The Integrated i31-GEP Test Outperforms the MSKCC Nomogram at Predicting SLN Status in Melanoma Patients.

BACKGROUND/AIM: Sentinel lymph node biopsy (SLNB) for patients with cutaneous melanoma is primarily a prognostic procedure that broadly identifies patients who may have disease progression and may warrant additional intervention. However, 88% of patients undergoing SLNB receive a negative result and of those, some will succumb to their disease. One clinical utility of the integrated 31-GEP test, which combines gene expression data with clinicopathologic factors to provide a personalized, precise risk of SLN positivity, is SLNB guidance. This study compared the i31-GEP for SLNB to a nomogram that predicts SLN positivity using only clinicopathologic factors. PATIENTS AND METHODS: Patients with T1-T2 tumors and known SLN status (N=465) were analyzed by the i31-GEP for SLNB and a nomogram developed at Memorial Sloan Kettering Cancer Center (MSKCC). A 5% risk threshold was used to conform with national guidelines. RESULTS: In patients with <5% predicted risk, SLN positivity was 2.7% (3/111) for i31-GEP versus 10.0% (11/110, p=0.026) for MSKCC. In each T-category, the i31-GEP maintained a false-negative rate below the 5% risk threshold in those predicted to have a <5% risk, while the MSKCC nomogram did not. CONCLUSION: Integrating the 31-GEP with traditional factors outperformed a nomogram that uses clinicopathologic factors alone to predict SLN status. Incorporating the i31-GEP into clinical practice could improve identification of patients for SLNB, resulting in better risk-aligned management.

Elemental Dynamics in Hair Accurately Predict Future Autism Spectrum Disorder Diagnosis: An International Multi-Center Study.

Autism spectrum disorder (ASD) is a neurodevelopmental condition diagnosed in approximately 2% of children. Reliance on the emergence of clinically observable behavioral patterns only delays the mean age of diagnosis to approximately 4 years. However, neural pathways critical to language and social functions develop during infancy, and current diagnostic protocols miss the age when therapy would be most effective. We developed non-invasive ASD biomarkers using mass spectrometry analyses of elemental metabolism in single hair strands, coupled with machine learning. We undertook a national prospective study in Japan, where hair samples were collected at 1 month and clinical diagnosis was undertaken at 4 years. Next, we analyzed a national sample of Swedish twins and, in our third study, participants from a specialist ASD center in the US. In a blinded analysis, a predictive algorithm detected ASD risk as early as 1 month with 96.4% sensitivity, 75.4% specificity, and 81.4% accuracy (n = 486; 175 cases). These findings emphasize that the dynamics in elemental metabolism are systemically dysregulated in autism, and these signatures can be detected and leveraged in hair samples to predict the emergence of ASD as early as 1 month of age.

Uveal melanoma patient attitudes towards prognostic testing using gene expression profiling.

Aim: This study explored uveal melanoma patient experiences and regret following molecular prognostic testing using a 15-gene expression profile (GEP) test. Materials & methods: A retrospective, cross-sectional survey study was conducted through an online questionnaire capturing patient-reported experiences with prognostic biopsy/molecular testing. Results: Of 177 respondents, 159 (90%) wanted prognostic information at diagnosis. Most 15-GEP-tested patients who shared their results (99%) reported gaining value from testing, as did patients tested with other methods. Patients who received prognostic testing experienced lower decision regret than those who opted out. Decision regret did not differ based on GEP class. Conclusion: Most uveal melanoma patients desire prognostic testing and gain value from the GEP, independent of a high- or low-risk result.

Uveal melanoma is a rare but aggressive eye cancer, resulting in distant metastasis in nearly 50% of patients. Molecular prognostic testing is often employed to determine who is at high or low risk of developing metastatic disease. A prognostic 15-gene expression profiling (GEP) test is commonly used throughout the USA and parts of Canada. The goal of this survey was to assess patient experiences with the 15-GEP and other prognostic methods. Of the 177 patients who participated in the survey, the majority reported that they wanted prognostic information at the time of diagnosis. Of patients who underwent 15-GEP testing, nearly all reported gaining value from their test result, regardless of their individual risk profile. This study supports prior findings using other prognostic methods that patients prefer information about their risk of metastasis and reinforces the importance of discussing prognostic testing options with newly diagnosed uveal melanoma patients.

Use of prognostic gene expression profiling tests in primary breast cancer treatment: a German real-world patient survey.

Aims: In primary breast cancer, gene expression profiling tests can support adjuvant chemotherapy treatment decisions. Real-world test use in Germany was investigated in an online survey of female breast cancer patients (n = 475). Materials & methods: Relationships between three groups were examined for clinical and statistical relevance: no test indication (n = 353), test indication and tested (n = 65), and test indication but not tested (n = 57). Results: A total of 47% of participants with a test indication were not tested. Test rates increased by 23% from 2012-2018 (49%) to 2019-2021 (60%). A total of 65% of patients without testing received chemotherapy, whereas only 38% of tested patients received chemotherapy. Conclusion: The use of gene expression profiling tests correlates with a real-world chemotherapy reduction. Gene expression profiling testing may improve patient confidence in the decision for or against chemotherapy.

In many cases, breast cancer can be removed by surgery. In addition to surgery, breast cancer patients may also receive chemotherapy; however, chemotherapy is not always useful. A gene expression profiling test can help physicians and patients decide if chemotherapy should be used. In a survey, 475 breast cancer patients in Germany were asked if they received such a test and chemotherapy. A total of 65% of patients who were not tested received chemotherapy compared with 38% of patients who were tested. Patients who received a test also felt more certain about their treatment decision. However, four of ten patients who were diagnosed between 2019 and 2021 and for whom a test would have helped in the treatment decision did not receive a test. Therefore, there is still room to increase the use of gene expression profiling tests for the benefit of breast cancer patients in Germany.

The future of laboratory testing in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) is a malignant lymphoproliferative disorder characterised by the accumulation of dysfunctional B-lymphocytes in the blood and lymphoid tissues. It is a clonally complex disease with a high degree of both intra-tumoural and inter-patient heterogeneity. This variability leads to a wide range of clinical outcomes and highlights the critical need for accurate prognostic tests in CLL. With the advent of a range of new targeted agents for CLL in recent years, there is also a clinical need for improved predictive tests to therapy. This review of laboratory testing in CLL focuses on emerging technologies for prognostication including single nucleotide polymorphism microarray for karyotypic analysis, targeted next generation sequencing analysis of the immunoglobulin heavy chain variable region gene as well as genes recurrently mutated in the disease such as TP53, and detection of minimal residual disease.

The role of preoperative CEA in the management of colorectal cancer: A cohort study from two cancer centres.

BACKGROUND: The primary aim of this study was to investigate whether a preoperative elevation in serum CEA is an independent prognostic factor for both 5-year overall and disease-free survival within an Australian patient cohort. MATERIALS AND METHODS: A retrospective study of a prospectively maintained colorectal neoplasia database for patients between January 2010 and June 2016 was performed. Patients were categorized into two groups according to the preoperative serum CEA level: low (<2.5), high CEA (≥2.5), and elevated (≥5 ng/ml); and further stratified by disease stage. Inclusion criteria were patients having had a resection for either a colonic or upper third rectal adenocarcinoma and with a preoperative CEA value. Data on patient demographics, mortality, and morbidity and survival were compiled. Five-year estimates of overall (OS) and disease-free survival (DFS) were assessed. RESULTS: 623 patients met the inclusion criteria. The median patient age was 73 (range 22-97) and 55% female (n = 340). There were 572 colonic cancers and 51 rectal cancers. The median follow-up time was 25 months (range 1-71). Eight patients (1%) had a local recurrence and 62 patients (10%) had evidence of metastatic disease after the initial curative resection. The 5-year OS and DFS rates for patients with CEA level <2.5 ng/ml were 85% and 86% respectively, which were higher than those with CEA level ≥2.5 ng/ml (73% and 79% respectively). Independent predictors of recurrence were a CEA ≥5 ng/ml (HR 1.8; 95% CI 1.09-3.00; p = 0.002) and stage II (HR 5.33; 95% CI 1.59-17.90; p = 0.007) and stage III (HR 10.91; 95% CI 3.34-35.60; p=<0.001). A CEA ≥5 ng/ml was associated with a higher risk of death (HR 1.79; 95% CI 1.00-3.19; p = 0.046). CONCLUSION: Preoperative CEA levels were associated with age, BMI, ASA and tumour stage. Overall, CEA remains a reliable predictor of recurrence and survival after curative surgery in patients with colorectal cancer.

Brachytherapy for patients with uveal melanoma: historical perspectives and future treatment directions.

Surgical management with enucleation was the primary treatment for uveal melanoma (UM) for over 100 years. The Collaborative Ocular Melanoma Study confirmed in 2001 that globe-preserving episcleral brachytherapy for UM was safe and effective, demonstrating no survival difference with enucleation. Today, brachytherapy is the most common form of radiotherapy for UM. We review the history of brachytherapy in the treatment of UM and the evolution of the procedure to incorporate fine-needle-aspiration biopsy techniques with DNA-and RNA-based genetic prognostic testing.

Clinical application of genetic testing for posterior uveal melanoma.

Uveal melanoma is the most common primary intraocular tumor in adults, and it has a strong potential to metastasize. Traditionally, clinicopathological features of these tumors were used to provide a limited prediction of the metastatic risk. However, early genetic studies using karyotype analysis, fluorescence in situ hybridization, and comparative genetic hybridization of posterior uveal melanoma samples identified multiple chromosomal abnormalities associated with a higher risk of fatal metastasis. This correlation between specific genetic abnormalities in uveal melanoma and a patient's risk for development of metastasis has recently been widely studied, and the development of new prognostic tests has allowed clinicians to predict this metastatic risk with increased accuracy. Such novel tests include gene expression profiling, which analyzes the RNA expression patterns of tumor cells, and multiplex ligation-dependent probe amplification, which detects deletions or and amplifications of DNA in tumor cells. This review discusses the current status of prognostic testing techniques available to clinicians and patients for posterior uveal melanomas.