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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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18FDG-PET scan of a patient with 18FDG-avid metastatic GIST showing significant uptake of this marker
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Fig4: 18FDG-PET scan of a patient with 18FDG-avid metastatic GIST showing significant uptake of this marker

Mentions: Most GI malignancies are metabolically active and take up the radiolabeled glucose analog 18F-fluorodeoxyglucose (18FDG), making 18FDG-PET a highly sensitive and valuable imaging tool for diagnosis and a predictor of clinical outcome (Fig. 4).22 The overall sensitivity of 18FDG-PET is approximately 80 % in detecting GISTs at initial presentation.20 Unfortunately, GISTs exhibit variable 18FDG uptake,36,37 and only some tumors are 18FDG-avid. 18FDG-PET is thus typically reserved for resolving ambiguous findings on CT or MRI (e.g., increase in size due to pseudo-progression versus true tumor progression) and for monitoring early response to imatinib treatment by serial scans. In phase II trials, 18FDG-PET revealed responses within the first 1–7 days of treatment in 69–85 % of patients, supporting its use to monitor early response to imatinib.38,39 Decreases in FDG uptake, as measured by changes in SUVmax, can occur as early as 24 h after imatinib treatment.20 At present, however, there are no standardized criteria for PET response for GIST, and this is an area of active research.Fig. 4


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

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

18FDG-PET scan of a patient with 18FDG-avid metastatic GIST showing significant uptake of this marker
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: 18FDG-PET scan of a patient with 18FDG-avid metastatic GIST showing significant uptake of this marker
Mentions: Most GI malignancies are metabolically active and take up the radiolabeled glucose analog 18F-fluorodeoxyglucose (18FDG), making 18FDG-PET a highly sensitive and valuable imaging tool for diagnosis and a predictor of clinical outcome (Fig. 4).22 The overall sensitivity of 18FDG-PET is approximately 80 % in detecting GISTs at initial presentation.20 Unfortunately, GISTs exhibit variable 18FDG uptake,36,37 and only some tumors are 18FDG-avid. 18FDG-PET is thus typically reserved for resolving ambiguous findings on CT or MRI (e.g., increase in size due to pseudo-progression versus true tumor progression) and for monitoring early response to imatinib treatment by serial scans. In phase II trials, 18FDG-PET revealed responses within the first 1–7 days of treatment in 69–85 % of patients, supporting its use to monitor early response to imatinib.38,39 Decreases in FDG uptake, as measured by changes in SUVmax, can occur as early as 24 h after imatinib treatment.20 At present, however, there are no standardized criteria for PET response for GIST, and this is an area of active research.Fig. 4

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