Oxaliplatin-induced pseudosepsis syndrome during FOLFOX-based hepatic arterial infusion chemotherapy for hepatocellular carcinoma

BACKGROUNDDuring hepatic arterial infusion chemotherapy (HAIC) for hepatocellular carcinoma (HCC), high-grade fever accompanied by markedly elevated procalcitonin (PCT) levels is frequently misinterpreted as a severe infection, leading to unnecessary antibiotic exposure and treatment delays. AIMTo despite the lack of documented cases, characterize an underrecognized condition known as oxaliplatin-associated inflammatory syndrome that mimics sepsis. METHODSPatients with HCC who developed severe inflammatory reactions following FOLFOXbased HAIC between January 2022 and August 2025 were retrospectively investigated.Oxaliplatin-induced pseudosepsis syndrome (OIPS) was characterized by high-grade fever (> 39 °C) occurring within 24 hours after oxaliplatin administration, high PCT levels (> 10 ng/mL), no documented infection after comprehensive clinical evaluation, and rapid recovery following supportive treatment. RESULTSAmong 4673 HAIC procedures performed in 1374 patients, 60 OIPS episodes were identified in 50 patients (episode-based incidence: 1.28%; patient-level incidence: 3.64%).All episodes presented with high-grade fever.Median serum PCT was 20.7 (interquartile range: 15.4-33.6)ng/mL.Among 39 episodes with available interleukin-6 (IL-6) measurements, 30 (76.9%) had IL-6 levels > 200 pg/mL.OIPS mainly occurred during the fourth HAIC cycle.Fever typically developed within 4-8 hours after oxaliplatin infusion and persisted for a median duration of 18 hours.Blood cultures [performed in 12/50 4 / 27 (24.0%)patients] were negative.No documented infectious source was identified during imaging assessment and clinical follow-up.Ten patients underwent oxaliplatin rechallenge, all of whom experienced recurrent episodes.All patients recovered rapidly following fluid resuscitation and supportive care.CONCLUSION OIPS is a reproducible, likely noninfectious, oxaliplatin-associated pseudoseptic inflammatory phenotype during FOLFOX-based HAIC.Early recognition may prevent misdiagnosis, unnecessary antibiotic exposure, and treatment delays.Further multicenter validation is needed.