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Early Recognition of Anorexia Through Patient-Generated Assessment Predicts Survival in Patients With Oesophagogastric Cancer

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Early Recognition of Anorexia Through Patient-Generated Assessment Predicts Survival in Patients With Oesophagogastric Cancer

Marc Abraham et al. PLoS One.

Abstract

Cancer cachexia is common in patients with oesophagogastric cancer (OG) and is linked to overall survival (OS). One of the key components of cachexia is anorexia; it is not known whether anorexia impacts on OS and there is no method of routine screening in current practice. Diagnosis relies on patients describing the symptoms, clinicians diagnosing anorexia and acting upon it. Patients with oesophageal/gastroesophageal junction or gastric cancer were assessed using the Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale (FAACT A/CS). FAACT A/CS includes 12 questions validated previously to diagnose anorexia in patients with cancer. Of the 182 patients included, 69% scored ≤37/48 and were considered to be anorexic; FAACT A/CS was a better predictor of OS in metastatic patients than body mass index or weight loss in the six months prior to cancer diagnosis. The median OS of patients with FAACT A/CS scores of >37 was longer than patients with scores of ≤37 (19.3 months vs 6.7 months, Hazard Ratio [HR] 2.9, 95% Confidence Interval [CI] 1.4-6.0, p<0.0001). Patients with performance status (PS) 0-2 and FAACT A/CS >37 had substantially longer OS than those with PS 0-2 and FAACT A/CS ≤37 (18.7 months vs 7.9 months, HR 2.5 (95% CI 1.2-5.1, P<0.0001). The FAACT A/CS questionnaire allows clinicians to identify patients with anorexia who may benefit from early nutrition interventions. Importantly, this is the first study to show the association between anorexia and survival in patients with metastatic OG cancers. This will form the basis of future interventional studies to improve patient outcomes.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Patient overview.
This is an overview of patients included in this study. *N = 14 patients were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss. Survival data was available for patients with metastatic cancer. GOJ; gastroesophageal junction cancer, N; number of patients.
Fig 2
Fig 2. Evaluation of BMI, pre-diagnosis weight loss and FAACT A/CS.
A. BMI levels; box and whisker plots show the median, upper and lower quartiles and maximum/minimum (excluding outliers), the dotted lines indicate the upper and lower limits of ‘normal’ BMI, B. Percent of patients with ≥5% weight loss, C. Total FAACT A/CS levels; box and whisker plots show the median, upper and lower quartiles and maximum/minimum (excluding outliers), the dotted line indicates the validated ≤37 threshold below which patients with cancer are considered to be anorexic.
Fig 3
Fig 3. Evaluation of BMI, pre-diagnosis weight loss and FAACT A/CS in all patients.
A. A comparison of the patients who are considered to be under-weight by using BMI (using the lower and upper thresholds of the normal range) and FAACT A/CS. B. Relationship between FAACT A/CS score and weight loss; 17% of people with high FAACT scores, had lost ≥5% weight and 62% of people with low FAACT scores, had lost ≥5% weight. C. Difference in BMI levels in patients who did and did not have ≥5% weight loss and D. Differences in FAACT A/CS in the same patient population, the dotted line indicates the validated ≤37 threshold below which patients with cancer are considered to be anorexic. N = 14 patients were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss. P values indicated are t-test (type 2, 2-tailed). N = 14 patients were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss. BMI; body mass index, FAACT A/CS; Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale, GOJ; gastroesophageal junction cancer.
Fig 4
Fig 4. Overall survival outcomes in N = 107 patients with metastatic cancer.
A. Survival outcomes for patients divided by BMI (using the upper limit of normal as a cut-point), the median OS for patients with higher BMI (> 25 kg/m2) was longer (11.6 months) than patients with lower BMI (6.5 months), log-rank (Mantel-Cox) Chi square = 3.9, HR 1.8, 95% CI 1.1–2.8 P = 0.05. B. Survival outcomes for patients divided by weight loss; the median OS for patients who had lost less than 5% weight loss in the six months prior to their cancer diagnosis was similar (9.0 months) than patients with who had experienced ≥5% weight loss (8.4 days), log-rank (Mantel-Cox) Chi square = 1.3, HR 0.93, 95% CI 0.56–1.56 P = 0.26. C. Survival outcomes for patients divided by FAACT A/CS; the median OS for patients with FAACT A/CS scores of >37 was longer (19.3 months) than patients with scored of ≤37 (6.7 months), log-rank (Mantel-Cox) Chi square = 20.7, HR 2.9, 95% CI 1.4–6.0 p<0.0001. BMI; body mass index, CI; confidence interval, FAACT A/CS; Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale, HR; hazard ratio, OS; overall survival, p; p-value relating to Mantel-Cox Chi square test, PS; performance status.
Fig 5
Fig 5. Effect of Performance Status in N = 107 patients with metastatic cancer.
A. Survival outcomes for patients divided by performance status; the median OS for patients with PS 3 was significantly lower (2.4 months) than this with PS0 (12.4 months), log-rank (Mantel-Cox) Chi square = 30.1, HR 5.2, 95% CI 2.5–11.2 P<0.001. There was little difference observed between PS0 and PS3. B. A comparison of survival outcomes for patients divided by PS and FAACT A/CS; between the PS0-2 groups, Log-rank (Mantel-Cox) Chi square = 18.1, P<0.0001, HR 2.5 (95% CI 1.2–5.1). C. Summary of survival outcomes in N = 107 patients with metastatic cancer; % shown are the % of N = 107 patients with metastatic disease in this study. *Not applicable because all N = 11 Performance Status 3 patients also had low FAACT A/CS. BMI; body mass index, FAACT A/CS; Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale, OS; overall survival, PS; performance status. P values indicated are t-test (type 2, 2-tailed). N = 14 patients were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss.
Fig 6
Fig 6. Effect of Performance Status in N = 107 patients with metastatic cancer.
A. The relationship between PS and BMI, B. The relationship between % weight loss and PS, C. The relationship between FAACT A/CS and PS; the light grey, dark grey and black dots indicate the three populations of patients in which survival outcomes are compared in Fig 4B. BMI; body mass index, FAACT A/CS; Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale, PS; performance status. P values indicated are t-test (type 2, 2-tailed). N = 14 patients were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss.
Fig 7
Fig 7. BMI-adjusted weight loss grading system for patients with cancer cachexia.
A weight loss grading system was devised9 which combines weight loss with BMI to produce a grade from 0 to 4; in two large studies9,10 higher weight loss grades have resulted in poorer survival outcomes. This weight loss grading system was applied to the N = 98 patients with metastatic cancer for whom we also have data for % weight loss in the 6 months prior to diagnosis. B. Shows the FAACT A/CS scores by weight loss grade. Weight loss grade 1–4 was not discriminatory for OS in this study (which may be due to the small number of patients in some categories. C. Shows the relationship between FAACT A/CS scores and weight loss grade (grouped by 0 & 1 and 2–4); the black, dark grey, mid-grey and light grey colours indicate the four populations of patients used in D, D. A comparison of survival outcomes for patients divided by weight loss grade and FAACT A/CS; this shows that FAACT A/CS scores are a more discriminatory tool compared with BMI-adjusted weight loss grade (which is related to OS, but only as a big population). Box and whisker plots show the median, upper and lower quartiles and max/min (excluding outliers), P values indicated are t-test (type 2, 2-tailed). N = 9 patients with metastatic cancers were categorised as ‘unclear’ weight loss over the previous 6 months, so have been removed from all evaluations involving weight loss. BMI; body mass index, FAACT A/CS; Functional Assessment of Anorexia Cachexia Therapy Anorexia/Cachexia Subscale, OS; overall survival, PS; performance status.

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