TPS397 Background: Tuberous sclerosis complex (TSC) is an autosomal dominant inherited disease that causes benign tumors called hamartoma all over the body as well as neuropsychiatric symptoms such as epilepsy. One-third of patients have a family history of the disease, but the remaining two-thirds are solitary cases and are caused by newly arising mutations. The TSC1 gene on chromosome 9 and TSC2 on chromosome 16 have been identified as the causative genes. Approximately 60%–80% of patients with TSC have renal lesions, and angiomyolipoma (AML) occurs bilaterally. The frequency of TSC-associated AML (TSC-AML) increases with age, reaching 60%–80% in adults, and the rate of death from renal disease increases with age in TSC patients. The current standard of care for AML is arterial embolization or surgery (partial nephrectomy or nephrectomy), but TSC is a hereditary disease and AMLs occur one after another with age. Repeated surgical procedures are technically difficult, and arterial embolization has a high recurrence rate. Under these circumstances, an mTOR inhibitor, everolimus, has shown a marked reduction of TSC-AML and is widely used. However, everolimus must be administered permanently because AML re-occurs after discontinuation of everolimus. Cryotherapy has been used as a treatment for renal tumors, and there have been some reports of cryotherapy for solitary AML, but the safety and efficacy of cryotherapy for TSC-AML have not been established. Therefore, we planned this study to establish the safety and efficacy of cryotherapy for TSC-AML. Methods: This is an open-label, single-arm, phase II study to evaluate the safety and efficacy of cryotherapy for TSC-AML of 4 cm or less in patients with 16 years of age or older. The exclusion criteria are an inability to withdraw from mTOR inhibitor and failure to maintain rest during cryotherapy. mTOR inhibitor medication should be withdrawn at least 7 days prior to cryotherapy and discontinued during the study period. Cryotherapy will be performed using Cryohit (GALIL MEDICAL LTD, Israel). Safety will be assessed at 1, 2, 6, and 9 months after cryotherapy, and efficacy will be assessed at 3 and 9 months after cryotherapy. The efficacy of cryotherapy will be evaluated according to modified RECIST or RECIST criteria. The primary endpoint will be the disease control rate of AML treated with cryotherapy, and secondary endpoints will be the overall response rate, safety, renal function, quality of life, and whether additional treatment is required. Clinical trial information: jRCTs072200039.