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Cytoreductive Surgery in Patients With Metastatic Succinate Dehydrogenase-Deficient Gastrointestinal Stromal Tumors
Katherine Y Chen1, Mark Antkowiak2, Ashwyn K Sharma2
1University of California San Diego School of Medicine, San Diego, California, USA.
Background And Objectives:
Succinate dehydrogenase-deficient (SDH-deficient) gastrointestinal stromal tumors (GIST) are characterized by variable disease biology with poor responses to traditional tyrosine kinase inhibitors. The role of surgical intervention has been highly debated.
Methods:
We performed a single-institution retrospective analysis of metastatic SDH-deficient GIST patients who underwent complete (CC-0) cytoreductive surgery (CRS) from 2017 to 2023. Pathologic-Peritoneal Cancer Index (P-PCI) and GIST Metastatectomy-Surgical Complexity Score (GM-SCS) were used to quantify complexity. Kaplan-Meier survival analysis compared time to progression on systemic therapy immediately before CRS (TTP-1L) and second to last line of systemic therapy before CRS (TTP-2L) versus time to recurrence (TTR) after CRS.
Results:
Nine patients met inclusion criteria. The median age at CRS was 29 years (range: 17-43). Median P-PCI was 13 (IQR: 10-15) and median GM-SCS was 19 (IQR: 16-28). Clavien-Dindo grade ≥ 3 complication rate was 33.3% (3/9) within 90-days postoperatively. Median TTP-1L was unreached and median TTP-2L was 3.4 months (95% CI: 2.5-unreached), as compared to TTR at 26.1 months (95% CI: 15.2-unreached) post CRS (p ≤ 0.0001).
Conclusions:
Patients who underwent CC-0 CRS achieved prolonged disease control versus prior systemic therapies, suggesting that CRS may be a management option for highly selected SDH-deficient GIST patients.
Insights
Complete cytoreductive surgery (CRS) in patients with succinate dehydrogenase-deficient (SDH-deficient) gastrointestinal stromal tumors (GIST) led to significantly longer disease control compared to systemic therapies. This suggests CRS may be a viable option for carefully selected GIST patients.
Area of Science:
- Gastrointestinal Stromal Tumors (GIST)
- Surgical Oncology
- Genetics and Genomics
Background:
- Succinate dehydrogenase-deficient (SDH-deficient) GIST exhibits aggressive biology and poor response to tyrosine kinase inhibitors.
- The efficacy of surgical intervention in SDH-deficient GIST remains a subject of debate.
Purpose of the Study:
- To evaluate the role of complete cytoreductive surgery (CC-0 CRS) in managing metastatic SDH-deficient GIST.
- To compare disease control after CRS with prior systemic therapy outcomes.
Main Methods:
- Retrospective analysis of 9 metastatic SDH-deficient GIST patients undergoing CC-0 CRS (2017-2023).
- Quantification of surgical complexity using Pathologic-Peritoneal Cancer Index (P-PCI) and GIST Metastatectomy-Surgical Complexity Score (GM-SCS).
- Kaplan-Meier survival analysis comparing time to progression on first-line (TTP-1L) and second-to-last line (TTP-2L) systemic therapy versus time to recurrence (TTR) post-CRS.
Main Results:
- Median P-PCI was 13 and median GM-SCS was 19.
- Postoperative complication rate (Clavien-Dindo grade ≥3) was 33.3% within 90 days.
- Median TTR post-CRS (26.1 months) was significantly longer than median TTP-2L (3.4 months) (p≤0.0001). Median TTP-1L was unreached.
Conclusions:
- Complete cytoreductive surgery (CC-0 CRS) in selected SDH-deficient GIST patients achieved prolonged disease control.
- CRS may represent a valuable management strategy for highly selected SDH-deficient GIST patients.
