P11.72.A INTRACRANIAL CONTROL OF BRAIN METASTASES IN PATIENTS TREATED WITH RADIOTHERAPY PLUS CHEMOTHERAPY, IMMUNOTHERAPY, TARGETED THERAPY AND IMMUNOCHEMOTHERAPY OR TARGETED THERAPY WITH CHEMOTHERAPY

Abstract

Abstract BACKGROUND Brain metastases (BM) are the most common intracranial malignancy. For many years, patients with BM were excluded from clinical trials of systemic cancer therapies based on their presumed bad prognosis, which results in a therapeutic nihilism as soon a BM is diagnosed. With the development of immunotherapies and targeted therapies as systemic cancer therapy, we questioned if there is a difference in intracranial response, regardless of the indicated radiotherapy (RT) for the BM. MATERIAL AND METHODS 67 patients older than 18 years, with multiple BM treated between December 2016 and October 2021, with in total 237 metastases were analyzed. The volume of each metastasis on MRI was calculated at the time of appearance and every 3 months thereafter. The primary outcome was intracranial control according to RANO-BM at 6 months. Because of missing data (MRI at 6 months), 92 metastases had to be excluded, leaving 145 for the analysis. Patients were divided into groups (RT+chemotherapy - CT-group, RT+immunotherapy/targeted therapy - IT/TT-group, RT+chemo-immunotherapy/targeted therapy - CT+IT/TT-group). The second outcome measure was time to progression of metastases; for this outcome 183 metastases could be analyzed. For statistical analysis chi-square test and Tarone-Ware test were performed. RESULTS In the CT-group (n=40)10% (n=4) had a progressive disease (PD), 33% (n=13) had a partial response (PR), 57 % (n=23) complete response (CR), and no one stable disease (SD). In the CT+IT/TT-group (n=28) 14% (n=4) had PD, 11% (n=3) SD, 11% (n=3) PR and 64% (n=18) CR. In the IT/TT-group (n=78) 14% (n=11) had PD, 4% (n=3) SD, 26% (n=20) PR and 56% (n=44) CR. The p values for difference in intracranial control were between CT-group/IT/TT-group 0,81 and between CT-group/CT+IT/TT-group 0,58. Patients in the IT/TT-group had a better outcome if a targetable mutation was present (p=0,005). The median time to progression (days) was 474 ± 30 for the CT-group; 581 ± 50 for the IT/TT- group and 360 ± 35 for the CT+IT/TT-group. Tarone-Ware test showed a trend in the progression distributions between the 3 groups favoring the IT/TT-group p= 0,082. CONCLUSION Intracranial response could be achieved in all analyzed subgroups without statistically significant difference. Against the background of this data, the therapeutic nihilism due to the presumed bad prognosis is not justified. A subgroup analysis of the IT /TT group showed a significantly better outcome for patients who had a matching gene. Patients who received immunotherapy or targeted therapies showed a trend towards later progression than chemotherapy or combination therapy. Larger patient cohorts should be investigated to see if this trend could be confirmed.