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MSK-IMPACT

This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

Treatment of Ba/F3 or lung cells expressing MDK::ERBB2 with ERBB2 inhibitors (afatinib, poziotinib, tucatinib) blocked phosphorylation of ERBB2 and downstream effectors, and inhibited growth of both cell lines. ERBB2 fusions are rare oncogenic drivers that are candidates for targeted therapy. The subset of recurrent ERBB2 fusions with C-terminal/3' partners may represent an alternative mechanism of fusion oncogenicity.

IDH1/2 mutations are identified in a small subset of NSCLCs. Our findings suggest that >25% of these mutations are hematopoietic in origin with important implications for diagnosis and management of these patients. Among those with mutations arising from the lung neoplasm, IDH1/2 mutations were primarily seen in conjunction with another driver and were subclonal in nature, suggesting patterns of clonal heterogeneity and evolution.

P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024

Radiographic findings such as enhancing disease and contact of the tumor with the ventricular space were positively associated with CSF ctDNA positivity. Additionally, CSF ctDNA was associated with positive cytology in 12/12 cases (100%).With our improved pipeline, we hypothesize CSF ctDNA may be used as a prognostic biomarker for survival, but confirmation requires further validation in a prospective study.

Alterations in key driver genes are associated with initial development and progression of CRC BM. BRAF alterations are enriched in PT of patients who develop BM. SMAD4 alterations are enriched in BM compared to extracranial disease and furthermore predict early IP after BM-targeted therapy.

Clinical germline sequencing identifies a germline mutation in a high proportion of patients with CNS tumors. Biallelic inactivation was most commonly identified in tumors from patients with germline TP53 or NF1 mutations and were less common in patients with a germline MMR alteration.

ctDNA positivity corresponded with shortened overall survival after CSF collection (HR: 3.23, 95% CI: 2.58-4.05, P < 0.001).NGS of CSF cfDNA can detect clinically actionable somatic alterations in a large subset of CNS cancer patients and allows tracking of tumor evolution. Detection of somatic alterations in CSF may be a useful prognostic biomarker for survival in cancer patients.

Dynamic modelling using a deep learning approach can be applied successfully to predict CAT. In the current use case, model discrimination was at its highest using a 7-day time horizon, even though longer time spans also yielded potentially clinically useful risk estimates. When appropriately implemented, this dynamic model may lead to adaptive and shortened exposure of therapeutic anticoagulation when patient’s temporal risk profile exceeds a predetermined threshold.

Our single center analysis confirmed AITL as the most common variant of nTFHL. AITL and non-AITL appear similar regarding clinical presentation, molecular profile, and outcomes. DNMT3A adversely impact outcomes, as previously reported.

Deleterious DDR alterations were associated with pathologic response following NAC in S1314. Functional validation of ERCC2 and other DDR alterations is underway to help refine such alterations as biomarkers of NAC in patients with bladder cancer.

P1, N=1, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

No abstract available

In colon adenocarcinoma, we observe a significantly higher rate of clinical detection for TP53-positive tumors, while in lung adenocarcinoma, the same is true for EGFR-positive tumors. Compared to classical MHNs, this approach eliminates several spurious suppressive interactions and uncovers multiple promoting effects.

Our study aims to systematically evaluate how Chr13q deletion impacts the progression of PC and its susceptibility to treatment. We anticipate that our study will establish a solid foundation of knowledge that can be used to identify aggressive primary PC and the related risk of progressing to lethal CRPC. This will help develop more effective treatments for patients with aggressive and lethal PC, particularly those with Chr13q..

P2, N=63, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.

Finally, patients who died of disease in less than 24 months (n=45; 28%) showed enrichment of bordetella (21% vs. 8%; OR 3.11; p = 0.050) compared to those with more durable survival. Conclusions These findings highlight potential biomarkers in the TME, suggesting several directions for future studies to leverage large-scale genomic sequencing to identify microbial signatures that can form the basis of prognostication and targeted therapeutics.

All pts received treatment for metastatic disease, 5 received first-line (1L) ChemoIO with platinum/etoposide plus durvalumab (N=3) or atezolizumab (N=2) and 8 received 1L Chemo with platinum/etoposide. A prospective trial of first-line chemoimmunotherapy in advanced extrapulmonary NECs is ongoing NCT05058651.4 Ethics Approval MSK IRB 19-006.View this table:View inline View popup Download powerpoint Abstract 708 Table 1 Download figure Open in new tab Download powerpoint Abstract 708 Figure 1 Kaplan-Meier curves denoting Progression Free Survival (PFS) for patients treated with first-line chemoimmunotherapy vs. first-line chemotherapy. The median PFS for chemoimmunotherapy group was 17.3 months (95% CI 11.6-NR) versus 5.8 months (95% CI 2.0-NR)

Introduction Mirvetuximab soravtansine-gynx (MIRV) is an antibody-drug conjugate that binds to folate receptor alpha and delivers a microtubule inhibitor payload...Median PFS did not significantly differ based on number of prior treatment lines (for 1-3 versus >3 lines, P = 0.3) or prior PARP inhibitor ( P = 0.9) or bevacizumab ( P = 0.4) use...Conclusion/Implications MIRV confers meaningful PFS benefit for a subset of individuals. Biomarkers of response and resistance are urgently needed to optimize patient selection for treatment.

Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Additional immunohistochemistry for p53 in patients with LADC histology in the Tokyo Medical and Dental University cohort showed a significant correlation between TP53 mutations and abnormal IHC pattern of p53 (Cramer's correlation coefficient V = 0.67). TP53 mutation is a potential marker for worse prognosis in surgically resected LADC; immunohistochemistry for p53 could be a surrogate method to identify patients with LADC with a worse prognosis.

ctDNA detection was associated with shortened overall survival following CSF collection. Next-generation sequencing of CSF, collected through a minimally invasive lumbar puncture in a routine hospital setting, provides clinically actionable cancer genotype information in a large fraction of patients with CNS tumors.

This study reveals how age-associated somatic mutations in the microenvironment may be driving DCC reactivation and relapse. These findings may provide a new genetic biomarker of relapse and inform CH-targeted trials to improve breast cancer patient outcomes.

In this workshop we review the development, validation and clinical implementation of Pillar Biosciences' rapid 21-gene solid tumor & heme panel oncoReveal Nexus by Memorial Sloan Kettering Cancer Center (MSKCC). We will review this assay's concordance with the MSKCC's MSK-IMPACT® panels and discuss how this type of rapid testing can be leveraged by other clinical laboratories as tool to help sub-select and inform which patients should have CGP testing performed.

Join us and experts from MSK to: • Discover the clinical utility of MSK-IMPACT® at MSK. • Explore the decentralized workflow, robust technology, and analytical performance of MSK-IMPACT® powered with SOPHiA DDM™.

Adding the CDK4/6 inhibitor palbociclib enhanced the antitumor activity of EP0062 or fulvestrant in ESR1-mutant models but not in HER2-enriched or PTEN-mutant PDX models...EP0062 triggers an E2F1 downmodulation which mediates a potent antiproliferative activity. For EP0062-resistant tumors that remain ER-driven, the addition of palbociclib displays a potent antitumor effect.

Well-differentiated papillary peritoneal mesothelial tumors were primarily incidental findings. There was no WDPMT-related mortality, so there was no distinct role for routine cytoreductive surgery or systemic therapy. Genomic profiles can help to differentiate WDPMT from DPM and PM.

P2; Trial completion date: Jun 2024 --> Dec 2024

HRAS-mutant tumors demonstrate lineage-dependent MAPK or PI3K pathway alterations, which confer resistance to tipifarnib. The combined use of FTIs and MEK inhibition is a promising strategy for HRAS-mutant tumors.

Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

While ULMS patients had a relatively low proportion of PGV, a high percentage of STLMS patients with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations.

Across the assessed cancers, GNAS-mut tumors exhibit a conserved molecular and clinical phenotype defined by mucinous tumor status, increased peritoneal metastasis, poor response to first-line systemic therapy, and worse survival.

By contrast ScfDNA samples had negligible contamination. Finally, ScfDNA testing exclusively used as a rescue strategy delivered successful results in 71% of cases where tumor tissue from CB was depleted.

The 3 rd -generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib (Osi), has extensively improved patients outcomes...Conclusions : Our results show that ILK is important in promoting EMT and DTP survival in EGFR-driven LUAD. Targeting ILK may be a viable strategy to manage minimal residual disease and EGFR TKI resistance in lung cancer.

ERK1/2 (ulixertinib and SCH772984), MEK1/2 (binimetinib), and PI3K (pictilisib) inhibitors inhibited growth of RRAS Q87L or RRAS2 Q72L cells more potently than cells expressing wildtype proteins. Oncogenic R RAS/RRAS2 mutations were detected in LUAD at a rate similar to some other well-characterized lung cancer drivers, such as HRAS/NRAS hotspot mutations or NRG1 fusions. Our study supports the inclusion of RRAS /RRAS2 into routine molecular diagnostic protocols for precision oncology and clinical development of pan-RAS inhibitors, such as RMC-6236, for patients with these driver mutations in order to fully realize the potential benefit of RAS-targeted therapies.

In newly diagnosed advanced GIST, ctDNA detection rate of the GIST genotype was low and inversely correlated with duration of rx exposure. However, ctDNA responses proceed radiographic responses, which may be further exploited for non-invasive monitoring of rx response and emerging therapeutic resistance mutations.

Despite numerous treatment strategies designed to overcome primary resistance to PD1/PD-L1 therapy, response to ICI remains limited in LMS. Neither MSI nor TMB status appear to be strong predictive markers for response to ICI in LMS.

Considering the recent approval of capivasertib for HR+/HER2- metastatic breast cancer (MBC) harboring PI3K-AKT pathway alts based on tissue NGS, we assessed the concordance of tissue and ctDNA NGS for PIK3CA, AKT1, PTEN as well as ESR1. We identified 367 HR+/HER2- MBC pts treated at MSK with tissue NGS by MSK-IMPACT within 60 days of ctDNA NGS by either Guardant360 or MSK-ACCESS, without intervening therapy... Tissue-ctDNA concordance for the detection of any oncogenic alteration was high for PIK3CA, AKT1, moderate for ESR1, and low for PTEN. More alts were detected in ctDNA for ESR1 and in tissue for PTEN, reflecting acquired ESR1 alts after estrogen deprivation and the current lack of ctDNA assay PTEN copy number loss detection. Additional correlative analyses (e.g.

Our study provides valuable insights into the understanding of age- and ethnic-driven molecular and clinical disparities in breast cancer patients. By unraveling the intricate relationship between genetic alterations and clinical outcomes, we underscore the potential for personalized treatment strategies in BC patients guided by molecular profiles. Nevertheless, further investigations are warranted to elucidate the underlying mechanisms that govern these dynamic processes.

The addition of 10 new cases, alongside the previously documented 20, enriches our understanding of ELOC-mutated RCC’s clinical and molecular features. Our findings suggest a fivefold higher incidence in Japan (3.9%, 13/337 combining Mutographs and Sato) compared to other studied countries (<1%), unrelated to the increased prevalence of mutational signature SBS12 recently discovered in Japan. Additionally, our study uncovers four novel mutation sites within the ELOC/VHL binding regions, expanding the known diversity beyond the initial four identified sites.

In addition, a study of comprehensive genomic profiling of metastatic mucinous carcinoma identified genetic abnormalities, including FGFR1 and ERBB2 amplification, which have been reported to be potential therapeutic targets. Although no genetic mutations were identified in this case, this data could be important in understanding the unique pathology