Timing of stereotactic radiosurgery within the first-line systemic treatment in non-small cell lung cancer brain metastases: a retrospective single-center cohort study.

Checkpoint inhibitors immunotherapy stereotactic radiosurgery (SRS) targeted treatment tyrosine kinase inhibitors (TKIs)

Journal

Translational lung cancer research
ISSN: 2218-6751
Titre abrégé: Transl Lung Cancer Res
Pays: China
ID NLM: 101646875

Informations de publication

Date de publication:
30 Jul 2024
Historique:
received: 06 02 2024
accepted: 30 05 2024
medline: 9 8 2024
pubmed: 9 8 2024
entrez: 9 8 2024
Statut: ppublish

Résumé

Stereotactic radiosurgery/radiotherapy (SRS/SRT) and novel systemic treatments, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have demonstrated to be effective in managing brain metastases in non-small cell lung cancer (NSCLC). However, the optimal treatment sequence of SRS/SRT and TKI/ICI remains uncertain. This retrospective monocentric analysis addresses this question by comparing the outcomes of patients with NSCLC brain metastases who received upfront SRS/SRT versus those who were initially treated with TKI/ICI. All patients treated with SRS/SRT and TKI/ICI for NSCLC brain metastases were collected from a clinical database. The patients who received first-line TKI or ICI for the treatment of brain metastases were then selected for further analysis. Within this cohort, a comparative analysis between upfront SRS/SRT and patients initially treated with TKI/ICI was conducted, assessing key parameters such as overall survival (OS), intracranial progression-free survival (iPFS) and treatment-related toxicity. Both OS and iPFS were defined as the time from SRS/SRT to either death or disease progression, respectively. The analysis encompassed 54 patients, of which 34 (63.0%) patients received SRS/SRT and TKI/ICI as their first-line therapy. Of the latter, 17 (50.0%) patients received upfront SRS/SRT and 17 (50.0%) were initially treated with TKI/ICI; 24 (70.6%) received SRS/SRT and ICI, and 10 (29.4%) received SRS/SRT and TKI. The cohorts did not significantly differ in the univariable analyses for the following parameters: sex, age, histology, molecular genetics, disease stage at study treatment, performance status, number of brain metastases, treatment technique, tumor volume, target volume, disease progression, radiation necrosis, dosimetry. While no significant differences were found in terms of iPFS and OS between patients treated with upfront SRS/SRT and patients initially treated with TKI, upfront SRS/SRT demonstrated significantly superior OS when compared to patients initially treated with ICI (median OS not reached In this retrospective, single-center cohort study, patients treated with upfront SRS/SRT demonstrated significantly longer OS compared to patients initially treated with ICI in the cohort receiving first-line therapy for brain metastases. However, given the retrospective design and the limited cohort size, definitive conclusions cannot be drawn from these findings. Nevertheless, the results suggest that the timing of SRS/SRT may play an important role in treatment outcomes. Further investigation, preferably through prospective randomized trials, is warranted to provide more conclusive answers to this important question.

Sections du résumé

Background UNASSIGNED
Stereotactic radiosurgery/radiotherapy (SRS/SRT) and novel systemic treatments, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have demonstrated to be effective in managing brain metastases in non-small cell lung cancer (NSCLC). However, the optimal treatment sequence of SRS/SRT and TKI/ICI remains uncertain. This retrospective monocentric analysis addresses this question by comparing the outcomes of patients with NSCLC brain metastases who received upfront SRS/SRT versus those who were initially treated with TKI/ICI.
Methods UNASSIGNED
All patients treated with SRS/SRT and TKI/ICI for NSCLC brain metastases were collected from a clinical database. The patients who received first-line TKI or ICI for the treatment of brain metastases were then selected for further analysis. Within this cohort, a comparative analysis between upfront SRS/SRT and patients initially treated with TKI/ICI was conducted, assessing key parameters such as overall survival (OS), intracranial progression-free survival (iPFS) and treatment-related toxicity. Both OS and iPFS were defined as the time from SRS/SRT to either death or disease progression, respectively.
Results UNASSIGNED
The analysis encompassed 54 patients, of which 34 (63.0%) patients received SRS/SRT and TKI/ICI as their first-line therapy. Of the latter, 17 (50.0%) patients received upfront SRS/SRT and 17 (50.0%) were initially treated with TKI/ICI; 24 (70.6%) received SRS/SRT and ICI, and 10 (29.4%) received SRS/SRT and TKI. The cohorts did not significantly differ in the univariable analyses for the following parameters: sex, age, histology, molecular genetics, disease stage at study treatment, performance status, number of brain metastases, treatment technique, tumor volume, target volume, disease progression, radiation necrosis, dosimetry. While no significant differences were found in terms of iPFS and OS between patients treated with upfront SRS/SRT and patients initially treated with TKI, upfront SRS/SRT demonstrated significantly superior OS when compared to patients initially treated with ICI (median OS not reached
Conclusions UNASSIGNED
In this retrospective, single-center cohort study, patients treated with upfront SRS/SRT demonstrated significantly longer OS compared to patients initially treated with ICI in the cohort receiving first-line therapy for brain metastases. However, given the retrospective design and the limited cohort size, definitive conclusions cannot be drawn from these findings. Nevertheless, the results suggest that the timing of SRS/SRT may play an important role in treatment outcomes. Further investigation, preferably through prospective randomized trials, is warranted to provide more conclusive answers to this important question.

Identifiants

pubmed: 39118877
doi: 10.21037/tlcr-24-132
pii: tlcr-13-07-1635
pmc: PMC11304149
doi:

Types de publication

Journal Article

Langues

eng

Pagination

1635-1648

Informations de copyright

2024 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-132/coif). R.B. received Open Access Fund from University of Tübingen, and received honoraria from NovoCure for participating in invited meetings of specialized centers. C.B. received grants or contracts not related to this manuscript from Viewray, Brainlab and Elekta, and received support for attending meetings and/or travel from BMS, Roche, Merck, AstraZeneca and Viewray. F.M. received an unrestricted Research Institutional Grant from AstraZeneca, received honoraria from AstraZeneca, Novartis, Roche, Lilly, Elekta and Brainlab, and serves in the advisory board of AstraZeneca and Novartis. M.N. received payments from Brainlab and AstraZeneca for speaking services. The other authors have no conflicts of interest to declare.

Auteurs

Raphael Bodensohn (R)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.
Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Tübingen, Germany.

Anna Kolorz (A)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.

Jonas Reis (J)

Institute of Neuroradiology, LMU University Hospital, LMU Munich, Munich, Germany.

Simone Werner (S)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.

Robert Forbrig (R)

Institute of Neuroradiology, LMU University Hospital, LMU Munich, Munich, Germany.

Sylvia Garny (S)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.

Julian Taugner (J)

Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.

Chiara de Colle (C)

Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.

Claus Belka (C)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
German Cancer Consortium (DKTK), partner site Munich, a partnership between DKFZ and LMU University Hospital, Munich, Germany.
Bavarian Cancer Research Center (BZKF), Munich, Germany.

Farkhad Manapov (F)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.

Louisa von Baumgarten (L)

Department of Neurosurgery, LMU University Hospital, LMU Munich, Munich, Germany.

Maximilian Niyazi (M)

Department of Radiation Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Department of Radiation Oncology, University Hospital Tübingen, Tübingen, Germany.
Center for Neuro-Oncology, Comprehensive Cancer Center Tübingen-Stuttgart, University Hospital Tübingen, Tübingen, Germany.
German Cancer Consortium (DKTK), partner site Tübingen, a partnership between DKFZ and University Hospital Tübingen, Tübingen, Germany.

Classifications MeSH