Weekly measurement of HMGB1 during neoadjuvant chemoradiotherapy in rectal cancer patients: correlations with MRI response and ctDNA.

BACKGROUND

Biomarkers are desirable to characterize individual tumors and to personalize multimodal treatment in locally advanced rectal cancer patients. In this regard, monitoring of High Mobility Group Box 1 (HMGB1) protein in blood samples is of interest in radiotherapy as HMGB1 is a consensus marker for immunogenic cell death (ICD) during anticancer treatment.

PATIENTS AND

METHODS

Plasma levels of HMGB1 were monitored weekly during long-term neoadjuvant chemoradiotherapy in 19 patients with locally advanced rectal cancer. HMGB1 levels were correlated with outcome and tumor volumes in magnetic resonance imaging (MRI) pre-therapeutically as well as in week 2 and week 5 of treatment. Furthermore, the association with circulating cell-free tumor DNA (ctDNA) was evaluated.

RESULTS

Higher pre-therapeutic levels of HMGB1 correlated positively with bigger initial MRI volumes and higher allele frequencies of ctDNA in the corresponding baseline blood sample. Courses of HMGB1 during treatment were variable and mostly undulating. Predominant ascent was observed in four patients who showed poor pathologic response. Declining levels in week 2 / 3 were associated with bigger percentage decrease of MRI tumor volume at the end of week 2.

CONCLUSIONS

HMGB1 seems to be associated mostly with tumor burden as indicated by correlation with MRI volumes and ctDNA levels, rather than ICD induction or side effects as previously reported. Changes during treatment might predict clinical disease course.