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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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Endoscopy image of an ulcerated proximal gastric GIST (a) and corresponding EUS (b) (images courtesy of Dr. Thomas Savides)
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Fig3: Endoscopy image of an ulcerated proximal gastric GIST (a) and corresponding EUS (b) (images courtesy of Dr. Thomas Savides)

Mentions: The endoscopic characteristics of GISTs include smooth shape, normal overlying mucosa, occasional mucosal ulceration, and firm consistency on compression (Fig. 3).22 However, standard endoscopy cannot reliably determine the size of these submucosal lesions nor provide adequate biopsy samples using standard forceps.23 EUS can determine additional lesion features, including hypoechoic appearance, oval shape, and wall layer of origin, which may aid in diagnosing GIST and determining malignant features.24,25 EUS-guided tissue acquisition for histological analysis is now preferred for GISTs because it provides adequate material for histologic and mutational analyses,26 with a diagnostic accuracy of ∼80 %.27–29 Moreover, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is preferred over percutaneous biopsy due to its lower risk of hemorrhage and tumor seeding.30 More recently, the utility of endoscopic ultrasound-guided Tru-Cut biopsy (EUS-TCB) for GISTs was evaluated in six patients to obtain specimens for pathological and immunohistochemical studies.31 All tumors were >2 cm, and core tissue samples were successfully procured in all cases. The final diagnosis was KIT-positive GIST in five patients and leiomyoma in one patient. No patients developed complications after the procedure, suggesting that EUS-TCB is safe. Additionally, EUS-TCB is faster to perform than endoscopic mucosal biopsy, providing sufficient tissue for pathological diagnosis.31Fig. 3


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

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

Endoscopy image of an ulcerated proximal gastric GIST (a) and corresponding EUS (b) (images courtesy of Dr. Thomas Savides)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Endoscopy image of an ulcerated proximal gastric GIST (a) and corresponding EUS (b) (images courtesy of Dr. Thomas Savides)
Mentions: The endoscopic characteristics of GISTs include smooth shape, normal overlying mucosa, occasional mucosal ulceration, and firm consistency on compression (Fig. 3).22 However, standard endoscopy cannot reliably determine the size of these submucosal lesions nor provide adequate biopsy samples using standard forceps.23 EUS can determine additional lesion features, including hypoechoic appearance, oval shape, and wall layer of origin, which may aid in diagnosing GIST and determining malignant features.24,25 EUS-guided tissue acquisition for histological analysis is now preferred for GISTs because it provides adequate material for histologic and mutational analyses,26 with a diagnostic accuracy of ∼80 %.27–29 Moreover, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is preferred over percutaneous biopsy due to its lower risk of hemorrhage and tumor seeding.30 More recently, the utility of endoscopic ultrasound-guided Tru-Cut biopsy (EUS-TCB) for GISTs was evaluated in six patients to obtain specimens for pathological and immunohistochemical studies.31 All tumors were >2 cm, and core tissue samples were successfully procured in all cases. The final diagnosis was KIT-positive GIST in five patients and leiomyoma in one patient. No patients developed complications after the procedure, suggesting that EUS-TCB is safe. Additionally, EUS-TCB is faster to perform than endoscopic mucosal biopsy, providing sufficient tissue for pathological diagnosis.31Fig. 3

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