Pediatric GIST
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More about the different types of pediatric GIST - Pediatric GIST | Carney's Triad
"True" Pediatric GIST
Background/incidence
Biology
Diagnosis and monitoring
Treatment
Background/incidence
Gastrointestinal stromal tumors (GISTs) belong to a group of cancers called soft tissue sarcomas. Sarcomas are a rare type of cancer that can occur in connective tissues, bones, muscles, fat, nerves, blood vessels, and cartilage. Sarcomas are derived from the general class of cells known as "mesenchymal cells".
Although the exact incidence is still somewhat unclear, it is now estimated that, in the United States, between 5,000 and 10,000 people each year develop GISTs. GISTs occuring in young patients (under age 18) is much rarer, occuring in perhaps 1% to 2% of all GIST patients1, 2.
Biology
Pediatric GIST has been considered to be a subset of adult GIST. There are however, important differences between adult GIST and pediatric GIST. At a historic meeting at the 2004 Connective Tissue Oncology Society (CTOS), a working definitition was developed. Pediatric GIST is now described as GISTs having a first occurence in patients less than 18 years of age.
 |
| Pictured at the first international pediatric GIST meeting clockwise from lower right are part of the group: Jaap Verweij (back to camera), Tricia McAleer, Cristina Antonescu, David Josephy, Karen Albritton, George Demetri, Alberto Papo, Dick Singleton and Daniel Stepan. |
Pediatic GIST is much more common in girls than in boys. It usually occurs between the ages of about 6 and 18, but a few cases of GISTs have occurred in younger patients (see neonatal GIST). Pediatric GIST typically occurs in the stomach (adult GIST can occur throughout the digestive tract). The table below describes the differences typically seen between adult GIST and pediatric GIST.
| Typical differences between adult and pediatric GIST | |
|---|---|
Adult |
Pediatric |
| Affects males slightly more than females | Affects females much more often than males |
| Can start anywhere in the GI tract (and elsewhere in the abdomen) | Usually starts in the stomach |
| Starts at a single tumor site | May present with multiple stomach tumors (not metasases). This is often described as "multifocal" or "multinodular" |
| Rarely metastasizes to the lymph nodes | Lymph node metastasis are more common |
| Faster growing; more aggressive | Slower growing; less aggressive |
| Tumor cells usually have a spindle shape | Tumor cells usually have an epetheloid shape (more rounded and similar to the shape of other, non-sarcoma cancers) |
| Has a high response rate to the current first-line drug treatment, Gleevec | Has an undefined; but generally believed to be lower, response rate to Gleevec. |
| Typically has mutations in either KIT or PDGFRA genes | Typically does not have KIT or PDGFRA mutations. There are excepts to this however (especially in boys) and mutational testing is available. |
Diagnosis and Monitoring
The most common symptoms of pediatric GIST are:
- Anemia and other symptoms related to bleeding (such as blood in the stool). In one series of 6 patients, all presented with iron-deficient anemia3.
- Abdominal pain or abdominal mass4
As in adult GIST, prior to about 2000, pediatric GIST patients may have previously been diagnosed with leiomyosarcoma, leiomyoma, leiomyoblastoma, or GANT. As understanding of the biology of GIST increased, it was recognized that many tumors in these other categories were actually GISTs.
Risk Assessment
Pediatric GISTs behave differently than Adult GISTs. Pediatric GIST may present with one or multiple tumors in the stomach (multi-focal). A tumor that is removed surgically may recur, either near the original site (a local recurrence) or at a distant site such as the liver. Local recurrences in the stomach may be a single tumor or multiple stomach tumors. When a tumor recurs at a distant site it is called a metastases.
The risk of recurrence in adults with GIST has been fairly well defined. Two factors, size of the primary tumor and rate of growth, (measured by the mitotic rate) are the primary factors that affect the risk of recurrence in adults. In pediatric GIST however, work done at the U.S. Armed Forces Institute of Pathology (AFIP), suggests that these factors probably do not accurately predict the risk of recurrence in pediatric GIST. The table below is probably one of the most complete risk comparisions between adult GIST and pediatric GIST.
|
||
|---|---|---|
|
(%) of Patients With Metastases in the Group |
||
Prognostic Group and Definition |
Children and Young Adults |
All Gastric GIST Patients |
| 2 (≤5 cm, ≤5/50 HPF) | 1/6 (17%) |
6/320 (2%) |
| 3A (5 ≤10 cm, ≤5/50 HPF) | 2/7 (28%) |
8/229 (3%) |
| 3B (> 10 cm, ≤5/50 HPF) | 1/2 (50%) |
17/140 (12%) |
| 5 (>2 ≤5 cm, >5/50 HPF) | 1/7 (14%) |
16/99 (16%) |
| 6A (>5 ≤10 cm, >5/50 HPF) | 3/5 (60%) |
52/96 (54%) |
| 6B (>10 cm, >5/50 HPF) | 2/3 (67%) |
89/108 (82%) |
Note: Only cases with follow-up and defined tumor size are included. Gastrointestinal Stromal Tumors of the Stomach
in Children and Young Adults |
||
Treatment
It is important to find doctors experienced in GIST. This experience comes in two basic types; experts in pediatric cancers and experts in adult GIST cancer. Both have unique perspectives and experiences. The best approach might be when doctors from both fields collaborate with each other. See Consolidating Resources
Surgical removal of the tumor(s) has historically been the primary treatment for pediatric GIST1,2,3,4. The types of operations have historically varied from a simple local excision to a total gastrectomy 2. In some cases, surgery provides long-term relief. In other cases, tumors return, either locally (near the original site, such as another stomach tumor(s)), or distant from the original site (metastases).
Recently, dramatic success has occurred in the treatment of adults with metastatic or inoperable GISTs (in cases where surgery is not possible). The genetic defects that cause adult GIST (KIT and PDGFRA mutations) can now be targeted with a drug called Gleevec® (also known as imatinib and Glivec®). While this drug (and a second generation inhibitor, Sutent®) is very effective in adult GIST, the vast majority of pediatric GISTs do not have the same types of mutations. Response data is limited, but the early ancedotal indications are that Gleevec is not as effective in pediatric GIST as it is in adult GIST. Some very preliminary data (3 patients reported at the 2006 American Society of Clinical Oncologists (ASCO) meeting) show some activity for Sutent 5.
1. Gastrointestinal Stromal Tumors
in Children and Young Adults.
A Clinicopathologic, Molecular, and Genomic Study
of 15 Cases and Review of the Literature. J Pediatr Hematol Oncol Volume 27, Number 4, April 2005. Sonam Prakash, MD, Lisa Sarran, MS, Nicholas Socci, PhD,
Ronald P. DeMatteo, MD, Jonathan Eisenstat, MD, Alba M. Greco, MD,
Robert G. Maki, MD, PhD,{ Leonard H. Wexler, MD,k Michael P. LaQuaglia, MD,
Peter Besmer, PhD, and Cristina R. Antonescu, MD
2. Gastrointestinal Stromal Tumors of the Stomach
in Children and Young Adults
A Clinicopathologic, Immunohistochemical, and Molecular
Genetic Study of 44 Cases With Long-Term Follow-Up
and Review of the Literature.
Am J Surg Pathol Volume 29, Number 10, October 2005
Markku Miettinen, MD,* Jerzy Lasota, MD,* and Leslie H. Sobin, MD†
3. Clinical and Molecular Characteristics of Pediatric Gastrointestinal Stromal Turmos (GISTs)
Victoria E. Price, Maria Zielenska, Susan Chilton-MacNeill, Charles R. Smith and Alberto S. Pappo
Pediatr Blood Cancer
4. Pediatric Gastrointestinal Stromal Tumors and Leiomyosarcoma
The St. Jude Children's Research Hospital Experience and a Review of the Lieterature
CANCER July 1, 2004 / Volume 101 / Number 1
5. Sunitinib treatment of pediatric metastatic GIST after failure of imatinib
K. A. Janeway, D. C. Matthews, J. E. Butrynski, G. Z. D'Amato, S. Agresta, C. Garrett, C. L. Corless, K. H. Albritton, G. D. Demetri
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 9519
