Effect of perioperative targeted therapy duration on prognosis in patients with gastrointestinal stromal tumors undergoing neoadjuvant imatinib therapy: A nationwide retrospective study.

BACKGROUND

Contemporary evidence highlights a paucity of systematic research addressing the prognostic implications of total targeted therapy duration in the neoadjuvant setting. Parallel to this, the optimal timeframe for preoperative therapy remains a subject of unresolved debate in clinical practice. In this study, we estimated the impact of total targeted therapy duration on prognosis in patients with gastrointestinal stromal tumors (GIST) undergoing neoadjuvant imatinib therapy.

METHODS

In this nationwide study, we retrospectively analyzed the clinical data from 186 GIST patients receiving neoadjuvant imatinib therapy from January 2010 to December 2021. Clinical data including baseline characteristics, treatment pattern, treatment outcome, adverse events and survival status were collected. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Cox regression analysis was used to analyze the prognostic factors of PFS and OS.

RESULTS

Among 186 patients, 149 (80.1%) were aged ≤65 years and 110 (59.1%) were male. Regarding neoadjuvant imatinib treatment duration, 59 patients (31.7%) had less than 6 months, 97 (52.2%) patients had 6 to 12 months, and 30 (16.1%) patients had more than 12 months. Multivariate Cox regression analysis indicated that residual mitotic index (>5/50 HPF: HR = 5.80, 95% CI: 2.56-13.15, P < 0.001), non-R0 resection (HR = 11.50, 95% CI: 4.71-28.08, P < 0.001), and adjuvant imatinib therapy (HR = 0.23, 95% CI: 0.07-0.74, P = 0.014) were independent prognostic factors for PFS, while residual mitotic index (>5/50 HPF: HR = 4.40, 95% CI: 1.29-15.06, P = 0.018), multivisceral resection (HR = 4.07, 95% CI: 1.09-15.19, P = 0.037), and adjuvant imatinib therapy (HR = 0.04, 95% CI: 0.01-0.17, P < 0.001) were independent prognostic factors for OS. Maximally selected log-rank analysis identified 35 months and 45 months as the optimal cut-offs for adjuvant and total targeted therapy durations, respectively. No significant difference was found in PFS and OS among patients with different neoadjuvant imatinib therapy durations (P = 0.233, P = 0.326).

CONCLUSIONS

Prolonged adjuvant and total targeted therapy durations correlate with improved survival in GIST patients receiving neoadjuvant imatinib, whereas neoadjuvant imatinib duration alone does not independently affect long-term outcomes. Additionally, a low residual mitotic index remains a robust histopathological predictor of favorable prognosis.