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      Early Loss of Fat Mass During Chemoradiotherapy Predicts Overall Survival in Locally Advanced Squamous Cell Carcinoma of the Lung, but Not in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

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          Abstract

          Background: Cancer cachexia is highly prevalent in advanced non-small cell lung cancer (NSCLC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC), and compromises treatment tolerance and overall survival (OS). NSCLC and LAHNSCC patients share similar risk factors, and receive comparable anti-cancer treatment regimens. The aim of this study was to determine the predictive value of body composition assessed by bioelectrical impedance analysis (BIA) and handgrip strength (HGS) (baseline and early changes during therapy) on OS in NSCLC and LAHNSCC patients treated with platinum-based chemoradiotherapy (CRT) or cetuximab-based bioradiotherapy (BRT). To elucidate potential underlying determinants of early changes in body composition and HGS, specific (fat and fat free) mass loss patterns of squamous NSCLC (sNSCLC) were compared to human papilloma virus negative (HPV–) LAHNSCC patients treated with CRT.

          Methods: Between 2013 and 2016, BIA and HGS were performed at baseline and after 3 weeks of CRT/BRT in LAHNSCC and NSCLC patients treated with curative intent.

          Results: Two hundred thirty-three patients were included for baseline measurements. Fat free mass index (FFMI) and HGS<10th percentile of reference values at baseline were both prognostic for poor OS in NSCLC and LAHNSCC [HR 1.64 [95%CI 1.13–2.39], p = 0.01 and HR 2.30 [95%CI 1.33–3.97], p = 0.003, respectively], independent of Charlson Comorbidity Index, cancer site, and gross tumor volume. Early fat mass (FM) loss during CRT was predictive for poor OS in sNSCLC ( n = 64) [HR 3.80 [95%CI 1.79–8.06] p ≤ 0.001] but not in HPV– LAHNSCC ( n = 61). In patients with significant weight loss (>2%) in the first 3 weeks of CRT (sNSCLC n = 24, HPV– LAHNSCC n = 23), the FM change was −1.4 ± 14.5% and −8.7 ± 9.0% in sNSCLC and HPV– LAHNSCC patients, respectively ( p < 0.05). Fat fee mass change was −5.6 ± 6.3% and −4.0 ± 4.3% for sNSCLC and HPV– LAHNSCC, respectively ( p = 0.31).

          Conclusion: FFMI and HGS<10th percentile at baseline are independent prognostic factors for poor OS in NSCLC and LAHNSCC patients treated with CRT/BRT. The specific composition of mass loss during first 3 weeks of CRT significantly differs between sNSCLC and HPV– LAHNSCC patients. Early FM loss was prognostic in sNSCLC only.

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          A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation

          Mary Charlson, Peter Pompei, Kathy Ales … (1987)
          The objective of this study was to develop a prospectively applicable method for classifying comorbid conditions which might alter the risk of mortality for use in longitudinal studies. A weighted index that takes into account the number and the seriousness of comorbid disease was developed in a cohort of 559 medical patients. The 1-yr mortality rates for the different scores were: "0", 12% (181); "1-2", 26% (225); "3-4", 52% (71); and "greater than or equal to 5", 85% (82). The index was tested for its ability to predict risk of death from comorbid disease in the second cohort of 685 patients during a 10-yr follow-up. The percent of patients who died of comorbid disease for the different scores were: "0", 8% (588); "1", 25% (54); "2", 48% (25); "greater than or equal to 3", 59% (18). With each increased level of the comorbidity index, there were stepwise increases in the cumulative mortality attributable to comorbid disease (log rank chi 2 = 165; p less than 0.0001). In this longer follow-up, age was also a predictor of mortality (p less than 0.001). The new index performed similarly to a previous system devised by Kaplan and Feinstein. The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death from comorbid disease for use in longitudinal studies. Further work in larger populations is still required to refine the approach because the number of patients with any given condition in this study was relatively small.
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            The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.

            Stephen Edge, Carolyn C. Compton (2010)
            The American Joint Committee on Cancer and the International Union for Cancer Control update the tumor-node-metastasis (TNM) cancer staging system periodically. The most recent revision is the 7th edition, effective for cancers diagnosed on or after January 1, 2010. This editorial summarizes the background of the current revision and outlines the major issues revised. Most notable are the marked increase in the use of international datasets for more highly evidenced-based changes in staging, and the enhanced use of nonanatomic prognostic factors in defining the stage grouping. The future of cancer staging lies in the use of enhanced registry data standards to support personalization of cancer care through cancer outcome prediction models and nomograms.
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              Definition and classification of cancer cachexia: an international consensus.

              Kenneth Fearon, Florian Strasser, Stefan D. Anker … (2011)
              To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Nutr
                Journal ID (iso-abbrev): Front Nutr
                Journal ID (publisher-id): Front. Nutr.
                Title: Frontiers in Nutrition
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-861X
                Publication date (Electronic): 26 November 2020
                Publication date Collection: 2020
                Volume: 7
                Electronic Location Identifier: 600612
                Affiliations
                [1] 1Division of Medical Oncology, Department of Internal Medicine, Maastricht University Medical Center+ , Maastricht, Netherlands
                [2] 2GROW School of Oncology and Developmental Biology, Maastricht University Medical Center+ , Maastricht, Netherlands
                [3] 3Department of Respiratory Medicine, Maastricht University Medical Center+ , Maastricht, Netherlands
                [4] 4NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+ , Maastricht, Netherlands
                [5] 5Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center+ , Maastricht, Netherlands
                [6] 6Department of Radiation Oncology (MAASTRO), Maastricht University Medical Center+ , Maastricht, Netherlands
                Author notes

                Edited by: Kazim Sahin, Firat University, Turkey

                Reviewed by: Deniz Can Guven, Hacettepe University, Turkey; Miguel Luiz Batista Júnior, University of Mogi das Cruzes, Brazil

                *Correspondence: A. C. H. Willemsen rianne.willemsen@ 123456maastrichtuniversity.nl

                This article was submitted to Clinical Nutrition, a section of the journal Frontiers in Nutrition

                †These authors have contributed equally to this work

                Article
                DOI: 10.3389/fnut.2020.600612
                PMC ID: 7726186
                PubMed ID: 33324671
                SO-VID: 176dcf4f-cf8e-4f73-a564-3f62a27f2d4b
                Copyright © Copyright © 2020 Willemsen, Degens, Baijens, Dingemans, Hoeben, Hoebers, De Ruysscher and Schols.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 30 August 2020
                Date accepted : 02 November 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 55, Pages: 11, Words: 7805
                Categories
                Subject: Nutrition
                Subject: Original Research

                Keywords: hand grip strength (hgs),locally advanced (stage iii) non-small cell lung cancer,locally advanced head and neck cancer,bioelectrical impedance analysis,cachexia,weight loss,chemoradiotherapy (crt)
                Data availability:
                Keywords: hand grip strength (hgs), locally advanced (stage iii) non-small cell lung cancer, locally advanced head and neck cancer, bioelectrical impedance analysis, cachexia, weight loss, chemoradiotherapy (crt)

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