Frank S. Lieberman, MD


Professor
Department of Neurology
University of Pittsburgh School of Medicine
5150 Centre Avenue, Rm 561
Pittsburgh, PA 15232, USA

Biography

Dr. Lieberman has been active clinical translational investigators focusing on develop of novel therapies for patients with malignant and low grade gliomas since 1985. He has extensive experience in the design, conduct, and interpretation of translational clinical trials of conventional cytotoxic drugs, molecularly targeted agents, and immunotherapeutic strategies. His clinical and translational research efforts have encompassed the application of molecular neuropathology and neuroimaging to strategies for personalized, molecularly targeted therapies for patients with primary central nervous system tumors. He currently serve as the director of the adult neurooncology program within the University of Pittsburgh Cancer Institute, where he oversee the design and conduct of clinical trials for patients with primary and metastatic brain tumors. He currently serve as our institution’s principal investigator for participation in the Adult Brain Tumor Consortium, NRG Consortium, the Collaborative Ependymoma Research Network, and ECOG-ACRIN. He serves on the CNS Tumor Committee of NRG and ECOG- ACRIN, the Biomarker and Experimental Imaging committees for ECOG-ACRIN, and the imaging committee for the ABTC. He had served as principal investigator as well as co-investigator in innovative glioma vaccine trials, for both high grade and low grade gliomas. He had a national leadership role in the translational imaging efforts to develop imaging biomarkers for treatment response in oncology clinical trials, focusing on malignant gliomas. He served as co-investigator (with James Mountz) for our institutional Quantitative Imaging Network U01 project assessing novel PET tracers and high field strength MRI spectroscopy and dynamic contrast imaging as early biomarkers of response in clinical trials for newly diagnosed and recurrent glioblastoma. He is a co-investigator for the QIN proposal expanding this work to evaluation of imaging biomarkers of response in immunotherapy trials for high grade gliomas. He served as chair of the working group for Clinical Trials Design and Development for the Quantitative Imaging Network and as a liaison between QIN and the NCI collaborative trial groups. He has been an institutional leader in the application of molecular profiling to management of patients with low grade gliomas, with our institution beginning molecular profiling of all gliomas beginning in 2002 with FISH and PCR based LOH analysis and more recently with next generation sequencing. He is an active participant in our institutional phase 1 program, specifically focusing on expanding phase 1 option for patients with malignant gliomas, through the use of molecular profiling.

Research Interest

His research interests include: Translational clinical trials for treatment of primary CNS tumors, including low grade and malignant gliomas, ependymomas, meningiomas, and medulloblastoma. He actively involved in the evaluation of molecularly targeted drugs and immunotherapeutics and in the development of quantitative MRI and PET imaging techniques to better define tumor response and progression in clinical trials for patients with low grade and malignant gliomas. Their center has been one of the leaders in applying genetic profiling using first FISH and microdissection based LOH analysis and more recently Next Generation Sequencing to refine the diagnosis of gliomas and to identify molecular subgroups for molecularly targeted therapies. He also had been a coinvestigator in one of the largest occupational exposure studies conducted to identify potential environmental agents associated with increased risk of developing malignant gliomas.

Scientific Activities

Memberships in Professional and Scientific Societies

• (1994-Present) American Association of Cancer Research
• (1995-Present) American Academy of Neurology – Neuro-Oncology Section
• (1996-Present) Society for Neuro-Oncology
• (1996-Present) American Society of Clinical Oncology
• (2004-Present) NRG Radiation Therapy Oncology Group-CNS Tumors Committee
• (2006-Present) ECOG-ACRIN: Biomarker Committee, CNS Tumor Committee
• (2006-Present) Collaborative Ependymoma Research Network

Honors

•(1975) Phi Beta Kappa
•(1978) Merck Award for Excellence in Clinical Medicine
•(1979) Alpha Omega Alpha
•(1985) Sigma Xi

Publications

REFERRED ARTICLES

1. Lieberman F, Marton LS, Stefansson K, Patter. Pattern of reactivity of IgM from the sear of 8 patients with IgM monoclonal gammopathy and neuropathy with components of neural tissue: evidence for interaction with more than one epitope. Acta Neuropathol (Berl). 1985; 68: 296-299.
2. Sitrin MD, Lieberman FS, Jensen WE, Noronha A, Milburn C, Addington W. Vitamin E deficiency and neurologic disease in adults with cystic fibrosis. Ann Intern Med. 1987; 107: 51-54. doi: 10.7326/0003-4819-107-1-51
3. Monestier M, Fasy TM, Bohm L, Lieberman FS. Anti-histone antibodies in subacute sensory neuropathy. J Neuro. 1991; 11: 71-75. doi: 10.1007/BF00167000
4. Hormigo A, Lieberman F. Nuclear localization of anti-Hu antibody is not associated with in vitro cytotoxicity. J Neuro Immunol. 1994; 55: 205-212. doi: http://dx.doi.org/10.1016/0165-5728(94)90011-6
5. Stockhammer G, Manley GT, Johnson R, Rosenblum MK, Samid D, Lieberman FS. Inhibition of proliferation and induction of differentiation in medulloblastoma- and astrocytoma-derived cell lines with phenylacetate. J Neurosurg. 1995; 83: 672-681. doi: 10.3171/jns.1995.83.4.0672
6. Verschuuren J, Chuang L, Rosenblum MK, et al. Inflammatory infiltrates and complete absence of Purkinje cells in anti-Yo-associated paraneoplastic cerebellar degeneration. Acta Neuropathol. 1996; 91: 519-525. doi: 10.1007/s004010050460
7. Lieberman F, Bulati S. Headaches after inadvertent lumbar puncture during bone marrow harvest. Neurology. 1996; 46: 268-269. doi: 10.1212/WNL.46.1.268
8. Lieberman F, Portlock C. Recurrent episodes of transient memory disturbance after unilateral thalamic infarction in a Hodgkin’s disease patient with herpes zoster. J Neurovasc Dis. 1996; 1: 9-12.
9. Hormigo A, Ball C, Lieberman F. Internalization of anti-Hu antibody is not Fcy receptor mediated. Neurology. 1996; 47: 607-609. doi: 10.1212/WNL.47.2.607
10. Lieberman FS, Odel J, Hirsch J, Heinemann M, Michaeli J, Posner JB. Bilateral optic neuropathy with IgGkappa multiple myeloma improved after myeloablative chemotherapy. Neurology. 1999; 52: 414-416.
11. Lieberman F, Korf BR. Emerging approaches toward the treatment of neurofibromatoses. Genet Med. 1999; 1: 158-164.
12. Lim DJ, Rubenstein AE, Evans DG, et al. Advances in neurofibromatosis 2 (NF2): a workshop report. J Neurogenet. 2000; 14(2): 63-106. doi: 10.3109/01677060009083477
13. Okada H, Pollack IF, Lotze MT, et al. Gene therapy of malignant gliomas: a phase I study of IL-4-HSV-TK gene-modified autologous tumor to elicit an immune response. Hum Gene Ther. 2000; 11(4): 637-653. doi: 10.1089/10430340050015824
14. Okada H, Pollack IF, Lieberman F, et al. Gene therapy of malignant gliomas: a pilot study of vaccination with irradiated autologous glioma and dendritic cells admixed with IL-4 transduced fibroblasts to elicit an immune response. Hum Gene Ther. 2001; 12(5): 575-595. doi: 10.1089/104303401300042528.
15. Pollack IF, Hamilton RL, Finklestein SD, Lieberman F. Molecular abnormalities and correlations with tumor response and outcome in glioma patients. Neuroimaging Clin N Am. 2002; 12(4): 627-639.
16. Lieberman FS, Schold SC. Distant effects of cancer on the nervous system. Oncology(Huntingt). 2002; 16(11): 1539-1548; discussion 1550-1551, 1554-1556.
17. Okada H, Lieberman FS, Edington HD, et al. Autologous glioma cell vaccine admixed with interleukin-4 gene transfect fibroblasts in the treatment of recurrent glioblastoma: preliminary observations in a patient with a favorable response to therapy. J Neurooncol. 2003; 64(1-2): 13-20. doi: 10.1023/A:1024969422010
18. Finkelstein SD, Mohan D, Hamilton R, Sasatomi E, Swalsky PA, Lieberman FS. Microdissection genotyping assists discrimination of reactive gliosis versus glioma. Am J Clin Pathol. 2004; 121/5: 671-678. doi: 10.1309/WF2HL03T7YP713NK
19. Mohan D, Finklestein SD, Swalsky PA, et al. Microdissection genotyping of gliomas: therapeutic and prognostic considerations. Mod Pathol. 2004; 17(11): 1346-1358. doi: 10.1038/modpathol.3800194
20. Pudavelli VK, Yung WK, Hess KR, et al. Phase II study of fenretinide(NCS 374551) in adults with recurrent malignant gliomas: A North American Brain Tumor Consortium study. J Clin Oncol. 2004; 22(21): 4282-4289. doi: 10.1200/JCO.2004.09.096
21. Cloughesy TF, Kuhn J, Robins HI, et al. Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. J Clin Oncol. 2005; 23(27): 6647-6656. doi: 10.1200/JCO.2005.10.068
22. Lassman, AB, Rossi MR, Raizer JR, et al. Molecular study of malignant gliomas treated with EGFR inhibitors: tissue analysis from North American Brain Tumor Consortium(NABTC) trials 01-03 and 00-01. Clin Cancer Res. 2005; 11(21): 7841-7850. doi: 10.1158/1078-0432.CCR-05-0421
23. Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol. 2006; 33(1): 15-49. doi: http://dx.doi.org/10.1053/j.seminoncol.2005.12.010
24. Cloughesy TF, Wen PY, Robins HI, et al. Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. J Clin Oncol. 2006; 24 (22): 3651-3656. doi: 10.1200/JCO.2006.06.2323
25. Wen PY, Yung WK, Lamborn KR, et al. Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res. 2006; 12(16): 4899-4907. doi: 10.1158/1078-0432.CCR-06-0773
26. Bernardi RJ, Bomgaars L, Fox E, et al. Phase I clinical trial of intrathecal gemcitabine in patients with neoplastic meningitis. Cancer Chemother Pharmacol. 2007. doi: 10.1007/s00280-007-0601-x
27. Loghin ME, Prados MD, Wen P, et al. Phase I study of temozolomide and irinotecan for recurrent malignant gliomas in patients receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium Study. Clin Cancer Res. 2007; 13(23): 7133-7138. doi: 10.1158/1078-0432.CCR-07-0874
28. Okada H, Lieberman F, Walter KA, et al. Autologous glioma cell vaccine admixed with interleukin-4 gene transfected fibroblasts in the treatment of patients with malignant gliomas. J Transl Med. 2007; 5(1): 67. doi: 10.1186/1479-5876-5-67
29. Lamborn KR, Yung WK, Chang SM, et al. Progression-free survival: an important end point in evaluating therapy for recurrent high-grade gliomas. North American Brain Tumor Consortium. Neuro Oncol. 2008; 10(2): 162-170. doi: 10.1215/15228517-2007-062
30. Kano H, Niranjan A, Khan A, et al. Does radiosurgery have a role in the management of ogliodendrogliomas? J Neurosurg. 2008. doi: 10.3171/2008.5.17582
31. Chang SM, Lamborn KR, Kuhn JG, et al. Neurooncology clinical trial design for targeted therapies: Lessons learned from the North American Brain Tumor Consortium. Neuro Oncol. 2008. doi: 10.1215/15228517-2008-021
32. Marsh GM, Buchanich JM, Youk AO, et al. Long-term health experience of jet engine manufacturing workers: I. Mortality from central nervous system neoplasms. J Occup Environ Med. 2008; 50(10): 1099-1116. doi: 10.1097/JOM.0b013e31818bc30e
33. Marsh GM, Buchanich JM, Youk AO, et al. Long-term health experience of jet engine manufacturing workers: II. Total and cause-specific mortality excluding central nervous system Neoplasms. J Occup Environ Med. 2008; 50 (10): 1117-1129. doi: 10.1097/JOM.0b013e31818bc327
34. Butowski N, Lamborn KR, Lee BL, et al. A North American Brain Tumor Consortium phase II study of poly-ICLC for adult patients with recurrent anaplastic gliomas. J Neurooncol. 2009; 91(2): 183-189. doi: 10.1007/s11060-008-9705-3
35. Buchanich JM, Youk AO, Marsh GM, et al. Methodological issues in a retrospective cancer incidence study. Am J Epidemiol. 2009; 170 (1): 112-119. doi: 10.1093/aje/kwp091
36. Park DM, Yeaney GA, Hamilton RL, et al. Identifying Muir-Torre syndrome in a patient with glioblastoma multiforme. Neuro Oncol. 2009; 11 (4): 452-455. doi: 10.1215/15228517-2008-101
37. Norden AD, Raizer JJ, Abrey LE, et al. Phase II trials of erlotinib or gefitinib in patients with recurrent meningioma. J Neurooncol. 2010; 96(2): 211-217. doi: 10.1007/s11060-009-9948-7
38. Raizer JJ, Abrey LE, Lassman AB, et al. A phase I trial or erolotinib on patients with nonprogressive glioblastoma multiforme postradiation therapy, and recurrent malignant gliomas and meniniomas. Neuro Oncol. 2010; 12 (1) : 87-97. doi: 10.1093/neuonc/nop017
39. Raizer JJ, Abrey LE, Lassman AB, et al. A phase II trial of erlotinib in patients with recurrent malignant gliomas and nonprogressive glioblastoma multiforme postradiation therapy. Neuro Oncol. 2010; 12 (1): 95-103. doi: 10.1093/neuonc/nop015
40. Yiin JJ, Hu B, Schornack PA, et al. ZD6474, a Multitargeted inhibitor for receptor tyrosine kinases, suppresses growth of gliomas expressing an epidermal growth factor receptor mutant, EGFRvIII, in the Brain. Mol Cancer Ther. 2010; 9 (1): 929-941. doi: 10.1158/1535-7163.MCT-09-0953
41. Marsh GM, Buchanich JM, Youk AO, et al. Long-term health experience of jet engine manufacturing workers: IV. A comparison of central nervous system cancer ascertainment using mortality and incidence data. Ann Epidemiol. 2010; 20 (10) 759-765. doi: 10.1016/j.annepidem.2010.06.008
42. Buchanich JM, Youk AO, Marsh GM, et al. Long-term health experience of jet engine manufacturing workers: IV. A comparison of central nervous system cancer ascertainment using mortality and incidence data. Ann Epidemiol. 2010; 20(10): 759-765. doi: 10.1016/j.annepidem.2010.06.008
43. de Groot JF, Lamborn KR, Chang SM, et al. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study. J Clini Onco. 2011; 29(19): 2689-2695. doi: 10.1200/JCO.2010.34.1636
44. Clarke JL, Ennis MM, Young WK, et al. Is surgery at progression a prognostic marker for improved 6-month progression-free survival or overall survival for patients with recurrent glioblastoma? Neuro Oncol. 2011; 13(10): 1118-1124. doi: 10.1093/neuonc/nor110
45. Iwamoto FM, Lamborn KR, Kuhn JG, et al. A phase I/II trial of the histone deacetylase inhibitor romidepsin for adults with recurrent malignant glioma; North American Brain Tumor Consortium Study 03-03. Neuro Oncol. 2011; 13(5): 509-516. doi: 10.1093/neuonc/nor017
46. Kofler J, Bartynski WS, Reynolds TQ, Lieberman FS, Murdoch GH, Hamilton RL. Posterior reversible encephalopathy syndrome (PRES) with immune system activation, VEGF up-regulation, and cerebral amyloid angiopathy. J Comput Assist Tomogr. 2011; 35(1): 39-42. doi: 10.1097/RCT.0b013e3181f31917.
47. Okada H, Kalinski P, Ueda R, et al. Induction of CD8+T-cell responses against novel glioma-associated antigen peptides and clinical activity by vaccinations with {alpha}-type 1 polarized dendritic cells and polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose in patients with recurrent malignant glioma. J Clin Oncol. 2011; 29(3): 330-336. doi: 10.1200/JCO.2010.30.7744
48. Nghiemphu PL, Wen PY, Lamborn KR, et al. A phase I trial of tipifarnib with radiation therapy, with and without temozolomide, for patients with newly diagnosed glioblastoma. Int J Radiat Oncol Biol Phys. 2011; 81(5): 1422-1427. doi: 10.1016/j.ijrobp.2010.07.1997
49. Vivanco I, Robins HI, Rohle D, et al. Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discovery. 2012; 2(5): 458-471. doi: 10.1158/2159-8290.CD-11-0284
50. Lieberman F, Yazbeck V, Raptis A, Felgar R, Boyiadzis M. Primary central nervous system post-transplant lymphoproliferative disorders following allogeneic hematopoietic stem cell transplantation. J Neuro-Oncol. 2012; 107(2): 225-232. doi: 10.1007/s11060-011-0739-6
51. Gilbert MR, Kuhn J, Lamborn KR, et al. Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery. J Neuro-Oncol. 2012; 106(1): 147-153. doi: 10.1007/s11060-011-0650-1
52. Lee EQ, Kuhn J, Lamborn KR, et al. Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma; North American Brain Tumor consortium study 05-02. Neuro Oncol. 2012; 14(12): 1511-1518. doi: 10.1093/neuonc/nos264
53. Lee EQ, Puduvalli VK, Reid JM, et al. Phase I study of vorinostat in combination with emozolomide in patients with high-grade gliomas: North American Brain Tumor Consortium Study 04-03. Clin Cancer Res. 2012; 18(21): 6032-6039. doi: 10.1158/1078-0432.CCR-12-1841
54. Kurland BF, Gerstner ER, Mountz JM, et al. Promise and pitfalls of quantitative imaging in oncology clinical trials. Magn Reson Imaging. 2012; 30(9): 1301-1312. doi: 10.1016/j.mri.2012.06.009
55. Laymon CM, Oborski MJ, Lee VK, et al. Combined imaging biomarkers for therapy evaluation in glioblastoma multiforme: correlating sodium MRI and F-18 FLT PET on a voxel-wise basis. Magn Reson Imaging. 2012; 30(9): 1268-1278. doi: 10.1016/j.mri.2012.05.011
56. Baldwin KJ, Zivović SA, Lieberman FS. Neurologic emergencies in patients who have cancer: diagnosis and management. Neurol Clin. 2012; 30(1): 101-128. doi: 10.1016/j.ncl.2011.09.004
57. Park KJ, Kano H, Iyer A, et al. Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study. J Neurooncol. 2012; 107(2): 323-333. doi: 10.1007/s11060-011-0744-9
58. Imani F, Boada FE, Lieberman FS, Davis DK, Deeb EL, Mountz JM. Comparison of proton magnetic resonance spectroscopy with fluorine-18 w-fluoro-deoxyglucose positron semission tomography for assessment of brain tumor progression. J Neuroimaging. 2012; 22(2): 184-190. doi: 10.1111/j.1552-6569.2010.00561.x
59. Oborski MJ, Laymon CM, Lieberman FS, Mountz JM. Distinguishing Pseudoprogression from progression in high-grade gliomas: A brief review of current clinical practice and demonstration of the potential value of 18F-FDG PET. Clin Nucl Med. 2013. doi: 10.1097/RLU.0b013e318286c148.
60. Oborski MJ, Laymon CM, Lieberman FS, Mountz JM. Distinguishing pseudoprogression from progression in high-grade gliomas: a brief review of current clinical practice and demonstration of the potential value of 18F-FDG PET. Clin Nucl Med. 2013; 38(5): 381-384. doi: 10. 1097/RLU. 0b013e318286c148
61. Marsh GM, Buchanich JM, Youk AO, et al. Long-term health experience of jet engine manufacturing workers: results from a 12-year exploratory investigation. J Occup Environ Med. 2013; 55(6): 652-653. doi: 10. 1097/JOM. 0b013e3182851605. doi: 10.1097/JOM.0b013e3182851605
62. Kondziolka D, Parry PV, Lunsford LD, et al. The accuracy of predicting survival in individual patients with cancer. J Neurosurg. 2013. doi: 10.3171/2013.9.JNS13788
63. Imani F, Boada FE, Lieberman FS, Davis DK, Mountz JM. Molecular and metabolic pattern classification for detection of brain glioma progression. Eur J Radiol. 2013; S0720-048X(13): 00590-00591. doi: 10. 1016/j. ejrad. 2013. 06. 033
64. Oborski MJ, Demirci E, Laymon CM, Lieberman FS, Mountz JM. Assessment of Early Therapy Response with 18F-FLT PET in Glioblastoma Multiforme. Clin Nucl Med. 2013. doi: 10.1097/RLU.0000000000000321
65. Imani F, Boada FE, Lieberman FS, Davis DK, Mountz JM. Molecular and metabolic pattern classification for detection of brain glioma progression. Eur J Radiol. 2014; 83(2): e100-e105. doi: 10.1016/j.ejrad.2013.06.033
66. Oborski MJ, Laymon CM, Qian Y, Lieberman FS, Nelson AD, Mountz JM. Challenges and Approaches to Quantitative Therapy Response Assessment in Glioblastoma Multiforme Using the Novel Apoptosis Positron Emission Tomography Tracer F-18 ML-10. Transl Oncol. 2014; 7(1): 111-119. doi: 10.1593/tlo.13868
67. Oborski MJ, Laymon CM, Lieberman FS, Drappatz J, Hamilton RL, Mountz JM. First use of (18)F-labeled ML-10 PET to assess apoptosis change in a newly diagnosed glioblastoma multiforme patient before and early after therapy. Brain Behav. 2014; 4(2): 312-315. doi: 10.1002/brb3.217
68. Ahmed R, Oborski MJ, Hwang M, Lieberman FS, Mountz JM. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods. Cancer Manag Res. 2014; 6: 149-170. doi: 10.2147/CMAR.S54726
69. Wen PY, Chang SM, Lamborn KR, et al. Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol. 2014; 16(4): 567-578.
70. Qian Y, Panigrahy A, Laymon CM, et al. Short-T2 imaging for quantifying concentration of sodium (23 Na) of bi-exponential T2 relaxation. Magn Reson Med. 2014. doi: 10.1002/mrm.25393
71. Vera-Bolanos E, Aldape K, Yuan Y, et al. Clinical course and progression-free survival of adult intracranial and spinal ependymoma patients. Neuro Oncol. 2014. nou162.
72. Oborski MJ, Demirci E, Laymon CM, Lieberman FS, Mountz JM. Assessment of early therapy response with 18F-FLT PET in glioblastoma multiforme. Clin Nucl Med. 2014; 39(10): e431-e432. doi: 10.1097/RLU.0000000000000321
73. Okada H, Butterfield LH, Hamilton RL, et al. Induction of robust type-1 CD8+ T-cell responses in WHO grade II low-grade glioma patients receiving peptide-based vaccines in combination with poly-ICLC. Clin Cancer Res. 2014; clincanres. 1790. 2014. doi: 10.1158/1078-0432.CCR-14-1790