Results from the inaugural clinic

Results from the inaugural Pediatric GIST clinic

Prior to arriving at the NIH, patients were requested to forward the entirety of their medical histories. This included clinic notes, laboratory studies, operation reports, pathology reports, radiology reports and copied images of all scans. Thousands of pages of documents were received and reviewed by physicians in the Pediatric Oncology Branch. Hundreds of radiographic scans arrived and were viewed by an oncologist in conjunction with a radiologist. Dozens of pathology reports and slides were examined by GIST team members and pediatric pathologists.

Twenty-one patients began the registration process, of which 14 were seen in the inaugural clinic.

Our patients included 10 females and 4 males (71% female)

Average age of patients	21.5 years (youngest is 11 and oldest is 39)
Age at the time of first symptoms	15.1 years (youngest was 9 and oldest was 21)
Age at the time of diagnosis	16.4 years (youngest was 9 and oldest was 22)
Time since diagnosis	5.1 years (shortest is 1 and longest is 15)

9 of 14 patients have Pediatric GIST (age less than or equal to 18 at the time of diagnosis)

Comparison between Pediatric versus Wildtype GIST patients

Pediatric patients

Average age of patients	18.1 years (youngest is 11 and oldest is 23)
Age at the time of first symptoms	12.8 years (youngest was 9 and oldest was 18)
Age at the time of diagnosis	13.9 years (youngest was 9 and oldest was 18)
Time since diagnosis	4.2 years (shortest is 2 and longest is 6)

Wildtype patients

Average age of patients	27.6 years (youngest is 22 and oldest is 39)
Age at the time of first symptoms	20.6 years (youngest was 20 and oldest was 22)
Age at the time of diagnosis	21.0 years (youngest was 20 and oldest was 22)
Time since diagnosis	6.6 years (shortest is 1 and longest is 15)

Gene Testing

11 of 14 patients had sequencing of their tumor samples and all 11 were wildtype for KIT and PDGFRA.

We have made arrangements to sequence the remaining three samples.

Dr. Constantine Stratakis has been studying the role of the succinate dehydrogenase (SDH) gene in patients with GIST and paragangliomas.

All of the patients who attended the inaugural clinic consented to have DNA testing to look for mutations in the SDH gene. Blood samples were collected and are currently being analyzed. A summary of these results may be available on this website, following the 2nd Pediatric and wildtype GIST clinic in January 2009.

First Symptoms

Pediatric patients

Fatigue and Anemia	4 patients
Abdominal pain	2 patients
Pain and Anemia	1 patient
Pain and Visible mass	1 patient
Vomiting and Visible mass	1 patient

Wildtype patients

Fatigue and Anemia	2 patients
Abdominal pain	1 patient
Pain and Dizziness	1 patient
Gastrointestinal bleeding	1 patient

There was no difference in the type of first symptoms between pediatric and wildtype patients

Tumor Characteristics

Location:	Isolated to the Stomach	9
	Stomach and Abdomen	2
	Retroperitoneum and Abdomen	1
	Multiple locations	2

Focality	Single nodule	3
	Multiple nodules	11

Metastatic	Yes	6
	No	8

Imaging Modality

4 patients	CT
9 patients	PET/CT
1 patient	MRI to monitor liver lesions

Preliminary results in other patients have revealed that PET changes may not accurately reflect changes in pediatric GIST tumors. PET should be used as an adjunct, but treatment decisions should be based solely on CT results.

The imaging studies that we received from the 14 participants of the inaugural Pediatric GIST clinic revealed that there were a few patients who showed fast progression. However, the vast majority of patients had very slow progression. Currently, we are measuring the size of each tumor on every scan, to be able to determine the rate of growth of the tumor, after which we will correlate this growth rate with clinical parameters.

However even now, we have enough evidence to say that for the majority of patients, imaging performed every three months is not necessary. The majority of tumors grow slow enough that the interval between scans should be increased. We suggest that following the initial diagnosis the first follow-up scan should be performed at a time no later than 3 months.

First follow-up scan	no later than 3 months	If there is growth of the tumor
Subsequent scans may be performed every 3 months or earlier

First follow-up scan	no later than 3 months	If there are no major changes
Second follow-up scan	at 4 months	If there are no major changes
Third follow-up scan	at 6 months	If there are no major changes
Subsequent scans may be performed every 6 months

Following the completion of our growth rate measurement study, we may be able to provide further recommendations on the suggested interval between imaging studies.

Patterns of Recurrence

Recurrence in All Patients

Nine of 14 patients had their original tumors completely removed by surgery. All were located in the stomach. Three patients continue to have no evidence of tumor at 16, 18 and 33 months. One patient was initially misdiagnosed and was told that follow-up was not necessary. Twelve years later, this patient again had stomach pain, at which time, imaging revealed recurrence of GIST. Five patients had their disease return after 22, 24, 38, 41 and 45 months (average of 34 months). Imaging studies resulted in the diagnosis, prior to any symptoms, in four of the five cases. Also four of the five patients did not receive any therapy after the initial surgery. One patient was treated with Imatinib for one year, and then stopped with no evidence of tumor at that time.

Site of recurrence: stomach (3), liver (2), lymph node (1)

Recurrence in Pediatric Patients

In the inaugural GIST clinic, there were nine pediatric patients. Three patients never achieved complete removal of the primary tumor. Four patients recurred following full resection after 22, 24, 38 and 41 months (average of 31 months). Two patients had complete surgical removal and after two years, they are free of tumor.

Site of recurrence: stomach (3), liver (1)

Treatment

3 patients currently have no evidence of tumor and are not on therapy
5 patients currently have a measurable tumor and are not on therapy

2 patients are on Imatinib	12 patients total have received Imatinib
1 patient is on Sunitinib	7 patients total have received Sunitinib
2 patients are on Nilotinib	4 patients total have received Nilotinib
1 patient is on Dasatinib	1 patient total has received Dasatinib
	3 patients total have received other agents

12 of 14 patients received some therapeutic agent (27 total)

The data presented below is a summary of patients on who have been treated with tyrosine kinase inhibitors. It excludes patients who have received an agent for less than six months. Also, the doses that patients received have varied.

Imatinib
2 patients appear to have slowing of progression of disease on Imatinib (currently 16 and 21 months).
2 patients with complete resection stopped (17 and 29 months), due to lack of data on the optimal duration of therapy.
1 patient discontinued Imatinib due to intolerance (6 months).

Sunitinib
1 patient with a second recurrence in the stomach has stablization on Sunitinib (currently 24 months).
3 patients progressed (6, 8 and 9 months.
1 patient discontinued Sunitinib due to intolerance (6 months).
1 patient had stabilization (22 months), but discontinued in order to monitor tumor status off therapy.

Nilotinib
2 patients with progressive disease have recently started Nilotinib (currently 2 and 7 months).
1 patient had stable disease (8 months), but then had abdominal complications possibly related to Nilotinib and discontinued use.

Dasatinib
1 patient who progressed through all three of the above tyrosine kinase inhibitors has recently started Dasatinib.

This page of the website will not be updated. The data presented above refer solely to the patients who attended the inaugural clinic.

Subsequent sections in this website will provide detailed updated information for all of the parameters described above.