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Published in: Annals of Surgical Oncology 6/2024

20-01-2024 | Sarcopenia | Thoracic Oncology

Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation

Authors: Xin Xiao, MD, Pin-Hao Fang, MD, Jian-Feng Zhou, MD, Xiao-Kun Li, MD, Qi-Xin Shang, MD, Yu-Shang Yang, MD, Si-Yuan Luan, MD, Long-Qi Chen, MD, PhD, Yong Yuan, MD, PhD

Published in: Annals of Surgical Oncology | Issue 6/2024

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Abstract

Background

The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial.

Patients and Methods

We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines.

Results

Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03–2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025).

Conclusions

Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.
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Literature
1.
go back to reference Li X, Chen L, Luan S, et al. The development and progress of nanomedicine for esophageal cancer diagnosis and treatment. Semin Cancer Biol. 2022;86:873–85.CrossRefPubMed Li X, Chen L, Luan S, et al. The development and progress of nanomedicine for esophageal cancer diagnosis and treatment. Semin Cancer Biol. 2022;86:873–85.CrossRefPubMed
2.
go back to reference Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, Version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(7):855–83.CrossRefPubMed Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, Version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(7):855–83.CrossRefPubMed
3.
go back to reference Eyck BM, van Lanschot JJB, Hulshof M, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS Trial. J Clin Oncol: Offic J Am Soc Clin Oncol. 2021;39(18):1995–2004.CrossRef Eyck BM, van Lanschot JJB, Hulshof M, et al. Ten-year outcome of neoadjuvant chemoradiotherapy plus surgery for esophageal cancer: the randomized controlled CROSS Trial. J Clin Oncol: Offic J Am Soc Clin Oncol. 2021;39(18):1995–2004.CrossRef
4.
go back to reference Kano K, Yamada T, Yamamoto K, et al. The impact of pretherapeutic naples prognostic score on survival in patients with locally advanced esophageal cancer. Ann Surg Oncol. 2021;28(8):4530–9.CrossRefPubMed Kano K, Yamada T, Yamamoto K, et al. The impact of pretherapeutic naples prognostic score on survival in patients with locally advanced esophageal cancer. Ann Surg Oncol. 2021;28(8):4530–9.CrossRefPubMed
5.
go back to reference Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23(2):646–54.CrossRefPubMed Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review and meta-analysis. Ann Surg Oncol. 2016;23(2):646–54.CrossRefPubMed
6.
go back to reference McGovern J, Dolan RD, Horgan PG, Laird BJ, McMillan DC. Computed tomography-defined low skeletal muscle index and density in cancer patients: observations from a systematic review. J Cachexia Sarcopenia Muscle. 2021;12(6):1408–17.CrossRefPubMedPubMedCentral McGovern J, Dolan RD, Horgan PG, Laird BJ, McMillan DC. Computed tomography-defined low skeletal muscle index and density in cancer patients: observations from a systematic review. J Cachexia Sarcopenia Muscle. 2021;12(6):1408–17.CrossRefPubMedPubMedCentral
7.
go back to reference Jogiat UM, Sasewich H, Turner SR, et al. Sarcopenia determined by skeletal muscle index predicts overall survival, disease-free survival, and postoperative complications in resectable esophageal cancer: a systematic review and meta-analysis. Ann Surg. 2022;276(5):e311–8.CrossRefPubMed Jogiat UM, Sasewich H, Turner SR, et al. Sarcopenia determined by skeletal muscle index predicts overall survival, disease-free survival, and postoperative complications in resectable esophageal cancer: a systematic review and meta-analysis. Ann Surg. 2022;276(5):e311–8.CrossRefPubMed
8.
go back to reference Ishida T, Makino T, Yamasaki M, et al. Quantity and quality of skeletal muscle as an important predictor of clinical outcomes in patients with esophageal cancer undergoing esophagectomy after neoadjuvant chemotherapy. Ann Surg Oncol. 2021;28(12):7185–95.CrossRefPubMed Ishida T, Makino T, Yamasaki M, et al. Quantity and quality of skeletal muscle as an important predictor of clinical outcomes in patients with esophageal cancer undergoing esophagectomy after neoadjuvant chemotherapy. Ann Surg Oncol. 2021;28(12):7185–95.CrossRefPubMed
9.
go back to reference Elliott JA, Doyle SL, Murphy CF, et al. Sarcopenia: prevalence, and impact on operative and oncologic outcomes in the multimodal management of locally advanced esophageal cancer. Ann Surg. 2017;266(5):822–30.CrossRefPubMed Elliott JA, Doyle SL, Murphy CF, et al. Sarcopenia: prevalence, and impact on operative and oncologic outcomes in the multimodal management of locally advanced esophageal cancer. Ann Surg. 2017;266(5):822–30.CrossRefPubMed
10.
go back to reference Nakashima Y, Saeki H, Nakanishi R, et al. Assessment of sarcopenia as a predictor of poor outcomes after esophagectomy in elderly patients with esophageal cancer. Ann Surg. 2018;267(6):1100–4.CrossRefPubMed Nakashima Y, Saeki H, Nakanishi R, et al. Assessment of sarcopenia as a predictor of poor outcomes after esophagectomy in elderly patients with esophageal cancer. Ann Surg. 2018;267(6):1100–4.CrossRefPubMed
11.
go back to reference Saeki H, Nakashima Y, Kudou K, et al. Neoadjuvant chemoradiotherapy for patients with cT3/nearly T4 esophageal cancer: is sarcopenia correlated with postoperative complications and prognosis? World J Surg. 2018;42(9):2894–901.CrossRefPubMed Saeki H, Nakashima Y, Kudou K, et al. Neoadjuvant chemoradiotherapy for patients with cT3/nearly T4 esophageal cancer: is sarcopenia correlated with postoperative complications and prognosis? World J Surg. 2018;42(9):2894–901.CrossRefPubMed
12.
go back to reference Paireder M, Asari R, Kristo I, et al. Impact of sarcopenia on outcome in patients with esophageal resection following neoadjuvant chemotherapy for esophageal cancer. Eur J Surg Oncol. 2017;43(2):478–84.CrossRefPubMed Paireder M, Asari R, Kristo I, et al. Impact of sarcopenia on outcome in patients with esophageal resection following neoadjuvant chemotherapy for esophageal cancer. Eur J Surg Oncol. 2017;43(2):478–84.CrossRefPubMed
13.
go back to reference Huang CH, Lue KH, Hsieh TC, Liu SH, Wang TF, Peng TC. Association between sarcopenia and clinical outcomes in patients with esophageal cancer under neoadjuvant therapy. Anticancer Res. 2020;40(2):1175–81.CrossRefPubMed Huang CH, Lue KH, Hsieh TC, Liu SH, Wang TF, Peng TC. Association between sarcopenia and clinical outcomes in patients with esophageal cancer under neoadjuvant therapy. Anticancer Res. 2020;40(2):1175–81.CrossRefPubMed
14.
go back to reference Yoon HG, Oh D, Ahn YC, et al. Prognostic impact of sarcopenia and skeletal muscle loss during neoadjuvant chemoradiotherapy in esophageal cancer. Cancers (Basel). 2020;12(4). Yoon HG, Oh D, Ahn YC, et al. Prognostic impact of sarcopenia and skeletal muscle loss during neoadjuvant chemoradiotherapy in esophageal cancer. Cancers (Basel). 2020;12(4).
15.
go back to reference Reisinger KW, Bosmans JW, Uittenbogaart M, et al. Loss of skeletal muscle mass during neoadjuvant chemoradiotherapy predicts postoperative mortality in esophageal cancer surgery. Ann Surg Oncol. 2015;22(13):4445–52.CrossRefPubMedPubMedCentral Reisinger KW, Bosmans JW, Uittenbogaart M, et al. Loss of skeletal muscle mass during neoadjuvant chemoradiotherapy predicts postoperative mortality in esophageal cancer surgery. Ann Surg Oncol. 2015;22(13):4445–52.CrossRefPubMedPubMedCentral
16.
go back to reference Kamitani N, Migita K, Matsumoto S, et al. Association of skeletal muscle loss with the long-term outcomes of esophageal cancer patients treated with neoadjuvant chemotherapy. Surg Today. 2019;49(12):1022–8.CrossRefPubMed Kamitani N, Migita K, Matsumoto S, et al. Association of skeletal muscle loss with the long-term outcomes of esophageal cancer patients treated with neoadjuvant chemotherapy. Surg Today. 2019;49(12):1022–8.CrossRefPubMed
17.
go back to reference Jarvinen T, Ilonen I, Kauppi J, Salo J, Rasanen J. Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study. World J Surg Oncol. 2018;16(1):27.CrossRefPubMedPubMedCentral Jarvinen T, Ilonen I, Kauppi J, Salo J, Rasanen J. Loss of skeletal muscle mass during neoadjuvant treatments correlates with worse prognosis in esophageal cancer: a retrospective cohort study. World J Surg Oncol. 2018;16(1):27.CrossRefPubMedPubMedCentral
18.
go back to reference Mayanagi S, Tsubosa Y, Omae K, et al. Negative impact of skeletal muscle wasting after neoadjuvant chemotherapy followed by surgery on survival for patients with thoracic esophageal cancer. Ann Surg Oncol. 2017;24(12):3741–7.CrossRefPubMedPubMedCentral Mayanagi S, Tsubosa Y, Omae K, et al. Negative impact of skeletal muscle wasting after neoadjuvant chemotherapy followed by surgery on survival for patients with thoracic esophageal cancer. Ann Surg Oncol. 2017;24(12):3741–7.CrossRefPubMedPubMedCentral
19.
go back to reference Liu J, Motoyama S, Sato Y, et al. Decreased skeletal muscle mass after neoadjuvant therapy correlates with poor prognosis in patients with esophageal cancer. Anticancer Res. 2016;36(12):6677–85.CrossRefPubMed Liu J, Motoyama S, Sato Y, et al. Decreased skeletal muscle mass after neoadjuvant therapy correlates with poor prognosis in patients with esophageal cancer. Anticancer Res. 2016;36(12):6677–85.CrossRefPubMed
20.
go back to reference von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7.CrossRef
21.
go back to reference Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35.CrossRefPubMed Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35.CrossRefPubMed
22.
go back to reference Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.CrossRefPubMed Mourtzakis M, Prado CM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.CrossRefPubMed
23.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRefPubMedPubMedCentral
24.
go back to reference Darragh TM, Colgan TJ, Cox JT, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136(10):1266–97.CrossRefPubMed Darragh TM, Colgan TJ, Cox JT, et al. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med. 2012;136(10):1266–97.CrossRefPubMed
25.
go back to reference Grotenhuis BA, Shapiro J, van Adrichem S, et al. Sarcopenia/muscle mass is not a prognostic factor for short- and long-term outcome after esophagectomy for cancer. World J Surg. 2016;40(11):2698–704.CrossRefPubMedPubMedCentral Grotenhuis BA, Shapiro J, van Adrichem S, et al. Sarcopenia/muscle mass is not a prognostic factor for short- and long-term outcome after esophagectomy for cancer. World J Surg. 2016;40(11):2698–704.CrossRefPubMedPubMedCentral
26.
go back to reference Yip C, Goh V, Davies A, et al. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol. 2014;24(5):998–1005.CrossRefPubMed Yip C, Goh V, Davies A, et al. Assessment of sarcopenia and changes in body composition after neoadjuvant chemotherapy and associations with clinical outcomes in oesophageal cancer. Eur Radiol. 2014;24(5):998–1005.CrossRefPubMed
27.
go back to reference Tamandl D, Paireder M, Asari R, Baltzer PA, Schoppmann SF, Ba-Ssalamah A. Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer. Eur Radiol. 2016;26(5):1359–67.CrossRefPubMed Tamandl D, Paireder M, Asari R, Baltzer PA, Schoppmann SF, Ba-Ssalamah A. Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer. Eur Radiol. 2016;26(5):1359–67.CrossRefPubMed
28.
go back to reference Murimwa GZ, Venkat PS, Jin W, et al. Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery. J Gastrointest Oncol. 2017;8(5):808–15.CrossRefPubMedPubMedCentral Murimwa GZ, Venkat PS, Jin W, et al. Impact of sarcopenia on outcomes of locally advanced esophageal cancer patients treated with neoadjuvant chemoradiation followed by surgery. J Gastrointest Oncol. 2017;8(5):808–15.CrossRefPubMedPubMedCentral
29.
go back to reference Rolland Y, Czerwinski S, Abellan Van Kan G, et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging. 2008;12(7):433–50.CrossRefPubMedPubMedCentral Rolland Y, Czerwinski S, Abellan Van Kan G, et al. Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives. J Nutr Health Aging. 2008;12(7):433–50.CrossRefPubMedPubMedCentral
30.
go back to reference Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int. 2010;21(4):543–59.CrossRefPubMed Lang T, Streeper T, Cawthon P, Baldwin K, Taaffe DR, Harris TB. Sarcopenia: etiology, clinical consequences, intervention, and assessment. Osteoporos Int. 2010;21(4):543–59.CrossRefPubMed
31.
go back to reference Cesari M, Kritchevsky SB, Baumgartner RN, et al. Sarcopenia, obesity, and inflammation–results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr. 2005;82(2):428–34.CrossRefPubMed Cesari M, Kritchevsky SB, Baumgartner RN, et al. Sarcopenia, obesity, and inflammation–results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr. 2005;82(2):428–34.CrossRefPubMed
32.
33.
go back to reference Awad S, Tan BH, Cui H, et al. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr. 2012;31(1):74–7.CrossRefPubMed Awad S, Tan BH, Cui H, et al. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin Nutr. 2012;31(1):74–7.CrossRefPubMed
34.
go back to reference Anandavadivelan P, Brismar TB, Nilsson M, Johar AM, Martin L. Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr. 2016;35(3):724–30.CrossRefPubMed Anandavadivelan P, Brismar TB, Nilsson M, Johar AM, Martin L. Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr. 2016;35(3):724–30.CrossRefPubMed
35.
go back to reference Tan BH, Brammer K, Randhawa N, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol. 2015;41(3):333–8.CrossRefPubMed Tan BH, Brammer K, Randhawa N, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol. 2015;41(3):333–8.CrossRefPubMed
36.
go back to reference Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–59.CrossRefPubMedPubMedCentral Cruz-Jentoft AJ, Landi F, Schneider SM, et al. Prevalence of and interventions for sarcopenia in ageing adults: a systematic review. Report of the International Sarcopenia Initiative (EWGSOP and IWGS). Age Ageing. 2014;43(6):748–59.CrossRefPubMedPubMedCentral
37.
go back to reference Liu K, Ji S, Xu Y, et al. Safety, feasibility, and effect of an enhanced nutritional support pathway including extended preoperative and home enteral nutrition in patients undergoing enhanced recovery after esophagectomy: a pilot randomized clinical trial. Dis Esophagus. 2020;33(2):doz030.PubMed Liu K, Ji S, Xu Y, et al. Safety, feasibility, and effect of an enhanced nutritional support pathway including extended preoperative and home enteral nutrition in patients undergoing enhanced recovery after esophagectomy: a pilot randomized clinical trial. Dis Esophagus. 2020;33(2):doz030.PubMed
38.
go back to reference Fang P, Zhou J, Xiao X, et al. The prognostic value of sarcopenia in oesophageal cancer: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022;14(1):3–16.CrossRefPubMedPubMedCentral Fang P, Zhou J, Xiao X, et al. The prognostic value of sarcopenia in oesophageal cancer: a systematic review and meta-analysis. J Cachexia Sarcopenia Muscle. 2022;14(1):3–16.CrossRefPubMedPubMedCentral
Metadata
Title
Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation
Authors
Xin Xiao, MD
Pin-Hao Fang, MD
Jian-Feng Zhou, MD
Xiao-Kun Li, MD
Qi-Xin Shang, MD
Yu-Shang Yang, MD
Si-Yuan Luan, MD
Long-Qi Chen, MD, PhD
Yong Yuan, MD, PhD
Publication date
20-01-2024
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 6/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-024-14936-3

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