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Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.

ABSTRACT: Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry.Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population.There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis.This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

SUBMITTER: Murphy JD

PROVIDER: S-EPMC4545693 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.

Murphy James D JD Ma Grace L GL Baumgartner Joel M JM Madlensky Lisa L Burgoyne Adam M AM Tang Chih-Min CM Martinez Maria Elena ME Sicklick Jason K JK

Cancer 20150430 17

<h4>Background</h4>Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry.<h4>Methods</h4>Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results dat ...[more]

PMID: 25930983

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Project description:BackgroundWe conduct a study in developing and validating four MRI-based radiomics models to preoperatively predict the risk classification of gastrointestinal stromal tumors (GISTs).MethodsForty-one patients (low-risk = 17, intermediate-risk = 13, high-risk = 11) underwent MRI before surgery between September 2013 and March 2019 in this retrospective study. The Kruskal-Wallis test with Bonferonni correction and variance threshold was used to select appropriate features, and the Random Forest model (three classification model) was used to select features among the high-risk, intermediate-risk, and low-risk of GISTs. The predictive performance of the models built by the Random Forest was estimated by a 5-fold cross validation (5FCV). Their performance was estimated using the receiver operating characteristic (ROC) curve, summarized as the area under the ROC curve (AUC). Area under the curve (AUC), accuracy, sensitivity, and specificity for risk classification were reported. Linear discriminant analysis (LDA) was used to assess the discriminative ability of these radiomics models.ResultsThe high-risk, intermediate-risk, and low-risk of GISTs were well classified by radiomics models, the micro-average of ROC curves was 0.85, 0.81, 0.87 and 0.94 for T1WI, T2WI, ADC and combined three MR sequences. And ROC curves achieved excellent AUCs for T1WI (0.85, 0.75 and 0.82), T2WI (0.69, 0.78 and 0.78), ADC (0.85, 0.77 and 0.80) and combined three MR sequences (0.96, 0.92, 0.81) for the diagnosis of high-risk, intermediate-risk, and low-risk of GISTs, respectively. In addition, LDA demonstrated the different risk of GISTs were correctly classified by radiomics analysis (61.0% for T1WI, 70.7% for T2WI, 83.3% for ADC, and 78.9% for the combined three MR sequences).ConclusionsRadiomics models based on a single sequence and combined three MR sequences can be a noninvasive method to evaluate the risk classification of GISTs, which may help the treatment of GISTs patients in the future.

Project description:Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection. Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival. Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90-81.10) months vs. 40 (95% CI: 29.53-50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386-0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439-0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine. Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.

Project description:Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT). Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836) and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836). CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively). Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic origins and provides a starting point for future candidate gene or gene-environment research.

Project description:Importance:There is a dearth of population-based evidence regarding outcomes of the adolescent and young adult (AYA) population with gastrointestinal stromal tumors (GISTs). Objectives:To describe a large cohort of AYA patients with GISTs and investigate the effect of surgery on GIST-specific survival (GSS) and overall survival (OS). Design, Setting, and Participants:This retrospective cohort study of 392 AYA patients and 5373 older adult (OA) patients in the Surveillance, Epidemiology, and End Results (SEER) database with GISTs histologically diagnosed from January 1, 2001, through December 31, 2013, with follow-up through December 31, 2015, compared the baseline characteristics of AYA (13-39 years old) and OA (?40 years old) patients and among AYA patients stratified by operative management. Kaplan-Meier estimates were used for OS analyses. Cumulative incidence functions were used for GSS analysis. The effect of surgery on survival was evaluated with a multivariable Fine-Gray regression model. Exposure:Tumor resection. Main Outcomes and Measures:GIST-specific survival and OS. Results:This study included 392 AYA and 5373 OA patients diagnosed with GISTs (207 [52.8%] male AYA patients, 2767 [51.5%] male OA patients, 277 [70.7%] white AYA patients, and 3661 [68.1%] white OA patients). Compared with the OA patients, more AYA patients had small-intestine GISTs (139 [35.5%] vs 1465 [27.3%], P?=?.008) and were managed operatively (332 [84.7%] vs 4212 [78.4%], P?=?.003). Multivariable analysis of AYA patients found that nonoperative management was associated with a more than 2-fold increased risk of death from GISTs (subdistribution hazard ratio, 2.27; 95% CI, 1.21-2.25; P?=?.01). On subset analysis of 349 AYA patients with tumors of the stomach and small intestine, small-intestine location was associated with improved survival (OS: 91.1% vs 77.2%, P?=?.01; GSS: 91.8% vs 78.0%, P?=?.008). On subset analysis of 91 AYA patients with metastatic disease, operative management was associated with improved survival (OS: 69.5% vs 53.7%, P?=?.04; GSS: 71.5% vs 56.7%, P?=?.03). Conclusions and Relevance:This study found that AYA patients are more likely to undergo surgical management than OA patients. Operative management is associated with improved OS and GSS in AYA patients, including those with metastatic disease.

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Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.

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Increased risk of additional cancers among patients with gastrointestinal stromal tumors: A population-based study.

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