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Underweight and weight loss are predictors of poor outcome in patients with brain metastasis

  • Clinical Study
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Abstract

Purpose

Overweight may be associated with favorable outcome whereas tumor cachexia may be associated with worse outcome in patients with metastatic cancer. Here we evaluate the association of abnormal body mass index and weight change with outcome in patients with brain metastasis.

Methods

Patients with a diagnosis of brain metastasis treated at the University Hospital Zurich (n = 703) were assessed for associations of body mass index, weight change, comorbidities and survival.

Results

Compared with patients with normal body mass index of 18.5–24.9 kg/m2 and a median overall survival of 9 months (95% confidence interval 7.5–10.5), overall survival was inferior in patients with body mass index < 18.5 kg/m2 (overall survival 6 months, 95% confidence interval 1.6–10.3, p = 0.04), but superior in patients with body mass index > 25 kg/m2 (overall survival 13 months, 95% confidence interval 11.0–15.0; p = 0.033). We report a median relative weight loss of 5% within the first 6 months of diagnosis of brain metastasis (95% confidence interval 3.3–6.5), and reduction exceeding the median was associated with an unfavorable outcome (weight loss < 5% 22.0 months, 95% confidence interval 19.2–24.8; weight loss > 5% 14.0 months, 95% confidence interval 11.9–16.).

Conclusion

High body mass index is associated with better, and underweight with worse outcome in patients with brain metastasis. Conversely, weight loss above median may predict poor outcome. Future studies need to address whether vigorous treatment of tumor cachexia, e.g. by specific nutrition management, might improve outcome of patients with brain metastasis. In contrast, regimens associated with weight loss such as ketogenic diet may be detrimental.

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Acknowledgements

We thank the colleagues involved in clinical management as well as patients and relatives for their support.

Funding

This research did not receive any specific funding.

Author information

Authors and Affiliations

  1. Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, 8091, Zurich, Switzerland

    Anna Lareida, Robert Terziev, Bettina Grossenbacher, Patrick Roth, Emilie Le Rhun, Michael Weller & Fabian Wolpert

  2. Department of Radiation Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Nicolaus Andratschke & Matthias Guckenberger

  3. Cancer Registry for the Canton of Zurich, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Sabine Rohrmann

  4. Department of Oncology, University Hospital and University of Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Rolf Stahel

  5. Neuro-Oncology, Department of Neurosurgery, CHU Lille, 59000, Lille, France

    Emilie Le Rhun

  6. Neurology, Breast Cancer Department, Oscar Lambret Center, 59000, Lille, France

    Emilie Le Rhun

  7. Inserm, U-1192, University of Lille, 59000, Lille, France

    Emilie Le Rhun

Authors
  1. Anna Lareida
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Contributions

All authors agreed with the content and gave explicit consent to submit this publication. Consent from the responsible authorities from involved institutions was obtained prior to submission. All authors made either substantial contributions to the conception or design of the work, the acquisition, analysis, or interpretation of data, drafted the work or revised it critically for important intellectual content. All authors approved the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Fabian Wolpert.

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Conflict of interest

NA has received honoraria for advisory board participation from AstraZeneca and research grants from Brainlab AG.PR has received honoraria for advisory board participation and lectures from Bristol-Myers Squibb, Molecular Partners, MSD, Novartis and Roche. RS has received honoraria for advisory boards from Abbvie, Astra Zeneca, Boehringer Ingelheim, MSD, Pfizer, Roche and Takeda. Honoraria as a speaker were received from Astra Zeneca, Boehringer Ingelheim, MSD and Roche. DMC activity for Roche and Takeda was declared as well as financial support for clinical trials by AstraZeneca, BMS, Boehringer Ingelheim, Genentech, MSD, Roche, and Pfizer. MG has received research grants from AstraZeneca and Varian and and honoraria for lectures or advisory board participation or consulting from AstraZeneca. ELR has received research grants from Mundipharma and Amgen and honoraria for lectures or advisory board participation from Abbvie, Daiichi Sankyo, Mundipharma and Novartis. MW has received research grants from Abbvie, Bayer, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, OGD2, Piqur, Roche and Adastra, and honoraria for lectures or advisory board participation or consulting from Abbvie, BMS, Celgene, Merck, Sharp & Dohme (MSD), Merck (EMD), Novocure, Orbus, Roche and Tocagen. FW has received travel support from Roche. AL no conflict of interest declared. RT no conflict of interest declared. BG no conflict of interest declared. RT no conflict of interest declared. SR no conflict of interest declared.

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Supplementary file1 (PDF 246 kb)

Figure S1: Association of weight and patients characteristics. A-C. Age (A), KPS (B) and number of brain metastases (C) (y-axis) are shown for each WHO adipositas grade (x-axis) (A,B) or per weight category (C) as whisker box-plots. Boxes represent the interquartile range and Whiskers 95% CI, medians are shown as broad, bold lines. Statistical evaluation was done by Kruskal-Wallis test, p values are indicated with brackets. In C, post-hoc testing by Dunn-Bonferroni-tests is shown with p-values for subgroups as indicated by brackets. D-F. Adipositas grades are shown for each tumor entity (D), operated vs. non-operated individuals (E) and absence versus presence of extracranial metastases as stacked columns (F).

Supplementary file2 (PDF 107 kb)

Figure S2: Evolution of weight change. Weight in kg (y-axis) is shown for assessment at the time of diagnosis of brain metastasis and 6 months later (x-axis) as Whisker box-plots. Boxes represent the interquartile range and Whiskers 95% CI, medians are shown as broad, bold lines. Statistical evaluation was done by Wilcoxon test for paired samples, p values are indicated with brackets.

Supplementary file3 (PDF 375 kb)

Figure S3: Adipositas grades and survival. A. The Kaplan-Meier curve shows survial for different WHO adipositas grades (see legend for color code), with the y-axis marking percentage of survival and the x-axis time in months. B. OS including 95% CI is annotated for all adipositas grades.

Supplementary file4 (PDF 564 kb)

Figure S4: Other tumor types and survival. A-E. The Kaplan-Meier curve shows survial for different subgroups of primary tumors other than lung cancer, including cancer of unknown primary site (A), gastrointestinal cancer (B), breast cancer (C), melanoma (D) and other primary tumors (E). Legends indicate different weight categories according to color code, with the y-axis marking percentage of survival and the x-axis time in months. F. OS including 95% CI is annotated for all primary tumors other than lung-cancer as a table (CUP = cancer of unknown primary site).

Supplementary file5 (DOCX 16 kb)

Table S1: Characteristics of brain metastasis patients during different periods of the study. The first column shows the respective item which was assessed, the second column results for all patients, the third column results for the first half of the study period, the fourth column for the second half of the stud period and the last column results of statistical testing (all Chi-square test).

Supplementary file6 (DOCX 16 kb)

Table S2: Multivariate analysis including weight loss after 6 months as candidate prognostic factor. The results of multivariate testing of candidate prognostic factors 6 months after diagnosis of BM are shown, which were calculated employing a Cox Hazard model. The first column depicts the respective candidate factor, the second one the two-sided p-values, the third column the respective Hazard ratios following 95% CI in the fourth and fifth column.

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Lareida, A., Terziev, R., Grossenbacher, B. et al. Underweight and weight loss are predictors of poor outcome in patients with brain metastasis. J Neurooncol 145, 339–347 (2019). https://doi.org/10.1007/s11060-019-03300-1

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