Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib

Andtbacka, Robert H.I.; Ng, Chaan S.; Scaife, Courtney L.; Cormier, Janice N.; Hunt, Kelly K.; Pisters, Peter W.T.; Pollock, Raphael E.; Benjamin, Robert S.; Burgess, Michael A.; Chen, Lei L.; Trent, Jonathan C.; Patel, Shreyaskumar; Raymond, Kevin; Feig, Barry W.

doi:10.1245/s10434-006-9034-8

Cited by 228 publications

(187 citation statements)

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“…4,[34][35][36] Although the tyrosine kinase inhibitor SU11248 and PKC412 can be used as the second-line treatments and some patients with imatinib-resistant GIST showed response to these drugs, 37 the median time to disease re-progression was only about 6 months. Because imatinib adjuvant as well as neoadjuvant treatment can dramatically improve the prognosis for highgrade malignant GISTs, 9 there are potential benefits to apply imatinib therapy preoperatively or postoperatively in patients with malignant GIST. Up to now, there is still no consensus on the selection of candidates for adjuvant therapy, mainly because the criteria predicting patients with a high risk of recurrence after the surgical removal of primary GISTs have yet to be established.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Therefore, the best treatment regimen for patients with malignant GISTs, like doing imatinib preoperatively or postoperatively, is still under debate. [7][8][9] The guideline for the selection of patients for adjuvant therapy varies among experts, mainly due to the criteria predicting patients with a high risk of recurrence after the surgical removal of primary GISTs have yet to be established. Clinically, some patients with malignant GIST are highly aggressive, developing recurrence within short time after surgical removal of the primary tumor, whereas others can be treated effectively by surgical resection alone or had a long latency to develop recurrence.…”

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confidence: 99%

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Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

Hou

Zhou

et al. 2009

Modern Pathology

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Tumor stage and grade for gastrointestinal stromal tumors are poorly defined. To develop a better evaluation system, we assessed 12 clinical and pathological parameters in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count Z10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia. The 5-year disease-free survival and overall survival of 293 patients without any of these predictive parameters of malignancy were 99% and 100%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the 5-year disease-free survival and overall survival rates were 44% (mean 6.7 years) and 60% (mean 9.3 years), respectively. The disease-free survival showed significant difference between patients with and without gross spread (Po0.0001), with and without microscopic spread (P ¼ 0.0009). Disease-free survival and overall survival were associated with the number of predictive parameters of malignancy in patients without gross spread (Po0.0001 for both disease-free survival and overall survival), but not in patients with gross spread (P ¼ 0.882 and 0.441, respectively). Malignant gastrointestinal stromal tumors could be divided into clinical stage I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. We found that the clinical stage and grade were strongly associated with prognosis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

Hou

Zhou

et al. 2009

Modern Pathology

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“…66,67 Neoadjuvant therapy has been shown to be well tolerated and to increase survival in advanced/metastatic patients postsurgery (2-year PFS of 61%-77%). [68][69][70] Overall, patients have been reported to receive neoadjuvant imatinib for 2 to 26 months.…”

Section: High-dose Imatinib In a Neoadjuvant Settingmentioning

confidence: 99%

“…[68][69][70] Overall, patients have been reported to receive neoadjuvant imatinib for 2 to 26 months. [66][67][68][69][70] Patients treated with imatinib too long before surgery have a risk of developing secondary resistance; a median of 3.5 months on imatinib therapy was reported as the time to best response, and ideally surgery should not be delayed much longer than that. 54,68 Various neoadjuvant or adjuvant combination studies have used different doses of imatinib to treat advanced patients; however, none was powered to distinguish efficacy between doses.…”

Section: High-dose Imatinib In a Neoadjuvant Settingmentioning

confidence: 99%

“…54,68 Various neoadjuvant or adjuvant combination studies have used different doses of imatinib to treat advanced patients; however, none was powered to distinguish efficacy between doses. 66,[68][69][70][71][72] In some cases, preoperative imatinib was given at an initial dose of 400 mg daily and increased to 600 to 800 mg daily on progression, or was given at 600 to 800 mg daily at the outset. 66,[69][70][71][72] One case study reported on a patient with a localized high-risk tumor, who received neoadjuvant imatinib therapy at an initial dose of 800 mg daily for 2 weeks, and was later reduced to 600 mg daily.…”

Section: High-dose Imatinib In a Neoadjuvant Settingmentioning

confidence: 99%

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The role of high‐dose imatinib in the management of patients with gastrointestinal stromal tumor

Gronchi¹,

Blay

Trent

2010

Cancer

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After an era of few treatment options for patients with locally advanced or metastatic gastrointestinal stromal tumor (GIST), imatinib has emerged as the standard of care and first-line treatment for these patients. Although imatinib was initially approved at the doses of 400 and 600 mg daily, results from clinical studies established 400 mg daily as the standard initial dose for the majority of advanced GIST patients. Nevertheless, the use of high-dose imatinib (800 mg daily) has been shown to benefit patients with advanced or metastatic GIST that progresses on the standard-dose, and has been recommended in this setting by the major management guidelines in Europe and the United States. Results from the Meta-GIST meta-analysis showed that patients whose GIST harbors a KIT exon 9 mutation garner a longer progression-free survival time when treated initially with high-dose imatinib (800 mg daily) compared with those patients with KIT exon 11 or no mutations. Thus, the use of high-dose imatinib is recommended by the clinical practice guidelines in these 2 specific clinical situations. In addition, clinicians should weigh the clinical benefit of administering high-dose imatinib against the associated toxicities, as well as the proper management of dose-related side effects. Cancer 2010;116:1847-58. V C 2010 American Cancer Society.KEYWORDS: gastrointestinal stromal tumor, GIST, imatinib, Glivec, Gleevec, high-dose.Gastrointestinal stromal tumors (GISTs) are rare tumors diagnosed in a small percentage of the population (10-20 cases per million).1,2 Nonetheless, GISTs are the most common sarcoma of the gastrointestinal tract, accounting for at least 5% of all sarcomas and 82% of all gastrointestinal mesenchymal tumors.3,4 GISTs may arise anywhere throughout the gastrointestinal tract, including the lower part of the esophagus and the anorectal region. However, GISTs most commonly occur in the stomach (60%), followed by the small intestine (30%), duodenum (4%-5%), rectum (4%), esophagus (<1%) and colon (1%-2%). 5GISTs are most often characterized by strong immunoreactivity to the CD117 antigen, that is, the KIT protein. This strong KIT expression is observed on the interstitial cells of Cajal-pacemaker cells that express high levels of KIT and from which GISTs are thought to derive. 6,7 Besides KIT, 70% to 75% of GISTs stain positive for CD34, 25% to 56% stain for smooth muscle actin, 32% express S100 protein, and 1% to <5% are desmin positive. 8,9 A landmark study by Hirota et al and subsequent reports found that KIT was mutated in approximately 80% of GISTs.10,11 These KIT mutations cause ligand-independent KIT phosphorylation of the mutated protein and constitutive activation of the pathway, leading to cell proliferation and malignant transformation.10 However, KIT mutational status is independent of KIT immunoexpression, as 1) high levels of KIT are a constitutional feature and not a direct consequence of KIT mutation-related autoactivation, 9 and 2) mutant activated KIT proteins are retained within intracellular ...

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Gastrointestinal Stromal Tumors

Mehren¹,

Flieder

Raut

2012

Textbook of Uncommon Cancer

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Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib

Cited by 228 publications

References 29 publications

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

Stage and histological grade of gastrointestinal stromal tumors based on a new approach are strongly associated with clinical behaviors

The role of high‐dose imatinib in the management of patients with gastrointestinal stromal tumor

Gastrointestinal Stromal Tumors

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