Management of initial and recurrent radiation-induced contrast enhancements following radiotherapy for brain metastases: Clinical and radiological impact of bevacizumab and corticosteroids

Eva Meixner; Juliane Hörner-Rieber; Jonathan W Lischalk; Tanja Eichkorn; Anna Krämer; Elisabetta Sandrini; Angela Paul; Philipp Hoegen; Maximilian Deng; Thomas Welzel; Sinem Erdem; Jürgen Debus; Laila König

doi:10.1016/j.ctro.2023.100600

Management of initial and recurrent radiation-induced contrast enhancements following radiotherapy for brain metastases: Clinical and radiological impact of bevacizumab and corticosteroids

Clin Transl Radiat Oncol. 2023 Feb 14:39:100600. doi: 10.1016/j.ctro.2023.100600. eCollection 2023 Mar.

Authors

Eva Meixner^{1

2

3}, Juliane Hörner-Rieber^{1

2

3

4}, Jonathan W Lischalk⁵, Tanja Eichkorn^{1

2

3}, Anna Krämer^{1

2

3}, Elisabetta Sandrini^{1

2

3}, Angela Paul^{1

2

3}, Philipp Hoegen^{1

2

3}, Maximilian Deng^{1

2

3}, Thomas Welzel^{1

2

3}, Sinem Erdem^{1

2}, Jürgen Debus^{1

2

3

6

4}, Laila König^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
² Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany.
³ National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁴ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
⁵ Department of Radiation Oncology, Perlmutter Cancer Center, New York University Langone Health, New York, NY 10023, United States.
⁶ Heidelberg Ion Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany.

Abstract

Purpose: The appearance of radiation-induced contrast enhancements (RICE) after radiotherapy for brain metastases can go along with severe neurological impairments. The aim of our analysis was to evaluate radiological changes, the course and recurrence of RICE and identify associated prognostic factors.

Methods: We retrospectively identified patients diagnosed with brain metastases, who were treated with radiotherapy and subsequently developed RICE. Patient demographic and clinical data, radiation-, cancer-, and RICE-treatment, radiological results, and oncological outcomes were reviewed in detail.

Results: A total of 95 patients with a median follow-up of 28.8 months were identified. RICE appeared after a median time of 8.0 months after first radiotherapy and 6.4 months after re-irradiation. Bevacizumab in combination with corticosteroids achieved an improvement of clinical symptoms and imaging features in 65.9% and 75.6% of cases, respectively, both significantly superior compared to treatment with corticosteroids only, and further significantly prolonged RICE-progression-free survival to a median of 5.6 months. Recurrence of RICE after initially improved or stable imaging occurred in 63.1% of cases, significantly more often in patients after re-irradiation and was associated with high mortality of 36.6% after the diagnosis of flare-up. Response of recurrence significantly depended on the applied treatment and multiple courses of bevacizumab achieved good response.

Conclusion: Our results suggest that bevacizumab in combination with corticosteroids is superior in achieving short-term imaging and symptom improvement of RICE and prolongs the progression-free time compared to corticosteroids alone. Long-term RICE flare-up rates after bevacizumab discontinuation are high, but repeated treatments achieved effective symptomatic control.

Keywords: Blood brain barrier disruption; Chemotherapy; Radiation necrosis; Re-irradiation. stereotactic radiosurgery; anti-VEGF antibody Bevacizumab.