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      Sarcopenia is negatively associated with long‐term outcomes in locally advanced rectal cancer

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          Abstract

          Background

          The association of sarcopenia and visceral obesity to treatment outcome is not clear for locally advanced rectal cancer. This study evaluates the influence of skeletal muscle and visceral fat on short‐term and long‐term outcomes in locally advanced rectal cancer patients treated with neoadjuvant chemoradiation therapy followed by curative resection.

          Methods

          A total of 188 patients with locally advanced cancer were included between January 2009 and December 2013. Neoadjuvant chemoradiotherapy was followed by curative resection. Sarcopenia and visceral obesity were identified in initial staging CT by measuring the muscle and visceral fat area at the third lumbar vertebra level.

          Results

          Among the 188 included patients, 74 (39.4%) patients were sarcopenic and 97 (51.6%) patients were viscerally obese. Sarcopenia and high levels of preoperative carcinoembryonic antigen were significant prognostic factors for overall survival ( P = 0.013, 0.014, respectively) in the Cox regression multivariate analysis. Visceral obesity was not associated with overall survival; however, it did tend to shorten disease‐free survival ( P = 0.079).

          Conclusions

          Sarcopenia is negatively associated with overall survival in locally advanced rectal cancer patients who underwent neoadjuvant chemoradiation therapy and curative resection. Visceral obesity tended to shorten disease‐free survival. Future studies should be directed to optimize patient conditions according to body composition status.

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          Most cited references18

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          Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years.

          Rolf Sauer, Torsten Liersch, Susanne Merkel … (2012)
          Preoperative chemoradiotherapy (CRT) has been established as standard treatment for locally advanced rectal cancer after first results of the CAO/ARO/AIO-94 [Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society] trial, published in 2004, showed an improved local control rate. However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months. A total of 823 patients with stage II to III rectal cancer were randomly assigned to preoperative CRT with fluorouracil (FU), total mesorectal excision surgery, and adjuvant FU chemotherapy, or the same schedule of CRT used postoperatively. The study was designed to have 80% power to detect a difference of 10% in 5-year overall survival as the primary end point. Secondary end points included the cumulative incidence of local and distant relapses and disease-free survival. Of 799 eligible patients, 404 were randomly assigned to preoperative and 395 to postoperative CRT. According to intention-to-treat analysis, overall survival at 10 years was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P = .85). The 10-year cumulative incidence of local relapse was 7.1% and 10.1% in the pre- and postoperative arms, respectively (P = .048). No significant differences were detected for 10-year cumulative incidence of distant metastases (29.8% and 29.6%; P = .9) and disease-free survival. There is a persisting significant improvement of pre- versus postoperative CRT on local control; however, there was no effect on overall survival. Integrating more effective systemic treatment into the multimodal therapy has been adopted in the CAO/ARO/AIO-04 trial to possibly reduce distant metastases and improve survival.
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            The role of body composition evaluation by computerized tomography in determining colorectal cancer treatment outcomes: a systematic review.

            G Malietzis, O Aziz, N Bagnall … (2015)
            Strong evidence indicates that excessive adipose tissue distribution or reduced muscle influence short-, mid-, and long-term colorectal cancer outcomes. Computerized tomography-based body composition (CTBC) analysis quantifies this in a reproducible parameter. We reviewed the evidence linking computerized tomography (CT) based quantification of BC with short and long-term outcomes in colorectal cancer (CRC).
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              Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

              Jeanette McCollum, David J. O’Connell, Donna Niedzwiecki … (2004)
              To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.
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                Author and article information

                Contributors
                Daeyoun David Won: twrainmaking@gmail.com
                Journal
                Journal ID (nlm-ta): J Cachexia Sarcopenia Muscle
                Journal ID (iso-abbrev): J Cachexia Sarcopenia Muscle
                Journal ID (doi): 10.1007/13539.2190-6009
                Journal ID (publisher-id): JCSM
                Title: Journal of Cachexia, Sarcopenia and Muscle
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 2190-5991
                ISSN (Electronic): 2190-6009
                Publication date (Electronic): 28 August 2017
                Publication date (Print): February 2018
                Volume: 9
                Issue: 1 ( doiID: 10.1002/jcsm.v9.1 )
                Pages: 53-59
                Affiliations
                [ 1 ] Department of Radiology, Seoul St. Mary's Hospital, College of Medicine The Catholic University of Korea 222 Banpo‐daero, Seocho‐gu Seoul 06591 South Korea
                [ 2 ] Cancer Research Institute, College of Medicine The Catholic University of Korea 222 Banpo‐daero, Seocho‐gu Seoul 06591 South Korea
                [ 3 ] Department of Surgery, Seoul St. Mary's Hospital The Catholic University of Korea 222 Banpo‐daero, Seocho‐gu Seoul 06591 South Korea
                [ 4 ] Department of Surgery, Uijeongbu St. Mary's Hospital The Catholic University of Korea Cheonbo‐ro 271 Uijeongbu‐si, Gyeonggi‐do 11765 South Korea
                Author notes
                [*] [* ]Correspondence to: Daeyoun David Won, Department of Surgery, Seoul St Mary's Hospital, The Catholic University of Korea, 222 Banpo‐daero, Seocho‐gu, Seoul 06591, South Korea. Fax: 82‐2‐595‐2822, Email: twrainmaking@ 123456gmail.com
                Article
                Publisher ID: JCSM12234 Other ID: JCSM-D-17-00054
                DOI: 10.1002/jcsm.12234
                PMC ID: 5803619
                PubMed ID: 28849630
                SO-VID: f71f4b0e-9181-436f-9683-b7f910c29809
                Copyright © © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders
                License:

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 28 February 2017
                Date revision received : 13 June 2017
                Date accepted : 17 July 2017
                Page count
                Figures: 4, Tables: 4, Pages: 7, Words: 2516
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                component-id jcsm12234
                cover-date February 2018
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:08.02.2018

                ScienceOpen disciplines: Orthopedics
                Keywords: sarcopenia,visceral obesity,rectal cancer,prognosis
                Data availability:
                ScienceOpen disciplines: Orthopedics
                Keywords: sarcopenia, visceral obesity, rectal cancer, prognosis

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