65MO - Clinicopathological risk score following neoadjuvant imatinib predicts relapse-free survival in patients with GIST

Background

Surgery remains the cornerstone of localized GIST management. Neoadjuvant (NA) imatinib facilitates surgery and allows in vivo monitoring of tumour response to therapy. This study evaluated the impact of initial tumour size (ITS), maximal tumour shrinkage (MTS) and residual mitotic count (RMC) after NA imatinib, on relapse-free survival (RFS).

Methods

Single-centre retrospective study of 90 GIST patients who underwent radical surgery after NA imatinib. Univariate and multivariate Cox regression analyses were performed to determine the association of clinicopathological variables to RFS. Evaluate Cutpoints were used to identify values associated with significantly different outcomes. Between-group differences were assessed with the use of the stratified log-rank test.

Results

The median age in our cohort was 64 years. The most prevalent primary tumour site was the stomach (62.2%), followed by the rectum (18.9%) and the small bowel (15.6%). A significant majority of patients (76.7%) harboured a KIT exon 11 mutation. Univariate Cox regression analyses showed a significant association of RFS with ITS (HR 1.11, p = 0.002), MTS (HR 11.7, p = 0.023) and RMC (HR 1.09, p << 0.001). These results were confirmed in a multivariate model (ITS, p = 0.001; MTS, p = 0.003; RMC, p << 0.001). Cut-points for ITS, MTS and RMC were established at 9.7 cm, 44% reduction in size and 2 mitoses, respectively. Patients with large tumous ≥ 9.7 cm, ≤ 44% reduction in size and ≥ 2 mitoses had shorter RFS. A combined score of these three variables allowed for accurate classification into two risk categories (p <<< 0.001): low (0 or 1 factor) and high-risk (2 or 3 factors). Over 70% of patients continued imatinib post-operatively. Adjuvant imatinib did not influence survival outcomes neither in low-risk (HR 1.2, p = 0.83) nor high-risk patients (HR 1.6, p = 0.35).

Conclusions

ITS, CTS and RMC are associated with shorter RFS in patients with localized GIST treated with NA imatinib. Prospective evaluation of discontinuation/intensification of adjuvant treatment in selected populations is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.