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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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RFS (a) and OS (b) in patients with primary GIST treated with 1 versus 3 years of adjuvant imatinib in the SSGXVIII/AIO phase III trial13
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Fig5: RFS (a) and OS (b) in patients with primary GIST treated with 1 versus 3 years of adjuvant imatinib in the SSGXVIII/AIO phase III trial13

Mentions: Subsequently, to explore whether increasing duration of imatinib therapy would result in improved RFS at long-term follow-up, the open-label Scandinavian Sarcoma Group/Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) phase III trial randomized patients who underwent gross resection of primary KIT-positive GIST to receive 1 or 3 years of adjuvant imatinib (400 mg/day). These patients were judged to be at high risk of recurrence if they had tumors with one or more of the following characteristics: diameter >10 cm; MI >10 mitoses per 50 HPF; tumor diameter >5 cm with >5 mitoses per HPF; or tumor rupture before or at surgery. Patients had significantly greater RFS and OS with 3 years adjuvant imatinib versus 1 year of treatment (Fig. 5). At 5-year follow-up, RFS and OS rates were 65.6 and 92.0 % in the 3-year arm versus 47.9 and 81.7 % in the 1-year arm (P < 0.001 and P = 0.02), respectively.13 Accordingly, NCCN guidelines now recommend at least 3 years of adjuvant imatinib treatment for patients with KIT-positive GIST who are at high risk of recurrence based on tumor size, MI, site, rupture, and completeness of surgery.14Fig. 5


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

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

RFS (a) and OS (b) in patients with primary GIST treated with 1 versus 3 years of adjuvant imatinib in the SSGXVIII/AIO phase III trial13
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: RFS (a) and OS (b) in patients with primary GIST treated with 1 versus 3 years of adjuvant imatinib in the SSGXVIII/AIO phase III trial13
Mentions: Subsequently, to explore whether increasing duration of imatinib therapy would result in improved RFS at long-term follow-up, the open-label Scandinavian Sarcoma Group/Sarcoma Group of the Arbeitsgemeinschaft Internistische Onkologie (SSGXVIII/AIO) phase III trial randomized patients who underwent gross resection of primary KIT-positive GIST to receive 1 or 3 years of adjuvant imatinib (400 mg/day). These patients were judged to be at high risk of recurrence if they had tumors with one or more of the following characteristics: diameter >10 cm; MI >10 mitoses per 50 HPF; tumor diameter >5 cm with >5 mitoses per HPF; or tumor rupture before or at surgery. Patients had significantly greater RFS and OS with 3 years adjuvant imatinib versus 1 year of treatment (Fig. 5). At 5-year follow-up, RFS and OS rates were 65.6 and 92.0 % in the 3-year arm versus 47.9 and 81.7 % in the 1-year arm (P < 0.001 and P = 0.02), respectively.13 Accordingly, NCCN guidelines now recommend at least 3 years of adjuvant imatinib treatment for patients with KIT-positive GIST who are at high risk of recurrence based on tumor size, MI, site, rupture, and completeness of surgery.14Fig. 5

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