TO THE EDITOR
Esophageal cancer (EC) remains a disease with poor prognosis. The introduction of combined treatment (systemic therapy, radiation therapy and radical surgery in various combinations) has improved outcomes to some extent in the last two decades but has at the same time exposed patients to some of the most demanding treatment regimens in medicine that often straddle the limit of what the human organism is able to withstand. Disturbances in body composition (BC), mainly sarcopenia, myosteatosis, and adipose tissue loss are not only among the most dire consequences of the disease but are also powerful independent predictors of poor treatment outcomes[1-4]. Perioperative complications, oncological treatment toxicity, and reduced survival in patients with EC have been consistently shown to be associated with various markers of body depletion. Sarcopenia (impaired muscle function and muscle mass loss) is the most studied in various malignant and non-malignant diseases[5]. Myosteatosis is also a potent predictor of poor outcome in many diseases including upper gastrointestinal cancer[3]. Recent studies have reported on the negative effects of adipose tissue loss on multimodality treatment tolerance and prognosis[4]. Some studies have evaluated the effects of more than one of these BC parameters in EC mainly with computed tomography (CT) image analysis (planimetry) since these are readily available as part of the standard workup[6-8]. Planimetric measurements identifying patients with low muscle mass (LMM) (also frequently referred to as myopenia), myosteatosis and/or adipose tissue loss from these CT images are however not readily available to clinicians because they require special image processing software and competence for its use. Other methods of assessing BC disturbances (such as bioimpedance analysis) are easier to use but less reliable[9]. There is great interest in the last few years in the emerging ultrasonic method of muscle mass assessment[10].
PERSPECTIVE ON BMI AS A PROGNOSTIC FACTOR
I have read with great interest the paper Body mass index (BMI) predicts LMM in esophageal squamous cell carcinoma patients undergoing chemoradiotherapy by Xiao et al[11] in World Journal of Clinical Oncology. It reports on a retrospective cohort study on the association between BMI and LMM in esophageal squamous cell carcinoma patients undergoing chemoradiotherapy as well as the impact of LMM on survival. LMM is used instead of sarcopenia because the study only investigated planimetrically defined muscle mass and did not investigate for poor muscle function. That precludes using the term sarcopenia as defined by the European working group on sarcopenia in older people[5]. Nevertheless, it is in line with a growing body of evidence in literature studying the same subject but using the term “sarcopenia” more liberally. The studies’ take away message is not surprising, the authors report that a combined detection of low BMI and LMM enables the early identification of high-risk individuals that can benefit from treatment adjustment and nutritional interventions.
The use of BMI in an era that is decisively moving away from this readily available metric is an interesting choice. In certain populations, such as the one reported on in the study, it is a useful tool for identifying patients with LMM and inferior survival.
The seminal paper from the Alberta group on sarcopenic obesity[12] has however shifted the focus from crude metrics on body weight and weight loss towards BC analysis and muscle function evaluation. They have shown that patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight. It can be observed, however, that studies on different populations of the world can have conflicting results. This reflects different prevalences of obesity in western and Asian countries. Asian populations remain less affected by the obesity pandemic, but trends are unfavorable there as well. It is of note that negative metabolic consequences of being overweight are seen in lower BMI values in Asian populations and that in some countries like Japan BMI cutoff values for obesity are lower (≥ 25 kg/m2)[13,14].
What most reports share is the association between a low BMI (18.5 and lower) and poor outcomes. This is not specific to EC patients as the J shaped survival curve is observed in populations for all-cause mortality[15]. It is not the left side of the BMI curve where we need to be careful with interpretation, though. Underweight patients will receive proper nutritional screening, counselling and interventions most of the time. It is the patients with normal or even high BMI values that can go undetected for serious BC disturbances, mainly LMM and myosteatosis.
It has been shown that BMI reflects comprehensive information on BC in Japanese EC patients, although its correlation with muscle mass and muscle strength was moderate. Decreased BMI was proposed as an indicator for sarcopenia in this population, in which the presence of sarcopenic obesity is rare[16]. Sarcopenia was more likely in patients with lower BMI in Irish EC patients as well and was associated with increased operative morbidity independent of body weight or BMI[17].
However, sarcopenia and sarcopenic obesity were present in 43% and 14% of EC patients, respectively, in Swedish EC patients prior to chemotherapy. Logistic regression with BMI as an interaction term was non-significant but indicated higher dose limiting toxicity risk in sarcopenic patients with normal BMI (odds ratio = 1.60; 95% confidence interval: 0.30-8.40). In the sarcopenic obese, risk of dose limiting toxicity increased significantly (odds ratio = 5.54; 95% confidence interval: 1.12-27.44)[18]. A review of the impact of sarcopenic obesity on surgical complications and oncologic outcomes of upper gastrointestinal tumors (16 studies and 5378 patients from various continents) reported a prevalence of sarcopenic obesity of 10% and an association with increased risk of complications and worse overall survival[19].
A recent systematic review and meta-analysis on the impact of sarcopenic obesity on postoperative outcomes in patients with oesophago-gastric cancer has shown that sarcopenic obesity worsens overall survival and increases the risk of postoperative complications[20]. They included 13 studies (involving 4912 patients) and the prevalence of sarcopenic obesity ranged from 5.7% to 28.7%. These are important percentages of EC patient population that are at risk of underdiagnosing when using only BMI as a BC disturbance marker.
Patients with higher BMIs are more likely to present with myosteatosis at the time of diagnosis compared to those with lower BMIs[6]. While a higher BMI is a risk factor for developing myosteatosis, its impact on survival in EC is complex. In some cases of esophageal squamous cell carcinoma, a higher BMI is actually associated with better overall survival (the obesity paradox), likely due to greater nutritional reserves to tolerate treatment. Once myosteatosis is present, however, it is often an independent predictor of poor outcomes, including decreased overall survival and an increased risk of postoperative complications such as anastomotic leaks[3].
CONCLUSION
BC analysis as basis of risk stratification and nutritional and rehabilitation intervention guide is becoming indispensable in modern medicine. Oncology is in the forefront of research and its implementation in patient care. The need to identify patients affected by BC disturbances is clear and the minimal armamentarium to be used in clinical practice is under development. The proven tools of questionnaires such as Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and/or Nutritional Risk Screening-2002 (NRS-2002) and anthropometric measurements are complemented with more advanced techniques. Some are readily available and non-invasive but lack specificity and sensitivity and are used mainly as therapy efficacy assessment, such as bioimpedance analysis. The gold standard for myopenia, myosteatosis and adipose tissue loss is planimetric analysis of CT imaging that is readily available in cancer patients but is not part of standard interpretation yet. Therefore, its availability is limited to studies and specialized centers where software and know-how is at hand. More recent methods in BC analysis are easier to perform and less invasive. Ultrasound seems to be gaining acceptance in BC analysis but specific investigation protocols that would allow routine bedside use are still being developed. It is, however, entirely feasible and likely that in the near future a simple US investigation will have a far greater sensitivity and specificity for BC disturbances than the currently used anamnestic and anthropometric investigations.
BMI remains in use and is readily available but must be interpreted with caution especially in the normal and overweight patients where unsuspected myopenia and myosteatosis may elude detection.
