Abstract

Background: To evaluate the overall survival, disease free survival, clinicopathological characteristics and prognostic factors of patients with gastrointestinal stromal tumors (GISTs) who were treated at Faculty of Medicine Vajira Hospital.

Methods: A retrospective review data of 39 GISTs patients who underwent surgery at Vajira hospital from 2007 to 2011 was performed. The patient characteristics, overall survival, disease-free survival of patients and prognostic factors were evaluated.

Results: The median age of patients was 60 years (22-90 years), 54% were female and the main presenting symptom was abdominal pain (33%). Stomach (62%) and small intestine (30%) were the most common locations of tumor respectively. Complete resections (R0) were performed in 31 patients (80% ). All patients (100%) were positive for CD117 and 84.6% for CD34. According to the Armed Forces Institute of Pathology criteria, 56.4% of patients were characterized as a high risk. With a median follow-up time of 46 months (1-139 months). The overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. Two patients received Imatinib in neoadjuvant setting while 10 patients for disease control. Eight patients (20.5%) developed recurrences. R0 resection, mitotic figure and location of tumor were the significant prognostic factors.

Conclusions: The overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. R0 resection, mitotic figure and location of tumor were the significant prognostic factors.

Keywords: gastrointestinal stromal tumor; gists; prognostic factors; survival.

Citation: Keawmanee P, Kasetsermwiriya W, Sukhvibul P, Techapongsatorn S, Sirivongs N, Srimontayamas S. The long-term outcome of gastrointestinal stromal tumors treatment. Japanese J Gastroenterol Res. 2021; 1(4): 1016.

Introduction

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, accounting for 80% of all digestive mesenchymal tumors. It is widely accepted that GISTs arise from the interstitial cells of Cajal, and the term 'stromal tumor' was first introduced by Mazur and Clark in 1983 [1]. The incidence of GISTs has been reported ranging between 11 and 15 per million annually [2-4] and 60% of GISTs are located in the stomach, 30% in the jejunum or ileum, 5% in the duodenum and 4% in the colorectal. Extra gastrointestinal GISTs have been reported in the liver, omentum and mesentery [5].

The standard curative treatment of GIST is complete surgical resection with negative margin. The risk s of recurrence and metastasis depend on various factors including tumor location, mitotic rate, tumor size, and tumor rupture. [6] Armed Forces Institute of Pathology (AFIP) risk classification criteria are commonly used to predict the prognosis of GISTs [7-8]. Previous reports have shown 5-year survival rate of GISTs varies from 48% to 92.1% [1-9].

The objectives of this study are to evaluate the overall survival, progression free survival, clinicopathological characteristics and prognostic factors affecting patient's survival with gastroKeywords intestinal stromal tumors (GISTs) at Faculty of Medicine Vajira Hospital.

Material and methods

From January 2007 to December 2011, 45 patients diagnosed with GIST and treated at Vajira hospital. Patients were followed up and enrolled into the database of the department of Surgery. Demographic data of the patients including clinical presentation, extent of disease and the prior treatment before patients were treated at Vajira Hospital were recorded. Tumors were categorized as primary, metastatic, or local recurrent disease. The histologic diagnosis of all tumors was confirmed by members of the pathology department at Vajira Hospital. There were 3 patients who were under 18 years old, 2 patients did not receive surgery and 1 patient had surgery at other hospital, these were excluded from this study. Finally, total of 39 patients were enrolled for analysis.

Tumor size was recorded by using the largest diameter in any dimension of the primary tumor and was stratified as <10 cm, or >10 cm. Margins of resected specimens were analyzed for the presence of microscopic disease. The surgeons at Vajira Hospital share a treatment philosophy of GIST which emphasizes the complete gross removal of the tumor. Resections are classified as incomplete or complete. Incomplete resection is considered when the tumor is unresectable at exploration or gross residual of the disease is present after resection. Complete resection is considered when all gross tumor were resected, regardless of microscopic margins. Resection of metastases is performed in selected patients in whom the primary tumor is controlled.

Statistical analysis

Categorized variables were summarized as percentage. Continuous variables were summarized as median. Analysis of cumulative disease free survival and cumulative survival was performed by Kaplan meier analysis. A log rank test was used for univariate analysis. P value <0.05 were considered statistically significant. All statistical analyses were perform using SPSS software version 24.0 (IBM Corp., Armonk, NY, USA).

Results

Clinicopathological characteristics

As shown in Table 1 and 2, total of 39 patients with GISTs were analyzed in the present study. Of all the patients, 18 (46%) were male, and 21 (54%) were female. The median age of the patients was 60 (range, 22–90) years at the time of GIST detection. Stomach was the most common site, accounting for 61% of cases, followed by the small intestine (31%), colorectum and anus (5%), and retroperitoneum (3%). Abdominal pain, abdominal mass and gastrointestinal bleeding were the main presenting symptoms, reported in 33, 23 and 18% of the patients, respectively. The median tumor size was 7 (0.4–60) cm. All of which, 25 (64.1%) <10 cm, 14(35.9%) greater than 10cm. All patients were tested positive for CD117 and 86.4% for CD 34. Most patients, 23 case (59%) had tumor of low mitotic rate (<5 mitoses per 50 HPFs). The histological subtypes included spindle 89.7%, epithelioid or mixed 10.3%. When classified according to Armed Forces Institute of Pathology classification, 2 patients (5.1%) were classified into the very low-risk group, 5 (12.8%) into the low-risk group, 10 (25.6%) into the intermediate-risk group, and 22 (56.4%) into the high-risk group.

Oncologic outcome and recurrence

Twenty nine patients (74%) underwent open surgery and 10 patients (26%) underwent laparoscopic surgery. Complete resection (R0) was accomplished in 31 case (80%), R2 or tumor rupture was 12.3% and R1 resection 7.7%. Two patients (0.78%) had postoperative intra-abdominal collection complications. The average length of stay was 11.5 days (3–73 day).

Imatinib was administered in 10 patients who had incomplete resection, tumor rupture, recurrence or metastasis as an adjuvant therapy, 2 of which were treated as neoadjuvant imatinib therapy. Imatinib were given for a median time of 53 months (19-87 months) at a daily dose of 400 mg. 1 patient developed abnormal liver function. The remaining high-risk cases or cases that should be receiving neoadjuvant therapy but refused imatinib were mainly due to the high cost of the treatment, which was not covered by health insurance or private funding.

In survival analysis based on the 39 GISTs patients, The overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively (Figure 1). A total of 8 patients developed liver metastases or local recurrence during follow-up show as Table 3. The results of the univariate analysis of potential prognostic factors are presented in Table 4. Complete resection (R0), tumor location at stomach and less mitotic figure (<5 mitoses per 50 HPFs) are contributed toward good survival (OS and DFS; P<0.05). However, sex, histological cell type , tumor size and risk category had no significant (OS and DFS; P>0.05).

Figure 1:5-year Overall survival and disease free survival curves.

Table 1: Patients' characteristics.

Table 2: Pathological characteristics.

Table 3: Characteristics of recurrent patients.

Table 4: Univariate analysis of the prognostic factors.

Discussion

This retrospective study, based on 39 patients with GIST, aimed to investigate the clinicopathological and prognostic characteristics of this disease. The results are comparable with those of previous studies in other populations [15-19]. The stomach was the most common site of tumor origin in this series. The distribution of sites was similar to that published in 1965 by Skandalakis [20]. Joensuu et al [21] pooled individual data from 3,067 patients and reported similar demographics of GISTs. They found that GIST patients had a slight female predominance with the median age of 60 years at the time of GIST detection. In addition, a review from Miettinen et al reported that the median age in the major series varied between 60–65 years [22].

Furthermore, positive immunohistochemistry staining for CD117 was 100%, which is supported by the previously study [23]. Radical tumor resection is the most important factor affecting patient prognosis. Furthermore, non-gastric disease location, higher mitotic rate and tumor metastasis or local invasion prior to treatment were revealed to be predictors of a poor prognosis [31-34]. There are no standard criteria for assessing the aggressive behavior and predicting the clinical prognosis of GISTs, although the NIH and AFIP criteria are widely use [7,8]. It is commonly accepted that all GISTs are considered to have malignant potential. Through univariate analysis, higher mitotic rate , non gastric location and incomplete resection or tumor rupture are associated with poor survival for GIST patients. Similarly, the British study [24] identified high mitotic index as an independent poor prognostic factor, and non-gastric disease location is associated with tumor recurrence, which is consistent with the results of previous studies [21]. Large tumor size is considered to be a prognostic factor in the NIH and AFIP risk classification criteria [16,18]. However, it is not an independent risk factor in the present study.

For resectable localized GISTs, radical surgery with clear margins without lymphadenectomy is the standard and forefront of curative treatment [25,33]. Radical tumor resection significantly improves survival and reduces risk of tumor recurrence [33]. Various surgical approaches, including open and laparoscopic surgery were performed in the present study. There was no significant difference in OS or DFS among these surgical strategies. Several studies comparing the effect of minimally invasive and open surgery in the treatment of GISTs were performed [25]. The results are generally accepted that minimally invasive surgery has similar or superior peri-operative outcomes [3,13] without compromising the oncological outcomes; it may also be safely applied for larger tumors or tumors located in unfavorable sites. Imatinib has an important role in the treatment of advanced GISTs and was used in the adjuvant setting to reduce the risk of recurrence and metastasis [26-34]. Recently, imatinib treatment as adjuvant therapy for patients with intermediate-to-high risk GIST are recommended [33,34]. However, there was no observed improvement in OS and DFS in the 10 patients with advance disease who received adjuvant imatinib therapy in our study. The possible reason is limited sample size. Imatinib was also administered to patients with incomplete resection and those with disease progression. Despite of the treatment, advanced disease will inevitably progress and associated with lower the OS and DFS rates.

With the median follow-up time of 46 months (1-139 months), the overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively ; which is higher than the results of DeMatteo et al, who reported 54% survival at 5 years in a group of 200 patients encountered during 16 years [13]. These results are similar to those published previously, which reported 5 year survival rates of 48% to 92.1% [9-14].

There were certain limitations to this study: The study design was retrospective; the selection of surgical approach and adjuvant therapy were not randomized, the use of imatinib was limited to 10 patients with a potential selection bias due approved indication for adjuvant treatment problem which is not covered by the universal health insurance system in Thailand. Only recurrence or metastasis disease that can be reached to therapy. Therefore, the benefit of using imatinib as adjuvant therapy cannot be evaluated based on this study.

Furthermore, the benefit of imatinib treatment for intermediate or high risk patients needs to be verified.

Conclusion

The findings of this retrospective review of 39 cases of GISTs at a single center showed, the overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. R0 resection, mitotic figure and location of tumor were the significant prognostic factors.

The findings of this retrospective review of 39 cases of GISTs at a single center showed, the overall survival and disease-free survival at 5 years were 84.6% and 66.7%, respectively. R0 resection, mitotic figure and location of tumor were the significant prognostic factors.

Disclosure statement: All authors declare that they have no conflict of interest.

Ethical approval: Committee on Human Rights Related to Research Involving Human Subjects, Faculty of Medicine, vajira Hospital, Navamindradhiraj University. Protocol Number: ID 086/61.

Author contribution: The authors confirm contribution to the paper as follows: study conception and design: Putticha Keawmanee, Wisit Kasetsermwiriya, Suphakarn Techapongsatorn; data collection: Putticha Keawmanee; analysis and interpretation of results: Wisit Kasetsermwiriya, Putticha Keawmanee; draft manuscript preparation: Putticha Keawmanee, Wisit Kasetsermwiriya, Suphakarn Techapongsatorn, Nathan Sirivongs. All authors reviewed the results and approved the final version of the manuscript.

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