Diagnostic criteria for cancer cachexia: Reduced food intake and inflammation predict weight loss and survival in an international, multi-cohort analysis

Abstract Background Cancer‐associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C‐reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer‐associated WL (primary endpoint) and overall survival (OS, secondary endpoint). Methods The data set included a total of 12,253 patients at risk for cancer‐associated WL. Patient‐reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively. Results Patients had a mean weight change of −7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5–5.9% (19.7%), 6.0–10.0% (23.2%), 11.0–14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P  100 mg/L: OR 2.30 (95% CI 1.62–3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5–10.3), with median follow‐up of 39.7 months (95% CI 38.8–40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001). Conclusions Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer‐associated cachexia

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

Cancer Appetite and Symptom Questionnaire (CASQ) for Brazilian Patients: Cross-Cultural Adaptation and Validation Study

Background Appetite and symptoms, conditions generally reported by the patients with cancer, are somewhat challenging for professionals to measure directly in clinical routine (latent conditions). Therefore, specific instruments are required for this purpose. This study aimed to perform a cultural adaptation of the Cancer Appetite and Symptom Questionnaire (CASQ), into Portuguese and evaluate its psychometric properties on a sample of Brazilian cancer patients. Methods This is a validation study with Brazilian cancer patients. The face, content, and construct (factorial and convergent) validities of the Cancer Appetite and Symptom Questionnaire, the study tool, were estimated. Further, a confirmatory factor analysis (CFA) was conducted. The ratio of chi-square and degrees of freedom (χ2 /df), comparative fit index (CFI), goodness of fit index (GFI) and root mean square error of approximation (RMSEA) were used for fit model assessment. In addition, the reliability of the instrument was estimated using the composite reliability (CR) and Cronbach’s alpha coefficient (α), and the invariance of the model in independent samples was estimated by a multigroup analysis (Δχ2). Results Participants included 1,140 cancer patients with a mean age of 53.95 (SD = 13.25) years; 61.3% were women. After the CFA of the original CASQ structure, 2 items with inadequate factor weights were removed. Four correlations between errors were included to provide adequate fit to the sample (χ2 /df = 8.532, CFI = .94, GFI = .95, and RMSEA = .08). Themodel exhibited a low convergent validity (AVE = .32). The reliability was adequate (CR = .82 α = .82). The refined model showed strong invariance in two independent samples (Δχ2 : λ: p = .855; i: p = .824; Res: p = .390). A weak stability was obtained between patients undergoing chemotherapy and radiotherapy (Δχ2 : λ: p = .155; i: p < .001; Res: p < .001), and between patients undergoing chemotherapy combined with radiotherapy and palliative care (Δχ2 : λ: p = .058; i: p < .001; Res: p < .001). Conclusion The Portuguese version of the CASQ had good face and construct validity and reliability. However, the CASQ still presented invariance in independent samples of Brazilian patients with cancer. However, the tool has low convergent validity and weak invariance in samples with different treatment

Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer

OBJECTIVES: The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. METHODS: The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. RESULTS: The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Diseasespecific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year survival. On multivariate analysis, pathological stage I (P = 0.01) and GPS 0 (P = 0.04, hazard ratio: 2.13, 95% confidence interval 1.036-4.393) were significant prognostic factors. CONCLUSIONS: The preoperative GPS appears to be a useful predictor of overall survival and could be a simple prognostic tool for elderly patients with clinical stage I NSCLC

Α multicenter phase II study of pegylated liposomal doxorubicin in combination with irinotecan as second-line treatment of patients with refractory small-cell lung cancer

International audienc

Evaluation of the nutritional status in patiets with lung cancer with the MNA protocol: correlation with clinico-laboratory parameters related with malnutrition cachexia and with survival

Cancer cachexia syndrome frequently accompanies lung cancer and is related with increased morbidity and adverse prognosis. The syndrome is characterized by loss of muscle mass with or without loss of fat tissue as a consequence of an underline disease. Cytokines seem to play a major pathophysiologic role as they modify orexiogenic signals, they influence energy balance and they stimulate muscle degradation as well as fat loss. In its early stage, when the syndrome is theoretically reversible, usually it does not provoke clinical suspicion. On the other part of the spectrum, when the syndrome is fully established, any intervention might be not only ineffective but also futile. Sarcopenic obesity is another confounding factor which masks syndrome’s timely diagnosis as muscle loss occurs under a layer of fat. Till now, diagnosis of the syndrome is based solely on the quantification of weight loss. However, and besides the lack of agreement among physicians on the exact percentage of weight loss and the time period in which this should occur, this method of nutritional assessment represents a rather oversimplified approach. On the other hand, an in-depth nutritional evaluation performed by a registered dietitian is time consuming, costly, requires specialized equipment and, thus, could not applied routinely. Screening questionnaires like the Mini Nutritional Assessment (MNA), originally developed for elderly patients with non malignant diseases, have been proposed as a more accurate nutritional assessment. In the present study MNA was validated and compared against the weight loss history in patients with metastatic lung cancer. MNA identifies more patients as candidates for nutritional support and outperforms weight loss in terms of its correlation with clinico-laboratory related with malnutrition, response to antineoplastic therapy and prognosis. Despite the fact that MNA is a geriatric protocol, its prognostic value was also demonstrated in the subgroup of non-elderly patients. Interestingly, according to MNA, more than 50% of the obese patients were at nutritional risk and, thus, they should be referred for nutritional support. In the present study MNA was validated in metastatic lung cancer patients, and based on our results could be used for the nutritional evaluation in this population. Moreover, it is possible to consider MNA as a new standard method against which any proposed nutritional assessment tool could be tested.Το σύνδρομο της καχεξίας συνοδεύει συχνά τον καρκίνο του πνεύμονα και σχετίζεται με αυξημένη νοσηρότητα και πτωχότερη επιβίωση. Κύριο χαρακτηριστικό του είναι η απώλεια μυϊκής μάζας με ή χωρίς απώλεια λιπώδους ιστού ως αποτέλεσμα της υποκείμενης κακοήθειας. Παθοφυσιολογικά, οι κυττοκίνες που παράγονται από τον όγκο ή τον ξενιστή φαίνεται να έχουν κεντρικό ρόλο τροποποιώντας ορεξιογόνα ερεθίσματα, εκτρέποντας το ενεργειακό ισοζύγιο, προκαλώντας μυϊκό καταβολισμό και προάγοντας τη λιπόλυση. Στη πρώιμή του φάση, και όταν το σύνδρομο είναι θεωρητικά αναστρέψιμο, κατά κανόνα διαλάθει της κλινικής υποψίας. Αντιθέτως, όταν γίνει κλινικά εμφανές, οποιαδήποτε παρέμβαση είναι όχι μόνο αναποτελεσματική αλλά πιθανώς και άσκοπη. Η σαρκοπενική παχυσαρκία είναι ένας παράγοντας που δυσχεραίνει ακόμη περισσότερο την έγκαιρη διάγνωσή του διότι η απώλεια της μυϊκής μάζας καλύπτεται από το υποδόριο λίπος και δε γίνεται κλινικά αντιληπτή. Μέχρι τώρα η διάγνωση του συνδρόμου βασίζεται στη ποσοτικοποίηση της απώλειας του σωματικού βάρους. Ωστόσο, και πέραν της ασυμφωνίας μεταξύ των κλινικών για το ποσοστό της απώλειας του βάρους και το χρονικό διάστημα που πρέπει αυτό να συμβεί, η μέθοδος αποτελεί γενικά έναν υπεραπλουστευμένο τρόπο εκτίμησης της θρέψης. Από την άλλη πλευρά μία λεπτομερής διαιτολογική εκτίμηση από εξειδικευμένο διαιτολόγο έχει αυξημένες απαιτήσεις σε χρόνο, εξειδικευμένο εξοπλισμό και κόστος και είναι πρακτικά μη εφαρμόσιμη. Για την ακριβέστερη εκτίμηση της θρέψης έχει προταθεί η χρήση ερωτηματολογίων όπως το ΜΝΑ που αναπτύχθηκαν αρχικά για ηλικιωμένους ασθενείς χωρίς νεοπλασματικό νόσημα. Με την παρούσα διατριβή το MNA αξιολογήθηκε συγκριτικά έναντι της απώλειας βάρους σε ασθενείς με μεταστατικό καρκίνο του πνεύμονα. Το MNA αναγνωρίζει περισσότερους ασθενείς σαν υποψήφιους για να λάβουν κάποια διαιτολογική παρέμβαση και επιπλέον φάνηκε πως υπερτερεί σε σχέση με την απώλεια βάρους τόσο όσον αφορά τη σχέση του με κλινικο-εργαστηριακούς παράγοντες που σχετίζονται με την υποθρεψία όσο και την προβλεπτική και προγνωστική του αξία. Αν και το MNA είναι ουσιαστικά ένα γηριατρικό πρωτόκολλο, η συσχέτισή του με την επιβίωση διατηρήθηκε και για την υποομάδα ασθενών ηλικίας <65 έτη. Επίσης, για την υποομάδα των ασθενών με δείκτη μάζας σώματος πάνω από τα όρια της παχυσαρκίας, ποσοστό πάνω από το 50% ήταν, κατά το MNA, αυξημένου κινδύνου για υποθρεψία και επομένως θα έπρεπε να υποστηριχθεί διαιτολογικά. Με βάση τα αποτελέσματα της παρούσας διδακτορικής διατριβής, μπορεί να υποστηριχθεί ότι το ΜΝΑ αποτελεί πλέον ένα ερωτηματολόγιο εκτίμησης της θρέψης αξιολογημένο και σε ογκολογικούς ασθενείς και γι’ αυτό θα μπορούσε να χρησιμοποιηθεί τόσο ως νέο standard για την εκτίμηση της θρέψης όσο και για τη σύγκριση νέων μεθόδων που θα αναπτυχθούν εξ αρχής σε ασθενείς με νεοπλασματικό νόσημα