Liver metastasis (LIM) of gastrointestinal stromal tumor (GIST) is associated with poor prognosis. The present study aimed at developing and validating nomogram to predict LIM in patients with GIST, thus helping clinical diagnosis and treatment. The data of GIST patients derived from Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016, which were then screened by univariate and multivariate logistic regression for the construction of LIM nomogram. The model discrimination of LIM nomogram was evaluated by concordance index (C-index) and calibration plots, while the predictive accuracy and clinical values were measured by decision curve analysis (DCA) and clinical impact plot. Furthermore, we validated predictive nomogram in the internal testing set. A total of 3797 patients were enrolled and divided randomly into training and validating groups in a 3-to-1 ratio. After logistic regression, the significant variables were sex, tumor location, tumor size, N stage and mitotic rate. The calibration curves showed the perfect agreement between nomogram predictions and actual observations, while the DCA and clinical impact plot showed the clinical utility of LIM nomogram. C-index of the nomogram was 0.812. What’s more, receiver operating characteristic curves (ROC) also showed good discrimination and calibration in the training set (AUC = 0.794, 95% CI 0.778–0.808) and the testing set (AUC = 0.775, 95% CI 0.748–0.802). The nomogram for patients with GIST can effectively predict the individualized risk of liver metastasis and provide insightful information to clinicians to optimize therapeutic regimens.

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A novel nomogram for predicting liver metastasis in patients with gastrointestinal stromal tumor: a SEER-based study.

Aim To explore the cytological spectrum of the gastrointestinal stromal tumour (GIST) including its metastatic sites. Material and methods A total of 42 patients (45 sites) diagnosed with GIST or its metastases on fine needle aspiration cytology were studied over a period of 5 years. May-Grunwald Giemsa- and haematoxylin and eosin-stained smears were reviewed and analysed for the cytomorphological spectrum of GIST. Results Primary GIST alone was seen in 24 cases, E-GIST in eight cases and metastasis in 11 cases (one patient showing metastasis at two distinct sites), whereas concurrent primary and metastatic lesions were noted in two cases. Amongst primary sites, the most commonly affected location was stomach (n = 22), followed by ileum (n = 2), duodenum (n = 1) and rectum (n = 1). Extra-GIST was seen in retroperitoneum and pelvis (n = 3 each), omentum and mediastinum (n = 1 each). Fine needle aspiration cytology was done from 11 metastatic sites of GIST which included liver, gall bladder fossa, chest wall, and thigh. The classic spindle cell arrangement was the predominant cytological pattern. About 8.8% cases showed predominant epithelioid cell morphology and 15.5% cases had a mixed cytomorphology comprising of both spindle cell and epithelioid cell patterns. Nuclear pseudoinclusions, perinuclear vacuoles and multinucleation were seen in four cases. Immunocytochemistry on cell-block sections for confirmation was performed in 18 cases and all these cases showed strong c-KIT positivity. Conclusion In this largest case series of cytomorphological diagnosis of GIST, we describe the cytomorphology and immunocytochemistry of primary and metastatic GIST. GISTs with predominant epithelioid cell morphology may pose a diagnostic dilemma therefore in all suspected cases of GIST, immunocytochemistry for c-KIT and/or DOG1 should be employed on cell-block preparations to confirm the diagnosis of GIST.

Fine needle aspiration cytology of primary and metastatic gastrointestinal stromal tumour.

Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.

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Clinical Trial Eligibility Criteria and Recently Approved Cancer Therapies for Patients With Brain Metastases

Background With the occurrence and improvement of immunohistochemistry and other pathological diagnostic techniques, gastrointestinal stromal tumor (GIST) has been gradually recognized. With the prolonged survival of patients with GISTs, reports about the bone metastasis of GIST increased. However, the knowledge of GISTs is rather limited due to its very low incidence. Methods Cochrane and Medline database (via PubMed) were searched in July 2019 with related keywords to acquire the literature related to the bone metastasis of GIST. Then, the literature was reviewed and references were also scanned to identify the possible related reports. Study data comprising age, sex, primary location, metastasis interval time, immunohistochemistry index, management and prognosis were recorded and analyzed. Results Forty-five patients with bone metastases of GIST, with a mean age of 61.09 years, were included. The small intestine and stomach were the most common primary sites, followed by the rectum. Patients with small intestine primary sites had bone metastases that occurred earlier than the bone metastases stomach and rectum primary sites. The spine was the most common site of bony metastases. The mean survival time after GIST diagnosis was more than 64.02 months. Patients younger than 60 years old had a worse prognosis than those older than 60 years old. Furthermore, patients with spinal involvement had a worse prognosis than those without spinal involvement. Surgical interventions combined with targeted therapies guaranteed a better prognosis. Conclusion Bone metastasis of GIST, which mainly occurs in the spine, is rather rare. Patients with GISTs of the small intestine and stomach suffered from bone metastasis more frequently and earlier than patients with GISTs in other primary sites. Age, sex, primary tumor location, treatment mode for the primary lesions and metastases, and spine involvement may be potential factors that affect the prognosis of GIST patients with bone metastases.

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Bone Metastases of Gastrointestinal Stromal Tumor: A Review of Published Literature.

https://journals.viamedica.pl/rpor/article/download/74106/54199

Stereotactic ablative radiotherapy for bone metastasis of gastrointestinal stromal tumor: Case report and review of the literature

This SEER-based study aimed to explore and analyze the relationship of metastasis of liver, lung and bone of GIST patients and their prognosis. The data of GIST patients were from Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 and all the statistical analyses were conducted by statistical software package SPSS (Version 22.0). A total of 4224 GIST patients were identified, of which 388 (9.19%) patients with liver metastasis, 20 (0.47%) patients with bone metastasis and 32 (0.76%) patients with lung metastasis. There was no significant difference of risk of bone or lung metastasis between patients with and without liver metastasis (P = 0.935). The median overall survival of patients with liver, bone, or lung metastasis was, respectively, 49 months, 18 months, and 20 months, which were all shorter than that of patients without metastasis. The overall survival of patients with both liver and bone metastasis and those with metastasis of all three sites was not significantly different from that of patients with only liver metastasis. The multivariate analysis showed age of less than 65 years, female patients, married status and receiving surgery were all the beneficial factors for prognosis of GIST patients with liver metastasis. Patients with metastasis had a poorer prognosis than those without. Liver metastasis might have no relationship with bone or lung metastasis and liver might play a more dominant role than the other two sites in the prognosis of GIST patients with metastasis. So, more attention should be paid to liver status in diagnosis and treatment of GIST patients.

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D. Y. Yang

Papers

Metastatic pattern and prognosis of gastrointestinal stromal tumor (GIST): a SEER-based analysis