Background
Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies.
Methods
Recent, relevant ...peer‐reviewed evidence were critically reviewed and summarized.
Results
This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed.
Conclusion
Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies.
Objective
Unprecedently investigate associations of prognostic‐awareness‐transition patterns with (changes in) depressive symptoms, anxiety symptoms, and quality of life (QOL) during cancer patients' ...last 6 months.
Methods
In this secondary analysis study, 334 cancer patients in their last 6 months transitioned between four prognostic‐awareness states (unknown and not wanting to know, unknown but wanting to know, inaccurate awareness, and accurate awareness), thus constituting three transition patterns: maintaining‐accurate‐, gaining‐accurate‐, and maintaining‐inaccurate/unknown prognostic awareness. A multivariate hierarchical linear model evaluated associations of the transition patterns with depressive symptoms, anxiety symptoms, and QOL determined at final assessment and by mean difference between the first and last assessment.
Results
At the last assessment before death, the gaining‐accurate‐prognostic‐awareness group reported higher levels of depressive symptoms (estimate 95% confidence interval = 1.59 0.35–2.84) and the maintaining‐ and gaining‐accurate‐prognostic‐awareness groups suffered more anxiety symptoms (1.50 0.44–2.56; 1.42 0.13–2.71, respectively) and poorer QOL (−7.07 −12.61 to 1.54; −11.06 −17.76 to −4.35, respectively) than the maintaining‐inaccurate/unknown‐prognostic‐awareness group. Between the first and last assessment, the maintaining‐ and gaining‐accurate‐prognostic‐awareness groups' depressive symptoms (1.59 0.33–2.85; 3.30 1.78–4.82, respectively) and QOL (−5.04 −9.89 to –0.19; −8.86 −14.74 to −2.98, respectively) worsened more than the maintaining‐inaccurate/unknown‐prognostic‐awareness group, and the gaining‐accurate‐prognostic‐awareness group's depressive symptoms increased more than the maintaining‐accurate‐prognostic‐awareness group (1.71 0.42–3.00).
Conclusions
Unexpectedly, patients who maintained/gained accurate prognostic awareness suffered more depression, anxiety, and poorer QOL at end of life. Promoting accurate prognostic awareness earlier in the terminal‐cancer trajectory should be supplemented with adequate psychological care to alleviate patients' emotional distress and enhance QOL.
Trial registration: ClinicalTrials.gov:NCT01912846.
Negative selection-based circulating tumor cell (CTC) isolation is believed valuable to harvest more native, and in particular all possible CTCs without biases relevant to the properties of surface ...antigens on the CTCs. Under such a cell isolation strategy, however, the CTC purity is normally compromised. To address this issue, this study reports the integration of optically-induced-dielectrophoretic (ODEP) force-based cell manipulation, and a laminar flow regime in a microfluidic platform for the isolation of untreated, and highly pure CTCs after conventional negative selection-based CTC isolation. In the design, six sections of moving light-bar screens were continuously and simultaneously exerted in two parallel laminar flows to concurrently separate the cancer cells from the leukocytes based on their size difference and electric properties. The separated cell populations were further partitioned, delivered, and collected through the two flows. With this approach, the cancer cells can be isolated in a continuous, effective, and efficient manner. In this study, the operating conditions of ODEP for the manipulation of prostate cancer (PC-3) and human oral cancer (OEC-M1) cells, and leukocytes with minor cell aggregation phenomenon were first characterized. Moreover, performances of the proposed method for the isolation of cancer cells were experimentally investigated. The results showed that the presented CTC isolation scheme was able to isolate PC-3 cells or OEC-M1 cells from a leukocyte background with high recovery rate (PC-3 cells: 76-83%, OEC-M1 cells: 61-68%), and high purity (PC-3 cells: 74-82%, OEC-M1 cells: 64-66%) (set flow rate: 0.1 μl min(-1) and sample volume: 1 μl). The latter is beyond what is currently possible in the conventional CTC isolations. Moreover, the viability of isolated cancer cells was evaluated to be as high as 94 ± 2%, and 95 ± 3% for the PC-3, and OEC-M1 cells, respectively. Furthermore, the isolated cancer cells were also shown to preserve their proliferative capability. As a whole, this study has presented an ODEP-based microfluidic platform that is capable of isolating CTCs in a continuous, label-free, cell-friendly, and particularly highly pure manner. All these traits are found particularly meaningful for exploiting the harvested CTCs for the subsequent cell-based, or biochemical assays.
Background:
Factors facilitating/hindering concordance between preferred and received life-sustaining treatments may be distorted if preferences and predictors are measured long before death.
Aim:
To ...examine factors facilitating/hindering concordance between cancer patients’ preferred and received life-sustaining-treatment states in their last 6 months.
Design:
Longitudinal, observational design.
Setting/participants:
States of preferred and received life-sustaining treatments (cardio-pulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, and nasogastric tube feeding) were examined in 218 Taiwanese cancer patients by a latent transition model with hidden Markov modeling. Multivariate logistic regression modeling was used to examine factors facilitating/hindering concordance between preferred and received life-sustaining-treatment states.
Results:
Concordance between preferred and received life-sustaining-treatment states was poor (40.8%, kappa value (95% confidence interval): 0.05 –0.03, 0.14). Patients who accurately understood their prognosis and preferred comfort care were significantly more likely to receive preferred life-sustaining treatments before death than those who did not know their prognosis but wanted to know, those who were uniformly uncertain about what life-sustaining treatments they preferred to receive, and those who preferred nutritional support but declined other life-sustaining treatments. Patient age, physician–patient end-of-life-care discussions, symptom distress, and functional dependence were not associated with concordance between preferred and received life-sustaining-treatment states.
Conclusion:
Prognostic awareness and preferred states of life-sustaining treatments were significantly associated with concordance between preferred and received life-sustaining-treatment states. Personalized interventions should be developed to cultivate terminally ill cancer patients’ accurate prognostic awareness, allowing them to formulate realistic life-sustaining-treatment preferences and facilitating their receiving value-concordant end-of-life care.
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.
Background/Objective
Cognitive prognostic awareness (PA) and emotional preparedness for death are distinct but related concepts that have rarely been investigated conjointly and without considering ...the dynamic nature of death preparedness. To fill this gap, this secondary‐analysis study identified distinct patterns/states of death preparedness and their changes within cancer patients' last 6 months.
Methods
Distinct death‐preparedness states, determined by conjoint cognitive PA and emotional preparedness for death, as well as their changes between consecutive times were identified and estimated, respectively, by latent transition modeling with hidden Markov modeling among 383 cancer patients within their last 6 months.
Results
Four death‐preparedness states (prevalence) were initially identified: no death preparedness (17.1%), cognitive death preparedness only (23.3%), emotional death preparedness only (39.9%), and sufficient death preparedness (19.7%). Patients in the no‐death‐preparedness state had neither accurate PA nor adequate emotional preparedness for death. The sufficient‐death‐preparedness state was characterized by both accurate PA and adequate emotional preparedness for death. In the cognitive‐ and emotional‐death‐preparedness‐only states, patients were accurately aware of their prognosis and adequately emotionally prepared for their forthcoming death only, respectively. As death approached, state prevalence fluctuated within a narrow range for the no‐ and sufficient‐death‐preparedness states, whereas prevalence of cognitive‐ and emotional‐death‐preparedness‐only states increased and decreased substantially, respectively.
Conclusion
Cancer patients heterogeneously experienced conjoint cognitive PA and emotional preparedness for death, and prevalence of death‐preparedness states changed substantially as death approached. Effective interventions are warranted to cultivate cognitive PA and facilitate emotional death‐preparedness to improve end‐of‐life‐care quality, thereby helping patients achieve a good death.
Objective
Quality of life (QOL) and psychological distress at end of life (EOL) heavily depend on symptom distress and functional impairment, which may not deteriorate synchronously at EOL.
Methods
...Using multivariate hierarchical linear modeling, we simultaneously evaluated the differential association of 5 previously identified, worsening conjoint symptom‐functional states with QOL, anxiety symptoms, and depressive symptoms over 317 terminally ill cancer patients' last year of life. Quality of life, anxiety symptoms, and depressive symptoms were measured by the McGill Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale, respectively.
Results
Quality of life, anxiety symptoms, and depressive symptoms deteriorated significantly more for patients in the 4 worst symptom‐functional states (states 2‐5) than in the best state (state 1). Quality of life did not differ significantly among patients in states 2 to 5. However, patients in state 4 had significantly lower anxiety‐symptom levels than patients in states 2, 3, and 5, whose anxiety‐symptom levels did not differ significantly. In contrast, depressive‐symptom levels differed significantly between participants in any 2 of the worst symptom‐functional states, except between participants in states 3 and 5 as well as between those in states 2 and 4.
Conclusion
The 5 distinct symptom‐functional states contributed to worsening QOL, anxiety symptoms, and depressive symptoms, but each was negatively and uniquely associated with psychological well‐being in terminally ill cancer patients' last year of life.
Clinical Implications
The psychological well‐being and QOL of high‐risk patients in states 3 and 5 may be improved at EOL by targeting them with appropriate symptom management interventions and facilitating their functioning.
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.
What's new?
While second generation androgen receptor (AR)‐targeted therapies are promising for the treatment of chemotherapy‐naïve metastatic castration‐resistant prostate cancer (mCRPC), data on survival benefit and cardiovascular safety are lacking. Here, using a multi‐institutional electronic health records database, the authors investigated the effectiveness, long‐term outcome, and cardiovascular safety of the AR‐targeted mCRPC therapies enzalutamide and abiraterone. Compared to abiraterone, enzalutamide is more efficacious in terms of prostate‐specific antigen response and carries a lower risk of major adverse cardiac events. The findings are relevant for treatment decisions regarding AR‐targeted therapies for chemotherapy‐naïve mCRPC patients with high risk of adverse cardiovascular events.
Terminally ill cancer patients do not engage in end-of-life (EOL) care discussions or do so only when death is imminent, despite guidelines for EOL care discussions early in their disease trajectory. ...Most studies on patient-reported EOL care discussions are cross sectional without exploring the evolution of EOL care discussions as death approaches. Cross-sectional studies cannot determine the direction of association between EOL care discussions and patients' prognostic awareness, psychological well-being, and quality of life (QOL).
We examined the evolution and associations of accurate prognostic awareness, functional dependence, physical and psychological symptom distress, and QOL with patient-physician EOL care discussions among 256 terminally ill cancer patients in their last six months by hierarchical generalized linear modeling with logistic regression and by arranging time-varying modifiable variables and EOL care discussions in a distinct time sequence.
The prevalence of physician-patient EOL care discussions increased as death approached (9.2%, 11.8%, and 18.3% for 91–180, 31–90, and 1–30 days before death, respectively) but only reached significance in the last month. Accurate prognostic awareness facilitated subsequent physician-patient EOL care discussions, whereas better patient-reported QOL and more anxiety symptoms hindered such discussions. The likelihood of EOL care discussions was not associated with levels of physical symptom distress, functional dependence, or depressive symptoms.
Physician-patient EOL care discussions for terminally ill Taiwanese cancer patients remain uncommon even when death approaches. Physicians should facilitate EOL care discussions by cultivating patients' accurate prognostic awareness early in their cancer trajectory when they are physically and psychologically competent, with better QOL, thus promoting informed and value-based EOL care decision making.
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