Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib

Abstract

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Long-term survival of patients with metastatic disease has only been observed in patients with completely resected disease. Recently, the tyrosine kinase inhibitor imatinib has been found to yield responses in the majority of patients with metastatic GIST suggesting improved resectability in responding patients. Combined treatment approaches including resective surgery after imatinib treatment in patients with advanced metastatic disease have rarely been explored. We report a series of 90 patients with metastatic GIST in whom treatment with imatinib enabled 12 patients with mostly recurrent and extensive disease to be considered for resection of residual disease. In 11 of these patients, complete resection could be achieved. Viable tumor cells were found in all but one resected specimens suggesting that despite favorable radiological or clinical responses, imatinib is unlikely to induce pathological complete responses. Until more mature data from prospective trials are available, these data suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST. Further trials investigating a combined surgical and pre/ postoperative treatment with imatinib in patients with advanced metastatic GIST are warranted. ' 2005 Wiley-Liss, Inc.

KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway

“…GIST62 was derived from a primary GIST with a homozygous KIT exon 11 mutation and despite retaining this KIT mutation in all cells expresses KIT protein at very low levels. The GIST62 cell line model may be relevant to clinical GISTs, where approximately 15% of KIT-positive GISTs lose KIT expression at time of clinical progression during imatinib therapy (Fletcher et al, 2003;Debiec-Rychter et al, 2005;Bauer et al, 2005a). These findings underscore the considerable therapeutic potential of drugs targeting key signaling intermediates downstream of KIT.…”

“…In addition, there is evidence that imatinib exhibits more cytostatic than cytotoxic effects, as complete responses to imatinib in metastatic GIST are rare (p5%) and most responding patients develop secondary resistance (Verweij et al, 2004). Notably, a subset of viable tumor cells can be found in most patients who undergo GIST resections during imatinib therapy, indicating that imatinib-resistant clones are present in most GISTs (Bauer et al, 2005a).…”

Surgical management of gastrointestinal stromal tumours

“…These data are in accordance with the findings of a previous smaller series of 11 patients. They suggest that an early aggressive surgical approach should be considered for all patients with metastatic GIST who have demonstrated an initial response to medical therapy, provided an R0 resection can be achieved 91 . These encouraging results, however, are likely to reflect the biased experience of tertiary care institutions, with highly selected patients.…”

Detection of Mutant Free Circulating Tumor DNA in the Plasma of Patients with Gastrointestinal Stromal Tumor Harboring Activating Mutations of CKIT or PDGFRA

“…In a recent study, the sensitivity and specificity of FDG-PET/CT for detecting intraoperatively occult metastases in patients with GIST and R0 resection was 25% and 88%, respectively (15). Even in cases with FDG-PET/CT complete response, lesions contained viable tumor (16).…”