The combined use of PD-1 antibodies and anti-angiogenic TKIs induces intractable thoracoabdominal wall ulcer in patients undergoing cryoablation for superficial metastases of hepatocellular carcinoma

Background: Percutaneous cryoablation has been widely used for local analgesia, especially for pain caused by superficial metastases. However, during the process of cryoablation for symptomatic superficial metastases of hepatocellular carcinoma (HCC), we observed that some patients developed intractable thoracoabdominal wall ulcer at the periphery of puncture points. In order to explore the potential causes of thoracoabdominal wall ulcer after cryoablation, we carried out this retrospective study. Methods: We screened out 36 patients who underwent local cryoablation for superficial metastases (chest wall, abdominal wall, rib, clavicle and scapula) of HCC, of which 6 patients developed refractory thoracoabdominal wall ulcer. Clinical characteristics between ulcer and no ulcer groups were compared using the Pearson Chi square test. Risk factors for thoracoabdominal wall ulcer were screened using binary logistic regression model. Results: All clinical factors, except for the administration of PD-1 antibodies plus anti-angiogenic tyrosine kinase inhibitors (TKIs) within 2 months before (p = 0.016) and after (p = 0.000) cryoablation, were balanced between the ulcer and no ulcer groups (all p > 0.05). Combined use of PD-1 antibodies and anti-angiogenic TKIs within 2 months after cryoablation was the only significant risk factor for thoracoabdominal wall ulcer (OR = 55.55, 95% confidence interval (CI) 2.62-1179.46, p = 0.010) in multivariate logistic regression model. Among the 8 patients who received combination therapy within 2 months after procedure , thoracoabdominal wall ulcer occurred in 5 patients (62.5%). Among the 6 patients who developed thoracoabdominal wall ulcer, 3 patients died due to tumor progression, 2 patients improved their ulcers after PD-1 antibodies withdrawal and 1 patient was still under monitoring after stopping anti-PD-1 therapy. Conclusions: HCC patients underwent combination therapy of PD-1 antibodies and anti-angiogenic TKIs within 2 months after cryoablation for superficial metastases is prone to develop thoracoabdominal wall ulcer.