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Optimizing surgical and imatinib therapy for the treatment of gastrointestinal stromal tumors.

Sicklick JK, Lopez NE - J. Gastrointest. Surg. (2013)

Bottom Line: Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes.In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities.Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgical Oncology, Department of Surgery, Moores UCSD Cancer Center, University of California, San Diego, UC San Diego Health System, 3855 Health Sciences Drive, Mail Code 0987, La Jolla, CA, 92093-0987, USA, jsicklick@ucsd.edu.

ABSTRACT

Introduction: The discovery of activating KIT and PDGFRα mutations in gastrointestinal stromal tumors (GISTs) represented a milestone as it allowed clinicians to use tyrosine kinase inhibitors, like imatinib, to treat this sarcoma. Although surgery remains the only potentially curative treatment, patients who undergo complete resection may still experience local recurrence or distant metastases. Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes. In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities. Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy. However, it is critical that patients with GIST be evaluated by a multidisciplinary team to coordinate surgery and targeted therapy in order to maximize clinical outcomes.

Discussion: Following a systematic literature review, we describe the presentation, diagnosis, and treatment of GIST, with a discussion of the risk assessment for imatinib therapy. The application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib, and their potential impact on survival for patients with primary, recurrent, or metastatic GIST are discussed.

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Related in: MedlinePlus

Many GISTs are or become hypervascular, as shown in this pathologic specimen
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Fig2: Many GISTs are or become hypervascular, as shown in this pathologic specimen

Mentions: GISTs originate in the muscularis propria, likely originating from the interstitial cells of Cajal. Most GISTs present as a single endophytic or exophytic nodule with a well-defined border and a median size of 3–5 cm (range of a few millimeters to ≥35 cm).5 They rarely invade adjacent structures, but penetration through the bowel wall, organ invasion, adenopathy, cystic degeneration, irregular margins, mesenteric fat infiltration, ulceration, hemorrhage, and necrosis likely indicate malignancy. GISTs are also highly vascular (Fig. 2) and friable. Thus, they are prone to rupture and dissemination, which greatly increase the risk of recurrence.19Fig. 2


Optimizing surgical and imatinib therapy for the treatment of gastrointestinal stromal tumors.

Sicklick JK, Lopez NE - J. Gastrointest. Surg. (2013)

Many GISTs are or become hypervascular, as shown in this pathologic specimen
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824223&req=5

Fig2: Many GISTs are or become hypervascular, as shown in this pathologic specimen
Mentions: GISTs originate in the muscularis propria, likely originating from the interstitial cells of Cajal. Most GISTs present as a single endophytic or exophytic nodule with a well-defined border and a median size of 3–5 cm (range of a few millimeters to ≥35 cm).5 They rarely invade adjacent structures, but penetration through the bowel wall, organ invasion, adenopathy, cystic degeneration, irregular margins, mesenteric fat infiltration, ulceration, hemorrhage, and necrosis likely indicate malignancy. GISTs are also highly vascular (Fig. 2) and friable. Thus, they are prone to rupture and dissemination, which greatly increase the risk of recurrence.19Fig. 2

Bottom Line: Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes.In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities.Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy.

View Article: PubMed Central - PubMed

Affiliation: Division of Surgical Oncology, Department of Surgery, Moores UCSD Cancer Center, University of California, San Diego, UC San Diego Health System, 3855 Health Sciences Drive, Mail Code 0987, La Jolla, CA, 92093-0987, USA, jsicklick@ucsd.edu.

ABSTRACT

Introduction: The discovery of activating KIT and PDGFRα mutations in gastrointestinal stromal tumors (GISTs) represented a milestone as it allowed clinicians to use tyrosine kinase inhibitors, like imatinib, to treat this sarcoma. Although surgery remains the only potentially curative treatment, patients who undergo complete resection may still experience local recurrence or distant metastases. Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes. In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities. Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy. However, it is critical that patients with GIST be evaluated by a multidisciplinary team to coordinate surgery and targeted therapy in order to maximize clinical outcomes.

Discussion: Following a systematic literature review, we describe the presentation, diagnosis, and treatment of GIST, with a discussion of the risk assessment for imatinib therapy. The application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib, and their potential impact on survival for patients with primary, recurrent, or metastatic GIST are discussed.

Show MeSH
Related in: MedlinePlus