(P 407) PRECISION AND PERSONALIZED TREATMENT FOR SOFT TISSUE SARCOMAS. RESULTS OF A 10 PATIENTS SERIES WITH MOLECULAR PROFILING USING NEXT-GENERATION MASSIVE SEQUENCING

Objective: Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors with a diverse behavior and evolution. Surgery is the only curative treatment for this disease; however, multimodal, individualized treatment supported by molecular studies has improved the prognosis of these patients, especially in cases of advanced and metastatic disease. We present a 10 patient series illustrating a personalized and precision treatment guided by next-generation massive sequencing

Methods: Between January 2018 and January 2023, 10 patients with a diagnosis of soft tissue sarcoma were studied by massive DNA and RNA sequencing tumor genome with Ion Torrent platform (Oncomine Comprehensive Assay V3 panel) and tumor transcriptome (technique Ampliseq). All the cases were managed by a personalized multidisciplinary therapeutic approach: 2 cases with surgical planning through 3D reconstruction (Cella Medical Solution), 4 cases with intraoperative radiotherapy (IORT) administration, 1 case with isolated limb perfusion and 1 with electrochemotherapy treatment.

Results: The cases registered included: 3 retroperitoneal sarcomas, 3 extremity, 2 uterine, 1 splenic and 1 head and neck. 6 of them were primary, 1 metastatic, 1 recurrence, and 2 persistence due to initial surgery R2. We illustrate the precision treatment through 2 representative cases of a personalized treatment and therapeutic strategy guided by the molecular profile.

Case 1: 73-year-old woman, January 2014 retroperitoneal leiomyosarcoma of the ureter
- R0 en bloc resection with partial resection of the ureter and left hemicolectomy
- Transcriptome-guided adjuvant treatment: Sorafenib and Riluzole due to GRM1 gene overexpression
- Scapular recurrence with bone infiltration in Sept. 2019. Planning with 3D model, R0 wide resection, IORT application on bone margin
- 2021 oligometastatic bilateral lung progression
- Genome of metastasis: loss of function of SMARCB. Treatment with Tazemetostat in December 2022. Pulmonary disease in remission in April 2023. Overall survival: 108 months

Case 2: A 49-year-old woman with pleomorphic sarcoma (UPS) of the left lower limb in October 2018.
- Neoadjuvant chemotherapy and radiotherapy treatment, R0 wide surgery with adequate preservation of functionality and IORT
- Early chest wall dermal/subcutaneous recurrence (resected) after initiation of immunotherapy – Nivolumab – due to a favorable profile for immunotherapy in tumor transcriptome
- Genome of recurrence: BRAF V600E mutation. Treatment with Dabrafenib + Trametinib.
- Complete remission of metastatic disease. April 2023 disease free. Overall survival: 64 months

The molecular results of the 10 cases demonstrate the heterogeneity of these tumors and suggest new therapeutic possibilities. They will be presented in the final work.

Conclusion: STS are tumors with complex surgical and oncological management and a poor response to conventional chemotherapy protocols. Given its heterogeneity, precision oncology through molecular profiling with next-generation massive sequencing (panels for tumor genome and transcriptome) allows the development of personalized therapeutic strategies in patients with STS, and opens up the possibilities for targeted treatments for molecular alterations, immunotherapy and the development of new agents.