Late hepatic toxicity after breast cancer intensity-modulated radiotherapy using helicoidal tomotherapy

Helical tomotherapy (HT) is a rotational intensity-modulated radiation therapy (IMRT) technique that allows target conformal irradiation and efficient organs at risk (OAR) sparing in the case of complex target volumes and specific anatomic considerations, but increases the "low-dose bath" to non-target volumes. The aim of this study was to analyze the delayed hepatotoxicity after rotational IMRT (HT) radiation therapy for non-metastatic breast cancer.

This single-center retrospective study included all non-metastatic breast cancer patients with a normal pre-radiotherapy biological hepatic function who were treated with tomotherapy between January 2010 and January 2021 and for whom the dosimetric parameters for the whole liver were assessable. A logistic regression analysis was employed. The selected covariates for the multivariate analysis were those with a P-value that was less or equal to 0.20 in the univariate analysis.

Forty-nine patients were included in this study: 11 patients (22%) received Trastuzumab for 1 year in tumors with an HER2-expression; 27 patients (55%) received radiation therapy for cancer of the right or bilateral breasts; 43 patients (88%) received lymph node irradiation and 41 patients (84%) received a tumor bed boost. Mean and maximum doses to the liver were 2.8Gy [0.3-16.6] and 26.9Gy [0.7-51.7], respectively. With a median follow-up after irradiation was 5.4 years (range, 6 to 115 months), 11 patients (22%) had developed delayed low grade biological hepatic abnormalities: all patients had grade 1 delayed hepatotoxicity; 3 patients (6%) had additional grade 2 delayed hepatotoxicity. There was no hepatotoxicity at grade 3 or higher. According to the univariate and multivariate analysis, Trastuzumab was a significant predictive variable of late biological hepatotoxicity (OR=4.4 [1.01-20.18], P=0.04). No other variable was statistically associated with delayed biological hepatotoxicity.

Delayed hepatotoxicity after multimodal non-metastatic breast cancer management including rotational IMRT was negligible. Consequently, the liver doesn't have to be considered like an organ-at-risk in the analysis of breast cancer radiotherapy but future prospectives studies are needed to confirm these findings.