Locoregional Treatments for Metastatic Gastrointestinal Stromal Tumor in British Columbia: A Retrospective Cohort Study from January 2008 to December 2017

Abstract

Introduction: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC). Methods: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures. Results: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23–90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control (n = 9). A few patients (n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients (n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29–40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7–64.69) and no LRT (45.27 months; 95% CI: 33.25–58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation. Discussion: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.

Radiotherapy in the Management of Gastrointestinal Stromal Tumors: A Systematic Review

“…Through the analysis of symptomatic GISTs, we found that the symptom palliation rate of radiotherapy alone and radiotherapy with concomitant previously resistant TKIs reached 78.6% (22/28), which supports the application of radiotherapy in GISTs for palliative purposes recommended by the guidelines [2]. In addition to pain, radiotherapy may also be used to relieve the symptoms of bleeding and spinal cord compression [51,53]. Patterson et al reported that among 12 patients with advanced or metastatic GISTs treated by radiotherapy, 9 had improvement in symptoms to varying degrees [53].…”

“…In addition to pain, radiotherapy may also be used to relieve the symptoms of bleeding and spinal cord compression [51,53]. Patterson et al reported that among 12 patients with advanced or metastatic GISTs treated by radiotherapy, 9 had improvement in symptoms to varying degrees [53]. However, all 12 patients received TKIs during radiotherapy.…”

“…Two patients did not achieve palliation, and the other four patients were not available. The symptom palliation rate was 78.6% (22/28).In addition, the other case series reported symptom palliation in 12 patients with advanced or metastatic GISTs treated by radiotherapy with concomitant TKIs [53]. Pain, spinal cord compression, and bleeding were the main symptoms.…”

Evolution of Patterns of Care and Outcomes in the Real-Life Setting for Patients with Metastatic GIST Treated in Three French Expert Centers over Three Decades

“…Metastatic GIST are currently treated with oral KIT and PDGFR tyrosine-kinase inhibitors (TKI) such as imatinib, sunitinib and regorafenib [2][3][4]. Over two decades, significant changes in drug discovery and locoregional (LR) procedures have impacted treatment strategies [5][6][7][8]. Recently, two new drugs have been approved in metastatic GIST, namely ripretinib after failure of at least three lines, including imatinib [9], and avapritinib in GIST with the PDGFRA exon 18 D842V mutation [10].…”

“…Recently, two new drugs have been approved in metastatic GIST, namely ripretinib after failure of at least three lines, including imatinib [9], and avapritinib in GIST with the PDGFRA exon 18 D842V mutation [10]. However, data about real-life multimodal treatment strategies and their outcomes for patients with metastatic GIST are limited [8].…”