Surgical treatment of locally advanced, non-metastatic, gastrointestinal stromal tumours after treatment with imatinib

Tielen, R.; Verhoef, Cornelis; Coevorden, Frits van; Gelderblom, Hans; Sleijfer, Stefan; Hartgrink, Henk H.; Bonenkamp, Johannes J.; Graaf, Winette T.A. van der; Wilt, Johannes H. W. de

doi:10.1016/j.ejso.2012.09.004

Cited by 63 publications

(55 citation statements)

References 29 publications

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“…Our results differ from the RTOG 0132 phase 2 trial in which 83% of patients had SD amongst the 31 patients with primary GIST and lesser PR rates. This is possibly due to the shorter duration of neoadjuvant IM given in this trial (8)(9)(10)(11)(12) weeks) compared to our study (12).…”

Section: Discussionmentioning

confidence: 43%

“…Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib spillage of tumor cells (8)(9)(10). There is growing evidence for neoadjuvant IM therapy in terms of disease free survival (DFS) and overall survival (OS), with major evidence of benefit shown in the EORTC-STBSG retrospective analysis (11)(12)(13)(14)(15).…”

Section: Original Articlementioning

confidence: 99%

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Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib

Ramaswamy¹,

Jain²,

Sahu³

et al. 2016

J. Gastrointest. Oncol.

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Background: Multimodality treatment of gastrointestinal stromal tumor (GIST) with surgery and adjuvant imatinib mesylate (IM), along with an emerging role for neoadjuvant IM prior to evaluation for resectability has resulted in high survival rates. Methods: We conducted a retrospective analysis of prospectively collected data of patients who underwent surgery for GIST, prior to or followed by IM therapy. A total of 112 patients underwent surgery between January 2009 and March 2015 at our centre. This included 27 patients with upfront resectable disease, 76 patients with locally advanced GIST who received neoadjuvant IM followed by surgery and 9 patients with metastatic disease who had excellent response to IM and were taken for surgery. Results: The primary tumor in the non metastatic patients was in the stomach (53%), duodenum (16%), rectum (12%), jejunum (11%), ileum (7%), and others (2%). Median duration of neoadjuvant IM was 5 months with 4 patients showing disease progression during neoadjuvant IM. Ninety-three percent of all patients had R0 resections, while 7% had R+ resections. The estimated 3-and 5-year DFS in non-metastatic patients was 86.1% and 67% respectively with a 3-and 5-year median OS of 95.4% and 91.7% respectively.Five-year PFS and OS for the metastatic patients was 88.8% and 100% respectively. Lack of adjuvant IM was the only factor related to inferior PFS and OS. Conclusions: Longer duration of neoadjuvant IM should be considered in locally advanced GIST prior to surgery and resection may be considered in responding metastatic patients. J Gastrointest Oncol 2016;7(4):624-631 jgo.amegroups.com spillage of tumor cells (8-10). There is growing evidence for neoadjuvant IM therapy in terms of disease free survival (DFS) and overall survival (OS), with major evidence of benefit shown in the EORTC-STBSG retrospective analysis (11)(12)(13)(14)(15).The purpose of this study was to evaluate the demographic profile, presentation and outcomes of 112 patients with GIST who underwent surgery at our institution and were potential candidates for either neoadjuvant or adjuvant IM over a period of 6 years. We also attempted to identify potential prognostic factors with respect to outcomes and placed special emphasis on patients receiving neoadjuvant IM. MethodsA retrospective analysis of prospectively maintained database of all GIST patients who underwent surgery and presented between January 2009 to March 2015 at Department of GI & Hepatopancreaticobiliary Oncology, Tata Memorial Hospital, Mumbai, was performed. Clinical and radiological data were recorded from patient files and electronic medical records. Patients presenting in the above study period were subdivided on the basis of clinical presentation and treatment received into localized operable, locally advanced, operated elsewhere on adjuvant treatment and incidental GISTs. Locally advanced GISTs were defined by the size, need for multivisceral resections, anatomic proximity with major vessels and risk of intraoperative tumor spillage. Patients opera...

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Section: Discussionmentioning

confidence: 43%

Section: Original Articlementioning

confidence: 99%

Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib

Ramaswamy¹,

Jain²,

Sahu³

et al. 2016

J. Gastrointest. Oncol.

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“…In most patients a substantial reduction in tumor size can be observed within 2-8 months of treatment. In a Dutch multicentric retrospective study of 57 patients with locally advanced GISTs, neoadjuvant treatment with imatinib achieved almost 50% tumor size reduction, leading to successful R0 resection in 84% of patients [60]. In a prospective phase II study, imatinib was administered to 41 patients with locally advanced, non-metastatic GISTs.…”

Section: Management Of Localized Gistsmentioning

confidence: 99%

State of the Art in the Treatment of Gastrointestinal Stromal Tumors

Garlipp

Bruns

2014

Gastrointest Tumors

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Background: Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. Summary: From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. Key Message: Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. Practical Implications: The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment. Molecular characterization of the tumor (with respect to the PDGFRA and KIT genes) is mandatory prior to imatinib therapy. Sunitinib and regorafenib are established as alternative treatments for patients demonstrating generalized disease progression on imatinib. New tyrosine kinase inhibitors such as ponatinib and crenolanib as well as drugs targeting alternative pathways are currently under investigation. Surgery and locally ablative treatments may be indicated in some metastatic patients.

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“…Subsequently, the development of an IM-based neoadjuvant treatment strategy has been proposed (22). In selected cases of locally advanced GIST, IM facilitates resection and decreases surgical morbidity by reducing the need for extensive resection and the perioperative risk of tumor rupture (15,23).…”

Section: Postoperative Complications and Follow-upmentioning

confidence: 99%

Organ-preserving surgery for locally advanced duodenal gastrointestinal stromal tumor after neoadjuvant treatment

Qian

Qiu

et al. 2017

BST

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Surgical treatment of locally advanced, non-metastatic, gastrointestinal stromal tumours after treatment with imatinib

Abstract: Imatinib in locally advanced GIST is feasible and enables a high complete resection rate without tumour rupture. The combination of imatinib and surgery in patients with locally advanced GIST seems to improve PFS and OS.

Cited by 63 publications

References 29 publications

Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib

Neoadjuvant imatinib: longer the better, need to modify risk stratification for adjuvant imatinib

State of the Art in the Treatment of Gastrointestinal Stromal Tumors

Organ-preserving surgery for locally advanced duodenal gastrointestinal stromal tumor after neoadjuvant treatment

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