Small bowel sarcoma: Tumor biology and advances in therapeutics

• Resection is cornerstone for GIST and Leiomyosarcoma. Imatinib decreases recurrence in GIST.
• Imatinib resistance is common, dose escalation, sunitinib, regorafenib are treatment options.
• Combining TKI and immune check point inhibitor (anti CTLA-4, ipilimumab) may improve response.
• Dual blockade of both KIT and MAPK signaling pathway may improve response rates in GIST.
• Newer therapy for leiomyosarcoma includes targeted TKI (pazopanib) and trabectedin.

Spindle cell neoplasms are rare mesenchymal tumors of the gastrointestinal tract. GIST (Gastrointestinal stromal tumor) and leiomyosarcoma share similar clinical presentations, gross and microscopic characteristics making distinction difficult in the absence of immunohistochemical (IHC) studies. A multidisciplinary approach is required for treatment planning and ensuring best outcomes. Surgery remains the mainstay of curative treatment for both tumors. Significant advances in targeted molecular therapies have occurred in the past decade in the treatment of GIST with improvement in morbidity and mortality. Similar newer discoveries for treatment of leiomyosarcoma have failed to show any significant survival benefits as yet. Early diagnosis and R0 surgical resection offers the best long term outcome for leiomyosarcoma. Here in we review and discuss the concepts of genetic alterations, newer markers, possible cancer pathways and advances in treatment strategies for these sarcomas.