Abstract：Objective： To evaluate the feasibility and safety of a presurgical treatment approach with Everolimus for angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) and explore its potential ability to reduce the surgical morbidity. Methods： From May 2014 to Dec. 2017, 5 TSC-AML patients (including four females and one male) were treated with Everolimus and subsequently underwent resection. The average age was 35 years old (range from 27 to 50). All the patients were diagnosed according to the TSC Clinical Diagnosis Guideline (2012). All patients had only one tumor with the diamber of more than 4 cm (5.6 to 15.0 cm). All patients received Everolimus (10 mg, once every day) for 3 months and discontinued one week before operation. All patients received laparoscopy renal partial nephrectomy. The feasibility and safety of Everolimus, surgical complications and tumor responses were monitored. Results： One month after Everolimus treatment, the greatest diameter of the primary renal tumors was averagely decreased by 2.45 (1.0-4.5) cm. Three months later, the greatest diameter of the primary renal tumors was averagely decreased by 2.74 (1.0-5.0) cm. The main side effects included mouth ulceration in 4 cases, menstrual disorder in 2 cases and urinary tract infection in one case. The average operation time was 106 min (80-130 min ), the average amount of bleeding was 144 mL (50-400 mL), the average time of hospitalization after operation was 6.5 days. Recurrence occurred in one cases at 6th month after operation and the rest 4 cases had no tumors with the diameter of more than 4 cm during the follow-up period of 6 to 36 months. Conclusions： The administration of preoperative Everolimus can impact the size and density of the primary tumor and appears safe and feasible. More TSC-AML patients can receive nephron-sparing partial nephrectomy.
[1] CURATOLO P, BOMBARDIERI R, JOZWIAK S.Tuberous sclerosis. Lancet, 2008,372(9639):657-668.
[2] BASKIN J.The pathogenesis and imaging of the tuberous sclerosis complex. Pediatr Radiol, 2008,38(9):936-952.
[3] GUO G, CAI W, LI HZ, et al.Presurgical neoadjuvant targeted molecular therapy for kidney cancer with concomitant vena cava tumor embolus: A clinical study. Oncol Lett, 2017,14(1, A):369-375.
[4] KRUEGER DA, NORTHRUP H.International Tuberous Sclerosis Complex Consensus Group.Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediat Neurol, 2013,49(4):255-265.
[5] CAI Y, LI HZ, ZHANG YS.Assessment of tuberous sclerosis complex associated with renal lesions by targeted next-generation sequencing in mainland China. Urology, 2017,101(SI):e1-e7.
[6] DUFFAUD F, THERASSE P.New guidelines to evaluate the response to treatment in solid tumors. Bull Cancer, 2000,87(12):881-886.
[7] Cancer Therapy Evaluation Program, Common Terminology Criteria for Adverse Events, Version3.0, March 31,2003 (http://ctep.cancer.gov), Publish Date: August 9,2006.
[8] YAMAKADO K, TANAKA N, NAKAGAWA T, et al.Renal angiomyolipoma: Relationships between tumor size, aneurysm formation, and rupture. Radiology, 2002,225(1):78-82.
[9] SIROKY BJ, YIN H, BISSLER JJ.Clinical and molecular insights into tuberous sclerosis complex renal disease. Pediatr Nephrol, 2011,26(6):839-852.
[10] HUANG J, MANNING BD.The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J, 2008,412(2):179-190.
[11] HALPENNY D, SNOW A, MCNEILL G, et al.The radiological diagnosis and treatment of renal angiomyolipoma-current status. Clin Radiol, 2010,65(2):99-108.
[12] NELSON CP, SANDA MG.Contemporary diagnosis and management of renal angiomyolipoma. J Urol, 2002,168(4 Pt 1):1315-1325.
[13] SUN P, LIU J, CHARLES H, et al.Outcomes of angioembolization and nephrectomy for renal angiomyolipoma associated with tuberous sclerosis complex: a real-world US National study. Curr Med Res Opin, 2017,33(5):821-827.
[14] FADDEGON S, SO A.Treatment of angiomyolipoma at a tertiary care centre: the decision between surgery and angioembolization. Can Urol Assoc J, 2011,5(6):E138-E141.
[15] BISSLER JJ, KINGSWOOD JC, RADZIKOWSKA EA, et al.Everolimus long-term use in patients with tuberous sclerosis complex: Four-year update of the EXIST-2 study. PLoS One, 2017,12(8):e0180939.
[16] JOHN JB, JOHN CK, ELZBIETA R, et al.Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet, 2013,381(9869):817-824.
[17] STAEHLER M, SAUTER M, HELCK AA, et al.Nephron-sparing resection of angiomyolipoma after sirolimus pretreatment in patients with tuberous sclerosis. Int Urol Nephrol, 2012,44(6):1657-1661.
[18] THIERRY K, JULIEN G, HERVÉ L, et al.Percutaneous cryoablation for tuberous sclerosis-associated renal angiomyolipoma with neoadjuvant mTOR inhibition. BMC Urol, 2014,14(1):77.
[19] HATANO T, ATSUTA M, INABA H, et al.Effect of everolimus treatment for renal angiomyolipoma associated with tuberous sclerosis complex: an evaluation based on tumor density. Int J Clin Oncol, 2018,23(3):547-552.
