Surgical Approaches and Oncological Outcomes in the Management of Duodenal Gastrointestinal Stromal Tumors (GIST)

Background: Duodenal gastrointestinal stromal tumors (GIST) are a rare subset of GIST. Their surgical management in this anatomically complex region consists of varied approaches, and the administration of imatinib mesylate (IM) has not been clarified. Methods: We retrospectively reviewed patients with duodenal GIST treated during a 10-year-period. We analysed the clinicopathological characteristics and survival factors and evaluated the perioperative and long-term outcomes based on the extent of resection ((ocal-resection (LR) versus pancreaticoduodenectomy (PD)) and the IM-administration. The median follow-up period was 60 months (range, 12–140). Results: A total of thirteen patients (M:F = 7:6) with median age of 64 years (range, 42–77) underwent resection of duodenal GIST. Median tumor size was 5.2 cm (range, 1.5–13.3). Eight patients (61.5%) underwent LR and five patients (38.5%) PD. R0-resection was achieved in 92.5%. Neoadjuvant IM-therapy was administered in five patients leading to tumor downsizing and in 40% to less-extended resection. The PD group consisted of larger tumors with higher mitotic count, mostly located in D2 (p = 0.031). The PD group had longer operative time (p = 0.026), longer hospital stay (p = 0.016), and higher rate of postoperative complications (p = 0.128). The actuarial 1-, 3-, and 5-year overall survival were 92.5%, 84%, and 73.5%, respectively, whereas the disease-free survival rates at 1, 3, and 5 years were 91.5%, 83%, and 72%, respectively. A tendency towards increased risk of disease recurrence was demonstrated for patients with tumor >5 cm and high-risk potential. There was not statistic survival benefit for one or the other surgical approach. Conclusion: The type of resection depends on duodenal site of origin and tumor size. LR can be the treatment of choice for duodenal GIST whenever technically feasible. Recurrence of duodenal GIST is dependent on tumor biology rather than surgical approach. Administration of IM in neaodjuvant setting should be considered in cases with high-risk GIST scheduled for PD since it might facilitate less-extended resection.

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Outcomes of multivisceral resection of gastric gastrointestinal stromal tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.91 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 91-91

Author(s):

Sabha Ganai ◽

Mitchell Posner ◽

Vivek N. Prachand ◽

John C. Alverdy ◽

Eugene A. Choi ◽

...

Keyword(s):

Tumor Size ◽

Gastrointestinal Stromal Tumors ◽

Disease Free Survival ◽

Multivisceral Resection ◽

Response To Therapy ◽

Hospital Length Of Stay ◽

Free Survival ◽

Stromal Tumors ◽

Gastric Gists ◽

Disease Free

91 Background: Despite the recent introduction of imatinib and laparoendoscopic techniques to the management of gastric gastrointestinal stromal tumors (GISTs), outcomes remain uncertain in the setting of multivisceral involvement. Methods: We conducted a retrospective review of 69 consecutive patients who underwent resection of gastric GISTs from October 2002 through August 2011. Median follow-up was 19 months (interquartile range [IQR] 4-37). Results: Patients were 51% female, with a mean age of 65 ± 13 years and BMI of 30 ± 8 kg/m2. Patients undergoing multivisceral resection (n=13) had a longer interval from diagnosis to surgery (7.4 [IQR 1.9 – 15.0] vs. 1.3 [IQR 0.7-3.5] months, p<0.01), greater use of neoadjuvant imatinib (62% vs. 4%, p<0.001), and greater preoperative tumor size (12 ± 8 vs. 4 ± 3 cm, p<0.001) in comparison to gastric-only resections (n=56). Patients were less likely to be managed laparoscopically (8% vs. 71%, p<0.001), had a longer operative time (286 ± 92 vs. 152 ± 65 min, p<0.001), and were less likely to be R0 (69% vs. 98%, p<0.001). While patients undergoing multivisceral resection were more likely to have a pathological complete response to therapy (23% vs. 0, p<0.01), they were also more likely to have metastatic disease present (31% vs. 0, p<0.01). Hospital length of stay was greater (median 8 [IQR 7-9] vs. 3 [IQR 2-6] days, p<0.001). There were no significant differences in grade or mitotic index between groups, or in the use of adjuvant imatinib (54% vs. 23%). Overall survival was less in patients undergoing multivisceral resection (63% vs. 86% at 3 years, p<0.05), as was disease-free survival (52% vs. 71% at 3 years, p<0.05). Median disease-free survival was 50 and 66 months, respectively (p<0.01). Controlling for tumor size, grade, resection status, and the use of neoadjuvant imatinib, multivisceral resection was an independent predictor of disease-free survival (p<0.05). Conclusions: Multivisceral involvement is associated with tumors of greater size, and despite an increased use of neoadjuvant imatinib, it is associated with poor outcome for patients with gastric GISTs.

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Gastrointestinal Stromal Tumors: Alexandria University Experience

Asian Journal of Oncology ◽

10.1055/s-0041-1735343 ◽

2021 ◽

Author(s):

Maher Soliman

Keyword(s):

Risk Score ◽

Tumor Size ◽

Gastrointestinal Stromal Tumors ◽

Multivariate Analyses ◽

Disease Free Survival ◽

Margin Status ◽

High Power Field ◽

Mesenchymal Tumors ◽

Male Predominance ◽

Stromal Tumors

Abstract Introduction Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) that can arise in any parts of the GIT. The clinical behavior and prognosis of GISTs remain unpredictable. The purpose of this study was to evaluate the clinicopathological features and prognostic factors of GISTs. Methods The medical files of 93 patients with nonmetastatic GIST presented to our hospital were reviewed. The clinical and pathological parameters, treatment, and follow-up data were collected and correlated to survival outcome using univariate and multivariate analyses. Results The median age of patients was 48.9 years with a slight male predominance. Abdominal pain (39.8%) was the commonly presenting symptom. About 60% of GISTs originated from the stomach and 22% from the small intestine. Tumors stained positive for CD117 in 95.7%. The median diameter of the tumors was 7 cm. Mitotic counts were < 5/50 high power field in 55.9% of tumors. About 44% of patients had high risk tumors. All patients underwent surgery and about 60.2% of patients received adjuvant imatinib mesylate.The 5-year disease-free survival (DFS) and overall survival (OS) were 74.5 and 80%, respectively. Margin status, tumor site, tumor size, mitotic counts, and risk score were significantly associated with DFS and OS in both univariate and multivariate analyses. Conclusion Surgery is the mainstay treatment for nonmetastatic GISTs. Tumor size, tumor location, margin status, mitotic count, and risk score were predictive factors for DFS and OS of GISTs.

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Gastrointestinal stromal tumors: Immune protein expression and clinical outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.124 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 124-124

Author(s):

Andrew M. Blakely ◽

Andres Matoso ◽

Thomas J. Miner

Keyword(s):

Clinical Outcomes ◽

Tumor Size ◽

Gastrointestinal Stromal Tumors ◽

Care Center ◽

Treatment Options ◽

Tertiary Care ◽

Tumor Biology ◽

Benign Tumors ◽

Stromal Tumors ◽

Significant Difference

124 Background: The immune microenvironment is emerging as an important prognostic factor with potential therapeutic targets for various malignancies. Although programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) have been studied in some tumor types, significance of their expression in gastrointestinal stromal tumors (GISTs) is largely unknown. Methods: Tissue microarrays at an academic tertiary care center were constructed from pathology files from 1996 to 2016. Immunohistochemistry for PD-L1 and IDO was performed and correlated with tumor size, mitoses, and clinical outcomes. Tumor infiltrating lymphocytes (TILs) were counted using image analysis software. Results: 131 GISTs were analyzed. Median patient age was 64 years (range 30-89); 51.1% were male. Tumor location included 89 stomach (67.9%), 34 small bowel (26.0%), 4 colorectal (3.1%), and 4 other (3.1%). Median follow-up was 58 months. Mean tumor size was 5.6±4.5cm, range 0.5 to 24; mean mitoses were 7.2/50HPF. 19 (14.5%) metastasized to mesentery (n = 8), liver (n = 6), and elsewhere (n = 5). Mean survival was 61 months (range 7-127); 5 patients died of disease (3.8%). PD-L1 immunostain was positive in 89 (67.9%), including 11 of 19 (57.9%) malignant and 78 of 112 (69.6%) benign tumors (p = 0.4). PD-L1 positive tumors were larger (6.3±4.4 vs. 4.4±3.4 cm; p = 0.02) and had more mitoses/50HPF (8.9±5.4 vs. 3.9±3.5; p = 0.006) than PD-L1 negative tumors. IDO immunostain was positive in 116 (88.5%), including 14 of 19 (73.7%) malignant and 102 of 112 (91.1%) benign tumors (p = 0.07). There was no significant difference in size or mitotic count between IDO positive and negative tumors. Mean number of CD8-positive TILs was 168±35/mm2 and mean number of PD-L1 positive TILs was 147±28/mm2 in PD-L1 positive tumors. PD-L1 positive tumors had significantly more TILs than PD-L1 negative tumors (113±21 vs. 104±18; p < 0.001). Conclusions: The majority of GISTs express PD-L1 and IDO. Expression of PD-L1 was associated with increased tumor size and higher mitotic activity. PD-L1 and IDO could play a significant role in the tumor biology of GISTs; immunotherapy targeting one or both may provide novel treatment options.

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Hydroxysteroid 11-Beta Dehydrogenase 1 Overexpression with Copy-Number Gain and Missense Mutations in Primary Gastrointestinal Stromal Tumors

Journal of Clinical Medicine ◽

10.3390/jcm7110408 ◽

2018 ◽

Vol 7 (11) ◽

pp. 408 ◽

Cited By ~ 2

Author(s):

Chien-Feng Li ◽

Ting-Ting Liu ◽

Jui-Chu Wang ◽

Shih-Chen Yu ◽

Yen-Yang Chen ◽

...

Keyword(s):

In Situ Hybridization ◽

High Risk ◽

Copy Number ◽

Gastrointestinal Stromal Tumors ◽

Disease Free Survival ◽

Copy Number Gain ◽

Missense Mutations ◽

Stromal Tumors

The lipid-metabolizing enzymes remain underexplored in gastrointestinal stromal tumors (GISTs). Through transcriptomic reappraisal, hydroxysteroid 11-beta dehydrogenase-1 (HSD11B1) was identified as a top-upregulated, progression-associated gene. To validate the clinical relevance of HSD11B1, the informative results of Sanger sequencing (n = 58), mRNA quantification by branched-chain DNA in situ hybridization assay (n = 70), copy number assay by fluorescent in situ hybridization (n = 350), and immunohistochemistry (n = 350) were correlated with clincopathological variables, KIT/PDGFRA/BRAF genotypes, and disease-free survival (DFS). HSD11B1 was stably silenced to explore its oncogenic function. HSD11B1 mRNA varied between high-risk and non-high-risk groups (p = 0.009) and positively correlated with HSD11B1 immunoexpression (r = 0.783, p < 0.001). HSD11B1 copy-number gain (CNG), including polysomy (5.4%) and amplification (12%), associated with HSD11B1 overexpression (p < 0.001). Predominantly involving the homodimer interface-affecting exon 6 or exon 7, missense HSD11B1 mutations (17.2%) were related to high risk (p = 0.044), age ≥70 years (p = 0.007), and shorter DFS among relapsed cases (p = 0.033). CNG was related to unfavorable KIT/PDGFRA/BRAF genotypes (p = 0.015), while HSD11B1 overexpression was preferential in non-gastric cases (p < 0.001). Both abnormalities strongly associated with risk levels (both p < 0.001) and shorter univariate DFS (both p < 0.0001), and HSD11B1 CNG remained prognostically independent (p < 0.001) with a 3-fold increased hazard ratio. In vitro, HSD11B1 knockdown significantly inhibited proliferation and caused G2/M arrest. In conclusion, HSD11B1 overexpression may occur owing to CNG, confer a pro-proliferative function, and predict a worse prognosis in GISTs.

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Clinicopathological Features and Clinical Outcomes of Primary Hepatic Gastrointestinal Stromal Tumors: Evaluation of a Pooled Case Series

10.21203/rs.3.rs-66778/v1 ◽

2020 ◽

Author(s):

Xing Xu ◽

Guoliang Zheng ◽

Zhichao Zheng

Keyword(s):

High Risk ◽

Mitotic Index ◽

Tumor Size ◽

Gastrointestinal Stromal Tumors ◽

Multivariable Analysis ◽

Case Series ◽

Risk Classification ◽

Clinicopathological Features ◽

Stromal Tumors ◽

Gastric Gists

Abstract Background: Due to the extremely rare incidence, data of clinicopathological features and prognosis of primary hepatic gastrointestinal stromal tumors (GISTs) is limited. Methods: 36 cases of hepatic GISTs were from the literature, PUBMED, EMBASE, China National Knowledge Infrastructure and WANFANG DATA, and 1 case came from our center. Clinicopathological features and outcomes were analyzed between 37 hepatic GISTs and 254 gastric GISTs from our center. Results: A majority of hepatic GISTs exceeded 5 cm (83.7%), displayed mixed density (69.4%) and spindle morphology (74.2%) and were classified as high risk (91.4%). Larger tumors of hepatic GISTs were likely to display mixed lesion and tumors with mixed lesion were prone to be classified as high risk. In comparisons to gastric GISTs, hepatic GISTs differed from gastric GISTs in tumor size, main symptoms, histologic type, mitotic index, CD34 expression, NIH risk classification. In patients with hepatic GISTs, 5-year DFS and DSS rates were 19.4% and 53.7%, which were worse than that of gastric GISTs (P＜ 0.001), especially for those with tumor size exceeding 5 cm or mitotic indices exceeding 5/50 HPF (P < 0.001). Multivariable analysis showed location and NIH risk classification were independent prognostic factors for DFS in patients with GISTs, and size and location were significantly associated with DSS. Conclusions: Hepatic GISTs distinguished from gastric GISTs in respect to clinicopathological features and outcomes. Mitotic index exceeding 5/50 HPF or tumor size exceeding 5 cm may be important factor to distinguish hepatic GISTs from gastric GISTs in DFS and DSS.

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Spectrum of KIT and PDGFRA mutations in primary gastrointestinal stromal tumors: Polish Clinical GIST Registry experience

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e21504 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e21504-e21504

Author(s):

A. Wozniak ◽

P. Rutkowski ◽

M. Debiec-Rychter ◽

J. Siedlecki ◽

W. Michej ◽

...

Keyword(s):

High Risk ◽

Gastrointestinal Stromal Tumors ◽

Prognostic Significance ◽

Point Mutations ◽

Gene Mutations ◽

Disease Free Survival ◽

Primary Tumors ◽

Stromal Tumors ◽

Pdgfra Gene ◽

Exon 11

e21504 Background: KIT or PDGFRA gene mutations are found in 80–90% of gastrointestinal stromal tumors (GIST). The prognostic value of those mutations for the outcome in primary tumors is controversial. Objective: To assess the spectrum, frequency and prognostic significance of the KIT and PDGFRA gene mutations in Polish group of surgically treated primary GISTs. Methods: DNA isolated from paraffin blocks from 300 patients (pts) with histologically diagnosed primary GISTs included in clinical registry database, were analyzed using denaturing high performance liquid chromatography (DHPLC) and direct sequencing for KIT (exons 9, 11, 13, 17) and PDGFRA (exons 12, 14, 18) mutations. For primary GIST risk assessment the Miettinen stratification was used. Results: KIT/PDGFRA genes mutations were found in 82% tumors: KIT was mutated in 69% and PDGFRA in 13% of tumors. KIT exon 11 and 9 mutations were found in 61.5% and 7.5% respectively. Among KIT exon 11 mutants the most frequent were deletions (32.7%) followed by point mutations (15.3%), duplications (8.4%) and complex rearrangements (5.1%). KIT exon 11 mutations were found at the similar rates in tumors with gastric and non-gastric localization (53.9% vs. 46.1% respectively) while KIT exon 9 duplications were more often observed in non-gastric GISTs (86.4%, p=0.00036) and PDGFRA mutations were more frequently found in tumors originated from the stomach (86.8%; p=0.00017). In high risk tumors KIT exon 11 deletions were more frequently found than point mutations (p=0.017). On the other hand mutations in PDGFRA were more often observed in very low-/low- than high risk GISTs as compared to KIT exon 11 (p=0.0026). There was no statistically significant correlation between disease-free survival and the spectrum or frequency of mutations. Conclusions: Spectrum and frequency of KIT and PDGFRA mutations in Polish GIST population are similar to the previously described groups. No significance of mutations for disease outcome after surgery of primary tumors was found. [Table: see text]

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Outcomes of multivisceral resection of gastric gastrointestinal stromal tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.10090 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 10090-10090

Author(s):

Sabha Ganai ◽

Mitchell Posner ◽

Vivek N. Prachand ◽

John C. Alverdy ◽

Eugene A. Choi ◽

...

Keyword(s):

Tumor Size ◽

Gastrointestinal Stromal Tumors ◽

Disease Free Survival ◽

Multivisceral Resection ◽

Response To Therapy ◽

Adjuvant Imatinib ◽

Free Survival ◽

Stromal Tumors ◽

Gastric Gists ◽

Disease Free

10090 Background: Despite the recent introduction of imatinib and laparoendoscopic techniques to the management of gastric gastrointestinal stromal tumors (GISTs), outcomes remain uncertain in the setting of multivisceral involvement. Methods: We conducted a retrospective review of 73 consecutive patients who underwent resection of gastric GISTs from October 2002 through December 2011. Median follow-up was 22 months (interquartile range [IQR] 6-37). Results: Patients were 51% female, with a mean age of 65 ± 12 years and BMI of 30 ± 8 kg/m2. Patients undergoing multivisceral resection (n=14) had a longer interval from diagnosis to surgery (7.3 [IQR 1.9 – 15.0] vs. 1.3 [IQR 0.7-4.2] months, p<0.01), greater use of neoadjuvant imatinib (64% vs. 3%, p<0.0001), and greater preoperative tumor size (12 ± 8 vs. 4 ± 3 cm, p<0.0001) in comparison to gastric-only resections (n=59). Patients were less likely to be managed laparoscopically (7% vs. 71%, p<0.0001), had a longer operative time (310 ± 117 vs. 145 ± 62 min, p<0.0001), and were less likely to be R0 (71% vs. 98%, p<0.001). While patients undergoing multivisceral resection were more likely to have a pathological complete response to therapy (29% vs. 0, p<0.001), they were also more likely to have metastatic disease present (29% vs. 0, p<0.001). Hospital length of stay was greater (median 8 [IQR 6-9] vs. 3 [IQR 2-6] days, p<0.0001). There were no significant differences in grade or mitotic index between groups. There was greater use of adjuvant imatinib (64% vs. 25%, p<0.05). Overall survival was less in patients undergoing multivisceral resection (64% vs. 87% at 3 years, p<0.05), as was disease-free survival (52% vs. 71% at 3 years, p<0.05). Median overall and disease-free survival were 43 and 22 months after multivisceral resection for gastric GISTs. Controlling for tumor size, grade, resection status, and the use of neoadjuvant imatinib, multivisceral resection and use of adjuvant imatinib were both independent predictors of disease-free survival (p<0.05). Conclusions: Multivisceral involvement is associated with tumors of greater size and, despite an increased use of neoadjuvant imatinib, it is associated with poor outcome for patients with gastric GISTs.

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Patterns of recurrence after resection of rectal gastrointestinal stromal tumors and the effect of adjuvant therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.531 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 531-531 ◽

Cited By ~ 1

Author(s):

Masayoshi Yasui ◽

Masaki Mori ◽

Tsuyoshi Takahashi ◽

Yasuo Nakashima ◽

Tsutomu Dousei ◽

...

Keyword(s):

High Risk ◽

Recurrence Rate ◽

Surgical Resection ◽

Local Excision ◽

Gastrointestinal Stromal Tumors ◽

Regional Recurrence ◽

Extended Resection ◽

Stromal Tumors ◽

Rectal Gist ◽

Rectal Gists

531 Background: Since gastrointestinal stromal tumors (GISTs) of the rectum are rare, clinical features and treatment outcome have not been well documented. Methods: Data from patients with rectal GIST diagnosed and primarily treated between 2003-2007 at 17 institutions in Japan were collected and analyzed on clinical characteristics, pathologic features and recurrence patterns. Results: Twenty-five patients (11 men and 14 women) with rectal GISTs were collected. Median age was 67years old. Pathological examinations disclosed that the median number of mitoses and the size of tumors were 4 counts/50HPF and 4.5cm, respectively. By the Miettinen criteria, 44 percent (n = 11) were classified as high-risk, 32 percent (n = 8) as low-risk and 16 percent (n = 4) as none-risk gastrointestinal stromal tumors. Sixty-three percent (7/11) of patients with high-risk GISTs had developed recurrence. None of patients (n = 12) with low or none-risk gastrointestinal stromal tumors have recurred after a median follow-up of 1699 (range, 135-3871) days. 85 percent (6/7) of recurrent patients showed loco-regional recurrence. Twelve patients with rectal GISTs received local excision and thirteen patients received extended resection (abdominoperineal resection or low anterior resection). Loco-regional recurrence rate following local excision was 25% (3/12), which was similar with that of extended resection (23%, 3/13).7 patients received neoadjuvant and/or adjuvant imatinib. Only one patient of 7 patients who received perioperative imatinib treatment developed recurrence. Conclusions: Loco-regional recurrence was the most predominant pattern of recurrence after surgical resection of rectal GISTs. The Miettinen criteria were useful to differentiate the high risk group. Recurrence rate was lower in patients treated with perioperative imatinib. Rectal GIST may be optimally managed by perioperative multimodal treatment instead of extending surgical resection.

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