Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GISTs) is Effective and Safe: Results from a Prospective Single-Center Study with 108 Patients.

BACKGROUND: Neoadjuvant imatinib is considered for gastrointestinal stromal tumors (GISTs) when decreased tumor size provides less extensive surgery and higher R0 resection rates. This study evaluates the effectivity and safety of neoadjuvant imatinib for large or locally advanced GIST. PATIENTS AND METHODS: From the prospective database of the Dutch GIST Consortium, all patients who underwent surgery after neoadjuvant imatinib at our center between 2009 and 2022 were selected. Independent and blinded assessment of surgical strategy was performed by two surgeons, based on anonymized computed tomography (CT) scans before and after neoadjuvant imatinib. RESULTS: Of 113 patients that received neoadjuvant imatinib, 108 (95%) [mean age 61.6, standard deviation (SD) 11.5, 54% male] underwent a GIST resection. Of all GISTs, 67% was localized in the stomach and 25% in the duodenum or small intestine. In 74% of the patients with GIST, a KIT exon 11 mutation was found. Decreased tumor size was seen in 95 (88%) patients. Having a KIT exon 11 mutation [odds ratio (OR) 5.64, 95% confidence interval (CI) 1.67-19.1, p < 0.01] or not having a mutation (OR 0.19, 95% CI 0.04-0.89, p = 0.04) were positive and negative predictive values for partial response, respectively. In 55 (51%) patients, there was deescalation of surgical strategy after neoadjuvant imatinib. Surgical complications were documented in 16 (15%) patients (n = 8, grade II; n = 5, grade IIIa; n = 3, grade IIIb) and R0 resection was accomplished in 95 (89%) patients. The 5-year disease-free and overall survival were 80% and 91%, respectively. CONCLUSION: This study shows that neoadjuvant imatinib is effective and safe for patients with large or locally advanced GIST.

Surgical outcomes of lymph node dissections for stage III melanoma after neoadjuvant systemic therapy are not inferior to upfront surgery.

BACKGROUND: Neoadjuvant systemic therapy has shown promising results in the treatment of high-risk stage III melanoma; however, the effects on surgery are currently unknown. This study aims to compare the surgical outcomes, in terms of postoperative complications, postoperative morbidity, duration of surgery and textbook outcomes, of patients with high-risk stage III melanoma who received neoadjuvant systemic therapy followed by lymph node dissection with patients who received an upfront lymph node dissection. METHODS: In this retrospective cohort study, patients with high-risk stage III melanoma treated with neoadjuvant anti-PD1 and anti-CTLA4 in the OpACIN (NCT02437279) and OpACIN-neo (NCT02977052) trial between October 2014 and August 2018 were included and compared to patients who received upfront surgery in the same time period. RESULTS: A total of 120 patients were included in this study, of whom 44 received neoadjuvant systemic therapy and 76 underwent upfront surgery. There was no significant difference in the overall rate of postoperative complications between the neoadjuvant group and the upfront surgery group (31.8% versus 36.8%, p = 0.578) and neither in rate of postoperative morbidity (seroma 56.8% versus 57.9%, p = 0.908) (lymphedema 22.7% versus 13.2%, p = 0.175). There was a non-significant difference towards a slightly longer duration of surgery after neoadjuvant immunotherapy (105 versus 90 min, p = 0.077). There were no differences in textbook outcomes (50% versus 49%, p = 0.889). CONCLUSION: This study shows that the surgical outcomes for patients who underwent a lymph node dissection after neoadjuvant systemic immunotherapy or underwent upfront lymph node dissection for high-risk stage III melanoma are comparable.