Title: ‘Pre-cachexia’: a non-existing phenomenon in cancer?
Abstract: We read with great interest the article by Blum et al. [1.Blum D. Stene G. Solheim T. et al.Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA).Ann Oncol. 2014; 25: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar] who reported an important validation study on the diagnostic framework of cancer cachexia. For patients with cancer, cachexia is a major problem associated with reduced physical functioning [2.Fearon K.C. Voss A.C. Hustead D.S. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.Am J Clin Nutr. 2006; 83: 1345-1350Crossref PubMed Scopus (563) Google Scholar], tolerance to anti-cancer therapy [3.Andreyev H.J. Norman A.R. Oates J. et al.Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?.Eur J Cancer. 1998; 34: 503-509Abstract Full Text Full Text PDF PubMed Scopus (658) Google Scholar] and survival [2.Fearon K.C. Voss A.C. Hustead D.S. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis.Am J Clin Nutr. 2006; 83: 1345-1350Crossref PubMed Scopus (563) Google Scholar]. Despite the growing knowledge on the pathophysiology of cachexia, assessment in clinical practice is limited due to lack of adequate diagnostic criteria. The past years, experts developed a diagnostic framework [4.Fearon K. Strasser F. Anker S.D. et al.Definition and classification of cancer cachexia: an international consensus.Lancet Oncol. 2011; 12: 489-495Abstract Full Text Full Text PDF PubMed Scopus (3377) Google Scholar] but validation studies were still awaited. Blum et al. reported that differentiation of cachexia from no cachexia using the proposed framework worked out successfully with significant and clinically relevant differences in laboratory values, food intake, performance status and survival [1.Blum D. Stene G. Solheim T. et al.Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA).Ann Oncol. 2014; 25: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar]. With limited treatment options for cancer cachexia, focus has been shifting to pre-cachexia, a potential early stage of cachexia, in which (multi-modal) interventions may slow down the process of cachexia [4.Fearon K. Strasser F. Anker S.D. et al.Definition and classification of cancer cachexia: an international consensus.Lancet Oncol. 2011; 12: 489-495Abstract Full Text Full Text PDF PubMed Scopus (3377) Google Scholar]. Blum et al. defined pre-cachexia as weight loss >1 kg but <5% of usual body weight/6 months [1.Blum D. Stene G. Solheim T. et al.Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA).Ann Oncol. 2014; 25: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar] and found that, by using these criteria, survival rates were not different from those of patients without cachexia. The authors state that 'the pre-cachexia stage might be better defined by additional factors representing the cachexia domain, for instance CRP and appetite loss' [1.Blum D. Stene G. Solheim T. et al.Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA).Ann Oncol. 2014; 25: 1635-1642Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar]. In our cancer centre, we assessed these additional factors and weight loss in 200 patients before start of treatment with (combination) chemotherapy in a prospective study. Pre-cachexia was defined as:1)Weight loss of >1.0 kg, but <5%;2)C-Reactive protein ≥8.0mmol/l, the upper limit of normality in our hospital;3)Appetite loss: the section AC/S-12 of the FAACT questionnaire ≤24 points [5.Muscaritoli M. Anker S.D. Argiles J. et al.Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics".Clin Nutr. 2010; 29: 154-159Abstract Full Text Full Text PDF PubMed Scopus (1192) Google Scholar]. We recruited 85 females and 115 males with a mean age of 64 years (±10 years). The patients were diagnosed with lung cancer (stages II–IV, n = 83, 41.5%), stage IV colorectal cancer (n = 54, 27.0%), prostate cancer (n = 40, 20.0%) or breast cancer (n = 23, 11.5%). Weight loss was present in 40 patients (20%); inflammation in 107 patients (64%) and anorexia in 16 patients (8.5%), but the combination of the three was only found in one patient, resulting in a pre-cachexia prevalence of 0.5%. Extending the cut-off value for anorexia measured by FAACT to ≤30, as has been suggested by the Special Interest Group 'Cachexia-Anorexia in Chronic Wasting Diseases' from ESPEN, increased the prevalence of pre-cachexia from one to four patients (2%). Based on these preliminary data, we conclude that the clinical relevance of pre-cachexia in patients with cancer seems to be limited, as the present framework identifies only very few patients, no matter what anorexia cut-off is used. We question whether further studies or refinement of the diagnostic framework will lead to a more adequate clinical tool for pre-cachexia. Still, we have the opinion that optimal early nutritional support for patients with cancer can prevent the development of cancer cachexia. Therefore, clinical trials confirming the relevance of optimal nutritional support for patients with cancer to improve their quality of life and treatment outcome are warranted. In addition, we look forward to further improve the diagnostic framework of cancer cachexia. MAE dvdS: Nutricia Advanced Medical Nutrition Oncology Advisory Board. All remaining authors have declared no conflicts of interest.