(P 078) GASTROINTESTINAL STROMAL TUMOURS (GIST) AND RISK OF SECOND NEOPLASMS. INCIDENCE RATE ANALYSIS

Objective: Gastrointestinal stromal tumours (GIST) are the most common sarcomas of the digestive tract. Most of these tumours appear in isolation. There are three syndromes in which GIST can be associated with other tumours: type 1 neurofibromatosis (Von Recklinghausen's disease), Carney's triad, and familial GIST syndrome. The coexistence of a GIST with other tumours outside these syndromes has been described in 4.5% –40% cases.
A recent systematic review estimated an incidence of associated tumours of 20.4%. The most frequently associated are digestive carcinomas (37.9%) followed by genitourinary (22.4%), haematological (6.2%), lung (5.4%) and breast (4.6%) tumours.
Knowing the incidence and type of these second neoplasms could help to establish early diagnostic measures in the follow-up of these patients, but only three studies have addressed this issue.
In addition to the scarcity of studies specifically addressing this issue, most have been clinical cases or series of cases in which there was great variability regarding the observed incidence of second neoplasms, as well as the type and site of the associated tumour.
The objective of this study was to analyse the incidence rates of these second neoplasms and compare them with those of the general population in a series of patients identified in a closed population setting with the diagnosis of GIST and with other associated tumour types, in order to characterize this association quantitatively and qualitatively, so that early diagnostic measures can be proposed.

Methods: We performed a retrospective observational study of patients diagnosed with GIST in whom second neoplasms were identified at the Department of Mesenchymal Tumors-Sarcomas, “La Arrixaca” Clinical University Hospital.
The diagnosis of GIST was established in patients with digestive tumours of mesenchymal origin with compatible histology that were immunohistochemically positive for CD 117. In suspected cases of GIST by histology that were negative for CD117, positivity for DOG-1 was considered for diagnosis.
For the diagnosis of associated neoplasia, the Warren criteria were followed: both tumours must be confirmed as malignant and with different histology; they must be separated by areas of normal mucosa and without connection at the submucosal level; and the possibility that one is a metastasis of the other must be excluded.
The tumour frequencies and types associated with GIST in our series were compared with those observed in the general population, based on data provided by the Murcia Region Cancer Registry (RCRM).
The incidence rates (number of new cases diagnosed per 100,000 inhabitants-year) were obtained according to the location of the tumour and sex, based on data from the RCRM and the International Agency for Research on Cancer of the World Health Organization.
Once the incidence rates of both groups (general population and series studied) were obtained, the ratio of the incidence rates of these groups was calculated.
All analyzes were performed using the Statistical Package for Social Sciences version 22.0 (SPSS Inc., Chicago, IL, USA).

Results: A total of 104 patients with the diagnosis of GIST were identified, of which 32 were diagnosed with at least one other different primary neoplasm (30.7%). In 8 cases the associated neoplasia was diagnosed before GIST (metachronous GIST), with a median time between both diagnoses of 52.5 months. On 14 occasions, the diagnosis of both neoplasms was synchronous. Finally, in 12 cases, the associated neoplasia was diagnosed after GIST, with a median time of 49 months. According to the temporal classification, GISTs with associated neoplasms were type 1s in 1 case (2.9%); 1m in 12 cases (35.3%); 2s in 13 cases (38.2%); and 2m in 8 cases (23.5%).
The most frequently associated neoplasms were those located in the digestive tract with 9 cases (26.4%), followed by those located in the genitourinary system (23.5%). Haematologic malignancies consisted of 1 chronic myeloid leukaemia, 1 large B-cell lymphoma, 1 promyelocytic leukaemia, and 1 thyroid Non-Hodgkin lymphoma.
A total of 85.7% of the tumours synchronous to GIST were tumours of the digestive system; after a diagnosis of GIST, the most frequent tumours were genitourinary (46.2%) followed by haematological (30.8%). A preferential location was not observed in the case of neoplasms before GIST, the most frequent tumours being breast (25%) and larynx (25%).
Incidence and incidence rate ratio
Most of the associated neoplasms in our series have an IRR that shows a higher risk of appearing in patients with GIST compared to patients without GIST. Among all of them, prostate neoplasms stand out (IRR = 8.62) followed by, lymphomas (IRR = 103.09), pancreatic neoplasms (IRR = 11.41), laryngeal tumours (IRR = 9.66) and connective tissue tumours (IRR = 40).
A statistically significant increase in the risk of presenting other neoplasms was observed in both men and women, with an IRR of 2.42 and 2.05, respectively.

Conclusion: The risk of development of associated neoplasms in GIST patients is increased, which has important prognostic and management implications for these patients. The early diagnosis of these neoplasms must be achieved based on follow-up and directed postoperative control. Larger epidemiological studies are needed in order to confirm these results and elucidate a potential common aetiopathogenic basis.