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01-03-2013 | Clinical Study

Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas

Authors: Thomas Hundsberger, Detlef Brügge, Paul M. Putora, Patrik Weder, Johannes Weber, Ludwig Plasswilm

Published in: Journal of Neuro-Oncology | Issue 1/2013

Abstract

The optimal treatment for recurrent high-grade gliomas is unknown and a standard of care does not exist. Re-irradiation with concomitant bevacizumab represents an option. Retrospectively, we analyzed a cohort of heavily pretreated patients (n = 14) with relapsing HGGs who underwent re-irradiation with conventional 3D-conformal or intensified modulated radiotherapy (IMRT). Ten of them received re-irradiation in combination with bevacizumab. The study population consisted of eight GBMs and six anaplastic gliomas. All patients had previously undergone irradiation for first-line therapy, including seven patients with radiochemotherapy with temozolomide. Patients without contraindications started with two infusions of bevacizumab (10 mg/kg of body weight every other week) prior to re-irradiation and continued through re-irradiation until progression. The median patient age was 45 years with a median Karnofsky performance scale of 70. The median dose of re-irradiation was 41.6 Gy [39–55 Gy]. The median physical cumulative radiation dose was 101.6 Gy [65–110.4 Gy]. The median PFS from re-irradiation was 5.1 months [1.6–17.4] based on clinical and RANO criteria. Median OS from re-irradiation was 9.0 months [6.4–17.8]. We detected radionecrosis due to advanced imaging in one patient. Other toxicities were expected and attributable well known side effects of bevacizumab. This retrospective study provides additional feasibility and safety data of conventional 3D-conformal re-irradiation and IMRT in combination with bevacizumab in relapsing high-grade gliomas.

van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ (2010) Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin 60:166–193PubMedCrossRef

Beal K, Abrey LE, Gutin PH (2011) Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: analysis of single-agent and combined modality approaches. Radiat Oncol. doi:10.1186/1748-717X-6-2 PubMed

Wick W, Steinbach JP, Kuker WM, Dichgans J, Bamberg M, Weller M (2004) One week on/one week off: a novel active regimen of temozolomide for recurrent glioblastoma. Neurology 62:2113–2115PubMedCrossRef

Brada M, Stenning S, Gabe R, Thompson LC, Levy D, Rampling R, Erridge S, Saran F, Gattamaneni R, Hopkins K, Beall S, Collins VP, Lee SM (2010) Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 28:4601–4608PubMedCrossRef

Yung WK, Prados MD, Yaya-Tur R, Rosenfeld SS, Brada M, Friedman AH, Albright R, Olson J, Chang SM, O’Neill AM, Friedman AH, Bruner J, Yue N, Dugan M, Zaknoen S, Levin VA (1999) Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. temodal brain tumor group. J Clin Oncol 17:2762–2771PubMed

Wick W, Puduvalli VK, Chamberlain MC, van den Bent MJ, Carpentier AF, Cher LM, Mason W, Weller M, Hong S, Musib L, Liepa AM, Thornton DE, Fine HA (2010) Phase III study of enzastaurin compared with lomustine in the treatment of recurrent intracranial glioblastoma. J Clin Oncol 28:1168–1174PubMedCrossRef

Wick W, Hartmann C, Engel C, Stoffels M, Felsberg J, Stockhammer F, Sabel MC, Koeppen S, Ketter R, Meyermann R, Rapp M, Meisner C, Kortmann RD, Pietsch T, Wiestler OD, Ernemann U, Bamberg M, Reifenberger G, von Deimling A, Weller M (2009) NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with procarbazine, lomustine, and vincristine or temozolomide. J Clin Oncol 27:5874–5880PubMedCrossRef

Vredenburgh JJ, Desjardins A, Herndon JE II, Marcello J, Reardon DA, Quinn JA, Rich JN, Sathornsumetee S, Gururangan S, Sampson J, Wagner M, Bailey L, Bigner DD, Friedman AH, Friedman HS (2007) Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 25:4722–4729PubMedCrossRef

Kreisl TN, Kim L, Moore K, Duic P, Royce C, Stroud I, Garren N, Mackey M, Butman JA, Camphausen K, Park J, Albert PS, Fine HA (2009) Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 27:740–745PubMedCrossRef

10.

Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, Levin VA, Yung WK (1999) Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578PubMed

11.

Hudes RS, Corn BW, Werner-Wasik M, Andrews D, Rosenstock J, Thoron L, Downes B, Curran WJ Jr (1999) A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Int J Radiat Oncol Biol Phys 43:293–298PubMedCrossRef

12.

Combs SE, Widmer V, Thilmann C, Hof H, Debus J, Schulz-Ertner D (2005) Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM). Cancer 104:2168–2173PubMedCrossRef

13.

Niyazi M, Ganswindt U, Schwarz SB, Kreth FW, Tonn JC, Geisler J, la Fougère C, Ertl L, Linn J, Siefert A, Belka C (2012) Irradiation and bevacizumab in high-grade glioma retreatment settings. Int J Radiat Oncol Biol Phys 82:67–76PubMedCrossRef

14.

Torcuator RG, Thind R, Patel M, Mohan YS, Anderson J, Doyle T, Ryu S, Jain R, Schultz L, Rosenblum M, Mikkelsen T (2010) The role of salvage reirradiation for malignant gliomas that progress on bevacizumab. J Neurooncol 97:401–407PubMedCrossRef

15.

Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B, Comber E, Maltenfort M, Dicker AP, Werner-Wasik M (2010) Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas. J Clin Oncol 28:3048–3053PubMedCrossRef

16.

Kong DS, Lee JI, Park K, Kim JH, Lim DH, Nam DH (2008) Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer 112:2046–2051PubMedCrossRef

17.

Combs SE, Gutwein S, Thilmann C, Debus J, Schulz-Ertner D (2005) Reirradiation of recurrent WHO grade III astrocytomas using fractionated stereotactic radiotherapy (FSRT). Strahlenther Onkol 181:768–773PubMedCrossRef

18.

Combs SE, Gutwein S, Thilmann CH, Huber P, Debus J, Schulz-Ertner D (2005) Stereotactically guided fractionated re-irradiation in recurrent glioblastoma multiforme. J Neurooncol 74:167–171PubMedCrossRef

19.

Combs SE, Thilmann C, Edler L, Debus J, Schulz-Ertner D (2005) Efficacy of fractionated stereotactic reirradiation in recurrent gliomas: long-term results in 172 patients treated in a single institution. J Clin Oncol 23:8863–8869PubMedCrossRef

20.

Cuneo KC, Vredenburgh JJ, Sampson JH, Reardon DA, Desjardins A, Peters KB, Friedman HS, Willett CG, Kirkpatrick JP (2012) Safety and efficacy of stereotactic radiosurgery and adjuvant bevacizumab in patients with recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 82:2018–2024PubMedCrossRef

21.

Veninga T, Langendijk HA, Slotman BJ, Rutten EH, van der Kogel AJ, Prick MJ, Keyser A, van der Maazen RW (2001) Reirradiation of primary brain tumours: survival, clinical response and prognostic factors. Radiother Oncol 59:127–137PubMedCrossRef

22.

Gutin PH, Iwamoto FM, Beal K, Mohile NA, Karimi S, Hou BL, Lymberis S, Yamada Y, Chang J, Abrey LE (2009) Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. Int J Radiat Oncol Biol Phys 75:156–163PubMedCrossRef

23.

Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760PubMedCrossRef

24.

Levin VA, Bidaut L, Hou P, Kumar AJ, Wefel JS, Bekele BN, Grewal J, Prabhu S, Loghin M, Gilbert MR, Jackson EF (2011) Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 79:1487–1495PubMedCrossRef

25.

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef

26.

Chamberlain MC, Raizer J, Schiff D, Sherman JH (2010) Optic neuropathy in patients with glioblastoma receiving bevacizumab. Neurology 75:289–290PubMedCrossRef

27.

Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, DeGroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972PubMedCrossRef

28.

Albanese MA, Clarke WR, Adams HP, Woolson RF Jr (1994) Ensuring reliability of outcome measures in multicenter clinical trials of treatments for acute ischemic stroke. The program developed for the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Stroke 25:1746–1751PubMedCrossRef

29.

Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D (2008) Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 359:1317–1329PubMedCrossRef

30.

Stummer W, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, Bink A, Pichlmeier U (2011) Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. Clinical article. J Neurosurg 114:613–623CrossRef

31.

Kaplan E, Meier (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481CrossRef

32.

Bauman GS, Sneed PK, Wara WM, Stalpers LJ, Chang SM, McDermott MW, Gutin PH, Larson DA (1996) Reirradiation of primary CNS tumors. Int J Radiat Oncol Biol Phys 36:433–441PubMedCrossRef

33.

Park JK, Hodges T, Arko L, Shen M, Dello Iacono D, McNabb A, Olsen Bailey N, Kreisl TN, Iwamoto FM, Sul J, Auh S, Park GE, Fine HA, Black PM (2010) Scale to predict survival after surgery for recurrent glioblastoma multiforme. J Clin Oncol 28:3838–3843PubMedCrossRef

34.

Dropcho EJ (2010) Neurotoxicity of radiation therapy. Neurol Clin 28:217–234PubMedCrossRef

35.

Gonzalez J, Kumar AJ, Conrad CA, Levin VA (2007) Effect of bevacizumab on radiation necrosis of the brain. Int J Radiat Oncol Biol Phys 67:323–326PubMedCrossRef

36.

Chamberlain MC, Raizer J, Schiff D, Sherman JH (2010) Optic neuropathy in patients with glioblastoma receiving bevacizumab 1. Neurology 75:289–290PubMedCrossRef

37.

Arcicasa M, Roncadin M, Bidoli E, Dedkov A, Gigante M, Trovo MG (1999) Reirradiation and lomustine in patients with relapsed high-grade gliomas. Int J Radiat Oncol Biol Phys 43:789–793PubMedCrossRef

38.

Mayer R, Sminia P (2008) Reirradiation tolerance of the human brain. Int J Radiat Oncol Biol Phys 70:1350–1360PubMedCrossRef

39.

Kesselheim JC, Norden AD, Wen PY, Joffe S (2011) Discontinuing bevacizumab in patients with glioblastoma: an ethical analysis. Oncologist 16:1435–1439PubMedCrossRef

40.

Zuniga RM, Torcuator R, Jain R, Anderson J, Doyle T, Schultz L, Mikkelsen T (2010) Rebound tumour progression after the cessation of bevacizumab therapy in patients with recurrent high-grade glioma. J Neurooncol 99:237–242PubMedCrossRef

41.

42.

43.

Kong DS, Lee JL, Park K, Kim JH, Lim DH, Nam DH (2008) Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent malignant gliomas. Cancer 112:2046–2051PubMedCrossRef

44.

Wick W, Wick A, Weiler M, Weller M (2011) Patterns of progression in malignant glioma following anti-VEGF therapy: perceptions and evidence. Curr Neurol Neurosci Rep 11:305–312PubMedCrossRef

Title: Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas
Authors: Thomas Hundsberger
Detlef Brügge
Paul M. Putora
Patrik Weder
Johannes Weber
Ludwig Plasswilm
Publication date: 01-03-2013
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-013-1044-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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