Tumour growth rate improves tumour assessment and first-line systemic treatment decision-making for immunotherapy in patients with liver metastatic uveal melanoma

Toulsie Ramtohul; Axel Cohen; Manuel Rodrigues; Sophie Piperno-Neumann; Luc Cabel; Nathalie Cassoux; Livia Lumbroso-Le Rouic; Denis Malaise; Sophie Gardrat; Gaëlle Pierron; Pascale Mariani; Vincent Servois

doi:10.1038/s41416-022-01793-8

Tumour growth rate improves tumour assessment and first-line systemic treatment decision-making for immunotherapy in patients with liver metastatic uveal melanoma

Br J Cancer. 2022 Jul;127(2):258-267. doi: 10.1038/s41416-022-01793-8. Epub 2022 Mar 26.

Authors

Toulsie Ramtohul¹, Axel Cohen², Manuel Rodrigues^{3

4}, Sophie Piperno-Neumann³, Luc Cabel³, Nathalie Cassoux^{5

6}, Livia Lumbroso-Le Rouic⁵, Denis Malaise^{5

7}, Sophie Gardrat^{4

8}, Gaëlle Pierron⁹, Pascale Mariani¹⁰, Vincent Servois¹¹

Affiliations

¹ Department of Radiology, Institut Curie, Paris, PSL Research University, Paris, France. toulsie.ramtohul@curie.fr.
² Department of Radiology, Institut Curie, Paris, PSL Research University, Paris, France.
³ Department of Medical Oncology, Institut Curie, PSL Research University, Paris and St. Cloud, Paris, France.
⁴ INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Paris, France.
⁵ Department of Ocular Oncology, Institut Curie, PSL Research University, Paris, France.
⁶ UMR 144 CNRS, Université de Paris, Paris, France.
⁷ INSERM U1288, PSL Research University, Laboratoire d'Imagerie Translationnelle en Oncologie, 91400, Orsay, France.
⁸ Department of Biopathology, Institut Curie, PSL Research University, Paris, France.
⁹ Somatic Genetic Unit, Department of Genetics, Institut Curie, PSL University, Paris, France.
¹⁰ Department of Surgical Oncology, Institut Curie, PSL Research University, Paris, France.
¹¹ Department of Radiology, Institut Curie, Paris, PSL Research University, Paris, France. vincent.servois@curie.fr.

Abstract

Background: The RECIST-based response variably matches the clinical benefit of systemic therapies for liver metastatic uveal melanoma (LMUM). The aims were to determine whether the tumour growth rate (TGR) can help predict the survival in patients with LMUM and to provide information for the management of first-line systemic treatment.

Methods: This retrospective study included 147 (training: n = 110, validation: n = 37) patients with LMUM treated with first-line systemic treatment between 2010 and 2021. Two TGR-derived parameters were calculated, TGR₀ and TGR_3m. Multivariate Cox analyses identified independent predictors of progression-free survival (PFS) and overall survival (OS).

Results: TGR_3m was a strong independent prognostic factor of PFS and OS (p < 0.001). The RECIST-based response was no longer significant in the OS analyses. Only immunotherapy regimens correlated with higher OS (HR = 0.2; 95% CI, 0.1-0.5; p < 0.001) in the low-TGR_3m (≤50%/m) subgroup. These findings were confirmed in the validation cohort. TGR₀, disease-free interval (DFI), and the sum of target lesions at baseline were predictive factors of low TGR_3m.

Discussion: The use of TGR_3m would improve tumour assessment by identifying patients who would benefit from first-line immunotherapy regimens despite PD. TGR₀, DFI and the sum of target lesions were correlated with TGR_3m, which can support first-line treatment decision-making for immunotherapy.

MeSH terms

Humans
Immunotherapy
Liver / pathology
Melanoma* / drug therapy
Melanoma* / pathology
Neoplasms, Second Primary*
Retrospective Studies
Uveal Neoplasms

Supplementary concepts

Uveal melanoma