Non-gastric Gastrointestinal Stromal Tumors Research Articles

Is lymph node metastasis an event indicating an advanced gastrointestinal stromal tumor?

754 Background: The clinicopathological features and prognosis of gastrointestinal stromal tumors (GISTs) with lymph node metastasis remain controversial owing to their low incidence. A multicenter retrospective cohort study was conducted to compare the clinicopathological features and oncologic outcomes of GIST with and without lymph node metastases. Methods: The medical records of patients with GISTs in 16 large medical centers in China from January 2014 to December 2020 were reviewed. Patients were divided into three groups: no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis. Propensity score matching (PSM) was performed to reduce confounding factors. Results: A total of 1109 cases of primary GIST were included in this study, comprising 607 males (54.7%) and 502 females (45.3%), with a mean age of 56.6±11.9 years. There were 1024 patients (92.3%) with no lymph node metastasis after surgery, and 85 patients (7.7%) had lymph node metastasis. Compared to that in GIST without lymph node metastasis, the proportion of non-gastric GIST was higher in GIST with lymph node metastasis (52.9% vs. 40.7%) with a larger tumor diameter (>10 cm: 36.5% vs. 18.1%) and more patients with distant metastasis (11.8% vs. 3.5%). Tumor location not in the stomach, the largest tumor diameter, and distant metastasis were independent risk factors for GIST with lymph node metastasis (all P < 0.05). After PSM, 96, 48, 24 patients comprised no metastasis, lymph node metastasis without distant metastasis, and distant metastasis without lymph node metastasis, respectively. The relapse-free survival (RFS) of the lymph node metastasis group was comparable to that of the distant metastasis group without lymph node metastasis ( P = 0.368) and significantly inferior to that of no metastases ( P = 0.042). Conclusions: The prognosis of patients with GIST with lymph node metastasis was comparable to that of patients with distant metastasis and significantly worse than that of patients without metastasis. Lymph node metastasis may be an advanced event in GIST.

Laparoscopic vs Open Treatment for Gastric and Non-Gastric Gastrointestinal Stromal Tumors: a Two-Center Experience.

We retrospectively reviewed the medical records of 109 patients who underwent curative laparoscopic or open resection for different types of gastrointestinal stromal tumors (GIST). Only primary GIST patients who did not receive preoperative chemotherapy or oral imatinib treatment were included in the analysis. We divided the patients into 2 groups according to the surgical approach:a laparoscopic group (LAP) and a laparotomic group (OPEN). Our aim was to confirm the feasibility and safety of laparoscopic surgery for GISTs that differed in size and location, and to assess its long-term oncologic outcome in terms of overall survival (OS) and disease-free survival (DFS). Furthermore, we performed a surgical short-term outcome analysis. The two groups did not differ with respect to age at operation, gender, BMI or comorbidities. Even the NIH and AFIP risk classifications were not significantly different between the two groups. Furthermore, in our analysis, there was no significant difference in mean tumor size or location between the two groups. Wedge resection was the most frequently performed procedure. The conversion rate was 7.8%. The operative time was 194.75 (60- 350) min for the open group and 181.70 (57-480) min for the laparoscopic group. Our data clearly indicated that the long-term oncologic outcome and DFS of laparoscopic resection were not inferior to those of traditional open operations and laparoscopic resection was still feasible in cases with large tumors: the median size of the tumor was 4.5 cm (3-25) and the tumor was larger than 4.5 cm in 47.7% of the cases in the LAP group. With regard to short-term outcomes, our study demonstrated that the LAP group had fewer complications, faster gastrointestinal recovery, reduced use of analgesic drugs and shorter postoperative hospital stay (each p<0.05). In conclusion, our experience confirms that GISTs are very uncommon cancers for which the prognosis is closely related to size, localization and class of risk. In light of our clinical data, laparoscopic resection for gastric and non-gastric GISTs is a safe, feasible and oncologically correct procedure. The most important advantage of this technique is that it ensures a better postoperative outcome compared with open surgery, without worsening the prognosis.

Endoscopic resection for the treatment of non-gastric gastrointestinal stromal tumors: A retrospective study from a large tertiary hospital in China

Background and aimsFew studies on endoscopic resection (ER) for the treatment of non-gastric gastrointestinal (GI) stromal tumors (GISTs) have been conducted, and most have been case reports or case series. The aim of this study was to evaluate the effectiveness and safety of ER for non-gastric GISTs. MethodsFrom January 2010 to December 2022, 329 patients who were diagnosed with GISTs underwent ER. After excluding 302 patients with gastric GISTs, we retrospectively assessed the data of 27 patients with non-gastric GISTs. The main outcome measures were en bloc resection, complete resection, residual disease, recurrence, and complications. ResultsA total of 15(55.6%) females and 12(44.4%) males with a mean age of 53.8 ± 11.0 years were assessed. There were 19 (70.4%) GISTs in the esophagus, 2 (7.4%) in the duodenum, 3 (11.1%) in the colon and 3 (11.1%) in the rectum. The median tumor size was 12.0 mm (range 4.0–35.0 mm). Most of the GISTs (20, 74.1%) were very low risk, and the remaining 7(25.9%) were low risk. Both en bloc resection and complete resection were achieved in 25(92.6%) patients. Piecemeal resection mainly resulted from a larger tumor size, an irregular shape, and an extraluminal growth pattern. No residual disease or recurrence was noted during the follow-up period. The median operation time was 23 min (range 2–125 min). After excluding the operation time of EER, the operation time was prolonged to 37 min (range 12–125 min). Only one patient experienced mild abdominal pain, leading to a complication rate of 3.7%. No severe complications requiring for surgical interventions occurred. ConclusionER was an effective and safe method for non-gastric GISTs in selected cases. GISTs of a small size and regular shape with an intraluminal growth pattern require complete resection.

Neoadjuvant versus adjuvant imatinib in primary localized gastrointestinal stromal tumor.

The effect of neoadjuvant therapy (NAT) with imatinib versus upfront resection (UR) followed by adjuvant therapy (AT) with imatinib on the outcomes of gastrointestinal stromal tumors (GIST) is unknown. This is a retrospective study at a high-volume center. All the patients with primary localized GIST were identified in a hospital database from 2007 to 2021. The endpoints included local recurrence-free survival (LRFS), distance recurrence-free survival (DRFS), and overall survival (OS). Cox regression was used to perform multivariate survival analyses. The sensitivity analysis was conducted with the inverse probability of treatment weighting (IPTW) method. A total of 211 patients were included (Group A: UR + AT, n=140; Group B: NAT + resection + AT, n=71). In the entire cohort, 5-year DRFS, LRFS, and OS were 85.6%, 90.7%, and 92.5%, respectively. In the multivariate analysis, better DRFS was linked to NAT, tumor size of 5 cm, and AT. Sixteen patients (11.4%) in Group A and 1 (1.4%) in Group B had distant recurrences after AT discontinuation. The sensitivity analysis by IPTW provided approximately similar results. An interaction effect was observed between NAT and tumor location on DRFS. In non-gastric GISTs, NAT was associated with better DRFS [hazard ratio =0.131, 95% confidence interval (CI): 0.017-0.989, P=0.049], which was not the case in gastric GIST (P=0.08). NAT was not independently associated with LRFS or OS. When compared to UR + AT, NAT + resection + AT may reduce the risk of distant recurrence in localized GIST and may be especially beneficial for patients with non-gastric GISTs.

Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

Factors affecting clinical outcomes in women with non-gastric gastrointestinal stromal tumors

ObjectiveThe clinical presentation of non-gastric GISTs might mimic adnexal cancer, and non-gastric GIST might be managed and treated by gynecologists. Knowledge of the clinical outcomes of women with non-gastric gastrointestinal stromal tumors (GISTs) is important. Our aim is to elucidate the factors affecting the clinical outcomes of women with non-gastric GISTs. Materials and methodsBetween January 2000 and October 2019, all consecutive women with non-gastric GISTs who underwent surgery in a tertiary referral center were reviewed. ResultsTwenty-six women were reviewed. Eight (31%) women experienced recurrence. The probabilities of recurrence-free survival (RFS) at 60 and 120 months were 65.2% and 55.9%, respectively. The probabilities of overall survival (OS) at 60 and 120 months were 71.1% and 63.9%, respectively. Cancer stage was the only independent predictor of RFS (hazard ratio = 6.00, p = 0.007) and OS (hazard ratio = 3.88, p = 0.04). However, excluding cancer stage, metastasis (hazard ratio = 8.74) was the only independent predictor of RFS, and tumor size (hazard ratio = 1.20) and metastasis (hazard ratio = 6.03) were independent predictors of OS. Tumor size ≥13.9 cm was the optimum cut-off value to predict death and had an area under the receiver operating characteristic curve of 0.75 (95% confidence interval = 0.53 to 0.98). Among the above 5 women with non-gastric GISTs admitted to the Gynecology Department, optimal debulking surgery was performed in two women, and small bowel resection was performed in three women; and all five women remained alive without disease. ConclusionNon-gastric GISTs may mimic gynecologic tumors. Metastasis was an independent predictor of PFS. In addition, metastasis and large tumor size (especially ≥13.9 cm) were independent predictors of OS in women with non-gastric GISTs.

Clinical and Prognostic Significance of Tumor-Infiltrating CD8+ T Cells and PD-L1 Expression in Primary Gastrointestinal Stromal Tumors.

PurposeImmunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs.MethodsA total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan–Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model.ResultsThere were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs.ConclusionsPD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.

Preoperative adjuvant therapy for locally advanced and recurrent/metastatic gastrointestinal stromal tumors: a retrospective study

BackgroundPreoperative imatinib mesylate therapy for gastrointestinal stromal tumors (GISTs) is controversial. This study aimed to explore the clinical efficacy and optimal duration of preoperative imatinib mesylate (IM) therapy in patients with locally advanced and recurrent/metastatic GISTs.MethodsWe retrospectively examined patients who received preoperative imatinib mesylate therapy from January 2013 to December 2018 at Xiangya Hospital, Central South University and the Second Xiangya Hospital of Central South University, China. Clinical data, including the results of tests for mutations in KIT and PDGFR, findings from regularly conducted re-examinations, abdominal-enhanced computed tomography/magnetic resonance imaging data, responses to imatinib, progression-free survival, and overall cancer-specific survival, were recorded.ResultsA total of 25 patients were enrolled in our study, including 18 with a locally advanced GIST and 7 with recurrent or metastatic GISTs. Their ages ranged from 22 to 70 years (M:F = 1.6:0.9), with a mean age of 50.48 ± 12.51 years. The tumor locations included the stomach (56.0%), rectum (16.0%), enterocoelic/retroperitoneal sites (12.0%), and the small intestine (12.0%). Based on testing for mutations in KIT and PDGFR, 22 patients received 400 mg/day KIT, and 3 patients received 600 mg/day PDGFR. The median duration of preoperative IM therapy was 8.96 ± 4.81 months, ranging from 3 to 26 months. According to the Choi criteria, 24 patients achieved a partial response (PR), and 1 patient had stable disease (SD). All patients underwent surgery after preoperative IM therapy, and no postoperative complications appeared. The 2-year PFS and 5-year PFS were 92% and 60%, respectively, and the total 5-year cancer-specific survival (CSS) was 92%.ConclusionPreoperative imatinib therapy is feasible for locally advanced and recurrent/metastatic GISTs and can effectively shrink the tumor size, allow organ sparing, and avoid extensive organ resection. Moreover, the optimal duration of preoperative IM therapy in patients with locally advanced and recurrent/metastatic GISTs was 8.96 ± 4.81 months, ranging from 3 to 26 months, and gastric GISTs had a better response to preoperative IM therapy than did non-gastric GISTs.

Prognostic Factors for Primary Localized Gastrointestinal Stromal Tumors After Radical Resection: Shandong Gastrointestinal Surgery Study Group, Study 1201.

Most previous risk-prediction models for gastrointestinal stromal tumors (GISTs) were based on Western populations. In the current study, we collected data from 23 hospitals in Shandong Province, China, and used the data to examine prognostic factors in Chinese patients and establish a new recurrence-free survival (RFS) prediction model. Records were analyzed for 5285 GIST patients. Independent prognostic factors were identified using Cox models. Receiver operating characteristic curve analysis was used to compare a novel RFS prediction model with current risk-prediction models. Overall, 4216 patients met the inclusion criteria and 3363 completed follow-up. One-, 3-, and 5-year RFS was 94.6% (95% confidence interval [CI] 93.8-95.4), 85.9% (95% CI 84.7-87.1), and 78.8% (95% CI 77.0-80.6), respectively. Sex, tumor location, size, mitotic count, and rupture were independent prognostic factors. A new prognostic index (PI) was developed: PI = 0.000 (if female) + 0.270 (if male) + 0.000 (if gastric GIST) + 0.350 (if non-gastric GIST) + 0.000 (if no tumor rupture) + 1.259 (if tumor rupture) + 0.000 (tumor mitotic count < 6 per 50 high-power fields [HPFs]) + 1.442 (tumor mitotic count between 6 and 10 per 50 HPFs) + 2.026 (tumor mitotic count > 10 per 50 HPFs) + 0.096 × tumor size (cm). Model-predicted 1-, 3-, and 5-year RFS was S(12, X) = 0.9926exp(PI), S(36, X) = 0.9739exp(PI) and S(60, X) = 0.9471exp(PI), respectively. Sex, tumor location, size, mitotic count, and rupture were independently prognostic for GIST recurrence. Our RFS prediction model is effective for Chinese GIST patients.

Clinical Outcome of Female Non-gastric Gastrointestinal Stromal Tumor

Clinical Outcome of Female Non-gastric Gastrointestinal Stromal Tumor

Gastrointestinal stromal tumors. A clinicopathological study.

Objectives:To evaluate the clinical presentations and immunohistochemical (IHC) properties of gastrointestinal stromal tumors (GISTs) and to compare them to internationally published data.Methods:Thirty-six patients diagnosed with GISTs between January 1997 and December 2015 were retrospectively studied in 2 tertiary hospitals. Immunohistochemical staining was carried out prospectively when it has not been completed fully at the beginning.Results:The median age of patients was 54 years (range; 17-81 years). Predominantly, we found more females were affected. The male to female ratio was 1:1.7. The most frequently affected organs were the stomach (63.8%) followed by small bowel (25%) and colorectal region (8.4%). Abdominal pain was the most frequent presentation in 33.3% of the patients then gastrointestinal (GI) bleeding in 30.5%. Most of the gastric GISTs were at early stages at presentation: stage 1 and II (60.8%), while in non-gastric GISTs, the tumor stage was advanced: stage III and IV (69.3%). The IHC characteristic of GIST in descending order showed positivity for vimentin (88.9%), CD117 (83.3%), CD34 (77.8%), Ki67 (63.9%), SMA (38.9%), desmin (27.8%), and S100 (19.4%).Conclusion:Gastrointestinal stromal tumors in our study demonstrates a major similar feature as the published international data. However, minor differences do exist in terms of clinical features and immunohistochemistry.

Comparison of three prognostic models for predicting cancer-specific survival among patients with gastrointestinal stromal tumors.

To evaluate the predictive value for cancer-specific survival of the models of the American Joint Committee on Cancer (AJCC) stage, NIH and Armed Forces Institute of Pathology (AFIP) among patients with gastrointestinal stromal tumors (GISTs). Surveillance, Epidemiology and End Results database (2010-2014) was accessed. Overall survival analysis and adjusted cancer-specific Cox regression hazard was calculated. For gastric GISTs, concordance-index according to AJCC was 0.834; according to NIH was 0.833; according to AFIP was 0.836. Concordance-index for nongastric GISTs according to AJCC was 0.800, according to NIH was 0.801 and according to AFIP was 0.799. The performance of the three models is comparable with regards to cancer-specific survival prediction.

Adjuvant imatinib for patients with high-risk gastrointestinal stromal tumors: a retrospective cohort study

The duration of adjuvant imatinib for high-risk patients with gastrointestinal stromal tumors (GISTs) is still controversial. Therefore, we retrospectively analyzed the data of high-risk patients with GISTs to investigate the appropriate duration. All 185 patients were divided into 4 groups: <1 year (Group A), 1–2 years (Group B), 2–3 years (Group C) and >3 years (Group D). The mean recurrence-free survival (RFS) in Groups A, B, and C were 44.3, 62.1, and 86.8 months, respectively (P < 0.001); the mean overall survival (OS) in Groups A, B and C was 75.2, 88.1, and 94.7 months, respectively (P = 0.009). The 5-year RFS in Groups A, B, C, and D was 15%, 26%, 83%, and 100%, respectively (P < 0.001); and the 5-year OS was 64%, 88%, 88%, and 100%, respectively (P < 0.001). The greatest impact on unfavorable outcomes was the tumor mitotic rate (HR, 2.01, 95% CI, 1.38–2.94; P < 0.001). Duration of adjuvant imatinib was the only favorable factor (HR, −0.95, 95% CI, 0.93–0.97; P < 0.001). For high-risk patients with high tumor size or mitotic rate, or non-gastric GISTs, we recommend that more than 3 years of adjuvant imatinib is feasible.

Revisiting a dogma: similar survival of patients with small bowel and gastric GIST. A population-based propensity score SEER analysis.

The objective of the present analysis was to assess whether small bowel gastrointestinal stromal tumor (GIST) is associated with worse cancer-specific survival (CSS) and overall survival (OS) compared with gastric GIST on a population-based level. Data on patients aged 18years or older with histologically proven GIST was extracted from the SEER database from 1998 to 2011. OS and CSS for small bowel GIST were compared with OS and CSS for gastric GIST by application of adjusted and unadjusted Cox regression analyses and propensity score analyses. GIST were located in the stomach (n=3011, 59%), duodenum (n=313, 6%), jejunum/ileum (n=1288, 25%), colon (n=139, 3%), rectum (n=172, 3%), and extraviscerally (n=173, 3%). OS and CSS of patients with GIST in the duodenum [OS, HR0.95, 95% confidence interval (CI) 0.76-1.19; CSS, HR0.99, 95% CI 0.76-1.29] and in the jejunum/ileum (OS, HR0.97, 95% CI 0.85-1.10; CSS, HR=0.95, 95% CI 0.81-1.10) were similar to those of patients with gastric GIST in multivariate analyses. Conversely, OS and CSS of patients with GIST in the colon (OS, HR1.40; 95% CI 1.07-1.83; CSS, HR1.89, 95% CI 1.41-2.54) and in an extravisceral location (OS, HR1.42, 95% CI 1.14-1.77; CSS, HR=1.43, 95% CI 1.11-1.84) were significantly worse than those of patients with gastric GIST. Contrary to common belief, OS and CSS of patients with small bowel GIST are not statistically different from those of patients with gastric GIST when adjustment is made for confounding variables on a population-based level. The prognosis of patients with nongastric GIST is worse because of a colonic and extravisceral GIST location. These findings have implications regarding adjuvant treatment of GIST patients. Hence, the dogma that small bowel GIST patients have worse prognosis than gastric GIST patients and therefore should receive adjuvant treatment to a greater extent must be revisited.

Clinicopathological features and prognosis of small gastrointestinal stromal tumors outside the stomach.

The aim of the present study was to assess the clinicopathological features and prognostic factors of primary small gastrointestinal stromal tumors (GISTs) outside the stomach. The clinical data, clinicopathological features and prognostic factors of 20 patients with a pathologically-confirmed diagnosis of non-gastric GIST that were treated at Liaoning Cancer Hospital & Institute between July 2006 and December 2013 were retrospectively analyzed. In total, 15 patients were male and 5 were female, with a median age of 58 years (range, 44–82 years). A change in bowel habits was the original symptom of rectal small GISTs in 6 out of 8 patients, while patients with small GISTs in other locations demonstrated no overt symptoms and the lesions were detected by systematic examinations of other diseases or abdominal surgical procedures performed on other organs. In total, 19 patients out of the total 20 patients underwent surgery, and 1 patient with rectal GIST received continuous oral imatinib mesylate (400 mg once a day) instead of undergoing surgery. The mean diameter of tumors was 1.55±0.54 cm (range, 0.3–2.0 cm) and the median was 1.70 cm. The pathomorphology of the lesions was mainly spindle cell, and immunohistochemistry revealed the expression rate of cluster of differentiation (CD)117, CD34 and discovered on GIST-1 were 85, 80 and 70%. According to the mitosis index, small rectal GISTs were more frequent compared with other positions (P<0.05), while the frequency of small GISTs >1 cm in size was not significantly different from the frequency of small GISTs ≤1 cm in size (P=0.995). All 20 patients were followed up, with a median follow-up duration of 49.5 months (range, 10.5–94.4 months). At the end of the follow-up period, tumor recurrence occurred in 5 patients and 1 patient succumbed following progression. According to the analysis of the tumor sites, the RFS time of patients with small rectal GISTs was significantly different than the RFS time in patients with small GISTs in other positions. The clinical symptoms of non-gastric small GISTs were not evident and were challenging to detect. Small GISTs, regardless of size, possessed malignant potential and once detected, GISTs should be surgically resected. Lesions located in the rectum demonstrated an increased degree of malignancy and were more likely to recur. The tumor size and Ki67 index could not be considered as prognostic factors of non-gastric small GISTs.

Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib.

BACKGROUNDLittle is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib.METHODSRisk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months.RESULTSFive factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence-free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P < .001 for each comparison).CONCLUSIONSThe scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence.

Clinical analysis of 156 patients with gastrointestinal stromal tumors receiving imatinib therapy

To evaluate the impact of primary site, NIH risk and imatinib treatment on the prognosis of patients with gastrointestinal stromal tumors(GIST). Clinicopathological data of 156 adult patients with GIST treated by imatinib in the Cancer Institute and Hospital of Tianjin Medical University from January 2006 to December 2010 were retrospectively analyzed. According to NIH risk classification, 30 patients were at moderate risk and 126 at high risk. Sixty-seven patients had advanced GIST. Prognosis of patients with different primary tumor site, different NIH risk and different treatment was compared respectively. Imatinib therapy was well tolerated in all the patients. Eighty-nine cases received radical operation and adjuvant imatinib treatment. Among 67 advanced GIST cases, 26 received radical operation and adjuvant imatinib treatment, 27 received palliative operation and adjuvant imatinib treatment, and 14 received simple adjuvant imatinib treatment without operation. All the patients had routine follow-up, ranging from 9 to 56(median 27) months. The overall survival (OS) rate was 96% in 1-year, 86% in 2-year, and 71% in 3-year. The OS rate was 95% in 1-year, 77% in 2-year, and 65% in 3-year for patients at high risk, and all 100% in 1-, 2-, 3-year for patients at moderate risk, the differences was statistically significant (P=0.001). The OS rate was 97% in 1-year, 90% in 2-year, and 84% in 3-year for patients with gastric GIST, and 95% in 1-year, 69% in 2-year, and 52% in 3-year for patients with non-gastric GIST, the difference was significant(P=0.000). The OS rate was 98% in 1-year, 95% in 2-year, and 90% in 3-year for patients undergoing radical resection and adjuvant imatinib therapy. For 67 advanced GIST patients with imatinib therapy, none had complete remission, 41 had part remission, 15 had stable disease, indicating 56 advanced GIST cases(83.6%) obtaining clinical benefit. The OS rate was 91% in 1-year, 58% in 2-year, and 43% in 3-year. The prognosis of high, and non-gastric and advanced GIST patients is poor. Radical resection combined with early imatinib treatment can improve the prognosis of GIST patients.

Prediction of Tumor Recurrence in Patients with Non-Gastric Gastrointestinal Stromal Tumors Following Resection according to the Modified National Institutes of Health Criteria.

Background/AimsFew studies have investigated the prognosis of non-gastric gastrointestinal stromal tumors (GISTs) under the modified National Institutes of Health (NIH) consensus criteria in Korea. This study aims to clarify the clinical usefulness of the modified NIH criteria for risk stratification.MethodsFrom January 2000 through October 2012, 88 patients who underwent curative resection for primary GISTs were included in this study. The enrolled patients were stratified to predict recurrence by the original NIH criteria and modified NIH criteria.ResultsIn all, 88 patients had non-gastric GISTs, including 82 and 6 patients with GISTs of the small intestine and colorectum, respectively. The mean age was 57.3±13.0 years, and the median follow-up duration was 3.40 years (range, 0.02-12.76 years). All patients who were placed in the intermediate-risk category according to the original NIH criteria were reclassified into the high-risk category according to the modified NIH criteria. Therefore, the proportion of cases in the intermediate-risk category declined to 0.0% from 25.0% (22/88), and the proportion of cases in the high-risk category increased to 43.2% (38/88) from 18.2% (16/88) under the modified NIH criteria. Among the 22 reclassified patients, 6 (27.3%) suffered a recurrence during the observational period, and the recurrence rate of high-risk category patients was 36.8% (14/38).ConclusionsPatients in the high-risk category according to the modified NIH criteria had a high GIST recurrence rate. Therefore, the modified NIH criteria are clinically useful in selecting patients who need imatinib adjuvant chemotherapy after curative surgical resection.

Gastrointestinal stromal tumors: A single institute experience from South India

Background: Gastrointestinal stromal tumors (GIST) represent an uncommon form of malignancy and one of best paradigms of molecularly targeted therapy. While the natural history of GIST following treatment with imatinib mesylate is relatively well known from various series in western literature, rarely any series from India has been published in this regard. Materials and Methods: Forty-four GISTs cases diagnosed and treated with imatinib between 2005 and 2011 were retrieved from the Department of Medical Oncology database, KMIO, Bangalore. Their clinical, histopathological data, and treatment outcome were analyzed. Kaplan-Meier survival analysis was done. Anatomic site, tumor size, mitotic activity, and extent of resection were correlated with overall survival (OS) using the logrank test. Results: Median age was 56 years with a male: female ratio of 2:1. Stomach was the most common site involved. Twenty-nine patients had localized disease of which majority had high risk (65%) features, with a mean tumor size of 10.5 cm (range 4-18 cm) and mitotic rate of 6 (range 4-9)/50 high-power field (HPF). Fourteen patients had metastatic disease at presentation with liver being the most common site. In the adjuvant group, median follow-up was 42 months (m) (range 10-70 m). Estimated recurrence free survival (RFS) and OS at 42 m were 59.9 and 80.6%, respectively. In metastatic group, median follow-up was 28 m (range 2-54 m). The median progression free survival (PFS) and OS were 18 m (95% CI 8.65-27.34 m) and 28 m (95% CI 17.90-38.09 m), respectively. Estimated PFS and OS at 28 m were 38.7 and 46.7%, respectively. Conclusion: Patients with GIST still present with larger bulky tumor at diagnosis, this leads to slightly inferior survival in our scenario. Nongastric GISTs; R1 and R2 resection; and mitotic rate >5/50 HPF are the other a factors which have a negative impact on survival.

A high risk group in the modified national institutes of health consensus criteria for the gastrointestinal stromal tumor: a clear indication of the adjuvant imatinib.

Since it is difficult to predict the prognosis of gastrointestinal stromal tumor (GIST) with the standard tumor-node-metastasis system, a system for assessment of the malignant potential according to risk stratification is commonly used in a clinical setting. Leading classification systems are the National Institutes of Health (NIH) consensus criteria,1 the modified NIH consensus criteria,2 the Armed Forces Institute of Pathology criteria and others. Jang et al.3 in this issue compared the most widely used NIH criteria and the modified NIH criteria. The NIH criteria1 proposed before 2002 classified the prognosis of GISTs into four subgroups (very low, low, intermediate or high risk) based on mitotic count and tumor size. The modified NIH criteria,2 developed by Dr. Joensuu in 2008, includes the primary tumor site and tumor rupture as two additional prognostic factors to the original NIH consensus criteria. According to the modified criteria, a part of individuals belonging to the intermediate risk group based on the NIH consensus criteria are re-classified into the high risk group. Based on the NIH consensus criteria, cases with mitotic count >10/50 high power fields (HPF) and tumor size >10 cm, or those with mitotic count >5/50 HPF and tumor size >5 cm are classified as the high risk group. This classification maintains identically only when GISTs are located in the stomach according to the modified NIH criteria. In contrast, when GISTs are detected in organs other than the stomach, cases with tumor size >5 cm are included in the high risk group, regardless of the mitotic count. If the mitotic activity is >5/50 HPF in the GISTs involving non-gastric organs cases with tumor size >2 cm are also classified into the high risk group. Thus, some non-gastric GISTs formerly grouped as the intermediate risk group are re-classified as the high risk group. All cases with the presence of a tumor rupture are classified as the high risk group, as well in the modified NIH consensus criteria. The need for re-classification has been raised to accurately determine the postoperative adjuvant Imatinib group. Although the effectiveness of postoperative adjuvant Imatinib has been clarified in the high risk group for GISTs, it still remains unclear in the intermediate risk group. The 2012 National Comprehensive Cancer Network (NCCN) guideline recommends postoperative adjuvant therapy for patients based on the following study results.4 A randomized trial (SSGXVIII/AIO) reported that 36 months, compared to 12 months, of adjuvant Imatinib was significantly better in extending relapse free survival and overall survival in patients with a high estimated risk of recurrence postoperatively (tumor >5 cm in size with a high mitotic rate [>5 mitoses/50 HPF] or a risk of recurrence greater than 50%).5 Moreover, the ACOSOG Z9001 study showed that adjuvant Imatinib significantly prolonged relapse free survival in patients with GISTs that were larger than 3 cm. In particular, the efficacy of Imatinib was noticeable in patients with a considerably higher risk of recurrence (intermediate and high-risk).6 When the parameters of these two studies are matched with the classification criteria, it is reasonable that the high risk group based on the modified NIH consensus criteria should be subject to adjuvant Imatinib treatment. From the aspects of clinical effectiveness, whether a classification system can better discriminate a single high risk group requiring adjuvant chemotherapy, the modified NIH consensus criteria are considered a more effective indicator. Follow-up without specific post-operative adjuvant treatment is required for very low, low and intermediate risk groups based on the modified NIH criteria, while adjuvant Imatinib treatment is recommended for the high risk group. In the study of Jang et al. in this issue, gastric GISTs were not included and there was no case involving a tumor rupture. For these reasons, evaluating the significance of the modified NIH criteria is difficult based on their study results. Moreover, additional chemotherapies, including postoperative use of Imatinib, were excluded to observe the natural progress of tumors. Considering the fact that the clinical effectiveness of the modified NIH criteria is critical in determining the use of postoperative adjuvant therapy, the study results would have been more useful if the differences in the prognosis had been compared between those with and without adjuvant therapy. However, this study demonstrated that some GISTs formerly categorized as the intermediate risk group, according to the original NIH criteria, were re-classified as the high risk group, and showed a significantly high recurrence rate. The study was meaningful in that it supported the view that the high risk group classified according to the modified NIH consensus criteria is subject to adjuvant Imatinib therapy.