المؤلفون: Schostak, Martin, Bradbury, Angela, Briganti, Alberto, Gonzalez, David, Gomella, Leonard, Mateo, Joaquin, Penault-Llorca, Frédérique, Stenzinger, Albrecht, Wyatt, Alexander W., Bjartell, Anders

المصدر: European Urology Oncology eSSENCE: The e-Science Collaboration EpiHealth: Epidemiology for Health. 7(3):344-354

مصطلحات موضوعية: Circulating tumour DNA, Metastatic castration-resistant prostate cancer, Molecular diagnostics, Multidisciplinary team, PARP inhibitors, Tumour testing, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi, Medical and Health Sciences, Clinical Medicine, Cancer and Oncology

الوصف: CONTEXT: Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach. OBJECTIVE: To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate pathway for molecular diagnostic testing. EVIDENCE ACQUISITION: We undertook a nonsystematic narrative review of the literature using PubMed to identify current guidelines and recommendations on molecular diagnostic testing for BRCA and/or homologous recombination repair gene alterations (HRRm) in patients with prostate cancer. In addition, selected articles that included BRCA/HRRm testing in clinical trials in metastatic castration-resistant prostate cancer and real-world evidence were also evaluated. Websites for relevant societies were reviewed for molecular diagnostic guidelines not published on PubMed. EVIDENCE SYNTHESIS: Our review of guidelines published by several international societies that include molecular testing in prostate cancer identified variations in molecular testing approaches. The review of testing approaches used in clinical trials and real-world settings also highlighted several aspects that require improvement. Therefore, we compiled practical guidance for establishing an appropriate BRCA/HRR mutation testing pathway. CONCLUSIONS: While there are several challenges to molecular testing and interpretation of test results that require enhancement, a multidisciplinary team approach will empower HCPs and their institutions to improve on or initiate their own molecular testing pathways. This in turn will lead to improvements in management strategies for patients with metastatic prostate cancer, for whom better treatment outcomes is a significant unmet need. PATIENT SUMMARY: Establishing a molecular testing pathway in clinical practice for patients with metastatic castration-resistant prostate cancer will lead to fairer and more equal access to personalised treatments. This should lead to better outcomes, particularly for patients whose disease has spread to other areas of the body.

الوصول الحر: https://lup.lub.lu.se/record/620bd8b0-5700-4e54-a147-0a9230ff2decTest
http://dx.doi.org/10.1016/j.euo.2023.08.004Test

المؤلفون: Nada Ezzeldin, Dalia El-Lebedy, Mirhane Hassan, Alaa Omar Shalaby, Sabah Ahmed Mohamed Hussein, Ahmed Mohamed Gharib, Gehan Hamdy, Asmaa Mahmoud Mohammed, Abeer Ramadan, Mohamed Emam Sobeih

المصدر: Journal of the Egyptian National Cancer Institute, Vol 36, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Circulating tumour DNA, Circulating cell-free DNA, NSCLC, DNA integrity index, ALU247, ALU115, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Analysis of free DNA molecules shed from tumour cells in plasma of patients referred as circulating tumour DNA (ctDNA) with reference to physiological circulating cell-free DNA (cfDNA) is nowadays exploited as liquid biopsy and is considered a new emerging promising biomarker for diagnosis, selection of proper treatment, and prognosis of cancer. DNA integrity index (DII) is assessed by calculating the ratio between the concentration of long cfDNA strands released from tumour cells (ALU247) and the short strands released from normal cells (ALU115). The aim of the current study was to evaluate DII as a potential diagnostic and prognostic biomarker of NSCLC. Methods Our study included 48 NSCLC patients diagnosed as primary NSCLC before starting treatment, 30 COPD patients diagnosed clinically, radiologically, and subjected to chest high-resolution computerized tomography, and 40 healthy controls. cfDNA concentration and DII were measured by quantitative real-time polymerase chain reaction (qPCR). Results ALU115, ALU247, and DII were significantly higher in NSCLC compared to COPD patients (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2589-0409Test

الوصول الحر: https://doaj.org/article/e91bae18ae024eb4a954fa00c3e0aa97Test

المؤلفون: George Zarkavelis, Anna Lea Amylidi, Nanteznta Torounidou, Melina Yerolatsite, Athanasia Keravasili, Varvara Keramisanou, Davide Mauri

المصدر: Contemporary Oncology, Vol 28, Iss 1, Pp 45-50 (2024)

مصطلحات موضوعية: circulating tumour dna, metastatic colorectal cancer, liquid biopsy, molecular monitoring, Medicine

وصف الملف: electronic resource

العلاقة: https://www.termedia.pl/Exploring-RAS-mutation-incidence-and-temporal-heterogeneity-in-metastatic-colorectal-cancer-patients-a-single-institution-experience-utilisingTest-circulating-tumour-DNA,3,53964,1,1.html; https://doaj.org/toc/1428-2526Test; https://doaj.org/toc/1897-4309Test

الوصول الحر: https://doaj.org/article/2ef943cde1e940508545ec53cd2b0af3Test

المؤلفون: Carl M. Post, Kim C. Ohaegbulam, Timur Mitin

المصدر: Journal of Medical Radiation Sciences, Vol 71, Iss 1, Pp 21-25 (2024)

مصطلحات موضوعية: Circulating tumour DNA, HPV, oropharyngeal cancer, PET/CT, surveillance, Medical physics. Medical radiology. Nuclear medicine, R895-920

الوصف: Abstract Introduction Circulating tumour human papillomavirus DNA (ctHPVDNA) is an emerging tool to assess post‐treatment response in patients with HPV+ oropharyngeal squamous cell carcinoma (OPSCC). Its use is not a standard practice, however, with interval F‐18 FDG PET/CT and fiberoptic examination preferred. Post‐treatment PET/CT at 3 months has a low positive predictive value (PPV), especially in patients with HPV+ OPSCC treated with (chemo)radiation therapy (CRT). We aimed to compare 3–6 month post‐treatment PET/CT and ctHPVDNA test results to determine the most effective option for post‐treatment response assessment. Methods Patients with HPV+ OPSCC that underwent commercially available ctHPVDNA blood testing after curative intent treatment were identified. Demographic, clinical, treatment, surveillance and oncologic outcome information were collected for each patient. Specificity and false positive rate were calculated for post‐treatment PET/CT and ctHPVDNA. Results 80% of patients had Stage I disease. 52% of the population was treated with definitive chemoradiation (43%) or accelerated radiation (9%), with the remaining patients treated with transoral robotic surgery (TORS) +/− risk‐adapted adjuvant therapy. In total, 25 patients underwent ctHPVDNA testing and PET/CT at 3–6 months after finishing treatment. At 3–6 months post‐treatment, specificity of ctHPVDNA and PET/CT was 96% and 56%, correlating to false positive rates of 4% and 44%, respectively. Conclusions ctHPVDNA is more reliable than PET/CT following treatment in patients with HPV+ OPSCC, and its incorporation in post‐treatment response assessment will decrease the rate of anxiety over persistent disease and lead to a decrease in unnecessary medical procedures, including completion of neck dissection.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2051-3895Test; https://doaj.org/toc/2051-3909Test

الوصول الحر: https://doaj.org/article/d694e89c9ee945d2993ee995a9e42349Test

المؤلفون: Rafal Dziadziuszko, Nir Peled, Tony Mok, Solange Peters, Santiago Ponce Aix, Jorge Alatorre-Alexander, Brian D. Vicuna, Margaret Maclennan, Vijay Bhagawati-Prasad, Sarah M. Shagan, Erica Schleifman, Thorsten Ruf, Michael S. Mathisen, Shirish M. Gadgeel

المصدر: Contemporary Oncology, Vol 27, Iss 4, Pp 217-223 (2024)

مصطلحات موضوعية: alectinib, blood-based assay, blood first assay screening trial (bfast), non small cell lung cancer, nsclc, ret fusion, ctdna, circulating tumour dna, liquid biopsy, ngs, Medicine

وصف الملف: electronic resource

العلاقة: https://www.termedia.pl/High-dose-alectinib-for-RET-fusion-positive-non-small-cell-lung-cancer-in-the-Blood-First-Assay-Screening-Trial,3,52369,1,1.htmlTest; https://doaj.org/toc/1428-2526Test; https://doaj.org/toc/1897-4309Test

الوصول الحر: https://doaj.org/article/de66fd03358a49bbbdeaeff487884027Test

المؤلفون: De‐Zhen Guo, Ao Huang, Ying‐Chao Wang, Shuang Zhou, Hui Wang, Xiang‐Lei Xing, Shi‐Yu Zhang, Jian‐Wen Cheng, Ke‐Hui Xie, Qi‐Chang Yang, Cheng‐Cheng Ma, Qing Li, Yan Chen, Zhi‐Xi Su, Jia Fan, Rui Liu, Xiao‐Long Liu, Jian Zhou, Xin‐Rong Yang

المصدر: Clinical and Translational Medicine, Vol 14, Iss 5, Pp n/a-n/a (2024)

مصطلحات موضوعية: circulating tumour DNA methylation, diagnosis, hepatocellular carcinoma, liquid biopsy, prognosis, Medicine (General), R5-920

الوصف: Abstract Background Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve patient survival. We aimed to develop a blood‐based assay to aid in the diagnosis, detection and prognostic evaluation of HCC. Methods A three‐phase multicentre study was conducted to screen, optimise and validate HCC‐specific differentially methylated regions (DMRs) using next‐generation sequencing and quantitative methylation‐specific PCR (qMSP). Results Genome‐wide methylation profiling was conducted to identify DMRs distinguishing HCC tumours from peritumoural tissues and healthy plasmas. The twenty most effective DMRs were verified and incorporated into a multilocus qMSP assay (HepaAiQ). The HepaAiQ model was trained to separate 293 HCC patients (Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 224) from 266 controls including chronic hepatitis B (CHB) or liver cirrhosis (LC) (CHB/LC, 96), benign hepatic lesions (BHL, 23), and healthy controls (HC, 147). The model achieved an area under the curve (AUC) of 0.944 with a sensitivity of 86.0% in HCC and a specificity of 92.1% in controls. Blind validation of the HepaAiQ model in a cohort of 523 participants resulted in an AUC of 0.940 with a sensitivity of 84.4% in 205 HCC cases (BCLC stage 0/A, 167) and a specificity of 90.3% in 318 controls (CHB/LC, 100; BHL, 102; HC, 116). When evaluated in an independent test set, the HepaAiQ model exhibited a sensitivity of 70.8% in 65 HCC patients at BCLC stage 0/A and a specificity of 89.5% in 124 patients with CHB/LC. Moreover, HepaAiQ model was assessed in paired pre‐ and postoperative plasma samples from 103 HCC patients and correlated with 2‐year patient outcomes. Patients with high postoperative HepaAiQ score showed a higher recurrence risk (Hazard ratio, 3.33, p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2001-1326Test

الوصول الحر: https://doaj.org/article/1701daf960ec4386839139f6dbdb08e8Test

المؤلفون: Trethewey, Christopher S.

مصطلحات موضوعية: Aggressive Lymphoid Malignancies, Circulating tumour DNA (ctDNA), next-generation sequencing (NGS), Cancer Research, thesis

الوصف: Circulating tumour DNA (ctDNA) can be used to profile, detect, and monitor cancers. Technical advances in next-generation sequencing (NGS) strategies to address limitations in ctDNA detection and the precise classification of lymphoid cancers, using mutational features and bioinformatics tools, may help diagnosis and have predictive value for treatment. Despite these advances, application of ctDNA in current clinical practice is absent, with translational studies yet to be carried out in the U.K. for patient stratification. This study describes the development of an effective NGS workflow, comprising design of a pan-lymphoma, targeted panel focusing upon molecular characteristics specific to B-cell and T-cell malignancies for profiling ctDNA, coupled with custom bioinformatic workflow 'Deep-sequencing and Evaluation of Lymphoid Variant Effects' (DELVE). DELVE enables detection of aberrant somatic hyper-mutation (aSHM) sites including immunoglobulin heavy chain locus (IGH), fusions and clonal immunoglobulin repertoire detection. Clinical utility of ctDNA and mutational profiling by pan-lymphoma targeted panel/DELVE were investigated in Diffuse Large B-cell Lymphoma (DLBCL), primary cutaneous diffuse large B-cell lymphoma (PCDLBCL-LT) and peripheral T-cell lymphoma (PTCL). A DLBCL discovery cohort of six patients comparing FFPE and baseline ctDNA was followed by a validation cohort and longitudinal analysis during treatment. 14/15 DLBCL exhibited detectable ctDNA at baseline. Sequencing of tissue and plasma revealed significant aSHM, with detectable HMRN and LymphGen classifications. In a case of PCDLBCL-LT, limitations in use of ctDNA to monitor treatment response were evidenced with no detectable ctDNA throughout clinical course, including following 2 systemic relapses and ctDNA was detectable only when the patient was treated with BTKi. Finally, in PTCL (n=6), proof of principle and comparison with Ion Torrent sequencing was performed. This work demonstrated the feasibility of using a pan-lymphoma targeted panel and the DELVE pipeline to profile tumours and monitor residual disease and set the basis for larger scale studies.

الوصول الحر: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.890441Test

المؤلفون: Joel Petit, Georgia Carroll, Jie Zhao, Peter Pockney, Rodney J. Scott

المصدر: Gastroenterology Insights, Vol 15, Iss 1, Pp 107-121 (2024)

مصطلحات موضوعية: colorectal cancer, prognosis, tumour biomarkers, circulating cell-free DNA, circulating tumour-DNA, KRAS, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: This study aims to investigate the long-term prognostic utility of circulating tumour DNA (ctDNA) KRAS mutations in colorectal cancer (CRC) patients and compare this with KRAS mutations in matched tissue samples. Tumour tissue (n = 107) and ctDNA (n = 80) were obtained from patients undergoing CRC resection and were analysed for KRAS mutations. The associations between KRAS mutation and overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were analysed. All outcomes were measured in years (y). A total of 28.8% of patients had KRAS mutations in ctDNA and 72.9% in tumour tissue DNA. The high frequency of KRAS mutations in tissue samples was due to 51.4% of these being a detectable low mutation allele frequency (KRAS mutant (KRASmut) to KRAS wild-type (KRASwt) in ctDNA, there was no association found with OS (mean 4.67 y vs. 4.34 y, p = 0.832), CSS (mean 4.72 y vs. 4.49 y, p = 0.747), or RFS (mean 3.89 y vs. 4.26 y, p = 0.616). Similarly, comparing KRASmut to KRASwt in tissue DNA there was no association found with OS (mean 4.23 y vs. 4.61 y, p = 0.193), CSS (mean 4.41 y vs. 4.71 y, p = 0.312), or RFS (mean 4.16 y vs. 4.41 y, p = 0.443). There was no significant association found between KRAS mutations in either tissue or ctDNA and OS, CSS, or RFS.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2036-7422/15/1/8Test; https://doaj.org/toc/2036-7414Test; https://doaj.org/toc/2036-7422Test

الوصول الحر: https://doaj.org/article/2180e40458624feab5dd8729c5eae078Test

المؤلفون: Megan Crumbaker, Leonard D. Goldstein, David H. Murray, Jiang Tao, Sarennya Pathmanandavel, Nicky Boulter, Lalith Ratnayake, Anthony M. Joshua, Sarah Kummerfeld, Louise Emmett

المصدر: European Urology Open Science, Vol 57, Iss , Pp 30-36 (2023)

مصطلحات موضوعية: Lutetium prostate-specific membrane antigen, Metastatic castrate-resistant prostate cancer, Circulating tumour DNA, Biomarkers, Diseases of the genitourinary system. Urology, RC870-923, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Lutetium-177-prostate-specific membrane antigen- 617 (Lu-PSMA) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC). However, treatment responses are heterogeneous despite stringent positron emission tomography (PET)-based imaging selection criteria. Molecularly based biomarkers have potential to refine patient selection and optimise outcomes. Objective: To identify circulating tumour DNA (ctDNA) features associated with treatment outcomes for men treated with Lu-PSMA. Design, setting, and participants: ctDNA from men treated with Lu-PSMA in combination with idronoxil for progressive mCRPC were analysed using an 85-gene customised sequencing assay. ctDNA fractions, molecular profiles, and the presence of alterations in aggressive-variant prostate cancer (AVPC) genes were analysed at baseline, cycle 3 and at disease progression. Intervention: Men received Lu-PSMA with idronoxil every 6 wk for up to six cycles. Outcome measurements and statistical analysis: Baseline and exit PSMA and fluorodeoxyglucose PET/computed tomography (CT) imaging was conducted at baseline and study exit. Single-photon emission CT (SPECT) scans were performed 24 h after Lu-PSMA. Blood samples were collected at baseline,cycle 3 and at disease progression. Cox proportional-hazards models were used to assess associations and derive hazard ratios (HRs) and confidence intervals (CIs) for associations between molecular factors, imaging features, and clinical outcomes. Results and limitations: Sixty samples from 32 men were sequenced (32 at baseline, 24 at cycle 3, four from patients with disease progression); two samples (baseline, on-treatment) from one individual were excluded from analysis owing to poor quality of the baseline sequencing data. Alterations in AVPC genes were associated with shorter prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival (OS) in univariate (HR 3.4, 95% CI 1.5–7.7; p = 0.0036; and HR 3.3, 95% CI 1.4–7.7; p = 0.0063, respectively) and multivariate analyses (HR 4.8, 95% CI 1.8–13; p = 0.0014; and HR 4.1, 95% CI 1.6–11; p = 0.004). Conclusions: ctDNA alterations in AVPC genes were associated with shorter PSA PFS and OS among men treated with Lu-PSMA and intermittent idronoxil. These candidate molecular biomarkers warrant further study to determine whether they have predictive value and potential to guide synergistic combination strategies to enhance outcomes for men treated with Lu-PSMA for mCRPC. Patient summary: Certain DNA/gene changes detected in the blood of men with advanced prostate cancer were associated with shorter benefit from lutetium PSMA, a targeted radioactive therapy. This information may be useful in determining which men may benefit most from this treatment, but additional research is needed.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666168323004123Test; https://doaj.org/toc/2666-1683Test

الوصول الحر: https://doaj.org/article/917bf043cf3d4ac389625c16e394999aTest

المؤلفون: Karl F. B. Payne, Peter Brotherwood, Harini Suriyanarayanan, Jill M. Brooks, Nikolaos Batis, Andrew D. Beggs, Deena M. A. Gendoo, Hisham Mehanna, Paul Nankivell

المصدر: Frontiers in Oncology, Vol 14 (2024)

مصطلحات موضوعية: head and neck cancer, HNSCC (head and neck squamous cell carcinoma), liquid biopsy, Ctdna (circulating tumour DNA), intra-tumor heterogeneity, temporal heterogeneity, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundAs circulating tumour DNA (ctDNA) liquid biopsy analysis is increasingly incorporated into modern oncological practice, establishing the impact of genomic intra-tumoural heterogeneity (ITH) upon data output is paramount. Despite advances in other cancer types the evidence base in head and neck squamous cell carcinoma (HNSCC) remains poor. We sought to investigate the utility of ctDNA to detect ITH in HNSCC.MethodsIn a pilot cohort of 9 treatment-naïve HNSCC patients, DNA from two intra-tumoural sites (core and margin) was whole-exome sequenced. A 9-gene panel was designed to perform targeted sequencing on pre-treatment plasma cell-free DNA and selected post-treatment samples.ResultsRates of genomic ITH among the 9 patients was high. COSMIC variants from 19 TCGA HNSCC genes demonstrated an 86.9% heterogeneity rate (present in one tumour sub-site only). Across all patients, cell-free DNA (ctDNA) identified 12.9% (range 7.5-19.8%) of tumour-specific variants, of which 55.6% were specific to a single tumour sub-site only. CtDNA identified 79.0% (range: 55.6-90.9%) of high-frequency variants (tumour VAF>5%). Analysis of ctDNA in serial post-treatment blood samples in patients who suffered recurrence demonstrated dynamic changes in both tumour-specific and acquired variants that predicted recurrence ahead of clinical detection.ConclusionWe demonstrate that a ctDNA liquid biopsy identified spatial genomic ITH in HNSCC and reliably detected high-frequency driver mutations. Serial sampling allowed post-treatment surveillance and early identification of treatment failure.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2024.1374816/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/e05145d79eb243d7a8953e7b92d45ddbTest