Early cancer detection should lead to an overall stage shift, less-intensive treatments and better patient outcomes. Current recommended screening programmes are limited to a handful of individual ...cancers. A multi-cancer early detection test that simultaneously detects and localises multiple cancers could reduce the morbidity and mortality associated with cancer.
The continuous improvement in cancer care over the past decade has led to a gradual decrease in cancer-related deaths. This is largely attributed to improved treatment and disease management ...strategies. Early detection of recurrence using blood-based biomarkers such as circulating tumour DNA (ctDNA) is being increasingly used in clinical practice. Emerging real-world data shows the utility of ctDNA in detecting molecular residual disease and in treatment-response monitoring, helping clinicians to optimize treatment and surveillance strategies. Many studies have indicated ctDNA to be a sensitive and specific biomarker for recurrence. However, most of these studies are largely observational or anecdotal in nature, and peer-reviewed data regarding the use of ctDNA are mainly indication-specific. Here we provide general recommendations on the clinical utility of ctDNA and how to interpret ctDNA analysis in different treatment settings, especially in patients with solid tumours. Specifically, we provide an understanding around the implications, strengths and limitations of this novel biomarker and how to best apply the results in clinical practice.
This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as ...accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development-analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).
This focused update addresses the use of Onco
DX in guiding decisions on the use of adjuvant systemic therapy.
ASCO uses a signals approach to facilitate guideline updating. For this focused update, ...the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease-free survival in women with Onco
DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Onco
DX assay to assess for evidence of clinical utility.
For patients with hormone receptor-positive, axillary node-negative breast cancer whose tumors have Onco
DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines.
Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate ...guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor-positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor-positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .
To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer.
A literature ...search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations.
The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens.
In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.
Epidermal growth factor receptor (EGFR) is a targetable receptor frequently overexpressed in basal-like breast cancer, which comprises most triple-negative breast cancers (TNBCs), the only subtype ...without established targeted therapy.
In this randomized phase II trial, patients with metastatic TNBC received anti-EGFR antibody cetuximab (400 mg/m(2) load then 250 mg/m(2) per week intravenously IV) alone, with carboplatin (area under the curve of 2, once per week IV) added after progression or as concomitant therapy from the beginning. Response rate (RR) was the primary end point; others included time to progression (TTP), overall survival (OS), and toxicity. Embedded correlative studies included molecular subtyping on archival tissue. Fresh tumor tissue before and after 7 to 14 days of therapy was used for microarray analyses exploring EGFR pathway activity and inhibition.
In 102 patients with TNBC, RRs were 6% (two of 31) to cetuximab and 16% (four of 25) to cetuximab plus carboplatin after progression. RR to those treated from the beginning with cetuximab plus carboplatin was 17% (12 of 71); 31% of patients responded or had prolonged disease stabilization. The cetuximab plus carboplatin regimen was well tolerated, but both TTP and OS were short at 2.1 months (95% CI, 1.8 to 5.5 months) and 10.4 months (95% CI, 7.7 to 13.1 months), respectively. Of 73 patients with archival tissue for analysis, 74% had basal-like molecular subtype. Sixteen patients had tumor biopsies before and 1 week after therapy; genomic patterns of the EGFR pathway showed activation in 13 and inhibition by therapy in five.
Despite strong preclinical data, combination cetuximab plus carboplatin in metastatic TNBC produced responses in fewer than 20% of patients. EGFR pathway analysis showed that most TNBCs involved activation. However, cetuximab blocked expression of the EGFR pathway in only a minority, suggesting that most had alternate mechanisms for pathway activation.
Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 ...TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers.
Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets.
In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets.
In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.
High-throughput genomic and proteomic technologies are widely used in cancer research to build better predictive models of diagnosis, prognosis and therapy, to identify and characterize key ...signalling networks and to find new targets for drug development. These technologies present investigators with the task of extracting meaningful statistical and biological information from high-dimensional data spaces, wherein each sample is defined by hundreds or thousands of measurements, usually concurrently obtained. The properties of high dimensionality are often poorly understood or overlooked in data modelling and analysis. From the perspective of translational science, this Review discusses the properties of high-dimensional data spaces that arise in genomic and proteomic studies and the challenges they can pose for data analysis and interpretation.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
There is a clear and unmet need for biomarkers in hepatocellular carcinoma (HCC). Circulating cell free deoxyribonucleic acid (cfDNA) is a fragmented DNA subtype, found in the blood circulation. ...Circulating tumor DNA (ctDNA) is the fraction of total cfDNA, which originates from the primary tumor or metastases in patients with cancer. Earlier studies reported that quantitative measurement cfDNA has diagnostic and prognostic role for HCC. More recently, improvement in next-generation sequencing technology and better understanding of genetic or epigenetic alteration of HCC have allowed comprehensive analysis of mutational and methylation landscape of ctDNA. Hotspot mutation panels and methylation panels have both shown promising performance. None of these tests have yet been validated in longitudinal cohorts for preclinical detection of HCC. In this article, the authors discuss the currently available ctDNA detection technologies, their diagnostic and prognostic performance in HCC, and future research directions.
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