192P Accuracy of patient-specific instrumentation versus free-hand in long bone tumor resection: A comparative study of 109 cases

Background: Perivascular epithelioid cell tumors (PEComas) are ultra-rare mesenchymal neoplasms frequently driven by TSC1/2-mTOR pathway alterations.mTOR inhibition is the standard approach in advanced disease, but responses are often short-lived.Strategies to overcome mTORi resistance, including mTORi plus antiestrogen therapy (OT), have been explored.Gemcitabine (GEM) combined with mTORi has also shown activity in TSC-mutated sarcomas.We report our experience with the combination of GEM, mTORi and OT (GEMTOR-X) in three advanced PEComa patients progressing to mTORi and to GEM used as single agents.Methods: GEMTOR-X (gemcitabine 800 mg/mq i.v.q14d; exemestane 25 mg p.o. daily; sirolimus 5 mg p.o. daily) was administered from October 2024 to three patients with advanced PEComa: one progressing to mTORi alone; one progressing sequentially to mTORi, mTORi+exemestane and GEM; and one progressing to both mTORi and GEM.Patients were monitored per clinical practice.Radiologic response, tolerability and survival outcomes were collected.Results: All three patients were female, aged 47, 58 and 60.One had TSC1 deletion, one had a PTEN mutation and one was TSC1/2 wild-type.One patient received GEMTOR-X immediately after mTORi progression; the other two in later lines.Best response to previous mTORi was PD (n=2) or SD (n=1).GEMTOR-X was administered for a mean of six months with good tolerance.Two patients achieved a partial response (PR) with necrotic changes on CT scan; one had SD.One patient developed an abdominal perforation requiring surgery but safely resumed treatment, achieving renewed SD.Two discontinued due to PD.One experienced sirolimus-related pneumonia (fully recovered) and is currently under surveillance with ongoing response eight months after GEMTOR-X initiation.Conclusions: GEMTOR-X showed clinical activity with confirmed radiologic responses in patients progressing to both mTORi and GEM single agents.These findings support further investigation of GEMTOR-X as a potential therapeutic option in this ultra-rare disease with no validated alternatives beyond mTOR inhibition.