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Prognostic value of total metabolic tumour volume and therapy-response assessment by [18F]FDG PET/CT in patients with metastatic melanoma treated with BRAF/MEK inhibitors

  • Oncology
  • Published:
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A Correction to this article was published on 09 March 2022

This article has been updated

Abstract

Objectives

Target therapy with BRAF/MEK inhibitors in metastatic melanoma is characterised by a high response rate; however, acquired resistance to treatment develops in many cases. We aimed to investigate if baseline total metabolic tumour volume (TMTV) and therapy-response assessment by [18F]FDG PET/CT have a prognostic role on progression-free survival (PFS) and overall survival (OS) in patients with metastatic melanoma receiving BRAF ± MEK inhibitors.

Methods

Fifty-seven patients who performed an [18F]FDG PET/CT at baseline and on treatment were retrospectively evaluated. A Cox proportional-hazard model was used to examine associations between OS and PFS with baseline clinical/PET parameters as well as for PET response.

Results

According to EORTC criteria, 34 patients were classified as responders (partial/complete metabolic response [PMR/CMR]) and 23 as non-responders (progressive/stable metabolic disease [PMD/SMD]). Baseline characteristics associated with a shorter PFS were more than two metastatic organ sites and TMTV > 56 cm3; the latter was the only independent feature at multivariate analysis. Patients achieving a CMR were associated with a prolonged PFS compared with those with PMR (median PFS 42.9 vs 8.8 months; p = 0.009). Disease progression occurred in new-onset disease sites in 87.5% of CMR, 7.1% of PMR and 34.8% of PMD/SMD (p < 0.001). High baseline TMTV and lack of treatment response were independent prognostic factors for OS, stratifying patients in three different prognostic classes (median OS 6.7, 18.3 and 102.2 months, respectively).

Conclusions

Baseline TMTV and metabolic response may be useful prognostic indicators for PFS and OS in patients with advanced melanoma treated with BRAF/MEK inhibitors.

Key Points

• In a retrospective cohort of 57 metastatic melanoma patients treated with BRAF/MEK inhibitors, a TMTV > 56 cm 3 at baseline [ 18 F]FDG PET/CT was significantly correlated with a shorter PFS and OS.

• The combined use of baseline TMTV along with PET response during treatment allowed for the identification of three groups of patients with very different median OS.

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Abbreviations

[18F]FDG PET/CT:

2-[18F]fluoro-2-deoxy-d-glucose positron emission/computed tomography

BRAFi:

BRAF inhibitors

CMR:

Complete metabolic response

MEKi:

MEK inhibitors

OS:

Overall survival

PFS:

Progression-free survival

PMD:

Progressive metabolic disease

PMR:

Partial metabolic response

SMD:

Stable metabolic disease

TMTV:

Total metabolic tumour volume

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Funding

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

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Authors and Affiliations

  1. Nuclear Medicine Unit, IRCCS – Regina Elena National Cancer Institute, Via Elio Chianesi, 53, 00144, Rome, Italy

    Alessio Annovazzi, Sandra Rea & Rosa Sciuto

  2. First Division of Medical Oncology, IRCCS – Regina Elena National Cancer Institute, Rome, Italy

    Virginia Ferraresi, Michelangelo Russillo & Davide Renna

  3. Sarcomas and Rare Tumors Unit, IRCCS – Regina Elena National Cancer Institute, Rome, Italy

    Virginia Ferraresi

  4. Second Division of Medical Oncology, IRCCS – Regina Elena National Cancer Institute, Rome, Italy

    Silvia Carpano

Authors
  1. Alessio Annovazzi
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Corresponding author

Correspondence to Alessio Annovazzi.

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Guarantor

The scientific guarantor of this publication is Dr. Alessio Annovazzi.

Conflict of Interest

Dr. Virginia Ferraresi: consulting or advisory role—Bristol Myers Squibb, Novartis, MSD; speaker—Bristol Myers Squibb, Novartis, Pierre Fabre; travel/accommodations: Bristol Myers Squibb, Pierre Fabre, MSD. Dott. Michelangelo Russilo: speaker—Novartis, Pierre Fabre. All remaining authors have declared no conflicts of interest.

Statistics and Biometry

Two of the authors have significant statistical expertise.

Informed Consent

Given the retrospective design of the study, the ethics committee allowed the use and processing of the patients’ clinical data even in the absence of written informed consent.

Ethical Approval

The study was approved by the local institutional ethics committee (prot. n° 1460/21) and it was performed in accordance with ethical standards.

Methodology

• retrospective

• observational

• performed at one institution

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The original online version of this article was revised: The reference 'C Nioche, F Orlhac, S Boughdad, S Reuzé, J Goya-Outi, C Robert, C Pellot-Barakat, M Soussan, F Frouin, and I Buvat. LIFEx: a freeware for radiomic feature calculation in multimodality imaging to accelerate advances in the characterization of tumor heterogeneity. Cancer Research 2018; 78(16):4786-4789' was added.

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Annovazzi, A., Ferraresi, V., Rea, S. et al. Prognostic value of total metabolic tumour volume and therapy-response assessment by [18F]FDG PET/CT in patients with metastatic melanoma treated with BRAF/MEK inhibitors. Eur Radiol 32, 3398–3407 (2022). https://doi.org/10.1007/s00330-021-08355-1

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