Gastrointestinal Stromal Tumor

Tumor invades pancreatic tail, and lymph node metastasis was observed. She was discharged on the postoperative day 27 and alive without tumor recurrence at 6 months after surgery, not undergoing adjuvant chemotherapy.

P1, N=30, Active, not recruiting, Deciphera Pharmaceuticals LLC | Recruiting --> Active, not recruiting

The follow-up CT scan revealed peritoneal nodules suggestive of peritoneal dissemination, and Entrectinib (a TRK inhibitor) was administered...The present case may offer new insights into the potential introduction of TRK inhibitors as treatments for GISTs with NTRK fusions. Additionally, the presence of abundant lymphoid infiltration in the present case may prompt further research into immunotherapy as a possible additional therapeutic option.

The novel nomogram developed based on the combined model helps predict the recurrence of MH-GIST. The nomogram of clinical and Delta-CT radiomics has important clinical value in predicting the recurrence of MH-GIST, providing reliable data reference for its diagnosis, treatment, and clinical decision-making.

P1/2, N=32, Terminated, Theseus Pharmaceuticals | Active, not recruiting --> Terminated; The Sponsor terminated the study due to early dose-limiting toxicities.

P1, N=240, Recruiting, IDRx, Inc. | N=143 --> 240

P1, N=30, Suspended, DNAtrix, Inc. | Trial completion date: Dec 2023 --> Dec 2026 | Recruiting --> Suspended | Trial primary completion date: Jul 2022 --> Jul 2026

We examined the TGF-β1 mRNA expression of 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. Finding TGF-β1 expression may indicate that this cytokine plays a part in the formation of desmoplasia within GIST cell proliferative areas.

Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

P1, N=78, Recruiting, Taiho Pharmaceutical Co., Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=38, Active, not recruiting, National Cancer Institute (NCI)

P2, N=28, Recruiting, Reema A. Patel | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2024 --> Dec 2025

Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

In vitro and in vivo studies demonstrated that the synergistic effect of tumor targeting with pH sensitivity plays a vital role in the high signal-to-noise ratio of the NIR imaging probe. Moreover, different kinds of tumor-targeting vectors could be conjugated simultaneously with the NIR dye, which would further improve the receptor affinity and targeting efficiency.

P2, N=28, Not yet recruiting, Asan Medical Center

P1, N=68, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

P=N/A, N=136, Not yet recruiting, Bayer

P1, N=100, Recruiting, Ascentage Pharma Group Inc. | N=60 --> 100

P=N/A, N=0, Withdrawn, University of Southern California | N=20 --> 0 | Trial completion date: Mar 2025 --> Mar 2024 | Recruiting --> Withdrawn

When an SMT of the stomach is identified, the possibility of gastric IMT should be considered.

After processing, 8600 variants were submitted programmatically from the INT2GRATE|HPPGL platform to ClinVar via a custom-made INT2GRATE|HPPGL variant submission schema and an application programming interface (API). This novel integrated variant assessment and data sharing in hereditary cancers aims to improve the clinical assessment of genomic variants and advance precision oncology.

In addition, IDO1+ dendritic cells (DC) were highly enriched in imatinib-resistant TME, interacting with various myeloid cells via the BTLA-TNFRSF14 axis, while the interaction was not significant in imatinib-sensitive TME. Our study highlights the transcriptional heterogeneity and distinct immunosuppressive microenvironment of advanced GIST, which provides novel therapeutic strategies and innovative immunotherapeutic agents for imatinib resistance.

They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

We show that coordinate disruption of four CTCF motifs in the boundary fuses the adjacent TADs, allows the ANO1 enhancer to contact FGF3, and causes its robust induction. High-resolution micro-C maps reveal specific contact between transcription initiation sites in the ANO1 enhancer and FGF3 promoter that quantitatively scales with FGF3 induction such that modest changes in contact frequency result in strong changes in expression, consistent with a causal relationship.

In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.

We conclude with presenting case studies that identify both the clinical utility and informatic challenges of variant calling specific to gene panel sequencing e.g., i) the capture of potential targetable rare and novel indels and multivariant mutations in exons 19 and 20 of EGFR, and ii) a unique KIT tandem duplication event in a gastrointestinal stromal tumor (GIST). We demonstrate the value in precision oncology for multiple cancer types and how the capture of unique variants can provide better targeted treatment options to cancer patients.

Clinically, about 80-90% of treatment-naive GIST patients harbor primary KIT mutations, and special KIT-targeted TKI, imatinib (IM) showing dramatic efficacy but resistance invariably occur, 90% of them was due to the second resistance mutations emerging within the KIT gene...In this review, we elucidate the biologic mechanism of KIT variants and update the underlying mechanism of the expression of KIT gene, which are exclusively regulated in GIST, providing a promising yet evidence-based therapeutic landscape and possible target for the conquer of IM resistance. Video Abstract.

This series highlights the fact that accurate histological diagnosis of hepatic or perihepatic PEComas is important to prevent unnecessary aggressive treatment, unlike primary hepatocellular carcinomas or hepatoid/epithelioid metastatic tumors.

Parasympathetic PGs showed a higher Hand2 H-score compared to sympathetic PGs (median H-scores 280 vs. 104, p < 0.0001). Hand2 positivity in NENs serves as a reliable marker of primary and metastatic PG, since other NENs only rarely exhibit limited Hand2 positivity.

Tumor location, tumor size and Ki-67 were independent risk factors for postoperative recurrence and metastasis in patients with low-risk GISTs. Based on the 2008 modified NIH recurrence risk grading system, combined with the above three factors, it can be used to evaluate the prognosis of patients with low-risk GISTs and provide personalized postoperative review and follow-up management recommendations.

P2, N=48, Recruiting, Asan Medical Center | Not yet recruiting --> Recruiting

P2, N=29, Recruiting, Asan Medical Center | Not yet recruiting --> Recruiting

This analysis of MUTYH alterations in a large set of solid cancers suggests that in addition to the established role of biallelic pathogenic MUTYH variants in cancer predisposition, a broader range of cancers may possibly arise in MUTYH heterozygotes via a mechanism involving somatic LOH at the MUTYH locus and defective BER. However, the effect is modest and requires confirmation in additional studies before being clinically actionable.

Overall, comparing NGS results with those of conventional methods showed high concordance. In conclusion, the NGS panel allows reliable analysis of 1p/19q codeletion and mutation at the same time.

Common differential diagnoses include leiomyoma, schwannoma, and solitary fibrous tumor. This article presents a classic GIST case and showcases relatively simple diagnostic clues for identifying similar lesions that may occur in diverse locations.

In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts.

Despite the limitation of sample size, our study identified actionable alterations in 28% of tumor samples submitted to CGP. A high level of evidence of clinical activity according to OncoKB criteria was noted in 41% of actionable alterations. These findings underscore the importance of comprehensive genomic profiling in managing sarcomas.

Immunohistochemistry revealed positive staining for CD34 and CD117, negative staining for SMA, positive staining for DOG1, and negative staining for S100. Additionally, the expression of ki67 was 3%.

P1, N=34, Terminated, Daiichi Sankyo | Completed --> Terminated; The study was terminated due to a business decision.

P2, N=48, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P3, N=185, Terminated, Jiangsu HengRui Medicine Co., Ltd. | N=304 --> 185 | Recruiting --> Terminated; R&D strategy adjustment

In our study, GISTs most frequently develop in the stomach, and CD117 and DOG1 are essential for correctly diagnosing these tumors. However, HER-2 immunoreactivity is a predictive marker of survival for personalized care.