Exacerbation of focal hepatotoxicity with Axitinib after Stereotactic Body Radiotherapy (SBRT) to malignant Renal mass in close proximity to Liver and resolution after short term drug holiday: Possible radio-sensitization effect.

Abstract

Stereotactic Body Radiation Therapy (SBRT) has emerged as an effective treatment option for patients with Renal cell carcinoma (RCC). Studies have shown that Tyrosine Kinase Inhibitors (TKI) after stereotactic radiosurgery (SRS) for brain metastasis may increase the risk of radiation necrosis. We hereby report a unique case of focal hepato necrosis in a patient on TKI (Axitinib), post SBRT to right upper pole renal tumor and resolution after holding TKI for 3 months MATERIALS AND METHODS: A 65-year-old male diagnosed with Clear cell RCC Left Kidney in 2015 - post left nephrectomy, stable on Axitinib for 7 years - developed a new right renal exophytic lesion in upper pole. He underwent Renal SBRT (50 Gy in 5 fractions) with deep inspiratory breath-hold technique (DIBH). Axitinib was withheld during SBRT and restarted after 2 weeks. After 11 weeks the patient developed right sided abdominal pain and was evaluated with a contrast enhanced positron emission tomography computed tomography (PET-CT) scan. Findings revealed interval decrease in the renal lesion enhancement, with mildly metabolically active hypointense concave lesion in adjacent segment VI of liver; differentials being metastasis or liver necrosis. On contouring the liver lesion and fusion with SBRT plan, the area corresponded to intermediate-dose region (25 Gy). Histopathological examination of liver lesions showed necrosis. Axitinib was with-held for 3 months and pentoxifylline (400mg twice daily) and vitamin E (400mg twice daily) were initiated empirically. Complete symptom relief occurred within 2 months. PET-CT scan at 3 months demonstrated complete resolution of liver lesion and complete metabolic response in right renal lesion. Axitinib was restarted and sequential PET-CT scans done in May 2026 showed avid lesion in the body. To our knowledge, this is the first reported case of TKI-exaggerated radiation hepato necrosis following SBRT. Exaggerated hepatotoxicity resolving on withholding Axitinib, highlights the susceptibility of normal liver volume to this type of interaction. Close monitoring with empirical initiation of vascular-protective agents (pentoxifylline + vitamin E) can be considered once such changes are evident radiologically, avoiding invasive biopsies.