(P 468) CLINICAL UTILITY OF TARGETED NEXT-GENERATION SEQUENCING IN GUIDING SARCOMA DIAGNOSIS AND PERSONALIZED MANAGEMENT: A SINGLE-CENTER STUDY FROM INDIA

Objective: To determine the diagnostic and therapeutic impact of RNA-based targeted NGS in patients with complex or ambiguous sarcoma histology.

Methods: A prospective study was conducted using a sarcoma-specific RNA-based NGS panel at AIIMS, New Delhi (2020–2025). Multidisciplinary Tumor Board–guided patient selection was based on clinical ambiguity and therapeutic relevance. NGS results were integrated with histopathology and IHC for diagnostic and treatment decisions.

Results: NGS was advised for 70 patients (median age: 38.5 years); 68 were evaluable (2 excluded due to inadequate tissue). Soft tissue sarcomas predominated (77.1%) and 67.1% presented with advanced/metastatic disease. Initial histology identified 17 (24.2%) round cell sarcomas (RC), 19 (27.1%) undifferentiated sarcomas (US), and 34 (48.5%) heterogeneous subtypes.
Of 16 evaluable RC cases, NGS identified diagnostic fusions in 14 (87.5%; 5 known, 9 novel), enabling reclassification in 11 (68.7%) and treatment changes in 3 (18.7%). Among 19 US cases, 4 (21.1%) harbored diagnostic fusions (2 known, 2 novel), all reclassified, with therapy modified in 3 (75%). In 33 other subtypes, diagnostic alterations were found in 16 (48.4%; 8 known, 8 novel), prompting reclassification in 13 (39.3%) and treatment changes in 7 (21.2%).
Non-diagnostic mutations (e.g., TP53, SLX4, NF1) were observed in 9 US cases (47.4%) and 6 of other subtypes (18.2%). Actionable variants (KIT, PIK3CA) were identified in 5.8% (4/68). Overall, NGS yielded clinically informative findings in 50% (34/68), enabled diagnostic refinement in 41.1% (28/68), and impacted treatment in 19.1% (16/68).

Conclusion: This first-of-its-kind study underscores the clinical utility of integrating targeted RNA-based NGS into multidisciplinary sarcoma management. Diagnostic reclassification was achieved in over 40% of cases, with the most pronounced impact observed in round cell sarcomas with atypical histomorphology. Both established and novel genomic alterations informed individualized treatment strategies, reinforcing NGS as a vital adjunct to enhance diagnostic accuracy and enable precision oncology in sarcoma care.

Impact of NGS on Sarcoma Diagnosis and Treatment