A Randomized, Phase II Study of Preoperative plus Postoperative Imatinib in GIST: Evidence of Rapid Radiographic Response and Temporal Induction of Tumor Cell Apoptosis

McAuliffe, John C.; Hunt, Kelly K.; Lazar, Alexander J.; Choi, Haesun; Qiao, Wei; Thall, Peter F.; Pollock, Raphael E.; Benjamin, Robert S.; Trent, Jonathan C.

doi:10.1245/s10434-008-0177-7

Cited by 158 publications

(112 citation statements)

References 28 publications

(24 reference statements)

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“…The optimal duration of neoadjuvant IM therapy is not clearly defined and usually ranges from 4-12 months (11,25). Within this duration, optimal response is usually achieved, risk of developing secondary resistance is low and best results can be achieved with surgery.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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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: 99%

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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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“…Concerning the duration of preoperative administration of imatinib, it has been reported to range from a few days to more than 1 year (13,(47)(48)(49). The optimal duration of preoperative imatinib is considered to be as long as 6 to 12 months to obtain a maximal response prior to surgery (3).…”

Section: Neoadjuvant Therapy For Esophageal Gistsmentioning

confidence: 99%

Gastrointestinal stromal tumor of the esophagus: current issues of diagnosis, surgery and drug therapy

Hihara

Mukaida

Hirabayashi

2018

Transl. Gastroenterol. Hepatol.

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“…The published trials show that preoperative imatinib is safe, and associated with a higher R0 rate, lower risk of tumor rupture, acceptable perioperative morbidity, and good disease-free survival [7][8][9][10]. However, the survival benefit is not well determinable since most of the patients included in these studies also received imatinib postoperatively for at least 2 years [7][8][9]. Thus, at the present time, the decision to use preoperative therapy for patients with resectable primary, locally advanced, or recurrent GIST should be made on an individual basis.…”

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Which is the best surgical approach for anorectal gastrointestinal stromal tumors in the post-imatinib era?

Pucciarelli

2013

Tech Coloproctol

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Anorectal gastrointestinal stromal tumors (GISTs) represent about 5 % of all GISTs. Local recurrence, although with a long latency period, occurs in more than a half of cases and is a major concern. Prognostic factors for recurrence are the tumor size and the mitotic index. However, for anorectal lesions, the particular location represents a main obstacle to achieving a radical (R0) resection.Surgery is the treatment of choice for patients with localized or potentially resectable GIST lesions. The goal is to achieve complete gross resection of the tumor with an intact pseudocapsule. Current guidelines recommend wide resection with clear margins (such as abdominoperineal or anterior resection) [1,2]. Local removal of the tumor has also been proposed, performed by a transanal, transsacral, or transvaginal approach, even if abdominal surgery is more likely to result in negative margins than local surgery [3]. In the article by Centonze et al. [4], a new local technique has been proposed for anorectal GIST excision. A transsphincteric approach was used, with a right ischiorectal fossa incision. Although in the two cases presented the tumor size was C8 cm and the mitotic index was high, the procedure seems feasible, with low morbidity and good early oncological outcomes. Both the patients underwent adjuvant therapy with imatinib, as recommended for high risk GISTs.There are two important considerations to be made. The first concerns the preoperative workup. All anorectal GIST patients should be managed by a multidisciplinary team with expertise in sarcoma. The workup should include: history, physical examination, abdominal/pelvic computed tomography (CT) scan with contrast and/or magnetic resonance imaging (MRI), and chest imaging. A positron emission tomography (PET) scan is not a substitute for CT, however, it may be used to clarify ambiguous findings seen on CT or MRI. Finally, endoscopic ultrasound-guided fine needle aspiration biopsy is necessary to confirm the diagnosis of primary GIST prior to the initiation of any preoperative therapy [5].The second concerns the use of imatinib associated with surgery. This selective inhibitor of the KIT protein tyrosine kinase has drastically improved the prognosis of patients with GIST. The results of a recently completed trial suggest that in patients with a high risk of recurrence adjuvant imatinib administered for 36 months significantly improves relapse-free and overall survival compared to 12 months of imatinib therapy [6]. Since sphincter-sparing surgery is a primary goal in treating rectal tumors, the use of preoperative imatinib has also been investigated. The published trials show that preoperative imatinib is safe, and associated with a higher R0 rate, lower risk of tumor rupture, acceptable perioperative morbidity, and good disease-free survival [7][8][9][10]. However, the survival benefit is not well determinable since most of the patients included in these studies also received imatinib postoperatively for at least 2 years [7][8][9]. Thus, at the present time, ...

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A Randomized, Phase II Study of Preoperative plus Postoperative Imatinib in GIST: Evidence of Rapid Radiographic Response and Temporal Induction of Tumor Cell Apoptosis

Cited by 158 publications

References 28 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

Gastrointestinal stromal tumor of the esophagus: current issues of diagnosis, surgery and drug therapy

Which is the best surgical approach for anorectal gastrointestinal stromal tumors in the post-imatinib era?

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