An exploratory study examining the relationship between performance status and systemic inflammation frameworks and cytokine profiles in patients with advanced cancer

The role of cytokines in the systemic inflammatory response (SIR) is now well established. This is in keeping with the role of the SIR in tumorigenesis, malignant spread, and the development of cachexia. However, the relationship between performance status/systemic inflammation frameworks and cytokine profiles is not clear. The aim of the present study was to examine the relationship between the Eastern cooperative oncology group performance status/modified Glasgow prognostic score (ECOG-PS/mGPS) and cooperative oncology group performance status/neutrophil platelet score (ECOG-PS/NPS) frameworks and their cytokine profile in patients with advanced cancer.This was a retrospective interrogation of data already collected as part of a recent clinical trial (NCT00676936). The relationship between the independent variables (ECOG-PS/mGPS and ECOG-PS/NPS frameworks), and dependent variables (cytokine levels) was examined using independent Mann-Whitney U and Kruskal Wallis tests where appropriate.Of the 40 patients included in final analysis the majority had evidence of an SIR assessed by mGPS (78%) or NPS (53%). All patients died on follow-up and the median survival was 91 days (4-933 days). With increasing ECOG-PS there was a higher median value of Interleukin 6 (IL-6, P = .016) and C-reactive protein (CRP, P < .01) and lower albumin (P < .01) and poorer survival (P < .001). With increasing mGPS there was a higher median value of IL-6 (P = .016), Macrophage migration inhibitory factor (MIF, P = .010), erythrocyte sedimentation rate (ESR, P < .01) and poorer survival (P < .01). With increasing NPS there was a higher median value of TGF-β (P < .001) and C-reactive protein (P = .020) and poor survival (P = .001). When those patients with an ECOG-PS 0/1 and mGPS0 were compared with those patients with an ECOG-PS 2 and mGPS2 there was a higher median value of IL-6 (P = .017) and poorer survival (P < .001). When those patients with an ECOG-PS 0/1 and NPS0 were compared with those patients with an ECOG-PS 2 and NPS1/2 there was a higher median value of IL-6 (P = .002), TGF-β (P < .001) and poorer survival (P < .01).In patients with advanced cancer IL-6 was associated with the ECOG-PS/mGPS and ECOG-PS/NPS frameworks and survival in patients with advanced cancer. Therefore, the present work provides supporting evidence that agents targeting IL-6 are worthy of further exploration

Discrepancy in patient-rated and oncologist-rated performance status on depression and anxiety in cancer: a prospective study protocol

Objective: Psychological distress is common in patients with cancer. We need a rapid means of screening for and identifying depression and anxiety in patients with cancer. The present study evaluates the potential of the Eastern Cooperative Oncology Group (ECOG) performance status (PS) scoring as a brief screening tool to assess psychological distress in routine cancer care. The ECOG PS is widely used by oncologists and the WHO, as a standardised measure to assess general well-being in patients with cancer and quality of life in cancer trials. We examine the discrepancy between patient-rated and oncologist-rated PS scores on the ECOG in a comparative assessment against the Hospital Anxiety and Depression Scale (HADS). Methods and design: This is a prospective evaluation of approximately 500 ambulatory adult cancer patients from a large academic medical centre. Participants will be asked to assess their own ECOG PS on a scale of 0–4, which will be compared to ECOG PS as rated by their oncologists. Higher ECOG PS scores indicate poorer daily functioning. Both patient-rated and oncologist-rated ECOG PS and their absolute differences will be tested for predictive and concurrent validity against the HADS. A HADS cut-off ≥15 will be used. Ethics approval for this study has been secured from the institutional ethics board. Outcomes are re-evaluated at 4-week to 6-week and 1-year follow-up. Conclusion: This study holds practical significance for rapid screening of psychological distress in the cancer clinic with the use of the ECOG PS scoring. Given the high prevalence of anxiety and depression in patients with cancer, screening is important to increase its recognition, which will, in turn, help to direct referrals and deliver appropriate intervention. This study also generates greater insight into the association between psychosomatic complaints and psychological distress. Trial registration number MEC 896.52

A prospective longitudinal study of performance status, an inflammation-based score (GPS) and survival in patients with inoperable non-small-cell lung cancer

The value of an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was compared with performance status (ECOG-ps) in a longitudinal study of patients (n=101) with inoperable non-small-cell lung cancer (NSCLC). At diagnosis, stratified for treatment, only the GPS (HR 2.32, 95% CI 1.52–3.54, P<0.001) was a significant predictor of survival. In contrast, neither the GPS nor ECOG-ps measured at 3–6 months follow-up were significant predictors of residual survival. This study confirms the prognostic value of the GPS, at diagnosis, in patients with inoperable NSCLC. However, the role of the GPS and ECOG-ps during follow-up has not been established

Prognostic value of baseline functional status measures and geriatric screening in vulnerable older patients with metastatic colorectal cancer receiving palliative chemotherapy – The randomized NORDIC9-study

Introduction Appropriate patient selection based on functional status is crucial when considering older adults for palliative chemotherapy. This pre-planned analysis of the randomized NORDIC9-study explored the prognostic value of four functional status measures regarding progression-free survival (PFS) and overall survival (OS) in vulnerable older patients with metastatic colorectal cancer (mCRC) receiving first-line palliative chemotherapy. Materials and methods Patients ≥70 years of age with mCRC not candidates for standard full-dose combination chemotherapy were randomized to receive full-dose S1 or reduced-dose S1 + oxaliplatin. At baseline, functional status was assessed using ECOG performance status (ECOG PS), frailty phenotype, Geriatric 8 (G8), and Vulnerable Elderly Survey-13 (VES-13). Multivariable regression models were applied and C-statistics were estimated. Results In total, 160 patients with a median age of 78 years (IQR: 76–81) were included. While in univariate analyses, ECOG PS, frailty phenotype, and VES-13 were statistically significantly associated with differences in OS between subgroups, G8 was not (HR = 1.55, 95%CI: 0.99–2.41, p = 0.050). In multivariable analyses adjusted for age, sex, body mass index, and treatment allocation, we found significant differences between subgroups for all applied tools and with C-statistics in the moderate range for ECOG PS and VES-13. Concerning PFS, statistically significant differences were observed between subgroups of ECOG PS, G8, and VES-13 both in uni- and multivariable analyses, but not for frailty phenotype. Discussion In this Nordic cohort of vulnerable older patients with mCRC, baseline ECOG PS, frailty phenotype, G8, and VES-13 showed prognostic value regarding overall survival, and moderate predictive value of models based on ECOG PS and VES-13 was demonstrated.publishedVersio

Inflammation and performance status:the cornerstones of prognosis in advanced cancer

Context: In advanced cancer, although performance status (PS), systemic inflammatory response and nutritional status are known to have prognostic value, geographical variations and sociodemographic indexes may also impact survival. Objectives: This study compares validated prognostic factors in two international cohorts and establishes a prognostic framework for treatment. Methods: Two international biobanks of patients (n=1.518) with advanced cancer were analyzed. Prognostic factors (Eastern Cooperative Oncology Group Performance Status [ECOG-PS], body mass index [BMI] and modified Glasgow Prognostic Score [mGPS]) were assessed. The relationship between these and survival was examined using Kaplan–Meier and Cox regression methods. Results: According to multivariate analysis, in the European cohort the most highly predictive factors were BMI &lt;20 kg/m2 (hazard ratio [HR] 1.644), BMI 20-21.9 kg/m2 (HR 1.347), ECOG-PS (HR 1.597–11.992) and mGPS (HR 1.843–2.365). In the Brazilian cohort, the most highly predictive factors were ECOG-PS (HR 1.678–8.938) and mGPS (HR 2.103–2.837). Considering gastrointestinal cancers in particular (n=551), the survival rate at 3 months in both cohorts together ranged from 93% (mGPS 0, PS 0–1) to 0% (mGPS 2, PS 4), and from 81% (mGPS 0, BMI &gt;28 kg/m2) to 44% (mGPS 2, BMI &lt;20 kg/m2). Conclusion: The established prognostic factors that were compared had similar prognostic capacity in both cohorts. A high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer survival of patients with advanced cancer in the prospective European and Brazilian cohorts

Die Bedeutung einer detaillierten geriatrischen Funktionsbeurteilung älterer Krebspatienten

Für ältere Krebspatienten ist der Erhalt oder die Wiedererlangung ihrer Fähigkeit, sich selbst zu versorgen, von großer Wichtigkeit. Welche Instrumente sind geeignet, um dies zu messen? In der geriatrischen und onkologischen Versorgung sind verschiedene Instrumente zur Beurteilung des funktionellen Status etabliert, die jedoch in der Vergangenheit nur unzureichend miteinander verglichen wurden. Patienten und Methoden: Im Rahmen einer prospektiven Kohortenstudie haben wir 483 Patienten eingeschlossen, 198 ältere Patienten mit Krebs, 156 jüngere Patienten mit Krebs und 129 ältere Patienten mit gutartigen Erkrankungen. Der Funktionsstatus wurde anhand des Eastern Cooperative Oncology Group Performance-Status (ECOG-PS), der Aktivitäten des täglichen Lebens (ADL) und der instrumentellen Aktivitäten des täglichen Lebens (IADL) beurteilt. Die Ergebnisse wurden dahingehend verglichen, Patienten mit Einschränkungen im funktionellen Status zu erfassen. Zusammenfassung: Die relative Häufigkeit von Krebspatienten mit Einschränkungen bei ECOG-PS, ADL und IADL stieg von 25,7 %, 13,5 % und 17,9 % bei den unter 60-Jährigen auf 50,0 %, 47,1 % und 66,7 % bei den 80-Jährigen und älteren. Die Ergebnisse bei älteren Patienten mit Krebs waren mit denen bei älteren Patienten mit gutartigen Erkrankungen vergleichbar. Bei älteren Krebspatienten wiesen 20,7 % der Patienten mit gutem ECOG-PS Einschränkungen bei den Aktivitäten des täglichen Lebens (ADL) und 21,6 % bei den instrumentellen Aktivitäten des täglichen Lebens (IADL) auf. Von den Patienten ohne Einschränkungen bei den Aktivitäten des täglichen Lebens (ADL) hatten 34,7 % einen schlechten ECOG-PS, und von den Patienten ohne Einschränkungen bei den instrumentellen Aktivitäten des täglichen Lebens (IADL) hatten 26,0 % einen schlechten ECOG-PS. Der Behandlungsansatz (kurativ vs. palliativ) ist signifikant mit funktionellen Einschränkungen verbunden

The Relationship between ECOG-PS, mGPS, BMI/WL Grade and Body Composition and Physical Function in Patients with Advanced Cancer

Cancer remains one of the leading causes of mortality worldwide and the associated reduction in physical function has a marked impact on both quality of life and survival. The aim of the present study was to examine the relationship between Eastern Cooperative Oncology Group-Performance status (ECOG-PS), modified Glasgow Prognostic Score (mGPS), Body Mass Index/Weight Loss grade (BMI/WL grade), and Computerised Tomography (CT)-derived body composition measurement and physical function in patients with advanced cancer. Nine sites contributed prospective data on patient demographics, ECOG-PS, mGPS, physical function tests, and CT-derived body composition. Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2-by-2 tables. Associations were analysed using binary logistic regression. A total of 523 cancer patients (266 males, 257 females) were included in the final analysis and most had metastatic disease (83.2%). The median overall survival was 5.6 months. On multivariate binary logistic regression analysis, a high ECOG-PS remained independently associated with a low skeletal muscle index (p < 0.001), low skeletal muscle density (p < 0.05), and timed up and go test failure (p < 0.001). A high mGPS remained independently associated with a low skeletal muscle density (p < 0.05) and hand grip strength test failure (p < 0.01). A high BMI/WL grade remained independently associated with a low subcutaneous fat index (p < 0.05), low visceral obesity (p < 0.01), and low skeletal muscle density (p < 0.05). In conclusion, a high ECOG-PS and a high mGPS as outlined in the ECOG-PS/mGPS framework were consistently associated with poorer body composition and physical function in patients with advanced cancer

PROGNOSIS IN ADVANCED NON-SMALL CELL LUNG CANCER - A RETROSPECTIVE STUDY EXAMINING ECOG PERFORMANCE STATUS SCORES OF PATIENTS

  Objective: Increasing prevalence and poor survival of advanced incurable non-small cell lung cancer (NSCLC) make it a major health problem globally, especially in developing countries. This awakens need for identification of the strongest prognostic factor that helps in the selection of appropriate treatment and hence palliates symptoms and improves survival. Lung cancer treatment guidelines advise performance status (PS) as the most established prognostic factor in advanced NSCLC patients. This study investigated the prognostic significance of PS.Methods: An observational study was done for 163 advanced NSCLC adult Malaysian patients in Radiotherapy and Oncology Clinic, Hospital Kuala Lumpur, Malaysia. Demographic and clinical data were recorded. Kaplan-Meier test was used to measure median overall survival (OS) and Cox proportional hazard model to calculate the hazard ratio for different categories of Eastern Cooperative Oncology Group (ECOG) PS.Results: The mean age and body weight were 56.7±10.1 years old and 57.42±13.5 kg, respectively. Majority patients were male (68.7%), Stage IV NSCLC (65.0%), and ECOG PS score of 2 (41.1%). ECOG PS had a significant association with age and body weight. Median OS was least for ECOG PS score of 4 (253 days) and was statistically significant (p=0.003). ECOG PS was a significant independent prognostic factor for survival in advanced NSCLC patients (p&lt;0.001).Conclusion: PS is a strong prognostic factor in advanced NSCLC

Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics

Background: Analyses of phase III trials showed that denosumab was superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) irrespective of age, history of SREs, or baseline pain status. This analysis assessed the risk of SREs across additional baseline characteristics. Patients and Methods: Patients (N Z 5543) from three phase III trials who had breast cancer, prostate cancer, or other solid tumours and one or more bone metastasis were included. Superiority of denosumab versus ZA in reducing risk of first SRE and first and subsequent SREs was assessed in subgroups defined by the Eastern Cooperative Oncology Group performance status (ECOG PS), bone metastasis location, bone metastasis number, visceral metastasis presence/absence, and urinary N-telopeptide (uNTx) level using Cox proportional hazards and AndersoneGill models. Subgroups except bone metastasis location were also assessed for each solid tumour type. Results: Compared with ZA, denosumab significantly reduced the risk of first SRE across all subgroups (hazard ratio [HR] ranges: ECOG PS, 0.79e0.84; bone metastasis location, 0.78e0.83; bone metastasis number, 0.78e0.84; visceral metastasis presence/absence, 0.80e0.82; uNTx level, 0.73e0.86) and reduced the risk of first and subsequent SREs in all subgroups (HR ranges: ECOG PS, 0.76e0.83; bone metastasis location, 0.78e0.84; bone metastasis number, 0.79e0.81; visceral metastasis presence/absence, 0.79e0.81; uNTx level, 0.74e0.83). Similar results were observed in subgroups across tumour types. Conclusion: Denosumab was superior to ZA in preventing SREs in patients with bone metastases from advanced cancer, regardless of ECOG PS, bone metastasis number, baseline visceral metastasis presence/absence, and uNTx leve

Comparison of the prognostic value of ECOG-PS, MGPS and BMI/WL: Implications for a clinically important framework in the assessment and treatment of advanced cancer

BACKGROUND AND AIMS:The systemic inflammatory response is associated with the loss of lean tissue, anorexia, weakness, fatigue and reduced survival in patients with advanced cancer and therefore is important in the definition of cancer cachexia. The aim of the present study was to carry out a direct comparison of the prognostic value of Eastern Cooperative Oncology Group Performance Status (ECOG-PS), modified Glasgow Prognostic Score (mGPS) and Body Mass Index/Weight Loss Grade (BMI/WL grade) in patients with advanced cancer. METHOD:All data were collected prospectively across 18 sites in the UK and Ireland. Patient's age, sex, ECOG-PS, mGPS and BMI/WL grade were recorded, as were details of underlying disease including metastases. Survival data were analysed using univariate and multivariate Cox regression. RESULTS:A total of 730 patients were assessed. The majority of patients were male (53%), over 65 years of age (56%), had an ECOG-PS&gt;0/1 (56%), mGPS≥1 (56%), BMI≥25 (51%), &lt;2.5% weight loss (57%) and had metastatic disease (86%). On multivariate cox regression analysis ECOG-PS (HR 1.61 95%CI 1.42-1.83, p &lt; 0.001), mGPS (HR 1.53, 95%CI 1.39-1.69, p &lt; 0.001) and BMI/WL grade (HR 1.41, 95%CI 1.25-1.60, p &lt; 0.001) remained independently associated with overall survival. In patients with a BMI/WL grade 0/1 both ECOG and mGPS remained independently associated with overall survival. CONCLUSION:The ECOG/mGPS framework may form the basis of risk stratification of survival in patients with advanced cancer