Changes in bone marrow fat fraction and immune cell counts in women with cervical cancer treated with primary chemoradiotherapy

Hematologic toxicity (HT) is a common effect of chemoradiotherapy in primary locally advanced cervical cancer (LACC) and related to bone marrow (BM) fat increase. However, longitudinal effects and dose-relationships are unknown. In this study, pre- and post-treatment BM fat fraction and blood immune cell counts were evaluated in women with primary LACC undergoing BM sparing chemoradiotherapy. Water-fat MRI scans and blood samples were obtained at baseline, during, and at 3 and 12 months (post-)treatment. The mean proton density fat fraction (PDFF) [%] was calculated for each vertebra, categorized into a no (<1 Gy), low (1-5 Gy), and high (>5 Gy) dose group, and the pelvic bones. Associations between PDFF and dose, immune cells, and patient characteristics were assessed with linear mixed models. Eighteen women were included. Vertebral PDFF in the no dose group remained unchanged, whereas the low and high dose group showed an increase of 24-35 PDFF% during treatment. PDFF in the low dose group recovered slightly but remained elevated up to 12 months post-treatment. Mean dose to pelvic subregions was ≥ 18.8 Gy and PDFF increase was 12-29 PDFF%. Only the lower pelvic PDFF recovered to baseline. Blood immune cell decline lasted up to 12 months post-treatment and was correlated with higher mean vertebral PDFF. Vertebral fat fraction increased during treatment for dose > 1 Gy, without post-treatment recovery for dose > 5 Gy. Immunosuppression persisted up to 12 months post-treatment and was related to a higher mean vertebral PDFF. 5 Gy might be relevant for BM damage, but this threshold should be validated.