(P 163) CHARACTERIZATION OF INTRAHEPATIC RECURRENCE FOLLOWING LIVER-DIRECTED SURGERY IN PATIENTS WITH METASTATIC SDH-DEFICIENT GASTROINTESTINAL STROMAL TUMOR (GIST): RISE AND STABILIZATION OF THE GISTLETS

Objective: Among patients with SDH-deficient gastrointestinal stromal tumor (GIST), the appearance of ‘GISTlets’ after hepatic metastasectomy can be quite discouraging. Yet, the actual clinical significance of this small-volume disease recurrence remains unclear. The aim of this study was to assess outcomes of hepatic debulking for SDH-deficient GIST and to better characterize intrahepatic recurrences in the liver over time in this unique patient population.

Methods: Twelve patients with SDH-deficient gastrointestinal stromal tumor (GIST) metastatic to the liver underwent hepatic debulking at a quaternary referral center between 2020 and 2023. Retrospective chart review was performed; oncologic history, mutational status, operative data, post-operative surveillance imaging studies and organ-specific recurrence were assessed. Continuous data were reported as median with interquartile range (IQR) and compared using Mann-Whitney U test.

Results: Of the 12 patients included in this study, 7 were female; the median age was 41 years. All 12 patients had GIST of gastric primary origin, of which 9 had germline mutations (SDHA (n=4), SDHB (n=2), SDHC (n=2), or SDHD (n=1)), two had SDHx epigenetic silencing, and one had only a somatic SDHA mutation. All patients underwent at least one partial hepatectomy (median number of liver lesions resected: 5, IQR 2-7), and 8 additionally underwent concurrent microwave ablation(s) (median number of lesions 3.5; IQR 2-5). Primary tumors and regional lymph nodes were concomitantly resected in 4 and 9 patients, respectively. Post-operatively, two patients had Grade III complications (bile leak requiring percutaneous drain placement). All 12 patients developed intrahepatic recurrence during follow-up (median follow-up 23.4 months; IQR 20.3-31.1); MRI was the surveillance imaging modality of choice. The median time to first post-operative MRI was 5.8 months (IQR 3.7-12.1), whereas the median time to suspected intrahepatic recurrence was 7.4 months (IQR 4.5-13.6); these time intervals were not significantly different (p=0.77). Most patients (75%) did not undergo further intervention or treatment for intrahepatic recurrence, as they remained stable during follow-up; one patient experienced spontaneous regression (Figure 1). Three patients were enrolled onto NCT04595747 and received rogaratinib with stability of disease. One patient underwent percutaneous ablation of recurrences 16 months after index operation to treat metastases that had grown to >2 cm in diameter, with no further treatment in 20 months since then. All patients are alive with disease that remains stable by Response Evaluation Criteria in Solid Tumors (RECIST).

Conclusion: In this cohort of metastatic SDH-deficient GIST, patients uniformly developed early hepatic recurrence following hepatectomy; however, in most patients, these hepatic recurrences were characterized by small size and relative stability or even spontaneous regression after initial growth. Treatment teams must be aware of this phenomenon to optimally counsel patients pre-operatively. That said, patients with SDH-deficient GIST liver metastases should still be considered for hepatic resection when appropriate, since durable debulking is achievable for most patients.