학술논문
Multicentric Assessment of Safety and Efficacy of Combinatorial Adjuvant Brain Metastasis Treatment by Intraoperative Radiation Therapy and Immunotherapy.
Document Type
Academic Journal
Author
Layer JP; Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany; Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany.; Shiban E; Department of Neurosurgery, University Hospital Augsburg, Augsburg, Germany.; Brehmer S; Department of Neurosurgery, University Medical Center Mannheim, Mannheim, Germany.; Diehl CD; Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.; de Castro DG; Department of Radiation Oncology, A. C. Camargo Cancer Center, São Paulo, Brazil.; Hamed M; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.; Dejonckheere CS; Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany.; Cifarelli DT; Department of Neurosurgery, West Virginia University, Morgantown, West Virginia.; Friker LL; Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany; Institute of Neuropathology, University Hospital Bonn, Bonn, Germany.; Herrlinger U; Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Bonn, Bonn, Germany.; Hölzel M; Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany.; Vatter H; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.; Schneider M; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.; Combs SE; Department of Radiation Oncology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.; Schmeel LC; Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany.; Cifarelli CP; Department of Neurosurgery, West Virginia University, Morgantown, West Virginia.; Giordano FA; Department of Radiation Oncology, University Medical Center Mannheim, Mannheim, Germany; DKFZ-Hector Cancer Institute of the University Medical Center Mannheim, Mannheim, Germany; Mannheim Institute of Intelligent Systems in Medicine (MIISM), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.; Sarria GR; Department of Radiation Oncology, University Hospital Bonn, Bonn, Germany. Electronic address: gustavo.sarria@ukbonn.de.; Kahl KH; Department of Radiooncology, University Hospital Augsburg, Augsburg, Germany.
Source
Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 7603616 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-355X (Electronic) Linking ISSN: 03603016 NLM ISO Abbreviation: Int J Radiat Oncol Biol Phys Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: After surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy by enabling superior organ-at-risk preservation, reduction of in-hospital times, and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess the safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs).
Methods and Materials: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival.
Results: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival.
Conclusions: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Methods and Materials: In a multicentric approach incorporating individual patient data from 6 international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis, leptomeningeal spread, local control, distant brain progression (DBP), and estimated overall survival.
Results: In total, 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow-up was 13.2 (range, 1.2-102.4) months, and the median IORT dose was 25 (range, 18-30) Gy prescribed to the applicator surface. There was 1 grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative radiation necrosis rate was observed. The 1-year local control rate was 98.0%, and the 1-year DBP-free survival rate was 60.0%. Median time to DBP was 5.5 (range, 1.0-18.5) months in the subgroup of patients experiencing DBP, and the cumulative leptomeningeal spread rate was 4.9%. The median estimated overall survival was 26 (range, 1.2 to not reached) months with a 1-year survival rate of 74.0%. Early initiation of immunotherapy/TTs was associated with a nonsignificant trend toward improved DBP rate and overall survival.
Conclusions: The combination of ICIs/TTs with IORT for resected BMs does not seem to increase toxicity and yields encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)