Metastatic melanoma: pretreatment contrast-enhanced CT texture parameters as predictive biomarkers of survival in patients treated with pembrolizumab

Abstract

Purpose

To determine whether texture analysis features on pretreatment contrast-enhanced computed tomography (CT) images can predict overall survival (OS) and progression-free survival (PFS) in patients with metastatic malignant melanoma (MM) treated with an anti-PD-1 monoclonal antibody, pembrolizumab.

Materials and methods

This institutional-approved retrospective study included 31 patients with metastatic MM treated with pembrolizumab. Texture analysis of 74 metastatic lesions was performed on CT scanners obtained within 1 month before treatment. Mean gray-level, entropy, kurtosis, skewness, and standard deviation values were derived from the pixel distribution histogram before and after spatial filtration at different anatomic scales, ranging from fine to coarse. Lasso penalized Cox regression analyses were performed to identify independent predictors of OS and PFS.

Results

Median OS and PFS were 357 days (range 42–1355) and 99 days (range 35–1185), respectively. Skewness at coarse texture scale (SSF = 6; HR (CI 95%) = 6.017 (1.39, 26.056), p = 0.016), Response evaluation criteria in solid tumors (RECIST) conclusion (HR (CI 95%) = 3.41 (1.17, 9.89), p = 0.024), and body weight (HR (CI 95%) = 0.96 (0.92, 0.995), p = 0.026) were independent predictors of OS. Skewness at coarse texture scale (SSF = 6; HR (CI 95%) = 4.55 (1.46, 14.13), p = 0.0089) and RECIST conclusion (HR (CI 95%) = 10.63 (3.11, 36.29), p = 0.00016) were independent predictors of PFS. Skewness values above − 0.55 at coarse texture scale were significantly associated with both lower OS and lower PFS after administration of pembrolizumab.

Conclusion

Pretreatment CT texture analysis–derived tumor skewness may act as predictive biomarker of OS and PFS in patients with metastatic MM treated with pembrolizumab.

Key Points

• Pretreatment skewness at coarse texture scale in metastases from malignant melanoma was an independent predictor of overall survival and progression-free survival.

• Skewness values above −0.55 at coarse texture scale were significantly associated with both lower OS and lower PFS after administration of pembrolizumab.

• In patients with metastatic MM, texture analysis performed on pretreatment CT may act as a useful tool to select the best candidates for pembrolizumab therapy.

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Abbreviations

CT:

Computed tomography

ECOG:

Eastern cooperative oncology group

HR:

Hazard ratio

LDH:

Serum lactate dehydrogenase

MM:

Malignant melanoma

OS:

Overall survival

PD-1:

Program cell death 1

PFS:

Progression-free survival

RECIST:

Response evaluation criteria in solid tumors

ROI:

Region of interest

SD:

Standard deviation

SSF:

Spatial scale image filtration

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The authors state that this work has not received any funding.

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Correspondence to Carole Durot.

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The scientific guarantor of this publication is Carole Durot, MD, Centre Hospitalo-universitaire de Reims.

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The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

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Written informed consent was obtained from all subjects (patients) in this study.

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Institutional Review Board approval was obtained.

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

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Durot, C., Mulé, S., Soyer, P. et al. Metastatic melanoma: pretreatment contrast-enhanced CT texture parameters as predictive biomarkers of survival in patients treated with pembrolizumab. Eur Radiol 29, 3183–3191 (2019). https://doi.org/10.1007/s00330-018-5933-x

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Keywords

  • Metastatic melanoma
  • Pembrolizumab
  • Tomography, X-ray computed
  • Biomarkers
  • Survival