A systematically structured review of biomarkers of dying in cancer patients in the last months of life; An exploration of the biology of dying

Abstract

BackgroundThe Neuberger review made a number of recommendations to improve end of life care, including research into the biology of dying. An important aspect of the biology of dying is the identification of biomarkers as indices of disease processes. Biomarkers have the potential to inform the current, limited understanding of the dying process and assist clinicians in recognising dying, in particular how to distinguish dying from reversible acute deterioration.ObjectivesTo critically appraise the literature on biological factors that may be used as prognostic indicators in advanced cancer patients and to identify candidate biomarkers of the dying process that can be measured serially in cancer patients’ bodily fluids.MethodsA systematically structured review was conducted using three electronic databases. A hand search of six peer-reviewed journals and conference abstracts was also conducted. Studies reporting prognostic biomarkers in cancer patients with a median survival of ≤90 days and post-mortem studies were included. Final levels of evidence and recommendations were made using the Evidence Based Medicine modified GRADE system.Results30 articles were included. Seven prognostic biological factors demonstrated Grade A evidence (lymphocyte count, white blood cell count, serum C-reactive protein, albumin, sodium, urea and alkaline phosphatase). An additional eleven prognostic factors were identified with Grade B evidence (platelet count, international normalised ratio, serum vitamin B12, prealbumin, bilirubin, cholesterol, aspartate aminotransferase, alanine transaminase, lactate dehydrogenase, pseudocholinesterase and urate). A number of biomarkers were specifically identified in the last two weeks of life but limitations exist. No post-mortem studies met the inclusion criteria.ConclusionThe biology of dying is an important area for future research, with the evidence focused on signs, symptoms and prognostic factors. This review identifies a number of common themes shared amongst advanced cancer patients and highlights candidate biomarkers which may be indicative of a common biological process to dying.

Survival time after marked reduction in oral intake in terminally ill noncancer patients: A retrospective study

“…There are several limitations to the present study. Since this was a retrospective medical record review, potential cofounding factors such as patient symptoms (including comatose, edema, and dyspnea) and other laboratory data as described by Reid VL et al may not have been considered. Furthermore, the present study was conducted at a single center.…”

“…A marked reduction in oral intake, for example, is a weekly to daily prognostic factor, which is one of the components of prognostic tools such as the Palliative Prognostic Index (PPI) . In addition to symptoms, many studies have been published on biomarkers in dying patients . Vital signs, which are routinely measured in daily practice, are also used to assess the prognosis of dying patients .…”

“…10 In addition to symptoms, many studies have been published on biomarkers in dying patients. 11 Vital signs, which are routinely measured in daily practice, are also used to assess the prognosis of dying patients. 12 The Shock Index (SI), defined as the ratio of heart rate to systolic blood pressure, has recently attracted attention for its relationship with short-term survival times in terminal cancer patients.…”

Hypernatremia predicts poor survival in patients with terminal cancer: a retrospective cohort study

“…Over the past few decades, a number of studies have been conducted in this setting to identify patient-related prognostic factors of potential use, such as performance status, anorexia-cachexia, delirium, and dyspnea [1]; and various laboratory abnormalities have similarly been identified. Serum markers of systemic inflammation (i.e., leukocytosis, lymphopenia, C-reactive protein (CRP) elevation, and inflammatory cytokines) are wellknown indices of poor survival [2]. Biomarkers of hepatic dysfunction (elevated lactate dehydrogenase [LDH], prolonged international normalized ratio [INR], hypoalbuminemia) and renal impairment (serum urea, creatinine, and uric acid elevations) have been implicated as well [2,3].…”

“…Serum markers of systemic inflammation (i.e., leukocytosis, lymphopenia, C-reactive protein (CRP) elevation, and inflammatory cytokines) are wellknown indices of poor survival [2]. Biomarkers of hepatic dysfunction (elevated lactate dehydrogenase [LDH], prolonged international normalized ratio [INR], hypoalbuminemia) and renal impairment (serum urea, creatinine, and uric acid elevations) have been implicated as well [2,3].…”