survival model was used to estimate the costs and effects of avelumab plus best supportive care versus best supportive care alone over a 20-year time horizon from the perspective of Taiwan's National Health Insurance Administration. Patient-level data from JAVELIN Bladder 100 on efficacy, safety, utility, and time on treatment were analyzed to provide parameters for the model. Log-normal and Weibull distributions were used for overall survival and progression-free survival, respectively. Costs of healthcare resources, drug acquisition, adverse events, and progression were identified through publicly available data sources and clinician interviews. The model estimated total costs, life years, and quality-adjusted life years. In the modeled base case, avelumab plus best supportive care increased survival versus best supportive care alone by 0.79 life years (2.93 vs. 2.14) and 0.61 quality-adjusted life years (2.15 vs. 1.54). The incremental cost-effectiveness ratio for avelumab plus best supportive care versus best supportive care alone was NT$1 827 680. Most (78%) of the probabilistic sensitivity analyses fell below three times the gross domestic product per capita. Scenario analysis indicated that life year and quality-adjusted life year gains were most sensitive to alternative survival extrapolations for both avelumab plus best supportive care and best supportive care alone. CONCLUSION: Avelumab first-line maintenance therapy combined with best supportive care was determined as a cost-effective treatment strategy for patients in Taiwan diagnosed with locally advanced or metastatic urothelial carcinoma that had not progressed with platinum-containing chemotherapy.

Avelumab first-line maintenance plus best supportive care (BSC) vs. BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Asian subgroup analysis.

BACKGROUND: The phase 3 JAVELIN Bladder 100 trial showed significantly prolonged overall survival (OS) with avelumab first-line maintenance + best supportive care (BSC) vs. BSC alone in patients with advanced urothelial carcinoma (UC) that had not progressed with first-line platinum-containing chemotherapy. Here, efficacy and safety were assessed from the initial analysis of the JAVELIN Bladder 100 trial (data cutoff October 21, 2019) in patients enrolled in Asian countries. METHODS: Patients with locally advanced or metastatic UC that had not progressed with 4 to 6 cycles of first-line platinum-containing chemotherapy (gemcitabine + cisplatin or carboplatin) were randomized 1:1 to receive avelumab first-line maintenance + BSC or BSC alone, stratified by best response to first-line chemotherapy and visceral vs. nonvisceral disease when initiating first-line chemotherapy. The primary endpoint was OS assessed from randomization in all patients and patients with PD-L1+ tumors (Ventana SP263 assay). Secondary endpoints included progression-free survival (PFS) and safety. RESULTS: A total of 147 patients in JAVELIN Bladder 100 were enrolled in Asian countries (Hong Kong, India, Japan, South Korea, and Taiwan). In this Asian subgroup, 73 and 74 patients received avelumab + BSC or BSC alone, respectively. Median OS was 25.3 months (95% CI, 18.6 to not estimable [NE]) in the avelumab + BSC arm vs. 18.7 months (95% CI, 12.8-NE) in the BSC alone arm (hazard ratio [HR], 0.74 [95% CI, 0.43-1.26]); median PFS was 5.6 months (95% CI, 2.0-7.5) vs. 1.9 months (95% CI, 1.9-1.9), respectively (HR, 0.58 [95% CI, 0.38-0.86]). In the avelumab + BSC vs. BSC alone arms, grade ≥3 treatment-emergent adverse events (any causality) occurred in 44.4% vs. 16.2%, respectively. The most common grade ≥3 treatment-emergent adverse events in the avelumab + BSC arm were anemia (9.7%), amylase increased (5.6%), and urinary tract infection (4.2%). CONCLUSIONS: Efficacy and safety results for avelumab first-line maintenance in the Asian subgroup of JAVELIN Bladder 100 were generally consistent with those in the overall trial population. These data support the use of avelumab first-line maintenance as standard of care for Asian patients with advanced UC that has not progressed with first-line platinum-containing chemotherapy. NCT02603432.

Decisional-Regret Trajectories From End-of-Life Decision Making Through Bereavement.

CONTEXT: Regret plays a central role in surrogate decision making. Research on decisional regret in family surrogates is scarce and lacks longitudinal studies to illustrate the heterogenous, dynamic evolution of decisional regret. OBJECTIVES: To identify distinct decisional-regret trajectories from end-of-life (EOL) decision making through the first two bereavement years among surrogates of cancer patients. METHODS: A prospective, longitudinal, observational study was conducted on a convenience sample of 377 surrogates of terminally ill cancer patients. Decisional regret was measured by the five-item Decision Regret Scale monthly during the patient's last six months and 1, 3, 6, 13, 18, and 24 months post loss. Decisional-regret trajectories were identified using latent-class growth analysis. RESULTS: Surrogates reported substantially high decisional regret (pre- and postloss mean [SD] as 32.20 [11.47] and 29.90 [12.47], respectively). Four decisional-regret trajectories were identified. The resilient trajectory (prevalence: 25.6%) showed a general low decisional-regret level with mild and transient perturbations around the time of patient death only. Decisional regret for the delayed-recovery trajectory (56.3%) accelerated before the patient's death and decreased slowly throughout bereavement. Surrogates in the late-emerging (10.2%) trajectory reported a low decisional-regret level before loss but their decisional regret increased gradually thereafter. The increasing-prolonged trajectory (6.9%) rapidly increased in decisional-regret levels during EOL decision making, peaked one-month post loss, then declined steadily but without a complete resolution. CONCLUSION: Surrogates heterogeneously suffered decisional regret from EOL decision making through bereavement as evident by four identified distinct decisional-regret trajectories. Early identification and prevention of increasing/prolonged decisional-regret trajectories is warranted.

Patient-reported Outcomes from JAVELIN Bladder 100: Avelumab First-line Maintenance Plus Best Supportive Care Versus Best Supportive Care Alone for Advanced Urothelial Carcinoma.

BACKGROUND: In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without disease progression with first-line platinum-containing chemotherapy. OBJECTIVE: To evaluate patient-reported outcomes (PROs) with avelumab plus BSC versus BSC alone. DESIGN, SETTING, AND PARTICIPANTS: A randomized phase 3 trial (NCT02603432) was conducted in 700 patients with locally advanced or metastatic urothelial carcinoma that had not progressed with first-line gemcitabine plus cisplatin or carboplatin. PROs were a secondary endpoint. INTERVENTION: Avelumab plus BSC (n = 350) or BSC alone (n = 350). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol five-level EQ-5D (EQ-5D-5L) assessments were analyzed using descriptive statistics and mixed-effect models. Time to deterioration (TTD; prespecified definition: a ≥3-point decrease from baseline in the FBlSI-18 disease-related symptoms-physical subscale for two consecutive assessments) was evaluated via Kaplan-Meier analyses. RESULTS AND LIMITATIONS: Completion rates for scheduled on-treatment PRO assessments were >90% (overall and average per assessment). Results from descriptive analyses and mixed-effect or repeated-measures models of FBlSI-18 and EQ-5D-5L were similar between arms. TTD was also similar, both in the prespecified analysis (hazard ratio 1.26 [95% confidence interval: 0.90, 1.77]) and in the post hoc analyses including off-treatment assessments and different event definitions. Limitations included the open-label design and limited numbers of evaluable patients at later time points. CONCLUSIONS: Addition of avelumab first-line maintenance to BSC in patients with aUC that had not progressed with first-line platinum-containing chemotherapy prolonged OS, with a relatively minimal effect on quality of life. PATIENT SUMMARY: In this trial of people with advanced urothelial carcinoma who had benefited from first-line chemotherapy (ie, had stable disease or reduced tumor size), treatment with avelumab maintenance plus best supportive care (BSC) versus BSC alone improved survival significantly, without compromising quality of life, as reported by the patients themselves.