TEST:

FoundationOne® Heme CDx

P=N/A, N=150, Recruiting, Medical University of Vienna | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Mar 2026

The presence of PPGVs warrants formal genetic counselling and germline testing. Given the similar prevalence of PPGVs in this study compared with data from other countries, and the diagnostic and therapeutic implications of detecting incidental PPGVs, we underscore the need for cancer genetics to be incorporated into standard oncologic care in the Philippines.

While exceedingly rarely, FH mutations may be found in uLMS. Confirmation of FH deficiency should not preclude the diagnosis of sarcoma in smooth muscle neoplasms that meet histologic criteria for malignancy.

Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.

Overall, in our uLMS analysis, CDK4 and/or MDM2 amplification was identified in a small subset (2%) of uLMS, the majority of which are TP53/RB1-wildtype. This may suggest that CDK4/MDM2 amplification can be an alternative tumorigenic mechanism in this distinct class of uLMS, which may have therapeutic clinical implications, including possible use of specific cyclin-dependent kinase inhibitors.

The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.

Our study identified biologic differences between Hispanic and non-Hispanic AML patients with heterogeneity in genetic mutations. While Hispanic patients had lower income, they were younger at diagnosis and more likely to have favorable risk AML. Hispanic patients had better PFS and a trend towards improvement in OS.

Our data offer a cellular and molecular insight into a case of clinical pseudoprogression observed during tolinapant treatment. Understanding pseudoprogression is important for clinical investigators and patients to ensure treatment with tolinapant, or other IAP antagonists, are not discontinued prematurely.

Blue indicates positive correlation, red indicated negative correlation. Only significant correlations (p<0.01) are shown.

CD36 mutations were frequent in AML and MDS in our series, which might have implications in pathogenesis of myeloid neoplasm. Certain mutations (e.g., splice site) might have association with lymphoid malignancies.

Our report represents one of the most extensive and detailed studies regarding the landscape of BCL11B point and indel mutations in human cancer. BCL11B alterations occur widely in mature, immature, B-cell, Tcell, and sarcomatous malignancies. TP53, PIM1, and SOCS1 are the most commonly co-mutated genes.

We further observed that sarcomas with alterations in RAD51B or GID4 were enriched in samples with high telomeric content, specifically within uterus leiomyosarcoma for RAD51B and soft tissue sarcoma (not otherwise specified, nos) for GID4, Furthermore, RAD51B and POT1 alterations were mutually exclusive with ATRX and DAXX alterations, suggestive of functional redundancy. Our results propose a role played by RAD51B and GID4 in telomere elongation in sarcomas and open research opportunities for agents aimed at targeting this critical pathway in tumorigenesis.

KMT2C A2254T has only been reported in astrocytoma. To our knowledge, this is the first case report of FBXW7 and KMT2C mutations in FDCS, which may indicate biologic and therapeutic relevance (Figure 1.82, A–D).

Conclusions Tumor-agnostic CGP provides more treatment options to patients with advanced solid tumors when compared to organ-directed NGS panel testing. The national MTB provides recommendations within a clinically relevant timeframe and enhances the uptake of MGTs.

This study demonstrates performance characteristics that suggest Duoseq would perform well as a clinical-grade assay. Local laboratory factors that include staffing, case volumes, and reimbursement affect adoption and turnaround times in the individual clinical laboratory. However, we anticipate that Duoseq implementation will accelerate the diagnosis of hematologic malignancies and facilitate rapid, more cost-effective care to improve patient outcomes.

Premalignant mutations (e.g., ASXL1, TET2) predominated in our patients and tended to co-occur, increasing the overall mutational burden. Non-White patients were more likely to have IDH2 mutations. Adverse markers were common among AML & MDS patients, likely contributing to their dismal survival.

P1/2 | N=320 | Recruiting | Sponsor: Centre Leon Berard | N=120 ➔ 320

RWD based clinical genomic profiling confirms that the vast majority of RAS-alterations in CRC are SVs in exons 2, 3 and 4. Both TMB-high and MSI-high samples are significantly more abundant in the RAS/BRAF-altered cohort. RWD confirms that PI3K-, ERBB- and FGFR-signaling pathways are frequently altered in CRC.

She completed radiotherapy with concurrent and adjuvant temozolomide (TMZ) per Stupp protocol...She failed bevacizumab (bev) alone or in combination with TMZ. Therefore, BEEP (Bev 15mg/kg D0, etoposide 70/m2 D1-D3, cisplatin 70/m2 D1, Q21D) was given for salvage...Nested RT-PCR or NGS are better options. Legal entity responsible for the study The authors.

uLMS with heterologous differentiation shows genomic overlap with conventional uLMS with similar driver alterations. Comprehensive genomic profiling of uLMS with aberrant differentiation can help diagnose and improve tumor classification.

Recognizing and referring patients with possible germline mutations for appropriate genetic evaluation and testing provides insight into best patient care strategies along with education and testing opportunities for family members. Leukemia based NGS panels may aid as screening tools for detecting potential pathogenic germline variants.

We are reporting a positive correlation between MYD88 allelic burden and Clonal B-cell fraction in LPL. Quantitative molecular assay for MYD88 might be useful for evaluation of residual disease in LPL.

Cohesin mutations were frequent in AML-MRC in our series. Additional studies are needed for delineating any prognostic differences between the types of Cohesin mutations and for exploring the possibility of novel therapeutic targets.

CGP of PCLs reveals biomarkers, genomic alterations, and molecular classifications predictive of BTKi efficacy and potential ICPI efficacy. Given the limitations of standard of care for PCL, CGP is critical to identify potential therapeutic approaches for patients in this rare form of lymphoma.

"LB detected relevant genomic alterations in the majority of patients with a variety of HNs. Given its analytical sensitivity, LB may also detect low-level residual or emerging therapy-resistant clones unable to be detected in a single tissue specimen and may play a role in the evaluation of the patient's disease course and in associated treatment decisions. This pilot study suggests the potential value of LB in the clinical management of patients; however, further prospective evidence would be required to quantify the utility of LB for patients with HNs."

Our results may suggest that when healthcare access is not a barrier to treatment, Hispanic patients with AML can have similar, if not improved, outcomes to other populations. However, access to transplant remains a major barrier that needs to be further addressed to improve outcomes for this patient population.

P2 | "Notably, a complete SMARCB1/INI1 deletion (targetable by tazemetostat) was identified... NGS in conjunction with OGM demonstrated improved detection of clinically actionable alterations for this patient. Thus, both tests should be routinely considered as a part of the diagnostic regimen to better characterize key mutations in rare tumors and uncover actionable targets for treatment. Combining multiple types of molecular analyses uncovered that this patient was eligible for a novel clinical trial."

While these also likely cause MAPK pathway activation, these non-BRAF variants are less common in PAs. Our report contributes to growing evidence that PMAs harbor a distinct molecular alteration profile, which is becoming increasingly important in the context of the evolving targeted therapeutics landscape.

Comprehensive genomic profiling tests can improve diagnostic accuracy and allow for a more reliable approach to the management of pediatric patients with nervous system tumors. Although in most patients there was no immediate therapeutic application of the potential targets found, the genomic data obtained could be very useful to patients who may have tumor progressions in the future.

"Two studies leveraging Foundation Medicine’s novel homologous recombination deficiency signature (HRDsig) to explore whether this biomarker is associated with FOLFIRINOX benefit in patients with metastatic pancreatic cancer via the Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB), and to understand the prevalence of HRDsig positivity in non-small cell lung cancer using FoundationOne^®CDx....A real-world analysis of 447 men in the CGDB with de novo metastatic prostate cancer treated in standard of care settings, found that the subgroup with SPOP mutations had much more favorable time to castration resistance and overall survival if treated with second generation hormonal agents versus docetaxel. Another study using Foundation Medicine’s tissue-based comprehensive genomic profiling (CGP) test found that SPOP mutations occur in a moderate number of Clinically Advanced Prostate Cancer (CAPC) cases..."

A diagnosis of SCCOHT was made in spite of neg-ative staining for WT1 and retained but attenuated staining for BRG1. It is the combination of elaborated immunostaining, FISH studies and extensive genetic analysis that brought to this rare diag-nosis. As genetic studies become more prevalent, it is expected to note growing variability in gene expression for any described gene alteration, that should not exclude the related diagnosis.

Furthermore, our results demonstrated that RAD51B and POT1 alterations were mutually exclusive with ATRX and DAXX alterations, suggestive of a redundancy between alterations in these genes. Conclusions Our results suggest a role played by RAD51B, GID4, and POT1 in telomere elongation in sarcomas and open research opportunities for agents aimed at targeting this pathway.

P2; N=50 --> 1 | Trial completion date: Dec 2025 --> May 2022 | Recruiting --> Terminated | Trial primary completion date: Aug 2025 --> May 2022; In a preliminary analysis the primary endpoint was negative and ongoing portions of the study have therefore been discontinued.

Targeted TKI therapies in the upfront setting are associated with excellent outcomes in patients with MLN-Eos. The elucidation of potential mechanisms needs further exploration.

Offered therapies included ibrutinib for DLBCL with a CD78B mutation, romidepsin for T cell lymphoma with a TET2 mutation, and ruxolitinib for T cell lymphoma with JAK2 fusion...Identified resistance mutations included alterations in BTK , PLCG2 , and BCL2 genes, which led to changes in therapy from a BTK inhibitor to venetoclax or vice versa...Conclusion Comprehensive genomic profiling of non-myeloid hematologic malignancies identified variants of clinical significance in 72% of patients and led to changes in practice in 22% of patients. CGP was often sent late in the clinical course.

Comprehensive genomic profiling of non-myeloid hematologic malignancies identified variants of clinical significance in 72% of patients and led to changes in practice in 22% of patients. CGP was often sent late in the clinical course.

The deletion of the SMARCB1/INI1 gene leads to activation of certain pathways, which can be targeted for treatment with the drug Tazemetostat... NGS in conjunction to OGM can provide improved detection of clinically relevant variants for genetic disease. Thus, both tests should be considered as a part of the diagnostic regimen to better characterize key mutations in rare tumors and uncover actionable targets for treatment.

P2 | N=50 | Recruiting | Sponsor: Hoffmann-La Roche | Trial primary completion date: Dec 2025 --> Aug 2025

Our study showed that clinical sequencing might be useful for detecting gene alterations in various cancer types and exploring treatment options. However, many issues still need to be improved.

P1/2, P3; This analysis supports the utility of NMF used in conjunction with targeted sequencing platforms for identifying patients with different prognostic subsets. The observed trend for improved overall survival in the BCL2/EZH2 group is consistent with the mechanism of action of venetoclax, suggesting that targeting sequencing and NMF has potential for identifying patients who are more likely to gain benefit from venetoclax therapy.

P1; Trial completion date: Mar 2024 --> Nov 2021 | Suspended --> Terminated | Trial primary completion date: Jul 2023 --> Nov 2021; low recruitment

Overall, in our pan-LMS analysis, HPV reads were identified in a subset of TP53/RB1-wildtype LMS. For all HPV51-associated LMS, the striking absence of any detectable TP53 or RB1 mutations and predilection for the female lower reproductive tract supports our hypothesis that high-risk HPV can be an alternative tumorigenic mechanism in this distinct class of LMS.