Advanced search

Online first
Review paper
Published online: 2024-04-19

open access

View PDF Download PDF file
Page views 182
Article views/downloads 127
Get Citation

Connect on Social Media

Connect on Social Media

Novel biomarkers in bone sarcomas — diagnosis, treatment selection, and clinical trials

Anna M. Czarnecka1, Piotr Błoński12, Paulina Chmiel12, Piotr Rutkowski1
DOI: 10.5603/ocp.99779

Abstract

Malignant bone tumors (MBT) are a rare and heterogeneous group of tumors, arising mostly in children. Localized disease is usually treated with surgery, but prognosis worsens in advanced stages. Currently, with limited biomarkers in clinical use, prognosis depends on histological grading and clinical features. However, the use of biomarkers remains inadequate, limiting treatment efficacy and increasing the risk of recurrence and disease progression for patients. Potential biomarkers based on genomics, proteomics, and clinical characteristics are currently entering clinical use in multiple cancers. Biomarker research in MBT faces additional challenges resulting fromthe rarity of these entities. Emerging biomarker concepts require clinical validation to create robust frameworks for precision oncology. This review of new biomarkers is based on relevant literature from Pubmed, Scopus, and clinicatrials.gov databases retrieved in November 2023. At present, the definition of prognostic markers in malignant bone tumors remains challenging. More research is needed, particularly to tailor treatments based on advanced genetic profiling and analysis of individual tumor and patient characteristics. Many newly identified biomarkers have not been clinically validated. 

Keywords: biomarkerbone tumorgeneticssarcoma

Article available in PDF format

View PDF Download PDF file

References

  1. Gatta G, Capocaccia R, Botta L, et al. RARECAREnet working group. Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol. 2017; 18(8): 1022–1039.
    CrossRefPubMed
  2. Strauss SJ, Frezza AM, Abecassis N, et al. ESMO Guidelines Committee, EURACAN, GENTURIS and ERN PaedCan. Electronic address: clinicalguidelines@esmo.org. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021; 32(12): 1520–1536.
    CrossRefPubMed
  3. Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National Cancer Data Base Report. Clin Orthop Relat Res. 2007; 459: 40–47.
    CrossRefPubMed
  4. Giuffrida AY, Burgueno JE, Koniaris LG, et al. Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J Bone Joint Surg Am. 2009; 91(5): 1063–1072.
    CrossRefPubMed
  5. Saab R, Merabi Z, Abboud MR, et al. Collaborative Pediatric Bone Tumor Program to Improve Access to Specialized Care: An Initiative by the Lebanese Children's Oncology Group. J Glob Oncol. 2017; 3(1): 23–30.
    CrossRefPubMed
  6. Xu Y, Shi F, Zhang Y, et al. Twenty-year outcome of prevalence, incidence, mortality and survival rate in patients with malignant bone tumors. Int J Cancer. 2024; 154(2): 226–240.
    CrossRefPubMed
  7. Cole S, Gianferante DM, Zhu B, et al. Osteosarcoma: A Surveillance, Epidemiology, and End Results program-based analysis from 1975 to 2017. Cancer. 2022; 128(11): 2107–2118.
    CrossRefPubMed
  8. Whelan J, McTiernan A, Cooper N, et al. Incidence and survival of malignant bone sarcomas in England 1979-2007. Int J Cancer. 2012; 131(4): E508–E517.
    CrossRefPubMed
  9. Hu X, Deng K, Ye H, et al. Trends in Tumor Site-Specific Survival of Bone Sarcomas from 1980 to 2018: A Surveillance, Epidemiology and End Results-Based Study. Cancers (Basel). 2021; 13(21).
    CrossRefPubMed
  10. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010; 5(6): 463–466.
    CrossRefPubMed
  11. Robb MA, McInnes PM, Califf RM. Biomarkers and Surrogate Endpoints: Developing Common Terminology and Definitions. JAMA. 2016; 315(11): 1107–1108.
    CrossRefPubMed
  12. Huss R. Biomarkers. Translational Regenerative Medicine. 2015: 235–241.
    CrossRef
  13. Aronson JK, Ferner RE. Biomarkers-A General Review. Curr Protoc Pharmacol. 2017; 76: 9.23.1–9.23.17.
    CrossRefPubMed
  14. Mishra A, Verma M. Cancer biomarkers: are we ready for the prime time? Cancers (Basel). 2010; 2(1): 190–208.
    CrossRefPubMed
  15. O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World J Gastroenterol. 2021; 27(26): 4045–4087.
    CrossRefPubMed
  16. Rosenthal AN, Jacobs IJ. The role of CA 125 in screening for ovarian cancer. Int J Biol Markers. 1998; 13(4): 216–220.
    CrossRefPubMed
  17. Iwamoto T, Kajiwara Y, Zhu Y, et al. Biomarkers of neoadjuvant/adjuvant chemotherapy for breast cancer. Chin Clin Oncol. 2020; 9(3): 27.
    CrossRefPubMed
  18. Piccart M, van 't Veer LJ, Poncet C, et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol. 2021; 22(4): 476–488.
    CrossRefPubMed
  19. Ring AE, Smith IE, Ashley S, et al. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004; 91(12): 2012–2017.
    CrossRefPubMed
  20. van der Hage JA, Mieog JS, van de Vijver MJ, et al. European Organization for Research and Treatment of Cancer. Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis. Breast Cancer Res. 2007; 9(5): R70.
    CrossRefPubMed
  21. Syed YY. Oncotype DX Breast Recurrence Score: A Review of its Use in Early-Stage Breast Cancer. Mol Diagn Ther. 2020; 24(5): 621–632.
    CrossRefPubMed
  22. Whirl-Carrillo M, Huddart R, Gong Li, et al. An Evidence-Based Framework for Evaluating Pharmacogenomics Knowledge for Personalized Medicine. Clin Pharmacol Ther. 2021; 110(3): 563–572.
    CrossRefPubMed
  23. Burns J, Wilding CP, L Jones R, et al. Proteomic research in sarcomas - current status and future opportunities. Semin Cancer Biol. 2020; 61: 56–70.
    CrossRefPubMed
  24. National Comprehensive Cancer Network. National Comprehensive Cancer Network Compendium.
  25. Amin MB, Edge S, Greene FL. (ed.). AJCC Cancer Staging Manual, 8th ed. Springer International Publishing AG, Chicago 2017.
  26. ENNEKING W, SPANIER S, GOODMAN M. A System for the Surgical Staging of Musculoskeletal Sarcoma. Clinical Orthopaedics and Related Research. 1980; 153(&NA;): 106???120.
    CrossRef
  27. Brierley J, Gospodarowicz MK, Wittekind C. (ed.). TNM Classification of Malignant Tumours, 8th Edition. Wiley Blackwell, Oxford 2017.
  28. WHO Classification of Tumours Editorial Board. Soft Tissue and Bone Tumours WHO Classification of Tumours, 5th Edition. WHO, Lyon 2020.
  29. Xu G, Wu H, Xu Y, et al. Homogenous and Heterogenous Prognostic Factors for Patients with Bone Sarcoma. Orthop Surg. 2021; 13(1): 134–144.
    CrossRefPubMed
  30. Strauss SJ, Frezza AM, Abecassis N, et al. ESMO Guidelines Committee, EURACAN, GENTURIS and ERN PaedCan. Electronic address: clinicalguidelines@esmo.org. Bone sarcomas: ESMO-EURACAN-GENTURIS-ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2021; 32(12): 1520–1536.
    CrossRefPubMed
  31. National Comprehensive Cancer Network Inc. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bone Cancer 07 Aug 2023. https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf (25.10.2023).
  32. Balachandran VP, Gonen M, Smith JJ, et al. Nomograms in oncology: more than meets the eye. Lancet Oncol. 2015; 16(4): e173–e180.
    CrossRefPubMed
  33. Sun Yu, Ouyang C, Zhang Yu, et al. Development and validation of a nomogram for predicting prognosis of high-grade chondrosarcoma: A surveillance, epidemiology, and end results-based population analysis. J Orthop Surg (Hong Kong). 2023; 31(2): 10225536231174255.
    CrossRefPubMed
  34. Wang J, Zhanghuang C, Tan X, et al. A Nomogram for Predicting Cancer-Specific Survival of Osteosarcoma and Ewing's Sarcoma in Children: A SEER Database Analysis. Front Public Health. 2022; 10: 837506.
    CrossRefPubMed
  35. Zheng Y, Lu J, Shuai Z, et al. A novel nomogram and risk classification system predicting the Ewing sarcoma: a population-based study. Sci Rep. 2022; 12(1): 8154.
    CrossRefPubMed
  36. Hsu CJ, Ma Y, Xiao P, et al. Overall survival comparison between pediatric and adult Ewing sarcoma of bone and adult nomogram construction: a large population-based analysis. Front Pediatr. 2023; 11: 1103565.
    CrossRefPubMed
  37. Duchman KR, Gao Y, Miller BJ. Prognostic factors for survival in patients with high-grade osteosarcoma using the Surveillance, Epidemiology, and End Results (SEER) Program database. Cancer Epidemiol. 2015; 39(4): 593–599.
    CrossRefPubMed
  38. Picci P, Rougraff BT, Bacci G, et al. Prognostic significance of histopathologic response to chemotherapy in nonmetastatic Ewing's sarcoma of the extremities. J Clin Oncol. 1993; 11(9): 1763–1769.
    CrossRefPubMed
  39. Albergo JI, Gaston CL, Laitinen M, et al. Ewing's sarcoma: only patients with 100% of necrosis after chemotherapy should be classified as having a good response. Bone Joint J. 2016; 98-B(8): 1138–1144.
    CrossRefPubMed
  40. Righi A, Pacheco M, Palmerini E, et al. Histological response to neoadjuvant chemotherapy in localized Ewing sarcoma of the bone: A retrospective analysis of available scoring tools. Eur J Surg Oncol. 2021; 47(7): 1778–1783.
    CrossRefPubMed
  41. Hawkins D, Schuetze S, Butrynski J, et al. [18F]Fluorodeoxyglucose Positron Emission Tomography Predicts Outcome for Ewing Sarcoma Family of Tumors. J Clin Oncol. 2005; 23(34): 8828–8834.
    CrossRefPubMed
  42. Smeland S, Bielack SS, Whelan J, et al. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. Eur J Cancer. 2019; 109: 36–50.
    CrossRefPubMed
  43. Pan HY, Morani A, Wang WL, et al. Prognostic factors and patterns of relapse in ewing sarcoma patients treated with chemotherapy and r0 resection. Int J Radiat Oncol Biol Phys. 2015; 92(2): 349–357.
    CrossRefPubMed
  44. Gelderblom H, Jinks RC, Sydes M, et al. European Osteosarcoma Intergroup. Survival after recurrent osteosarcoma: data from 3 European Osteosarcoma Intergroup (EOI) randomized controlled trials. Eur J Cancer. 2011; 47(6): 895–902.
    CrossRefPubMed
  45. Fu Y, Lan T, Cai H, et al. Meta-analysis of serum lactate dehydrogenase and prognosis for osteosarcoma. Medicine (Baltimore). 2018; 97(19): e0741.
    CrossRefPubMed
  46. Gu R, Sun Y. Does serum alkaline phosphatase level really indicate the prognosis in patients with osteosarcoma? A meta-analysis. J Cancer Res Ther. 2018; 14(Supplement): S468–S472.
    CrossRefPubMed
  47. Hao H, Chen L, Huang D, et al. Meta-analysis of alkaline phosphatase and prognosis for osteosarcoma. Eur J Cancer Care (Engl). 2017; 26(5).
    CrossRefPubMed
  48. Li S, Yang Q, Wang H, et al. Prognostic significance of serum lactate dehydrogenase levels in Ewing's sarcoma: A meta-analysis. Mol Clin Oncol. 2016; 5(6): 832–838.
    CrossRefPubMed
  49. Nakamura T, Grimer RJ, Gaston CL, et al. The prognostic value of the serum level of C-reactive protein for the survival of patients with a primary sarcoma of bone. Bone Joint J. 2013; 95-B(3): 411–418.
    CrossRefPubMed
  50. Aggerholm-Pedersen N, Maretty-Kongstad K, Keller J, et al. The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma. Transl Oncol. 2016; 9(4): 322–328.
    CrossRefPubMed
  51. Jiang M, Ma S, Hua Z, et al. Prognostic Value of Pretreated Blood Inflammatory Markers in Patients with Bone Sarcoma: A Meta-Analysis. Dis Markers. 2021; 2021: 8839512.
    CrossRefPubMed
  52. Yang Q, Chen T, Yao Z, et al. Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. World J Surg Oncol. 2020; 18(1): 24.
    CrossRefPubMed
  53. Jettoo P, Tan G, Gerrand CH, et al. Role of routine blood tests for predicting clinical outcomes in osteosarcoma patients. J Orthop Surg (Hong Kong). 2019; 27(2): 2309499019838293.
    CrossRefPubMed
  54. Ouyang H, Wang Z. Predictive value of the systemic immune-inflammation index for cancer-specific survival of osteosarcoma in children. Front Public Health. 2022; 10: 879523.
    CrossRefPubMed
  55. De Angulo G, Hernandez M, Morales-Arias J, et al. Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma. J Pediatr Hematol Oncol. 2007; 29(1): 48–52.
    CrossRefPubMed
  56. Laterza O, Hendrickson R, Wagner J. Molecular Biomarkers. Drug Information Journal. 2007; 41(5): 573–585.
    CrossRef
  57. Lou S, Balluff B, Cleven AHG, et al. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging. J Am Soc Mass Spectrom. 2017; 28(2): 376–383.
    CrossRefPubMed
  58. Lou S, Balluff B, de Graaff MA, et al. High-grade sarcoma diagnosis and prognosis: Biomarker discovery by mass spectrometry imaging. Proteomics. 2016; 16(11-12): 1802–1813.
    CrossRefPubMed
  59. Paulussen M, Bielack S, Jürgens H, et al. ESMO Guidelines Working Group. Ewing's sarcoma of the bone: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009; 20 Suppl 4: 140–142.
    CrossRefPubMed
  60. Mahmoud AM, Zekri W, Khorshed EN, et al. Prognostic significance of survivin expression in pediatric ewing sarcoma. Pediatr Hematol Oncol. 2022; 39(1): 16–27.
    CrossRefPubMed
  61. Shulman DS, Chen S, Hall D, et al. Adverse prognostic impact of the loss of STAG2 protein expression in patients with newly diagnosed localised Ewing sarcoma: A report from the Children's Oncology Group. Br J Cancer. 2022; 127(12): 2220–2226.
    CrossRefPubMed
  62. Abrahao-Machado LF, Pinto F, Antunes B, et al. Clinical impact of brachyury expression in Ewing sarcoma patients. Adv Med Sci. 2021; 66(2): 321–325.
    CrossRefPubMed
  63. Ge W, Li J, Fan W, et al. Tim-3 as a diagnostic and prognostic biomarker of osteosarcoma. Tumour Biol. 2017; 39(7): 1010428317715643.
    CrossRefPubMed
  64. Jiang K, Li S, Li Lu, et al. WNT6 is an effective marker for osteosarcoma diagnosis and prognosis. Medicine (Baltimore). 2018; 97(46): e13011.
    CrossRefPubMed
  65. Yu XW, Wu TY, Yi X, et al. Prognostic significance of VEGF expression in osteosarcoma: a meta-analysis. Tumour Biol. 2014; 35(1): 155–160.
    CrossRefPubMed
  66. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005; 69 Suppl 3: 4–10.
    CrossRefPubMed
  67. Jiang J, Liu C, Xu G, et al. CCT6A, a novel prognostic biomarker for Ewing sarcoma. Medicine (Baltimore). 2021; 100(4): e24484.
    CrossRefPubMed
  68. de Groot S, Gelderblom H, Fiocco M, et al. Serum levels of IGF-1 and IGF-BP3 are associated with event-free survival in adult Ewing sarcoma patients treated with chemotherapy. Onco Targets Ther. 2017; 10: 2963–2970.
    CrossRefPubMed
  69. Gounder MM, Agaram NP, Trabucco SE, et al. Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma. Nat Commun. 2022; 13(1): 3406.
    CrossRefPubMed
  70. Schaefer IM, Cote GM, Hornick JL. Contemporary Sarcoma Diagnosis, Genetics, and Genomics. J Clin Oncol. 2018; 36(2): 101–110.
    CrossRefPubMed
  71. Bennani-Baiti IM, Cooper A, Lawlor ER, et al. Intercohort gene expression co-analysis reveals chemokine receptors as prognostic indicators in Ewing's sarcoma. Clin Cancer Res. 2010; 16(14): 3769–3778.
    CrossRefPubMed
  72. Ohali A, Avigad S, Zaizov R, et al. Prediction of high risk Ewing's sarcoma by gene expression profiling. Oncogene. 2004; 23(55): 8997–9006.
    CrossRefPubMed
  73. Liu KX, Lamba N, Hwang WL, et al. Risk stratification by somatic mutation burden in Ewing sarcoma. Cancer. 2019; 125(8): 1357–1364.
    CrossRefPubMed
  74. Jain S, Xu R, Prieto VG, et al. Molecular classification of soft tissue sarcomas and its clinical applications. Int J Clin Exp Pathol. 2010; 3(4): 416–428.
    PubMed
  75. de Alava E, Gerald WL. Molecular biology of the Ewing's sarcoma/primitive neuroectodermal tumor family. J Clin Oncol. 2000; 18(1): 204–213.
    CrossRefPubMed
  76. Zoubek A, Dockhorn-Dworniczak B, Delattre O, et al. Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol. 1996; 14(4): 1245–1251.
    CrossRefPubMed
  77. de Alava E, Kawai A, Healey JH, et al. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol. 1998; 16(4): 1248–1255.
    CrossRefPubMed
  78. Tsuda Y, Zhang L, Meyers P, et al. The clinical heterogeneity of round cell sarcomas with EWSR1/FUS gene fusions: Impact of gene fusion type on clinical features and outcome. Genes Chromosomes Cancer. 2020; 59(9): 525–534.
    CrossRefPubMed
  79. Chen Z, Guo J, Zhang K, et al. TP53 Mutations and Survival in Osteosarcoma Patients: A Meta-Analysis of Published Data. Dis Markers. 2016; 2016: 4639575.
    CrossRefPubMed
  80. Ren W, Gu G. Prognostic implications of RB1 tumour suppressor gene alterations in the clinical outcome of human osteosarcoma: a meta-analysis. Eur J Cancer Care (Engl). 2017; 26(1).
    CrossRefPubMed
  81. Lugowska I, Teterycz P, Mikula M, et al. IDH1/2 Mutations Predict Shorter Survival in Chondrosarcoma. J Cancer. 2018; 9(6): 998–1005.
    CrossRefPubMed
  82. Nicolle R, Ayadi M, Gomez-Brouchet A, et al. Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression. Nat Commun. 2019; 10(1): 4622.
    CrossRefPubMed
  83. Gao P, Seebacher NA, Hornicek F, et al. Advances in sarcoma gene mutations and therapeutic targets. Cancer Treat Rev. 2018; 62: 98–109.
    CrossRefPubMed
  84. Tran D, Verma K, Ward K, et al. Functional genomics analysis reveals a MYC signature associated with a poor clinical prognosis in liposarcomas. Am J Pathol. 2015; 185(3): 717–728.
    CrossRefPubMed
  85. Barrios C, Castresana JS, Kreicbergs A. Clinicopathologic correlations and short-term prognosis in musculoskeletal sarcoma with c-myc oncogene amplification. Am J Clin Oncol. 1994; 17(3): 273–276.
    CrossRefPubMed
  86. Marinoff AE, Spurr LF, Fong C, et al. Clinical Targeted Next-Generation Panel Sequencing Reveals Amplification Is a Poor Prognostic Factor in Osteosarcoma. JCO Precis Oncol. 2023; 7: e2200334.
    CrossRefPubMed
  87. Hogeboom-Gimeno AG, van Ravensteijn SG, Desar IME, et al. MYC amplification in angiosarcoma depends on etiological/clinical subgroups - Diagnostic and prognostic value. Ann Diagn Pathol. 2023; 63: 152096.
    CrossRefPubMed
  88. Morrison C, Radmacher M, Mohammed N, et al. MYC amplification and polysomy 8 in chondrosarcoma: array comparative genomic hybridization, fluorescent in situ hybridization, and association with outcome. J Clin Oncol. 2005; 23(36): 9369–9376.
    CrossRefPubMed
  89. Cheng Ji, Gao J, Tao K. Prognostic role of Gli1 expression in solid malignancies: a meta-analysis. Sci Rep. 2016; 6: 22184.
    CrossRefPubMed
  90. Yoon JW, Lamm M, Chandler C, et al. Up-regulation of GLI1 in vincristine-resistant rhabdomyosarcoma and Ewing sarcoma. BMC Cancer. 2020; 20(1): 511.
    CrossRefPubMed
  91. Cheng D, Qiu X, Zhuang M, et al. MicroRNAs with prognostic significance in osteosarcoma: a systemic review and meta-analysis. Oncotarget. 2017; 8(46): 81062–81074.
    CrossRefPubMed
  92. Kim YH, Goh TS, Lee CS, et al. Prognostic value of microRNAs in osteosarcoma: A meta-analysis. Oncotarget. 2017; 8(5): 8726–8737.
    CrossRefPubMed
  93. Nakatani F, Ferracin M, Manara MC, et al. miR-34a predicts survival of Ewing's sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol. 2012; 226(5): 796–805.
    CrossRefPubMed
  94. Marino MT, Grilli A, Baricordi C, et al. Prognostic significance of miR-34a in Ewing sarcoma is associated with cyclin D1 and ki-67 expression. Ann Oncol. 2014; 25(10): 2080–2086.
    CrossRefPubMed
  95. Luo H, Wang P, Ye H, et al. Serum-Derived microRNAs as Prognostic Biomarkers in Osteosarcoma: A Meta-Analysis. Front Genet. 2020; 11: 789.
    CrossRefPubMed
  96. Xia WK, Lin QF, Shen D, et al. Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients. Onco Targets Ther. 2016; 9: 4645–4652.
    CrossRefPubMed
  97. Ma B, Li M, Zhang L, et al. Upregulation of long non-coding RNA TUG1 correlates with poor prognosis and disease status in osteosarcoma. Tumour Biol. 2016; 37(4): 4445–4455.
    CrossRefPubMed
  98. Wen JJ, Ma YD, Yang GS, et al. Analysis of circulating long non-coding RNA UCA1 as potential biomarkers for diagnosis and prognosis of osteosarcoma. Eur Rev Med Pharmacol Sci. 2017; 21(3): 498–503.
    PubMed
  99. Huo Y, Li Q, Wang X, et al. MALAT1 predicts poor survival in osteosarcoma patients and promotes cell metastasis through associating with EZH2. Oncotarget. 2017; 8(29): 46993–47006.
    CrossRefPubMed
  100. Han F, Wang C, Wang Yi, et al. Long noncoding RNA ATB promotes osteosarcoma cell proliferation, migration and invasion by suppressing miR-200s. Am J Cancer Res. 2017; 7(4): 770–783.
    PubMed
  101. Pinzani P, D'Argenio V, Del Re M, et al. Updates on liquid biopsy: current trends and future perspectives for clinical application in solid tumors. Clin Chem Lab Med. 2021; 59(7): 1181–1200.
    CrossRefPubMed
  102. Krumbholz M, Eiblwieser J, Ranft A, et al. Quantification of Translocation-Specific ctDNA Provides an Integrating Parameter for Early Assessment of Treatment Response and Risk Stratification in Ewing Sarcoma. Clin Cancer Res. 2021; 27(21): 5922–5930.
    CrossRefPubMed
  103. Shulman DS, Klega K, Imamovic-Tuco A, et al. Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group. Br J Cancer. 2018; 119(5): 615–621.
    CrossRefPubMed
  104. Li M, Lu Y, Long Z, et al. Prognostic and clinicopathological significance of circulating tumor cells in osteosarcoma. J Bone Oncol. 2019; 16: 100236.
    CrossRefPubMed
  105. Peneder P, Stütz AM, Surdez D, et al. Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden. Nat Commun. 2021; 12(1): 3230.
    CrossRefPubMed
  106. Lyskjær I, Kara N, De Noon S, et al. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA. Eur J Cancer. 2022; 168: 1–11.
    CrossRefPubMed
  107. Sha D, Jin Z, Budczies J, et al. Tumor Mutational Burden as a Predictive Biomarker in Solid Tumors. Cancer Discov. 2020; 10(12): 1808–1825.
    CrossRefPubMed
  108. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020; 38(1): 1–10.
    CrossRefPubMed
  109. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020; 21(10): 1353–1365.
    CrossRefPubMed
  110. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors.
  111. Chalmers ZR, Connelly CF, Fabrizio D, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017; 9(1): 34.
    CrossRefPubMed
  112. Lam SW, Kostine M, de Miranda NF, et al. Mismatch repair deficiency is rare in bone and soft tissue tumors. Histopathology. 2021; 79(4): 509–520.
    CrossRefPubMed
  113. Georgiadis A, Durham JN, Keefer LA, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357(6349): 409–413.
    CrossRefPubMed
  114. Carmagnani Pestana R, Moyers JT, Roszik J, et al. Impact of Biomarker-Matched Therapies on Outcomes in Patients with Sarcoma Enrolled in Early-Phase Clinical Trials (SAMBA 101). Clin Cancer Res. 2023; 29(9): 1708–1718.
    CrossRefPubMed
  115. Tap WD, Villalobos VM, Cote GM, et al. Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Safety and Clinical Activity in Patients With Advanced Chondrosarcoma. J Clin Oncol. 2020; 38(15): 1693–1701.
    CrossRefPubMed
  116. Italiano A, Mir O, Mathoulin-Pelissier S, et al. Cabozantinib in patients with advanced Ewing sarcoma or osteosarcoma (CABONE): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2020; 21(3): 446–455.
    CrossRefPubMed
  117. Anderson P, Ghisoli M, Crompton BD, et al. Pilot Study of Recurrent Ewing's Sarcoma Management with Vigil/Temozolomide/Irinotecan and Assessment of Circulating Tumor (ct) DNA. Clin Cancer Res. 2023; 29(9): 1689–1697.
    CrossRefPubMed
  118. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 - Identifier NCT04132895, ICONIC: Improving Outcomes Through Collaboration in OsteosarComa (ICONIC) 2023-06-09. https://clinicaltrials.gov/study/NCT04132895.
  119. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 - Identifier NCT05942456, Soluble B7-H3 as a Biomarker for Osteosarcoma 2023-07-12. https://clinicaltrials.gov/study/NCT05942456.
  120. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29 - Identifier NCT06068075, Liquid Biopsy in Ewing Sarcoma and Osteosarcoma as a Prognostic And Response Diagnostic: LEOPARD 2023-10-06. https://clinicaltrials.gov/study/NCT06068075.

About cookies

Necessary cookies

Allways active

These cookies are necessary for the proper display and operation of the website. Blocking them may cause the website to malfunction.

Analytical cookies

As part of our website, we use analytical tools, such as Google Analytics, that allow us to verify website traffic. These tools may require the use of cookies.

Community cookies

These are cookies associated with the social networks we use. Accepting them will allow us to associate your visit to the site with our social media profiles.

Marketing cookies

These are cookies responsible for carrying out advertising and marketing activities - consenting to their use will allow us to target you with advertisements based on your previous activities within our website.

Copyright © 2023 Via Medica Regulations Cookie policy Privacy policy Legal Notice