Brain Metastases: post-whole brain radiotherapy systemic treatment increases survival Junliang Liu, M.D., M.Sc. Ph.D., FRCPC Assistant Professor University of Manitoba, CancerCare Manitoba, Canada

Study Purpose/Objective

Brain metastases (BM) account for more than one- half of all intracranial malignancies. The prognosis of cancer patients with BM has been dismal even with the availability of stereotactic radiosurgery (SRS), surgery, whole brain radiotherapy (WBRT) or the combination of these modalities. This study is to explore the impact of post-WBRT systemic treatment.

Material/Methods

A consecutive cohort of 65 patients with BM were identified A consecutive cohort of 65 patients with BM were identified. The patients were treated with WBRT with daily treatment, five days per week: 30 Gy/12 Frs: n=27 30 Gy/10 Frs: n=25 20 Gy/5 Frs: n=11 24 Gy/8 Frs (planned for 30 Gy/10 Frs): n=1 15 Gy/5Frs (planned for 30 Gy/10 Frs): n=1

One patient with breast primary received SRS, 20Gyx1 to 50% iso-dose line, to 3 lesions. She was found with multiple new lesions 3 months later and substantial progression for the treated lesions 6.5 months later, then treated with WBRT Another patient with breast primary with diffuse BM received WBRT, 4 months later received SRS, 16-18 Gyx1, to 5 lesions, 3 months after SRS her BM had mixed response, but extensive progression 4 months after SRS

Data was analyzed by dividing patients into group1 patients who received post-WBRT systemic treatment and group2 patients who did not have post-WBRT systemic treatment Statistic analysis was conducted by using Student t test

Results

Between July 1, 2005 to May 1, 2016, 65 patients, male 31, female 34, aged 25 to 92 years old were identified. Fifty six out of 65 patients had multiple brain lesions. Eleven out of 65 patients received post-WBRT systemic treatment including chemotherapy (9 out of 11 patients) and target therapy (3 out of 11 patients)

The median post-WBRT survival for patients who received post-WBRT systemic treatment was 13.5 months, compared to a much short median survival of only 3.0 months for patients who did not receive post-WBRT systemic treatment

Table 1. Patient Characteristics Primary Number of patients Age (median) Post-WBRT systemic therapy Lung Cancer 37 45-84 (64) 7 Breast Cancer 13 25-92 (60) 2 Rectal Cancer 3 62-80 Colon Cancer 59-68 Stomach cancer 59-60 Endometrial Cancer 55-69 Ovarian Cancer 62-67 1 Unknown primary 34-70 Melanoma 57 Esophageal Cancer 64 Total 65 25-92 (63) 11

Table2. Summary of patients received post-WBRT systemic therapy age gender primary Extra- cranial disease WBRT Systemic therapy Time of systemic therapy Post- WBRT survival 1 74 m lung yes 30 Gy/10 fractions Afatinib 30 days 16 alive 2 53 30 Gy/12 fractions Carbo+Tax ol x4 cycles 60 days 7 3 61 f Carbo+Ge mx4 cycles 74 days 18 4 63 30Gy/10 fractions Carbo+Ge m, Erlotinib 150 days 13.5 5 57 melano ma Dabrafenib -14 days 6 62 ovarian Caely, Carbo 145 days 21 alive

Table 2 continues 7 59 f lung yes 30 Gy/10 fractions Carbo+Gem, Docetaxol 12 days 5 8 62 m 30 Gy/12 fractions Carbo + Gem 37 dyas 22 9 61 170 days 14 10 72 breast Xeloda 180 days 11.3 11 44 20 Gy/5 fractions Capecitabine 5 days

Figure 1. Patient distribution according to the primary cancer

Side effects for patients received post-WBRT systemic therapy Fatigue: 11/11 Alopecia: 11/11 Mild memory decease: 1/11 ( this 63 years old man presented with recurrence and abdominal plus brain metastases received post- WBRT chemo and erlotinib, passed away 13.5 months post-WBRT due to extra-cranial progression) Impaired hearing ability: 1/11 further decreased hearing ability on top of his pre-existing hearing disability. This 74 years old man presented with Stage IV NSCLC with spinal and BM. He has been on afatinib after WBRT and is alive 16 months after WBRT without evidence of cranial disease and no clear evidence of extra-cranial disease

Conclusion

Post-WBRT systemic treatment increases the overall survival of patients with brain metastases Systemic treatment with chemo and or target agents should be aggressively pursued

Thank you