DF/HCC Program Affiliation

Neuro-Oncology

DF/HCC Associations

MGH, Neuro-Oncology, Clinical Trial Chairs

Research Abstract

My work involves 1) the development of experimental trials of novel agents for patients with glioblastoma and primary CNS lymphoma (PCNSL) and 2) the identification of molecular markers of prognosis in patients with malignant glioma. With respect to therapeutic studies, I am the Principal Investigator (PI) of the MGH U01 grant, New Approaches to Brain Tumor Therapy (NABTT). In this role I have served as the PI of several national, multicenter therapeutic trials (CPT-11 for recurrent glioblastoma; oxaliplatin for newly diagnosed glioblastoma; Methotrexate for newly diagnosed PCNSL; Methotrexate and thio-TEPA for newly diagnosed PCNSL; rituximab for relapsed PCNSL). I am also the PI of an R21-funded study of AZD2171, an oral VEGFR2 tyrosine kinase inhibitor, in patients with recurrent glioblastoma. The study includes correlative investigations of possible drug effects on circulating endothelial and progenitor cells; circulating cytokines and such magnetic resonance imaging (MRI) parameters as arterial spin labeling; perfusion-weighted imaging and diffusion-weighted imaging. Other approved and funded studies of molecularly-targeted drugs in glioblastoma that I lead include: MLN518; PTK787; ZD6474 and sunitinib.

My work on molecular markers of prognosis incorporates data from two major resources: a longitudinal, electronic patient research database and a large brain tumor bank. In our studies we have demonstrated that the prognostic effects of EGFR and TP53 in glioblastoma (survival, response to radiation) are a function of the age of the patient. We have also demonstrated that BCL-6 is a significant positive prognostic marker in patients with PCNSL. Current molecular prognosis studies focus on anaplastic oligoastrocytomas; anaplastic oligodendrogliomas and glioblastoma.

Publications

• Cahill DP, Levine KK, Betensky RA, Codd PJ, Romany CA, Reavie LB, Batchelor TT, Futreal PA, Stratton MR, Curry WT, Iafrate AJ, Louis DN.Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomid
  17404084
• Norden AD, Batchelor TT.Reversible posterior leukoencephalopathy syndrome.Onkologie 2007 Mar;30(3):90-1.
  17341892
• Correa D, Maron L, Harder H, Klein M, Armstrong C, Calabrese P, Bromberg J, Abrey L, Batchelor T, Schiff D.Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines.Ann Oncol 2007 Feb 6.
  17284616
• Batchelor TT, Sorensen AG, di Tomaso E, Zhang WT, Duda DG, Cohen KS, Kozak KR, Cahill DP, Chen PJ, Zhu M, Ancukiewicz M, Mrugala MM, Plotkin S, Drappatz J, Louis DN, Ivy P, Scadden DT, Benner T, Loeffler JS, Wen PY, Jain RK.AZD2171, a pan-VEGF receptor ty
  17222792
• Mizoguchi M, Betensky RA, Batchelor TT, Bernay DC, Louis DN, Nutt CL.Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: correlation with EGFR status, tumor grade, and survival.J Neuropathol Exp Neurol 2006 Dec;65(12):1181-8.
  17146292
• Eichler AF, Batchelor TT.Primary central nervous system lymphoma: presentation, diagnosis and staging.Neurosurg Focus 2006;21(5):E15.
  17134117
• Batchelor TT, Byrne TN.Supportive care of brain tumor patients.Hematol Oncol Clin North Am 2006 Dec;20(6):1337-61.
  17113467
• Gerber DE, Grossman SA, Batchelor T, Ye X.Calculated versus measured creatinine clearance for dosing methotrexate in the treatment of primary central nervous system lymphoma.Cancer Chemother Pharmacol 2007 Jun;59(6):817-23.
  16972068
• Grossman SA, Carson KA, Batchelor TT, Lesser G, Mikkelsen T, Alavi JB, Phuphanich S, Hammour T, Fisher JD, Supko JG.The effect of enzyme-inducing antiseizure drugs on the pharmacokinetics and tolerability of procarbazine hydrochloride.Clin Cancer Res 2006
  16951236
• Hunter C, Smith R, Cahill DP, Stephens P, Stevens C, Teague J, Greenman C, Edkins S, Bignell G, Davies H, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Butler A, Clements J, Cole J, Dicks E, Forbes S, Gorton M, Gray K, Halliday K, Harri
  16618716
• Jahnke K, Korfel A, O'neill BP, Blay JY, Abrey LE, Martus P, Poortmans PM, Shenkier TN, Batchelor TT, Neuwelt EA, Raizer JJ, Schiff D, Pels H, Herrlinger U, Stein H, Thiel E.International study on low-grade primary central nervous system lymphoma.Ann Neur
  16586496
• Batchelor T, Loeffler JS.Primary CNS lymphoma.J Clin Oncol 2006 Mar 10;24(8):1281-8.
  16525183
• Shah GD, Kesari S, Xu R, Batchelor TT, O'Neill AM, Hochberg FH, Levy B, Bradshaw J, Wen PY.Comparison of linear and volumetric criteria in assessing tumor response in adult high-grade gliomas.Neuro-oncol 2006 Jan;8(1):38-46.
  16443946
• Rubenstein JL, Fridlyand J, Shen A, Aldape K, Ginzinger D, Batchelor T, Treseler P, Berger M, McDermott M, Prados M, Karch J, Okada C, Hyun W, Parikh S, Haqq C, Shuman M.Gene expression and angiotropism in primary CNS lymphoma.Blood 2006 May 1;107(9):3716
  16418334
• Aghi M, Gaviani P, Henson JW, Batchelor TT, Louis DN, Barker FG.Magnetic resonance imaging characteristics predict epidermal growth factor receptor amplification status in glioblastoma.Clin Cancer Res 2005 Dec 15;11(24 Pt 1):8600-5.
  16361543
• Batchelor T.Neuro-oncology update: 2005.Curr Opin Neurol 2005 Dec;18(6):631.
  16280672
• Mrugala MM, Batchelor TT, Plotkin SR.Peripheral and cranial nerve sheath tumors.Curr Opin Neurol 2005 Oct;18(5):604-10.
  16155448
• Fitzsimmons A, Upchurch K, Batchelor T.Clinical features and diagnosis of primary central nervous system lymphoma.Hematol Oncol Clin North Am 2005 Aug;19(4):689-703, vii.
  16083830
• Shih HA, Betensky RA, Dorfman MV, Louis DN, Loeffler JS, Batchelor TT.Genetic analyses for predictors of radiation response in glioblastoma.Int J Radiat Oncol Biol Phys 2005 Nov 1;63(3):704-10.
  15978739
• Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, Smith JR, Korfel A, Soussain C, DeAngelis LM, Neuwelt EA, O'Neill BP, Thiel E, Shenkier T, Graus F, van den Bent M, Seymour JF, Poortmans P, Armitage JO, Cavalli F,.Report of an
  15955902
• Plotkin SR, Betensky RA, Hochberg FH, Grossman SA, Lesser GJ, Nabors LB, Chon B, Batchelor TT.Treatment of relapsed central nervous system lymphoma with high-dose methotrexate.Clin Cancer Res 2004 Sep 1;10(17):5643-6.
  15355887
• Batchelor TT, Betensky RA, Esposito JM, Pham LD, Dorfman MV, Piscatelli N, Jhung S, Rhee D, Louis DN.Age-dependent prognostic effects of genetic alterations in glioblastoma.Clin Cancer Res 2004 Jan 1;10(1 Pt 1):228-33.
  14734474
• Batchelor T, Carson K, O'Neill A, Grossman SA, Alavi J, New P, Hochberg F, Priet R.Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07.J Clin Oncol 2003 Mar 15;21(6):1044-9.
  12637469
• Braaten KM, Betensky RA, de Leval L, Okada Y, Hochberg FH, Louis DN, Harris NL, Batchelor TT.BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma.Clin Cancer Res 2003 Mar;9(3):1063-9.
  12631608
• Kesari S, Schiff D, Henson JW, Muzikansky A, Gigas DC, Doherty L, Batchelor TT, Longtine JA, Ligon KL, Weaver S, Laforme A, Ramakrishna N, Black PM, Drappatz J, Ciampa A, Folkman J, Kieran M, Wen PY.Phase II study of temozolomide, thalidomide, and celecox
  18403492
• Reardon DA, Wen PY, Desjardins A, Batchelor TT, Vredenburgh JJ.Glioblastoma multiforme: an emerging paradigm of anti-VEGF therapy.Expert Opin Biol Ther 2008 Apr;8(4):541-53.
  18352856
• Grossman SA, Olson J, Batchelor T, Peereboom D, Lesser G, Desideri S, Ye X, Hammour T, Supko JG.Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma.Neuro-oncol 2008 Apr;10(2):190-8.
  18287342
• Sher DJ, Henson JW, Avutu B, Hochberg FH, Batchelor TT, Martuza RL, Barker FG 2nd, Loeffler JS, Chakravarti A.The added value of concurrently administered temozolomide versus adjuvant temozolomide alone in newly diagnosed glioblastoma.J Neurooncol 2008 Ma
  18231723
• Gerstner ER, Carson KA, Grossman SA, Batchelor TT.Long-term outcome in PCNSL patients treated with high-dose methotrexate and deferred radiation.Neurology 2008 Jan 29;70(5):401-2.
  18227422
• Gerstner ER, Duda DG, di Tomaso E, Sorensen G, Jain RK, Batchelor TT.Antiangiogenic agents for the treatment of glioblastoma.Expert Opin Investig Drugs 2007 Dec;16(12):1895-908.
  18041999
• Doolittle ND, Abrey LE, Shenkier TN, Tali S, Bromberg JE, Neuwelt EA, Soussain C, Jahnke K, Johnston P, Illerhaus G, Schiff D, Batchelor T, Montoto S, Kraemer DF, Zucca E.Brain parenchyma involvement as isolated central nervous system relapse of systemic
  17962515
• Voloschin AD, Betensky R, Wen PY, Hochberg F, Batchelor T.Topotecan as salvage therapy for relapsed or refractory primary central nervous system lymphoma.J Neurooncol 2008 Jan;86(2):211-5.
  17896078
• Jain RK, di Tomaso E, Duda DG, Loeffler JS, Sorensen AG, Batchelor TT.Angiogenesis in brain tumours.Nat Rev Neurosci 2007 Aug;8(8):610-22.
  17643088
• Drappatz J, Batchelor TT.Leptomeningeal Neoplasms.Curr Treat Options Neurol 2007 Jul;9(4):283-293.
  17580008
• Eichler AF, Batchelor TT, Henson JW.Diffusion and perfusion imaging in subacute neurotoxicity following high-dose intravenous methotrexate.Neuro-oncol 2007 May 23.
  17522329
• Duda DG, Batchelor TT, Willett CG, Jain RK.VEGF-targeted cancer therapy strategies: current progress, hurdles and future prospects.Trends Mol Med 2007 Apr 24.
  17462954
• Kesari S, Schiff D, Doherty L, Gigas DC, Batchelor TT, Muzikansky A, O'neill A, Drappatz J, Chen-Plotkin AS, Ramakrishna N, Weiss SE, Levy B, Bradshaw J, Kracher J, Laforme A, Black PM, Folkman J, Kieran M, Wen PY.Phase II study of metronomic chemotherapy
  17452651
• Grier JT, Batchelor T.Low-grade gliomas in adults.Oncologist 2006 Jun;11(6):681-93.
  16794247
• Nguyen P, Chakravarti A, Batchelor T, Hochberg F, Loeffler J.Results of Whole-Brain Radiation as Salvage of Methotrexate Failure in Patients with Primary Central Nervous System Lymphoma.J Am Diet Assoc;In press.
• Betensky RA, Nutt CL, Batchelor TT, Louis DN.Statistical considerations for immunohistochemistry panel development after gene expression profiling of human cancers.J Mol Diagn 2005 May;7(2):276-82.
  15858152
• DeAngelis L, Batchelor T.Primary CNS lymphoma: is there a role for prophylaxis against lymphomatous meningitis?.J Mol Diagn 2004 Jul;4(4 Suppl):S19-24.
  15853551
• Shenkier TN, Blay JY, O'Neill BP, Poortmans P, Thiel E, Jahnke K, Abrey LE, Neuwelt E, Tsang R, Batchelor T, Harris N, Ferreri AJ, Ponzoni M, O'Brien P, Rubenstein J, Connors JM.Primary CNS lymphoma of T-cell origin: a descriptive analysis from the intern
  15800313
• Nutt CL, Betensky RA, Brower MA, Batchelor TT, Louis DN, Stemmer-Rachamimov AO.YKL-40 is a differential diagnostic marker for histologic subtypes of high-grade gliomas.Clin Cancer Res 2005 Mar 15;11(6):2258-64.
  15788675
• Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS.Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma.J Clin Oncol 2005 Mar 1;23(7):1507-13.
  15735126
• Voloschin AD, Louis DN, Cosgrove GR, Batchelor TT.Neoadjuvant temozolomide followed by complete resection of a 1p- and 19q-deleted anaplastic oligoastrocytoma: case study.Neuro-oncol 2005 Jan;7(1):97-100.
  15701287
• Batchelor TT, Buchbinder BR, Harris NL.Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 1-2005. A 35-year-old woman with difficulty walking, headache, and nausea.N Engl J Med 2005 Jan 13;352(2):185-94.
  15647582
• Gaviani P, Gonzalez RG, Zhu JJ, Batchelor TT, Henson JW.Central neurogenic hyperventilation and lactate production in brainstem glioma.Neurology 2005 Jan 11;64(1):166-7.
  15642931
• Drappatz J, Batchelor T.Neurologic complications of plasma cell disorders.Clin Lymphoma 2004 Dec;5(3):163-71.
  15636691
• Grier J, Batchelor T.Metastatic Neurologic Complications of Non-Hodgkin's Lymphoma.Curr Oncol Rep 2005 Jan;7(1):55-60.
  15610687
• Jeyapalan SA, Batchelor T.Management of Brain Metastases.Curr Treat Options Neurol 2004 Jul;6(4):273-284.
  15157405
• Batchelor TT, Gilbert MR, Supko JG, Carson KA, Nabors LB, Grossman SA, Lesser GJ, Mikkelsen T, Phuphanich S,.Phase 2 study of weekly irinotecan in adults with recurrent malignant glioma: final report of NABTT 97-11.Neuro-oncol 2004 Jan;6(1):21-7.
  14769136
• He X, Batchelor TT, Grossman S, Supko JG.Determination of procarbazine in human plasma by liquid chromatography with electrospray ionization mass spectrometry.J Chromatogr B Analyt Technol Biomed Life Sci 2004 Jan 25;799(2):281-91.
  14670747
• Baehring JM, Betensky RA, Batchelor TT.Malignant peripheral nerve sheath tumor: The clinical spectrum and outcome of treatment.Neurology 2003 Sep 9;61(5):696-8.
  12963767
• Gilbert MR, Supko JG, Batchelor T, Lesser G, Fisher JD, Piantadosi S, Grossman S.Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma.Clin Cancer Res 2003 Aug 1;9(8):2940-9.
  12912940
• Fine HA, Wen PY, Maher EA, Viscosi E, Batchelor T, Lakhani N, Figg WD, Purow BW, Borkowf CB.Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas.J Clin Oncol 2003 Jun 15;21(12):2299-304.
  12805330
• Ferreri AJ, Abrey LE, Blay JY, Borisch B, Hochman J, Neuwelt EA, Yahalom J, Zucca E, Cavalli F, Armitage J, Batchelor T.Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, S
  12805341
• Ferreri AJ, Batchelor T, Zucca E, Cavalli F, Armitage J.International Collaborative Group against Primary CNS Lymphomas.J Clin Oncol 2003 Apr 15;21(8):1649-50.
  12697892
• Kesari S, Batchelor TT.Leptomeningeal metastases.Neurol Clin 2003 Feb;21(1):25-66.
  12690644
• Nutt CL, Mani DR, Betensky RA, Tamayo P, Cairncross JG, Ladd C, Pohl U, Hartmann C, McLaughlin ME, Batchelor TT, Black PM, von Deimling A, Pomeroy SL, Golub TR, Louis DN.Gene expression-based classification of malignant gliomas correlates better with surv
  12670911
• Batchelor TT, Kolak G, Ciordia R, Foster CS, Henson JW.High-dose methotrexate for intraocular lymphoma.Clin Cancer Res 2003 Feb;9(2):711-5.
  12576439
• Plotkin SR, Batchelor TT.Primary nervous system lymphoma.Curr Treat Options Oncol 2002 Dec;3(6):525-35.
  12392641
• Jaeckle KA, Batchelor T, O'Day SJ, Phuphanich S, New P, Lesser G, Cohn A, Gilbert M, Aiken R, Heros D, Rogers L, Wong E, Fulton D, Gutheil JC, Baidas S, Kennedy JM, Mason W, Moots P, Russell C, Swinnen LJ, Howell SB.An open label trial of sustained-releas
  12125986
• Plotkin SR, Batchelor TT.Primary nervous-system lymphoma.Lancet Oncol 2001 Jun;2(6):354-65.
  11905752
• Batchelor T, Stanley K, Andersen J.Clinical trials in neuro-oncology.Curr Opin Neurol 2001 Dec;14(6):689-94.
  11723375
• Batchelor T, Leahy N, Kaufman D.High-dose methotrexate for isolated central nervous system relapse in patients with testicular non-Hodgkin's lymphoma.Clin Lymphoma 2001 Sep;2(2):116-9; discussion 120-2.
  11707852
• Plotkin SR, Batchelor TT.Advances in the therapy of primary central nervous system lymphoma.Clin Lymphoma 2001 Mar;1(4):263-75; discussion 276-7.
  11707839
• Jaeckle KA, Phuphanich S, Bent MJ, Aiken R, Batchelor T, Campbell T, Fulton D, Gilbert M, Heros D, Rogers L, O'Day SJ, Akerley W, Allen J, Baidas S, Gertler SZ, Greenberg HS, LaFollette S, Lesser G, Mason W, Recht L, Wong E, Chamberlain MC, Cohn A, Glantz
  11161370
• Ciordia R, Supko J, Gatineau M, Batchelor T.Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.Curr Oncol Rep 2000 Sep;2(5):445-53.
  11122877
• Jeyapalan SA, Batchelor TT.Diagnostic evaluation of neurologic metastases.Cancer Invest 2000;18(4):381-94.
  10808374
• Batchelor T.Temozolomide for malignant brain tumours.Lancet 2000 Apr 1;355(9210):1115-6.
  10791369
• Quiñones-Hinojosa A, Friedlander RM, Boyer PJ, Batchelor TT, Chiocca EA.Solitary sciatic nerve lymphoma as an initial manifestation of diffuse neurolymphomatosis. Case report and review of the literature.J Neurosurg 2000 Jan;92(1):165-9.
  10616097
• Henson JW, Yang J, Batchelor T.Intraocular methotrexate level after high-dose intravenous infusion.J Clin Oncol 1999 Apr;17(4):1329.
  10561199
• Glantz MJ, LaFollette S, Jaeckle KA, Shapiro W, Swinnen L, Rozental JR, Phuphanich S, Rogers LR, Gutheil JC, Batchelor T, Lyter D, Chamberlain M, Maria BL, Schiffer C, Bashir R, Thomas D, Cowens W, Howell SB.Randomized trial of a slow-release versus a sta
  10506606
• Avgeropoulos NG, Batchelor TT.New treatment strategies for malignant gliomas.Oncologist 1999;4(3):209-24.
  10394589
• Dalmau J, Gultekin SH, Voltz R, Hoard R, DesChamps T, Balmaceda C, Batchelor T, Gerstner E, Eichen J, Frennier J, Posner JB, Rosenfeld MR.Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurolog
  10050892
• Batchelor TT, Platten M, Hochberg FH.Immunoadsorption therapy for paraneoplastic syndromes.J Neurooncol 1998 Nov;40(2):131-6.
  9892095
• Schiff D, Batchelor T, Wen PY.Neurologic emergencies in cancer patients.Neurol Clin 1998 May;16(2):449-83.
  9537970
• Batchelor TT, Platten M, Palmer-Toy DE, Hunter GJ, Lev MH, Dalmau J, Hochberg FH.Chorea as a paraneoplastic complication of Hodgkin's disease.J Neurooncol 1998 Jan;36(2):185-90.
  9525818
• Batchelor TT, Taylor LP, Thaler HT, Posner JB, DeAngelis LM.Steroid myopathy in cancer patients.Neurology 1997 May;48(5):1234-8.
  9153449
• Batchelor TT, Krol GS, DeAngelis LM.Neuroimaging abnormalities with hypoglossal nerve palsies.J Neuroimaging 1997 Apr;7(2):86-8.
  9128445
• Batchelor TT, Krol GS, DeAngelis LM.Neuroimaging abnormalities with hypoglossal nerve palsies.J Neuroimaging 1996 Oct;6(4):240-2.
  8903077
• Batchelor T, DeAngelis LM.Medical management of cerebral metastases.Neurosurg Clin N Am 1996 Jul;7(3):435-46.
  8823773