Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases

C Fenioux; I Troussier; A Amelot; P Y Borius; C H Canova; E Blais; J J Mazeron; P Maingon; C A Valéry

doi:10.1016/j.canrad.2022.11.004

Long duration of immunotherapy before radiosurgery might improve intracranial control of melanoma brain metastases

Cancer Radiother. 2023 May;27(3):206-213. doi: 10.1016/j.canrad.2022.11.004. Epub 2023 May 4.

Authors

C Fenioux¹, I Troussier¹, A Amelot², P Y Borius³, C H Canova¹, E Blais¹, J J Mazeron¹, P Maingon¹, C A Valéry⁴

Affiliations

¹ Service de radiothérapie oncologique, hôpital de la Pitié-Salpêtrière, Paris, France.
² Service de neurochirurgie, hôpital de la Pitié-Salpêtrière, Paris, France.
³ Service de neurochirurgie, hôpital de la Pitié-Salpêtrière, Paris, France; Unité de radiochirurgie gamma-knife, hôpital de la Pitié-Salpêtrière, Paris, France.
⁴ Service de neurochirurgie, hôpital de la Pitié-Salpêtrière, Paris, France; Unité de radiochirurgie gamma-knife, hôpital de la Pitié-Salpêtrière, Paris, France. Electronic address: capvalery@hotmail.fr.

PMID: 37149466
DOI: 10.1016/j.canrad.2022.11.004

Abstract

Purpose: Despite significant advances that have been made in management of metastatic melanoma with immune checkpoint therapy, optimal timing of combination immune checkpoint therapy and stereotactic radiosurgery is unknown. We have reported toxicity and efficiency outcomes of patients treated with concurrent immune checkpoint therapy and stereotactic radiosurgery.

Patients and methods: From January 2014 to December 2016, we analyzed 62 consecutive patients presenting 296 melanoma brain metastases, treated with gamma-knife and receiving concurrent immune checkpoint therapy with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure. Median follow-up time was 18 months (mo) (13-22). Minimal median dose delivered was 18 gray (Gy), with a median volume per lesion of 0.219 cm³.

Results: The 1-year control rate per irradiated lesion was 89% (CI 95%: 80.41-98.97). Twenty-seven patients (43.5%) developed distant brain metastases after a median time of 7.6 months (CI 95% 1.8-13.3) after gamma-knife. In multivariate analysis, positive predictive factors for intracranial tumor control were: delay since the initiation of immunotherapy exceeding 2 months before gamma-knife procedure (P=0.003) and use of anti-PD1 (P=0.006). Median overall survival (OS) was 14 months (CI 95%: 11-NR). Total irradiated tumor volume<2.1 cm³ was a positive predictive factor for overall survival (P=0.003). Ten patients (16.13%) had adverse events following irradiation, with four grade≥3. Predictive factors of all grade toxicity were: female gender (P=0.001) and previous treatment with MAPK (P=0.05).

Conclusion: A long duration of immune checkpoint therapy before stereotactic radiosurgery might improve intracranial tumor control, but this relationship and its ideal timing need to be assessed in prospective trials.

Keywords: Brain metastases; Immunotherapy; Immunothérapie; Melanoma; Mélanome; Métastases cérébrales; Radiochirurgie; Radiosurgery.

MeSH terms

Brain Neoplasms* / pathology
Brain Neoplasms* / radiotherapy
Female
Humans
Immunotherapy / methods
Melanoma* / radiotherapy
Prospective Studies
Radiosurgery* / methods
Retrospective Studies