NCMP-01. NOVEL BIOMARKERS FOR RADIATION-INDUCED NEUROTOXICITY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi147-vi147
Author(s):  
Chen Makranz ◽  
Asel Lubotzky ◽  
Hai Zemmour ◽  
Ruth Shemer ◽  
Benjamin Glaser ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Tumor Response ◽  
Unmet Need ◽  
Therapeutic Modality ◽  
Brain Cells ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
Methylome Analysis ◽  
Radiation Induced ◽  
Novel Biomarkers

Abstract BACKGROUND Brain radiotherapy is the main therapeutic modality for brain metastases (BM), but carries short and long term toxicities, termed radiation-induced neurotoxicity (RIN), and classified to acute, early-delayed and late-delayed RIN according to its time onset. Although diagnosis of RIN is crucial for patient management, there is an unmet need for sensitive biomarkers for RIN. Here we report on a novel non-invasive biomarker for detection and monitoring RIN. As radiotherapy is known to induce brain cells apoptosis as well as BBB disruption, we hypothesized that circulating cell free DNA fragments derived from dying brain cells will be elevated in the blood of patients with RIN. Using comparative methylome analysis we identified 13 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes, and astrocytes. We searched for these brain-derived cfDNA (bncfDNA) in plasma samples of patients following brain irradiation. METHODS We followed 24 patients treated by brain radiotherapy for BM by clinical and radiological examinations before, during and after treatment. In addition, we serially collected blood samples for DNA analysis, and correlated bncfDNA levels with clinical and radiological assessment. RESULTS Patient`s median age was 60 years. Most common primary tumor sites were breast (25%), lung (20.8%) and melanoma (12.5%). RIN was detected in 10 patients (62%). BncfDNA levels increased up to 292.4 fold in acute RIN, up to 138533.1 in early-delayed RIN, and up to 58.4 fold in late-delayed RIN. Resolution of RIN correlated with decrease in bncfDNA. Changes in bncfDNA levels were independent of tumor response and suggested to reflect both symptomatic and asymptomatic RIN. CONCLUSION Increase in bncfDNA levels characterizes RIN independent of tumor response. Thus, BncfDNA may serve as a novel biomarker for brain cells death incurred by radiotherapy. Further studies are required to explore the clinical utility of bncfDNA as a RIN biomarker.

scholarly journals Role of microRNA and Long Non-Coding RNA in Hepatocellular Carcinoma

2020 ◽  
Vol 26 (4) ◽  
pp. 415-428 ◽  
Author(s):  
Meenakshi Gupta ◽  
Kumari Chandan ◽  
Maryam Sarwat
Keyword(s):  
Hepatocellular Carcinoma ◽  
Unmet Need ◽  
Asia Pacific ◽  
Aberrant Expression ◽  
Non Coding Rna ◽  
Liver Cancers ◽  
Contaminated Food ◽  
Genetic Mechanisms ◽  
Novel Biomarkers

Hepatocellular carcinoma (HCC) accounts for about 80-90% of all liver cancers and is found to be the third most common cause of cancer mortality in the Asia-Pacific region. Risk factors include hepatitis B and C virus, cirrhosis, aflatoxin-contaminated food, alcohol, and diabetes. Surgically removing the tumor tissue seems effective but a high chance of recurrence has led to an urgent need to develop novel molecules for the treatment of HCC. Clinical management with sorafenib is found to be effective but it is only able to prolong survival for a few months. Various side effects like gastrointestinal and abdominal pain, hypertension, and hemorrhage are also associated with sorafenib, which calls for the unmet need of effective therapies against HCC. Similarly, the genetic mechanisms behind the occurrence of HCC are still unknown and need to be expounded further for developing newer candidates. Since unearthing the concept of these variants, transcriptomics has revealed the role of noncoding RNAs (ncRNAs) in many cellular, physiological and pathobiological processes. They are also found to be widely associated and abundantly expressed in a variety of cancer. Aberrant expression and mutations are closely related to tumorigenesis and metastasis and hence are classified as novel biomarkers and therapeutic targets for the treatment of cancer, including HCC. Herein, this review summarises the relationship between ncRNAs and hepatocellular carcinoma.

scholarly journals Honey Mitigates Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients without Affecting the Tumor Response

Foods ◽  
2017 ◽  
Vol 6 (9) ◽  
pp. 77 ◽  
Author(s):  
Suresh Rao ◽  
Sanath Hegde ◽  
Pratima Rao ◽  
Chetana Dinkar ◽  
Karadka Thilakchand ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Oral Mucositis ◽  
Tumor Response ◽  
Radiation Induced

scholarly journals Radiation-Induced Cognitive Dysfunction After Different Schemes of Fractionated Whole Brain Irradiation

2014 ◽  
Vol 5 (2) ◽  
pp. 26-35
Author(s):  
Zorkina Yana Аlexandrovna ◽  
Zubkov Еugene Аndreevich ◽  
Yusubalieva Gaukhar Maratovna ◽  
Gorlachev Gennadiy Efimovich ◽  
Golanov Andrey Vladimirivich ◽  
...  
Keyword(s):  
Cognitive Dysfunction ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Radiation Induced

Radiation-Induced Primary Brain Lymphoma: A Case Report

1995 ◽  
Vol 81 (3) ◽  
pp. 204-207 ◽  
Author(s):  
Moshe E. Stein ◽  
Nissim Haim ◽  
Menachem Ben-Shachar ◽  
Dorith Goldsher ◽  
Zvi Bernstein ◽  
...  
Keyword(s):  
Latency Period ◽  
High Dose ◽  
Low Grade ◽  
Whole Brain Irradiation ◽  
Brain Lymphoma ◽  
Brain Irradiation ◽  
Long Latency ◽  
Primary Brain Lymphoma ◽  
Radiation Induced ◽  
Acquired Immunodeficiency

A patient who developed primary brain lymphoma 6 years following whole brain irradiation due to a low-grade glioma is described. The patient had no evidence of congenital or acquired immunodeficiency state and achieved a good and prompt response to aggressive chemotherapy, including high-dose methotrexate. The previous radiation therapy is implicated in the etiology of the lymphoma because of the geometric coincidence, the relatively long latency period and the different histology. A brief review of current literature is reported.

scholarly journals Serum neurofilament light as a biomarker in progressive multiple sclerosis

Neurology ◽  
2020 ◽  
Vol 95 (10) ◽  
pp. 436-444 ◽  
Author(s):  
Raju Kapoor ◽  
Kathryn E. Smith ◽  
Mark Allegretta ◽  
Douglas L. Arnold ◽  
William Carroll ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Unmet Need ◽  
Progressive Multiple Sclerosis ◽  
Response To Treatment ◽  
Tissue Fluid ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Novel Biomarkers ◽  
Active Inflammation

There is an unmet need in multiple sclerosis (MS) therapy for treatments to stop progressive disability. The development of treatments may be accelerated if novel biomarkers are developed to overcome the limitations of traditional imaging outcomes revealed in early phase trials. In January 2019, the International Progressive MS Alliance convened a standing expert panel to consider potential tissue fluid biomarkers in MS in general and in progressive MS specifically. The panel focused their attention on neurofilament light chain (NfL) in serum or plasma, examining data from both relapsing and progressive MS. Here, we report the initial conclusions of the panel and its recommendations for further research. Serum NfL (sNfL) is a plausible marker of neurodegeneration that can be measured accurately, sensitively, and reproducibly, but standard procedures for sample processing and analysis should be established. Findings from relapsing and progressive cohorts concur and indicate that sNfL concentrations correlate with imaging and disability measures, predict the future course of the disease, and can predict response to treatment. Importantly, disease activity from active inflammation (i.e., new T2 and gadolinium-enhancing lesions) is a large contributor to sNfL, so teasing apart disease activity from the disease progression that drives insidious disability progression in progressive MS will be challenging. More data are required on the effects of age and comorbidities, as well as the relative contributions of inflammatory activity and other disease processes. The International Progressive MS Alliance is well positioned to advance these initiatives by connecting and supporting relevant stakeholders in progressive MS.

Standardized pathologic evaluation of the esophagus after neoadjuvant chemoradiation.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 136-136
Author(s):  
Christina T. Muijs ◽  
Justin K. Smit ◽  
Arend Karrenbeld ◽  
Jannet C Beukema ◽  
Johannes A. Langendijk ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Tumor Response ◽  
Tumor Regression ◽  
Neoadjuvant Chemoradiation ◽  
Reference Points ◽  
Adjuvant Chemoradiation ◽  
Pathologic Evaluation ◽  
Radiation Induced ◽  
Complete Tumor

136 Background: The main objective of this study was to develop and validate a method to reconstruct the gross and clinical tumor volume (GTV and CTV) on the esophageal specimen in order to facilitate a good pathologic examination of the original tumor area after neo-adjuvant chemoradiation (CRT). Methods: The GTV and CTV borders of 25 patients were defined by a radiation oncologist on the planning CT in relation to 5 anatomical reference points. After CRT, the GTV and CTV borders were marked in vivo on the esophagus during surgical resection. Finally, the pathologist evaluated the presence of macroscopic and microscopic tumor in- and outside the GTV and CTV. The radiation tumor response was scored according to the standardized 5-tier Mandard classification. Radiation induced side effects were scored as well. Results: The Mandard classification could be scored on basis of the GTV alone in 68% of the cases (N=17). For the other patients (N=8), the GTV and the CTV should both be incorporated for correct evaluation of the tumor response. Five patients (20%) showed complete tumor response (Mandard 1), 68% (N=17) showed partial response (Mandard 2-3) and 12% (N=3) showed hardly any response (Mandard 4-5). In the partial responders, macroscopic tumor was found within the delineated GTV and microscopic tumor remained within the CTV both in 100% of the cases. In two patients (40%) with hardly any response, microscopic tumor was also found outside the CTV. This might be caused by tumor growth during the neo-adjuvant treatment or by geographical miss. Nine patients turned out to have positive lymph nodes. On average 18 (range 8-30) lymph nodes were evaluated per patients. Giant cell reactions, lymphocyte infiltration, and fibrosis, which indicate tumor regression were seen in the CTV and GTV, and were most pronounced in the GTV. Conclusions: This study suggested that demarcation of the GTV and CTV on the esophagus in vivo is important for standardized pathologic evaluation of the esophagus after neo-adjuvant chemoradiation. Furthermore using this method we determined microscopic tumor outside the CTV in 40% of the cases (N=2) of the bad responders (Mandard 4-5), illustrating the importance of our method in this patient category.

Systematic review and REMARK scoring of renal cell carcinoma (RCC) prognostic circulating biomarker manuscripts.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 569-569
Author(s):  
Marco Adelmo James Iafolla ◽  
Sarah Louise Picardo ◽  
Kyaw Lwin Aung ◽  
Aaron Richard Hansen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Unmet Need ◽  
Cell Free Dna ◽  
Current State ◽  
Free Dna ◽  
Novel Biomarkers ◽  
Marker Study ◽  
Tumor Dna

569 Background: No validated biomarkers exist to help guide prognosis of RCC patients. This study seeks to determine the current state of published prognostic RCC biomarker manuscripts and evaluate their quality using the REMARK criteria. Methods: The phrase “(renal cell carcinoma OR renal cancer OR kidney cancer OR kidney carcinoma) AND circulating AND (biomarkers OR cell free DNA OR tumor DNA OR methylated cell free DNA OR methylated tumor DNA)” was searched in Embase, Medline and PubMed during March 2018. One author (MI) selected all relevant manuscripts from the search results, and two authors (MI and SP) independently scored all relevant manuscripts using the REMARK guidelines (maximum 20 points comprised of 20 items subdivided into 48 criteria). Results: The search identified 525 publications: 73 were valid, 436 were rejected, and 26 were uncertain of their relevance. Amongst the valid publications, 33 were manuscripts of primary research (remainder: 26 review papers, 14 abstracts): manuscripts evaluating ≥ 2 biomarkers (n = 8) and novel biomarkers not published elsewhere (n = 7) comprised the majority. The median REMARK score was 10.6 (range 6.4-14.2). All manuscripts stated their marker, study objectives and method of case selection. The lowest scoring criteria were lack of: description of time between storage of blood/serum and marker assay (n = 2); flow or study profile diagram (n = 2); blinding of the person making the marker assessment to clinical outcomes (n = 3); and pre-specified hypotheses (n = 3). In total, only 8 studies reported a hazard or odds ratio. Using Pearson’s correlation, there was no association with either year of publication (median 2014; range 2004-2018; r2 = 0.14; p = 0.44) or impact factor (median 5.168; range 1.2-26.303; r2 = 0.24; p = 0.17) with REMARK score. Conclusions: Despite several published manuscripts on RCC prognostic biomarkers, most poorly adhere to the REMARK guidelines; this may be the cause for the paucity of a validated RCC biomarker to help supplement or supplant current clinical prognostic criteria. Better designed studies and appropriate reporting of methods, results and interpretation are required to address this urgent unmet need.

scholarly journals An Updated Review on Memantine Efficacy in Reducing Cognitive Dysfunction of Whole-brain Irradiation for Adult Patients with Brain metastasis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Anya jafari ◽  
Zahra Siavashpour ◽  
Mohammad Houshyari
Keyword(s):  
Brain Metastasis ◽  
Verbal Learning ◽  
Whole Brain Radiotherapy ◽  
Protective Effects ◽  
Whole Brain Irradiation ◽  
Whole Brain ◽  
Brain Irradiation ◽  
Brain Radiotherapy ◽  
Delayed Recognition

Context: Increased survival of patients with cancer raises the need to pay attention to long-term side effects. Patients with brain metastasis experienced cognition failure after whole-brain radiotherapy. This review aimed at concluding the efficacy of Memantine in preserving cognitive function by reducing the brain toxicity of whole-brain radiotherapy for metastatic brain cancers. Evidence Acquisition: Published studies evaluating memantine protective effects during brain metastasis radiotherapy were searched for in scientific databases (e.g., Embase, PubMed, Cochrane database, Google Scholar, Scopus) using keywords including whole-brain radiotherapy and Memantine. Results: A total of 4 prospective clinical trials were included in the review. Effects of Memantine on cognition tests were evaluated in these trials. A significantly better Hopkins Verbal Learning Test-Revised (HVLT-R) delayed recognition at months 6 was achieved in RTOG 0614 and NRG CC001. Longer time to cognitive decline was found in the memantine arm of the RTOG trial and was statistically significant. Memantine effects were not statistically significant before 2 months. Conclusions: It seems reasonable to consider Memantine during radiation to prevent long-term cognitive failure in patients with brain metastasis due to the current results. Memantine improves cognition function during whole-brain radiotherapy (WBRT) without adding irreparable complications.

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