Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival

Stefanos Voglis; Valentina Schaller; Timothy Müller; Meltem Gönel; Sebastian Winklhofer; Joana Mangana; Reinhard Dummer; Carlo Serra; Michael Weller; Luca Regli; Emilie Le Rhun; Marian C Neidert

doi:10.1016/j.ejca.2022.08.020

Maximal surgical tumour load reduction in immune-checkpoint inhibitor naïve patients with melanoma brain metastases correlates with prolonged survival

Eur J Cancer. 2022 Nov:175:158-168. doi: 10.1016/j.ejca.2022.08.020. Epub 2022 Sep 17.

Authors

Affiliations

¹ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland. Electronic address: stefanos.voglis@usz.ch.
² Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
³ Department of Neuroradiology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
⁴ Department of Dermatology, University Hospital and University of Zurich, Zurich, Switzerland.
⁵ Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
⁶ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland.
⁷ Department of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland; Department of Neurosurgery, Cantonal Hospital St.Gallen, University of St.Gallen Medical School, St.Gallen, Switzerland.

PMID: 36126476
DOI: 10.1016/j.ejca.2022.08.020

Abstract

Background: Recent therapeutic advances in metastatic melanoma have led to improved overall survival (OS) rates, with consequently an increased incidence of brain metastases (BM). The role of BM resection in the era of targeted and immunotherapy should be reassessed. In the current study we analysed the role of residual intracranial tumour load in a cohort of melanoma BM patients.

Methods: Retrospective single-centre analysis of a prospective registry of resected melanoma BM from 2013 to 2021. Correlations of residual tumour volume and outcome were determined with respect to patient, tumour and treatment regimens characteristics.

Results: 121 individual patients (66% male, mean age 59.9 years) were identified and included in the study. Pre- and postoperative systemic treatments included BRAF/MEK inhibitors, as well as combination or monotherapy of immune-checkpoint inhibitors (ICIs). Median OS of the entire cohort was 20 months. Cox proportional-hazard analysis revealed postoperative anti-CTLA4+anti-PD-1 therapy (HR 0.07, p = .01) and postoperative residual intracranial tumour burden (HR 1.4, p = .027) as significant predictors for OS. Further analysis revealed that ICI-naïve patients with residual tumour volume ≤3.5 cm³ and postoperative ICI showed significantly prolonged OS compared to patients with residual volume >3.5 cm³ (p < .0001). Subgroup analysis of ICI-naïve patients showed steroid intake postoperatively to be negatively associated with OS, however residual tumour volume ≤3.5 cm³ remained independently correlated with superior OS (HR 0.14, p < .001).

Conclusion: Besides known predictive factors like postoperative ICI, a maximal intracranial tumour burden reduction seems to be beneficial, especially in ICI-naïve patients. This highlights the importance of local CNS control and the need to further investigating the role of initial surgical tumour load reduction in randomised clinical trials.

Keywords: Brain metastases; Extent of resection; Immunotherapy; Melanoma; Tumour residual.

MeSH terms

Brain Neoplasms* / secondary
Female
Humans
Immune Checkpoint Inhibitors / therapeutic use
Male
Melanoma* / drug therapy
Melanoma* / pathology
Melanoma* / surgery
Middle Aged
Mitogen-Activated Protein Kinase Kinases
Neoplasm, Residual
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins B-raf
Retrospective Studies
Tumor Burden

Substances

Immune Checkpoint Inhibitors
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
Mitogen-Activated Protein Kinase Kinases