Interventional Radiotherapy (Brachytherapy) Combined with Systemic Treatment-The Influence of RAS Gene Mutations and...

The aim of the study was to analyse the results and potential complications of local treatment with HDR (high dose-rate) brachytherapy of liver metastases from colorectal cancer, depending on the targeted therapy used and considering RAS gene mutation and chemotherapy in individual treatment lines.

The study included 142 patients with oligoprogressive liver metastases who underwent HDR brachytherapy without changing the line of treatment, based on a retrospective analysis of 270 patients treated between 2015 and 2022. The impact of RAS gene mutations, lines of chemotherapy depending on the treatment regimens used, PFS (progression free survival), OS (overall survival), LC (local control) and the degree of radiological response were analysed. The impact of these drugs on hepatotoxicity and the risk of haemorrhagic complications was also analysed.

The presence of mutations in KRAS/NRAS genes (exons 2, 3, 4) had a statistically significant impact on PFS in the first, third and fourth lines of treatment, and on OS and LC in the third and fourth lines of treatment. In the third and fourth lines of treatment, patients with a mutation in the RAS gene had a poorer radiological response to treatment regardless of the chemotherapy used. PFS, OS and LC differed depending on the line of treatment and amounted to 17.5, 11, 8.5, 6 and 4 months, 27, 19, 13, 11 and 11 months, and 27, 19, 11, 6 and 6 months, respectively. The greatest benefit in terms of PFS was achieved by patients treated with first-line chemotherapy combined with epidermal growth factor receptor (EGFR) inhibitors, in the absence of RAS gene mutations. In the third line, the greatest benefit was achieved by patients treated with trifluridine/tipiracil in the absence of RAS gene mutations. The greatest percentage reduction in the volume of treated lesions and the highest percentage of control were observed in the first three lines of treatment. The toxicity of the treatment was low; only in the third and fourth lines of treatment were differences in the decrease in albumin levels found depending on the type of treatment used.

A mutation in the RAS genes worsens the prognosis, regardless of the line of treatment and the systemic treatment used. The greatest benefit from brachytherapy is seen in patients in the first three lines of treatment without RAS mutations, treated with anti-EGFR chemotherapy in the first line and trifluridine/tipiracil in the third line. Combining brachytherapy of liver metastases with systemic treatment is safe, regardless of the systemic treatment used.