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Risk Stratification and Prognostic Factors in GIST

Insights From: Robert Hans Ingemar Andtbacka, MD, CM, Huntsman Cancer Institute ; Anthony P. Conley, MD, The University of Texas MD Anderson Cancer CenterSyma Iqbal, MD, UCS Norris Comprehensive Cancer Center and Hospital
Published: Wednesday, Nov 11, 2015

The majority of gastrointestinal stromal tumors (GISTs) are sporadic tumors, although a fraction can be due to familial causes, comments Robert H. I. Andtbacka, MD. Families with inherited mutations in c-KIT (CD117) or overexpression of c-KIT may develop GIST. While it is uncommon for children to have GIST, those who are diagnosed generally have specific mutations that led to its development, notes Andtbacka.

It is important to determine whether the tumor is confined to one area or if it is multifocal or metastatic disease, says Anthony P. Conley, MD. The most common sites of disease typically involve the stomach, small intestine, and to lesser degrees, other areas of the gastrointestinal tract. GIST rarely occurs in the lungs or lymph nodes, adds Conley.

Risk stratification to help determine the prognosis of GIST depends on the size of the tumor, the location from which the tumor arises, and the mitotic rate, explains Syma Iqbal, MD. Patients with small bowel GIST have a higher risk of recurrence compared to patients with gastric GIST, for example, and tumors larger than 5 cm have a substantially higher risk of recurrence compared with those smaller in size. Patients with tumors 10 cm in size have a very high risk of recurrence, adds Iqbal.

Several nomograms are available to help determine the percentage of risk of recurrence in these patients. Patients with high-risk tumors tend to benefit from additional adjuvant therapy following surgical resection.

Evaluating the mutations that are present in the tumor can also be prognostic, and can help predict response to therapies, says Iqbal. Patients with exon 11 mutations tend to be more responsive to treatment with imatinib. Exon 9 mutations tend to be more aggressive and respond better to higher doses of imatinib, or sunitinib, states Iqbal.
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The majority of gastrointestinal stromal tumors (GISTs) are sporadic tumors, although a fraction can be due to familial causes, comments Robert H. I. Andtbacka, MD. Families with inherited mutations in c-KIT (CD117) or overexpression of c-KIT may develop GIST. While it is uncommon for children to have GIST, those who are diagnosed generally have specific mutations that led to its development, notes Andtbacka.

It is important to determine whether the tumor is confined to one area or if it is multifocal or metastatic disease, says Anthony P. Conley, MD. The most common sites of disease typically involve the stomach, small intestine, and to lesser degrees, other areas of the gastrointestinal tract. GIST rarely occurs in the lungs or lymph nodes, adds Conley.

Risk stratification to help determine the prognosis of GIST depends on the size of the tumor, the location from which the tumor arises, and the mitotic rate, explains Syma Iqbal, MD. Patients with small bowel GIST have a higher risk of recurrence compared to patients with gastric GIST, for example, and tumors larger than 5 cm have a substantially higher risk of recurrence compared with those smaller in size. Patients with tumors 10 cm in size have a very high risk of recurrence, adds Iqbal.

Several nomograms are available to help determine the percentage of risk of recurrence in these patients. Patients with high-risk tumors tend to benefit from additional adjuvant therapy following surgical resection.

Evaluating the mutations that are present in the tumor can also be prognostic, and can help predict response to therapies, says Iqbal. Patients with exon 11 mutations tend to be more responsive to treatment with imatinib. Exon 9 mutations tend to be more aggressive and respond better to higher doses of imatinib, or sunitinib, states Iqbal.
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