Top

Published in:

01-03-2011 | Clinical Study - Patient Studies

Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53

Authors: Hyun-Cheol Kang, Chae-Yong Kim, Jung Ho Han, Ghee Young Choe, Jae Hyoung Kim, Jee Hyun Kim, In Ah Kim

Published in: Journal of Neuro-Oncology | Issue 1/2011

Abstract

We investigated pseudoprogression (psPD) in patients with malignant gliomas treated with radiotherapy (RT) and maintenance temozolomide (TMZ) in terms of incidence, outcomes, and predictive and prognostic factors. We evaluated p53 overexpression by immunohistochemical analysis of thirty-five tumor samples as a predictor for psPD. The time to progression and overall survival were compared between subgroups, psPD versus early progression (ePD) versus nonprogression (nonPD). Eight patients developed psPD among eighteen patients with lesion enlargement at the first MRI scan, and the others were classified as ePD. The remaining stable or improved patients were classified as nonPD. All patients with psPD were alive at last follow-up (median follow-up period was 12 months; range 5.8–58.5 months). Overall survival of psPD patients was significantly higher than ePD patients (P < 0.01). There was no significant survival difference between the psPD group and nonPD group (P = 0.25). Seven (87.5%) of eight tumors with psPD showed p53 overexpression, as compared to 3 (30%) of the ten tumors with ePD (P = 0.03). Our study indicates that psPD following chemoradiotherapy with TMZ is associated with significantly better overall survival compared to that of ePD, and is comparable to nonPD group. Overexpression of p53 was identified as a potential biomarker for predicting the development of psPD.

Chamberlain MC, Glantz MJ, Chalmers L, van Horn A, Sloan AE (2007) Early necrosis following concurrent Temodar and radiotherapy in patients with glioblastoma. J Neurooncol 82:81–83CrossRefPubMed

Jefferies S, Burton K, Jones P, Burnet N (2007) Interpretation of early imaging after concurrent radiotherapy and temozolomide for glioblastoma. Clin Oncol (R Coll Radiol) 19:S33

Taal W, Brandsma D, de Bruin HG, Bromberg JE, Swaak-Kragten AT, Smitt PA, van Es CA, van den Bent MJ (2008) Incidence of early pseudo-progression in a cohort of malignant glioma patients treated with chemoirradiation with temozolomide. Cancer 113:405–410CrossRefPubMed

Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A, Frezza G, Leonardi M, Spagnolli F, Ermani M (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26:2192–2197CrossRefPubMed

Takahashi A, Ohnishi K, Wang X, Kobayashi M, Matsumoto H, Tamamoto T, Aoki H, Furusawa Y, Yukawa O, Ohnishi T (2000) The dependence of p53 on the radiation enhancement of thermosensitivity at different let. Int J Radiat Oncol Biol Phys 47:489–494CrossRefPubMed

Kock H, Harris MP, Anderson SC, Machemer T, Hancock W, Sutjipto S, Wills KN, Gregory RJ, Shepard HM, Westphal M, Maneval DC (1996) Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo. Int J Cancer 67:808–815CrossRefPubMed

Srivenugopal KS, Shou J, Mullapudi SR, Lang FF Jr, Rao JS, Ali-Osman F (2001) Enforced expression of wild-type p53 curtails the transcription of the O(6)-methylguanine-DNA methyltransferase gene in human tumor cells and enhances their sensitivity to alkylating agents. Clin Cancer Res 7:1398–1409PubMed

Batista LF, Roos WP, Kaina B, Menck CF (2009) p53 mutant human glioma cells are sensitive to UV-C-induced apoptosis due to impaired cyclobutane pyrimidine dimer removal. Mol Cancer Res 7:237–246CrossRefPubMed

Macdonald DR, Cascino TL, Schold SC Jr, Cairncross JG (1990) Response criteria for phase II studies of supratentorial malignant glioma. J Clin Oncol 8:1277–1280PubMed

10.

Henson JW, Ulmer S, Harris GJ (2008) Brain tumor imaging in clinical trials. AJNR Am J Neuroradiol 29:419–424CrossRefPubMed

11.

Wiewrodt D, Nagel G, Dreimuller N, Hundsberger T, Perneczky A, Kaina B (2008) MGMT in primary and recurrent human glioblastomas after radiation and chemotherapy and comparison with p53 status and clinical outcome. Int J Cancer 122:1391–1399CrossRefPubMed

12.

Curtin K, Slattery ML, Holubkov R, Edwards S, Holden JA, Samowitz WS (2004) p53 alterations in colon tumors: a comparison of SSCP/sequencing and immunohistochemistry. Appl Immunohistochem Mol Morphol 12:380–386PubMed

13.

Sarkar C, Karak AK, Nath N, Sharma MC, Mahapatra AK, Chattopadhyay P, Sinha S (2005) Apoptosis and proliferation: correlation with p53 in astrocytic tumors. J Neurooncol 73:93–100CrossRefPubMed

14.

Hoffman WF, Levin VA, Wilson CB (1979) Evaluation of malignant glioma patients during the postirradiation period. J Neurosurg 50:624–628CrossRefPubMed

15.

de Wit MC, de Bruin HG, Eijkenboom W, Sillevis Smitt PA, van den Bent MJ (2004) Immediate post-radiotherapy changes in malignant glioma can mimic tumor progression. Neurology 63:535–537PubMed

16.

Jensen RL (2009) Brain tumor hypoxia: tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J Neurooncol 92:317–335CrossRefPubMed

17.

Brandsma D, Stalpers L, Taal W, Sminia P, van den Bent MJ (2008) Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas. Lancet Oncol 9:453–461CrossRefPubMed

18.

Khodarev NN, Labay E, Darga T, Yu J, Mauceri H, Gupta N, Kataoka Y, Weichselbaum RR (2004) Endothelial cells co-cultured with wild-type and dominant/negative p53-transfected glioblastoma cells exhibit differential sensitivity to radiation-induced apoptosis. Int J Cancer 109:214–219CrossRefPubMed

19.

Schmidt MC, Antweiler S, Urban N, Mueller W, Kuklik A, Meyer-Puttlitz B, Wiestler OD, Louis DN, Fimmers R, von Deimling A (2002) Impact of genotype and morphology on the prognosis of glioblastoma. J Neuropathol Exp Neurol 61:321–328PubMed

20.

Simmons ML, Lamborn KR, Takahashi M, Chen P, Israel MA, Berger MS, Godfrey T, Nigro J, Prados M, Chang S, Barker FG 2nd, Aldape K (2001) Analysis of complex relationships between age, p53, epidermal growth factor receptor, and survival in glioblastoma patients. Cancer Res 61:1122–1128PubMed

21.

Tada M, Matsumoto R, Iggo RD, Onimaru R, Shirato H, Sawamura Y, Shinohe Y (1998) Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations. Cancer Res 58:1793–1797PubMed

22.

Shiraishi S, Tada K, Nakamura H, Makino K, Kochi M, Saya H, Kuratsu J, Ushio Y (2002) Influence of p53 mutations on prognosis of patients with glioblastoma. Cancer 95:249–257CrossRefPubMed

23.

Hermisson M, Klumpp A, Wick W, Wischhusen J, Nagel G, Roos W, Kaina B, Weller M (2006) O6-methylguanine DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells. J Neurochem 96:766–776CrossRefPubMed

24.

Roos WP, Batista LF, Naumann SC, Wick W, Weller M, Menck CF, Kaina B (2007) Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine. Oncogene 26:186–197CrossRefPubMed

25.

Watanabe T, Katayama Y, Komine C, Yoshino A, Ogino A, Ohta T, Fukushima T (2005) O6-methylguanine-DNA methyltransferase methylation and TP53 mutation in malignant astrocytomas and their relationships with clinical course. Int J Cancer 113:581–587CrossRefPubMed

26.

Shamsara J, Sharif S, Afsharnezhad S, Lotfi M, Raziee HR, Ghaffarzadegan K, Moradi A, Rahighi S, Behravan J (2009) Association between MGMT promoter hypermethylation and p53 mutation in glioblastoma. Cancer Invest 27(8):825–829CrossRefPubMed

27.

Jesien-Lewandowicz E, Jesionek-Kupnicka D, Zawlik I, Szybka M, Kulczycka-Wojdala D, Rieske P, Sieruta M, Jaskolski D, Och W, Skowronski W, Sikorska B, Potemski P, Papierz W, Liberski PP, Kordek R (2009) High incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutations. Cancer Genet Cytogenet 188:77–82CrossRefPubMed

28.

Bouchet BP, de Fromentel CC, Puisieux A, Galmarini CM (2006) p53 as a target for anti-cancer drug development. Crit Rev Oncol Hematol 58:190–207CrossRefPubMed

29.

Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, Kros JM, Hainfellner JA, Mason W, Mariani L, Bromberg JE, Hau P, Mirimanoff RO, Cairncross JG, Janzer RC, Stupp R (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003CrossRefPubMed

Title: Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53
Authors: Hyun-Cheol Kang
Chae-Yong Kim
Jung Ho Han
Ghee Young Choe
Jae Hyoung Kim
Jee Hyun Kim
In Ah Kim
Publication date: 01-03-2011
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2011
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-010-0305-7

ACC 2024 Congress

Springer Medicine

Pseudoprogression in patients with malignant gliomas treated with concurrent temozolomide and radiotherapy: potential role of p53

Abstract

ACC 2024 Congress

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

Clinical emergence of neurometastatic merkel cell carcinoma: a surgical case series and literature review

Surgery guided by 5-aminolevulinic fluorescence in glioblastoma: volumetric analysis of extent of resection in single-center experience

Clinical characteristics and treatment of ectopic meningiomas

Non-enhancing relapse of a primary CNS lymphoma with multiple diffusion-restricted lesions

Helianthin induces antiproliferative effect on human glioblastoma cells in vitro

A prospective study of nonfunctioning pituitary adenomas: presentation, management, and clinical outcome