Neoadjuvant TKI Prior to Surgery Has Surgical Benefit in Non-Metastatic GIST

Neoadjuvant TKI treatment in non-metastatic GIST patients led to less complex surgery, with tumor size reduction within three months predicting benefit.

Among patients with non-metastatic gastrointestinal stromal tumor (GIST), those who were treated with neoadjuvant tyrosine kinase inhibitors (TKI) prior to curative-intended surgery experienced a benefit which led to less invasive or complex surgeries, according to results published in "Surgery Open Science."

In order to predict this benefit, investigators tracked tumor size reduction with contrast-enhanced computed tomography (CE-CT), which showed that surgical benefit was gained in 22 of 39 patients. Among those evaluated, the median neoadjuvant treatment interval was 8.3 months. Furthermore, tumor volume was reduced significantly in the surgical-benefit group compared with the non-benefit group within three months; 14 of 19 surgical-benefit patients had an initial volume reduction above 66%, after which volume reduced slightly with a median 3.1% reduction.

“This study shows that using size-based radiological response criteria based on CE-CT imaging could accurately predict surgical benefit achieved by neoadjuvant treatment in non-metastatic GIST,” lead study author, Dr. Ylva A. Weeda, wrote in a journal article of the data “Using tumor volumetry, patients where surgical benefit was obtained could already be identified within 3 months after treatment initiation.”

Weeda works in the Department of Radiology at Leiden University Medical Center in Leiden, South Holland, of the Netherlands.

GISTs are rare mesenchymal neoplasms, for which, neoadjuvant TKI treatment is used selectively to enhance the probability of complete surgical excision while preserving adjacent tissues. However, the planned surgical extent remains unchanged in approximately half of rectal, gastric and duodenal GIST patients, underscoring the need for precise patient selection and early response monitoring.

Notably, response to TKI therapy is commonly assessed using CE-CT imaging. The European Society for Medical Oncology recommends a treatment duration of six to 12 months, though this guideline is derived from studies on metastatic GISTs, leaving the optimal duration in non-metastatic cases unclear. Based on these unmet needs within the patient population, investigators aimed to evaluate the impact of neoadjuvant TKI treatment on surgical outcomes in non-metastatic GIST. Investigators did this by evaluating the correlation of radiological criteria and assessing the value of early prediction for surgical benefit.

Delving Into the Methods Of Research

Between October 2003 until April 2022, at the Leiden University Medical Center, 58 patients with confirmed non-metastatic primary GIST were referred for neoadjuvant TKI treatment or follow-up and were retrospectively evaluated. Participants were eligible for evaluation if they had neoadjuvant TKI treatment, followed by curative-intended surgical resection and were monitored using bi-phasic CE-CT imaging. Based on these criteria, 19 patients were excluded, therefor, 39 patients with GIST were included in the final analysis.

“Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity,” Weeda and study authors wrote.

Clinical investigators evaluated whether neoadjuvant TKI therapy led to de-escalation of surgical strategy in eligible participants or reduced surgical complexity. Notably, investigators were blinded for the radiological assessments and reports in this study.

Elaborating on Retrospective Study Results

“Comparison between the surgical-benefit and non-benefit group showed no statistical difference in age, sex and tumor characteristics,” Weeda and study authors wrote. “However, the interval between the start of TKI treatment and the last preoperative scan, together with the total treatment interval were significantly higher in patients with surgical benefit. The same trend was observed within the subset of patients.”

A median interval of 51 days was observed between the last response scan and surgery and TKI therapy was discontinued immediately prior to surgery, resulting in a median treatment duration of 9.9 months.

Several factors contributed to the de-escalation of surgical intervention, including improved visualization of tumor attachment and neutralization of adhesions. In six patients, the surgical approach was modified from a partial gastrectomy to a local excision due to a smaller tumor attachment area. Similarly, one patient initially scheduled for a total gastrectomy underwent a partial gastrectomy instead. TKI therapy facilitated organ preservation by neutralizing adhesions, enabling spleen- and anal sphincter-sparing procedures in five patients. In one case involving a cardiac GIST, the primary tumor was not detectable during intraoperative inspection, leading to the decision to forgo resection. 

TKI therapy also simplified the surgical procedure for many patients. Tumor size reduction and well-demarcated boundaries provided greater surgical oversight and flexibility, particularly for large intra-abdominal tumors or those in anatomically complex locations. However, in 17 patients, TKI therapy did not confer these surgical advantages.

“To the author's knowledge this is the first study investigating the relation between radiological response criteria and surgical benefit obtained after neoadjuvant treatment. Significant reductions in tumor size were observed within a time interval of three months,” Weeda and authors concluded. “This is in line with another study.”

Reference:

“Monitoring Neoadjuvant Treatment-Induced Surgical Benefit in GIST Patients Using CT-Based Radiological Criteria” by Dr. Ylva A. Weeda, et al., Surgery Open Science.

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