Study of prognostic markers in advanced cancer

Background: Prognostication is a core skill fundamental to the clinical management of patients with advanced cancer. This skill is exercised to guide appropriate clinical decisions, plan supportive services and allocate resource utilisation. Prognostication by clinicians is often erroneous, optimistic, informal and subjective. Clinicians base survival predictions upon clinical experience, clinical intuition and knowledge of cancer trajectories. Prognostic factors have been identified and validated in patients with cancer. These can be clinical markers or biomarkers. Clinical markers including weight loss and Performance Status (PS), and biomarkers such as C-reactive protein (CRP), lactate dehydrogenase (LDH), White cell count (WCC) and albumin, all representative of systemic inflammation, have been shown to be predictive of survival. Several prognostic factors have been combined to develop prognostic tools to improve prognostication accuracy. The aims were to examine all these prognostic markers and the tools, to clarify which prognostic markers are most predictive of survival in advanced cancer. Methods: To meet these aims a systematic review, an analysis of a prospectively collected biobank of patients with lung cancer and finally a large de novo multi-centre (UK) observational cohort study (Inflammatory biomarkers in Prognosis in Advanced Cancer [IPAC] study), were undertaken. The latter examined prognostic factors and was informed by the systematic review and biobank analysis. The prognostic factors evaluated throughout included demographic factors, disease characteristics, clinical factors and biomarkers. Literature appraisal and synthesis, survival analysis and logistic regression methods were employed as appropriate. Results: The systematic review concluded that numerous prognostic tools predict survival in patients with advanced cancer; however comparison was difficult due to the heterogeneity of the tools and the methods used to determine their accuracy. Some tools incorporate prognostic factors that have been independently validated to be of prognostic significance in advanced cancer whilst other tools may include some factors which are not validated. The prognostic tools demonstrating greatest accuracy in determining survival are the Palliative Performance Scale (PPS), the Palliative Prognostic Score (PaP), the Palliative Prognostic Index (PPI), and the Glasgow Prognostic Score (GPS) including the modified variant (mGPS). These tools have all been externally validated in more than 2000 patients with advanced cancer and were independently associated with survival (p<0.001). The biobank analysis identified the markers (clinical and biomarkers) which are most predictive of survival in advanced lung cancer. The prognostic markers included in many of the prognostic tools with greatest survival prediction accuracy are PS and mGPS (p<0.001). A prospectively acquired biobank identified the markers (clinical and biomarkers) which are most predictive of survival in advanced incurable lung cancer. The prognostic markers which are included in many of the prognostic tools with greatest survival prediction accuracy are PS and mGPS. The prospective observational study demonstrated that CPS (Clinician Predicted Survival), mGPS, ECOG-PS (Eastern Cooperative Oncology Group - Performance Status), dyspnoea, Global Health, cognitive impairment, anorexia, weight loss, LDH, WCC and neutrophil count (NC) predicted survival at 30 days (univariate analysis). CPS, ECOG-PS, mGPS, dyspnoea, Global Health, cognitive impairment, anorexia, weight loss, LDH, WCC and NC, predicted survival at 3 months. On multivariate analysis, ECOG-PS, mGPS and neutrophil count predicted survival at 30 days while ECOG-PS, mGPS, weight loss, LDH and WCC predicted survival at 3 months. Conclusion: In patients with advanced cancer, the most accurate prognostic factors include clinical markers (Performance Status, weight loss) and biomarkers of the systemic inflammatory response (CRP and albumin [combined in the mGPS], NC, WCC). The next step in this work is assessing how these can be utilised in clinical practice

Are CT-derived muscle measurements prognostic, independent of systemic inflammation in good performance status patients with advanced cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p &lt; 0.05) and mGPS (p &lt; 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p &lt; 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p &lt; 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer

Lactate dehydrogenase: Relationship with the diagnostic GLIM criterion for cachexia in patients with advanced cancer

Background: Although suggestive of dysregulated metabolism, the relationship between serum LDH level, phenotypic/aetiologic diagnostic Global Leadership Initiative on Malnutrition (GLIM) criteria and survival in patients with advanced cancer has yet to examined. Methods: Prospectively collected data from patients with advanced cancer, undergoing anti-cancer therapy with palliative intent, across nine sites in the UK and Ireland between 2011–2016, was retrospectively analysed. LDH values were grouped as &lt;250/250–500/&gt;500 Units/L. Relationships were examined using χ2 test for linear-by-linear association and binary logistics regression analysis. Results: A total of 436 patients met the inclusion criteria. 46% (n = 200) were male and 59% (n = 259) were ≥65 years of age. The median serum LDH was 394 Units/L and 33.5% (n = 146) had an LDH &gt; 500 Units/L. LDH was significantly associated with ECOG-PS (p &lt; 0.001), NLR (p &lt; 0.05), mGPS (p &lt; 0.05) and 3-month survival (p &lt; 0.001). LDH was significantly associated with 3-month survival independent of weight loss (p &lt; 0.01), BMI (p &lt; 0.05), skeletal muscle mass (p &lt; 0.01), metastatic disease (p &lt; 0.05), NLR (p &lt; 0.05) and mGPS (p &lt; 0.01). Discussion: LDH was associated with performance status, systemic inflammation and survival in patients with advanced cancer. LDH measurement may be considered as an aetiologic criteria and become a potential therapeutic target in the treatment of cancer cachexia

The relationship between the BMI-adjusted weight loss grading system and quality of life in patients with incurable cancer

Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)-adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer. A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI-adjusted WLGS into one of five distinct WL grades (grades 0-4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. The Kruskal-Wallis test and multivariate logistic regression analyses were used to assess the relationship between the WLGS and QoL scores. Overall survival was assessed using Kaplan-Meier curve and Cox proportional hazard models. A total of 1027 patients were assessed (51% male, median age: 66 years). Gastrointestinal cancer was most prevalent (40%), and 87% of patients had metastatic disease. Half (58%) of patients had a WL grade of 0-1, while 12%, 20%, and 10% had WL grades of 2, 3, and 4, respectively. Increasing WL grades were significantly associated with poorer QoL functioning and symptoms scales (all P &lt; 0.05). Physical, role, and emotional functioning decreased by a median of &gt;20 points between WL grade 0 and WL grade 4, while appetite loss, pain, dyspnoea, and fatigue increased by a median score &gt;20 points, indicative of a large clinical significant difference. Increasing WL grades were associated with deteriorating QoL summary score. WL grades 2, 3, and 4 were independently associated with a QoL summary score below the median (&lt;77.7) [odds ratio (OR) 1.69, P = 0.034; OR 2.06, P = 0.001; OR 4.29, P &lt; 0.001, respectively]. WL grades 3 and 4 were independently associated with reduced overall survival [hazard ratio 1.54 (95% confidence interval: 1.22-1.93), P &lt; 0.001 and hazard ratio 1.87 (95% confidence interval: 1.42-2.45), P &lt; 0.001, respectively]. Our findings support that the WLGS is useful in identifying patients at risk of poor QoL that deteriorates with increasing WL grades. WL grade 4 is independently associated with a particularly worse prognosis and increased symptom burden. Identification and early referral to palliative care services may benefit these patients

Determinants of quality of life in patients with incurable cancer

Optimizing quality of life (QoL) remains the central tenet of care in patients with incurable cancer; however, determinants of QoL are not clear. The objective of the current study was to examine which factors influence QoL in patients with incurable cancer. A multicenter study of adult patients with advanced cancer was conducted in Ireland and the United Kingdom between 2011 and 2016. Data were collected from patients at study entry and included patient demographics, Eastern Cooperative Oncology Group performance status (ECOG-PS), nutritional parameters (the percentage weight loss [%WL]), muscle parameters assessed using computed tomography images (skeletal muscle index and skeletal muscle attenuation), inflammatory markers (modified Glasgow Prognostic score [mGPS]), and QoL data (the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30). The relation between clinical, nutritional, and inflammatory parameters with QoL was assessed using the Spearman rank correlation coefficient and multivariate binary logistic regression. Components of the European Organization for Research and Treatment Quality-of-Life Questionnaire C-30 (physical function, fatigue, and appetite loss) and summary QoL scores were mean-dichotomized for the logistic regression analyses. Data were available for 1027 patients (51% men; median age, 66 years). Gastrointestinal cancer was most prevalent (40%), followed by lung cancer (26%) and breast cancer (9%). Distant metastatic disease was present in 87% of patients. The %WL, ECOG-PS, and mGPS were significantly correlated with deteriorating QoL functional and symptom scales (all P &lt; .001). On multivariate regression analysis, &gt;10% WL (odds ratio [OR], 2.69; 95% CI, 1.63-4.42), an ECOG-PS of 3 or 4 (OR, 14.33; 95% CI, 6.76-30.37), and an mGPS of 2 (OR, 1.58; 95% CI, 1.09-2.29) were independently associated with poorer summary QoL scores. These parameters were also independently associated with poorer physical function, fatigue, and appetite loss (all P &lt; .05). Low skeletal muscle attenuation was independently associated with poorer physical functioning (OR, 1.67; 95% CI, 1.09-2.56), but muscle parameters were not independently associated with fatigue, appetite loss, or QoL summary scores. The current findings indicate that QoL is determined (at least in part) by WL, ECOG-PS, and the systemic inflammatory response in patients with advanced cancer. Identifying early predictors of poor QoL may allow the identification of patients who may benefit from early referral to palliative and supportive care, which has been shown to improve QoL

“How Long Have I Got?”—A Prospective Cohort Study Comparing Validated Prognostic Factors for Use in Patients with Advanced Cancer

© AlphaMed Press 2019 Background: The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. Materials and Methods: A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician-predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG-PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C-reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. Results: Data were available on 478 patients, and the median survival was 4.27 (1.86–7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG-PS, mGPS, WCC, NC (all

Prognostic Tools in Patients with Advanced Cancer: A Systematic Review

Purpose: In 2005, the European Association for Palliative Care (EAPC) made recommendations for prognostic markers in advanced cancer. Since then, prognostic tools have been developed, evolved and validated. The aim of this systematic review was to examine the progress in the development and validation of prognostic tools. Methods: Medline, Embase Classic + and Embase were searched. Eligible studies met the following criteria: patients with incurable cancer; &#62;18 years; original studies; population n&#62;100; published after 2003. Descriptive and quantitative statistical analyses were performed. Results: Forty-nine studies were eligible, assessing seven prognostic tools across different care settings, primary cancer types and statistically assessed survival prediction. The (PPS) Palliative Performance Scale was the most studied (n=21,082), composed of 6 parameters (6 subjective), was externally validated and predicted survival. The Palliative Prognostic Score (PaP) composed of 6 parameters (4 subjective, 2 objective), the Palliative Prognostic Index (PPI) composed of 9 parameters (9 subjective), and the Glasgow Prognostic Score (GPS) composed of 2 parameters (2 objective), and were all externally validated in more than 2000 patients with advanced cancer and predicted survival. Conclusion: Various prognostic tools have been validated, but vary in their complexity, subjectivity and therefore clinical utility. The GPS would seem the most favourable as it uses only two parameters (both objective) and has prognostic value complementary to the gold standard measure, which is performance status. Further studies comparing all proven prognostic markers in a single cohort of patients with advanced cancer, are needed to determine the optimal prognostic tool

Prognosis in advanced lung cancer - a prospective study of examining key clinicopathological factors

AbstractObjectivesIn patients with advanced incurable lung cancer deciding as to the most appropriate treatment (e.g. chemotherapy or supportive care only) is challenging. In such patients the TNM classification system has reached its ceiling therefore other factors are used to assess prognosis and as such, guide treatment. Performance status (PS), weight loss and inflammatory biomarkers (Glasgow Prognostic Score (mGPS)) predict survival in advanced lung cancer however these have not been compared. This study compares key prognostic factors in advanced lung cancer.Materials and methodsPatients with newly diagnosed advanced lung cancer were recruited and demographics, weight loss, other prognostic factors (mGPS, PS) were collected. Kaplan–Meier and Cox regression methods were used to compare these prognostic factors.Results390 patients with advanced incurable lung cancer were recruited; 341 were male, median age was 66 years (IQR 59–73) and patients had stage IV non-small cell (n=288) (73.8%) or extensive stage small cell lung cancer (n=102) (26.2%). The median survival was 7.8 months. On multivariate analysis only performance status (HR 1.74 CI 1.50–2.02) and mGPS (HR 1.67, CI 1.40–2.00) predicted survival (p<0.001). Survival at 3 months ranged from 99% (ECOG 0–1) to 74% (ECOG 2) and using mGPS, from 99% (mGPS0) to 71% (mGPS2). In combination, survival ranged from 99% (mGPS 0, ECOG 0–1) to 33% (mGPS2, ECOG 3).ConclusionPerformance status and the mGPS are superior prognostic factors in advanced lung cancer. In combination, these improved survival prediction compared with either alone

"How long have I got?” – a prospective cohort study comparing validated prognostic factors for use in patients with advanced cancer

Background. The optimal prognostic factors in patients with advanced cancer are not known, as a comparison of these is lacking. The aim of the present study was to determine the optimal prognostic factors by comparing validated factors. Materials and Methods. A multicenter, prospective observational cohort study recruited patients over 18 years with advanced cancer. The following were assessed: clinician‐predicted survival (CPS), Eastern Cooperative Oncology Group performance status (ECOG‐PS), patient reported outcome measures (anorexia, cognitive impairment, dyspnea, global health), metastatic disease, weight loss, modified Glasgow Prognostic Score (mGPS) based on C‐reactive protein and albumin, lactate dehydrogenase (LDH), and white (WCC), neutrophil (NC), and lymphocyte cell counts. Survival at 1 and 3 months was assessed using area under the receiver operating curve and logistic regression analysis. Results. Data were available on 478 patients, and the median survival was 4.27 (1.86–7.03) months. On univariate analysis, the following factors predicted death at 1 and 3 months: CPS, ECOG‐PS, mGPS, WCC, NC (all p < .001), dyspnea, global health (both p ≤ .001), cognitive impairment, anorexia, LDH (all p < .01), and weight loss (p < .05). On multivariate analysis ECOG‐PS, mGPS, and NC were independent predictors of survival at 1 and 3 months (all p < .01). Conclusion. The simple combination of ECOG‐PS and mGPS is an important novel prognostic framework which can alert clinicians to patients with good performance status who are at increased risk of having a higher symptom burden and dying at 3 months. From the recent literature it is likely that this framework will also be useful in referral for early palliative care with 6–24 months survival

Corrigendum to "Prognosis in advanced lung cancer - a prospective study examining key clinicopathological factors" [Lung Cancer 88 (2015) 304-309]

No abstract available