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Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma

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Abstract

Background

Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status.

Methods

In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006–2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height.

Results

Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1–2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%).

Conclusions

In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.

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Data Availability

The raw data used in this study may be requested from the authors.

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Acknowledgements

Grant Support: Funding for this study was provided by the Lusi Wong Family Fund and the Alan Brown Chair.

Author information

Author notes

  1. Ulf Zeuge, Aline F. Fares, Geoffrey Liu, Dmitry Rozenberg and Micheal C. McInnis contributed equally.

Authors and Affiliations

  1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Ave., Toronto, ON, M5G 2M9, Canada

    Ulf Zeuge, Aline F. Fares, Joelle Soriano, Katrina Hueniken, Wanning Wang, Sabine Schmid, Sarah Rudolph-Naiberg, M. Catherine Brown, Jonathan Yeung, Eric X. Chen, Raymond W. Jang, Wei Xu, Elena Elimova & Geoffrey Liu

  2. Zuger Kantonsspital, Baar, Switzerland

    Ulf Zeuge

  3. Hospital de Base and Faculty of Medicine, São Jose Do Rio Preto, Brazil

    Aline F. Fares

  4. Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, Canada

    Katrina Hueniken & Wei Xu

  5. Department of Medical Imaging, University of Toronto, Toronto, Canada

    Jaspreet Bajwa

  6. Kantonsspital St. Gallen, St. Gallen, Switzerland

    Sabine Schmid

  7. Division of Respirology, Temerty Faculty of Medicine, Toronto General Hospital Research Institute, University of Toronto, Toronto, Canada

    Dmitry Rozenberg

  8. Division of Cardiothoracic Imaging, Joint Department of Medical Imaging, Toronto General Hospital, Toronto, ON, Canada

    Micheal C. McInnis

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  1. Ulf Zeuge
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Corresponding author

Correspondence to Geoffrey Liu.

Ethics declarations

Ethical Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for being included in the study.

Conflict of interest

On behalf of the co-authors of this manuscript, we declare the following conflicts of interests: Sabine Schmid: Grants or contracts from any entity (all institutional): Von Tobel Stiftung, Janssen, AstraZeneca, BMS; Fill the Gap (University of Zürich); Swiss Cancer League foundation. Advisory boards (all institutional): AstraZeneca, BMS, MSD. Dmitry Rozenberg: all support for the present manuscript: salary support for Sandra Faire and Ivan Fecan Professorship. The following authors declare no conflicts of interest: Ulf Zeuge, Aline F. Fares, Joelle Soriano, Katrina Hueniken, Jaspreet Bajwa, Wanning Wang, Sarah Rudolph-Naiberg, M. Catherine Brown, Jonathan Yeung, M. Catherine Brown, Eric X. Chen, Raymond W. Jang, Wei Xu, Elena Elimova, Geoffrey Liu, and Micheal C. McInnis.

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Supplementary Information

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10388_2022_981_MOESM1_ESM.docx

Supplementary file1 Supplementary Tab.1 Palliative treatment details of full cohort (left) and by sarcopenia status (right). Palliative treatments at UHN or affiliated hospitals. PNI, prognostic nutritional index (around time of baseline CT); SD, standard deviation (DOCX 30 KB)

10388_2022_981_MOESM2_ESM.docx

Supplementary file2 Supplementary Tab.2 Overall survival in adenocarcinoma patients: Univariable and multivariable Cox proportional hazards regression, associations between sarcopenia and overall survival. Abbreviations: BMI, Body mass index; ECOG, Eastern Cooperative Oncology Group; VA, visceral adipose tissue; SA, subcutaneous adipose tissue. †P-values computed from Wald test for global statistical significance of the indicated variable (DOCX 30 KB)

10388_2022_981_MOESM3_ESM.docx

Supplementary file3 Supplementary Tab.3 Overall survival in SCC patients: Univariable and multivariable Cox proportional hazards regression, associations between sarcopenia and overall survival. Abbreviations: BMI, Body mass index; ECOG, Eastern Cooperative Oncology Group; VA, visceral adipose tissue; SA, subcutaneous adipose tissue. †P-values computed from Wald test for global statistical significance of the indicated variable (DOCX 29 KB)

10388_2022_981_MOESM4_ESM.docx

Supplementary file4 Supplementary Fig.1 Body compositions at the level of L3 in three exemplary patients. Skeletal muscle is outlined (red) and psoas muscle (blue). Subcutaneous adipose tissue (cyan) and visceral adipose tissue (yellow)(a): SMI=39.8cm2/m2, VA=15.2cm2 SA=149cm2, BMI=31; (b): SMI=34.2cm2/m2, VA=28cm2 SA=28cm2, BMI=16.5; (c): SMI=72cm2/m2, VA=491cm2, SA 196cm2, BMI=36 (DOCX 487 KB)

Supplementary file5 Supplementary Fig.2 Patient inclusion diagram (DOCX 45 KB)

10388_2022_981_MOESM6_ESM.docx

Supplementary file6 Supplementary Fig3 Relationship between the sarcopenia status and different body composition metrics. These metrics are all at the third lumbar vertebra. Top: (total) muscle area (MA; Panel a), subcutaneous adipose tissue (SA; Panel b), Body Mass Index (BMI; Panel c), and visceral adipose tissue (VA; Panel d). Bottom: Pairwise Pearson correlations of the four body composition metrics. Abbreviations: rho = Spearman’s rho correlation coefficient for the correlation between each X and Y variable (DOCX 391 KB)

10388_2022_981_MOESM7_ESM.docx

Supplementary file7 Supplementary Fig4 Overall survival (left) and progression free survival (right) by sarcopenia status and histology. Adenocarcinoma (a and b) and squamous cell carcinoma (c and d). Overall survival in SCC adds up to 52 patients, because one sarcopenic patient was missing BMI for calculations. Abbreviations: SCC, Squamous cell carcinoma. Note that in this analysis, sarcopenic non-overweight/obese refers to individuals who are sarcopenic but with BMI < 25 mg/m2; sarcopenic overweight/obese is defined as sarcopenia in individuals who have BMI > 25mg/m2; non-sarcopenic refers to all patients who do not meet the definition of sarcopenia used throughout this study (DOCX 279 KB)

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Zeuge, U., Fares, A.F., Soriano, J. et al. Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma. Esophagus 20, 557–566 (2023). https://doi.org/10.1007/s10388-022-00981-y

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