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21.11.2023 | Original Article

Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma

verfasst von: Fabiana Gregucci, M.D., Fiorella Cristina Di Guglielmo, Alessia Surgo, Roberta Carbonara, Letizia Laera, Maria Paola Ciliberti, Maria Annunziata Gentile, Roberto Calbi, Morena Caliandro, Nicola Sasso, Valerio Davi’, Ilaria Bonaparte, Vincenzo Fanelli, David Giraldi, Romina Tortora, Valeria Internò, Francesco Giuliani, Giammarco Surico, Francesco Signorelli, Giuseppe Lombardi, Alba Fiorentino

Erschienen in: Strahlentherapie und Onkologie

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Abstract

Purpose

No standard treatment has yet been established for recurrent glioblastoma (GBM). In this context, the aim of the current study was to evaluate safety and efficacy of reirradiation (re-RT) by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association with regorafenib.

Methods

Patients with a histological or radiological diagnosis of recurrent GBM who received re-RT by SRS/FSRT and regorafenib as second-line systemic therapy were included in the analysis.

Results

From January 2020 to December 2022, 21 patients were evaluated. The median time between primary/adjuvant RT and disease recurrence was 8 months (range 5–20). Median re-RT dose was 24 Gy (range 18–36 Gy) for a median number of 5 fractions (range 1–6). Median regorafenib treatment duration was 12 weeks (range 3–26). Re-RT was administered before starting regorafenib or in the week off regorafenib during the course of chemotherapy. The median and the 6‑month overall survival (OS) from recurrence were 8.4 months (95% confidence interval [CI] 6.9–12.7 months) and 75% (95% CI 50.9–89.1%), respectively. The median progression-free survival (PFS) from recurrence was 6 months (95% CI 3.7–8.5 months). The most frequent side effects were asthenia that occurred in 10 patients (8 cases of grade 2 and 2 cases of grade 3), and hand–foot skin reaction (2 patients grade 3, 3 patients grade 2). Adverse events led to permanent regorafenib discontinuation in 2 cases, while in 5/21 cases (23.8%), a dose reduction was administered. One patient experienced dehiscence of the surgical wound after reintervention and during regorafenib treatment, while another patient reported intestinal perforation that required hospitalization.

Conclusion

For recurrent GBM, re-RT with SRT/FSRT plus regorafenib is a safe treatment. Prospective trials are necessary.

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ (2006) Cancer statistics, 2006. CA Cancer J Clin 56(2):106–130. https://doi.org/10.3322/canjclin.56.2.106CrossRefPubMed

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bog-dahn U et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996. https://doi.org/10.1056/NEJMoa043330CrossRefPubMed

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5‑year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. https://doi.org/10.1016/S1470-2045(09)70025-7CrossRefPubMed

Biswas T, Okunieff P, Schell MC, Smudzin T, Pilcher WH, Bakos RS, Vates GE, Walter KA, Wensel A, Korones DN et al (2009) Stereotactic radiosurgery for glioblastoma: retrospective analysis. Radiat Oncol 4:11. https://doi.org/10.1186/1748-717X-4-11CrossRefPubMedPubMedCentral

Niranjan A, Kano H, Iyer A, Kondziolka D, Flickinger JC, Lunsford LD (2015) Role of adjuvant or salvage radiosurgery in the management of unresected residual or progressive glioblastoma multiforme in the pre-bevacizumab era. J Neurosurg 122:757–765. https://doi.org/10.3171/2014.11.JNS13295CrossRefPubMed

Park KJ, Kano H, Iyer A, Liu X, Niranjan A, Flickinger JC, Lieberman FS, Lunsford LD, Kondziolka D (2012) Salvage gamma knife stereotactic radiosurgery followed by bevacizumab for recurrent glioblastoma multiforme: a case-control study. J Neurooncol 107:323–333. https://doi.org/10.1007/s11060-011-0744-9CrossRefPubMed

Patel M, Siddiqui F, Jin JY, Mikkelsen T, Rosenblum M, Movsas B, Ryu S (2009) Salvage reirradiation for recurrent glioblastoma with radiosurgery: Radiographic response and improved survival. J Neurooncol 92:185–191. https://doi.org/10.1007/s11060-008-9752-9CrossRefPubMed

Skeie BS, Enger PØ, Brøgger J, Ganz JC, Thorsen F, Heggdal JI, Pedersen PH (2012) γ knife surgery versus reoperation for recurrent glioblastoma multiforme. World Neurosurg 78:658–669. https://doi.org/10.1016/j.wneu.2012.03.024CrossRefPubMed

Bräutigam E, Lampl C, Track C, Nieder C, Pichler J, Hammer J, Geinitz H (2019) Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept. Clin Transl Oncol 21:582–587. https://doi.org/10.1007/s12094-018-1957-6CrossRefPubMed

10.

Frischer JM, Marosi C, Woehrer A, Hainfellner JA, Dieckmann KU, Eiter H, Wang WT, Mallouhi A, Ertl A, Knosp E et al (2016) Gamma knife radiosurgery in recurrent glioblastoma. Stereotact Funct Neurosurg 94:265–272. https://doi.org/10.1159/000448924CrossRefPubMed

11.

Yazici G, Cengiz M, Ozyigit G, Eren G, Yildiz F, Akyol F, Gurkaynak M, Zorlu F (2014) Hypofractionated stereotactic reirradiation for recurrent glioblastoma. J Neurooncol 120:117–123. https://doi.org/10.1007/s11060-014-1524-0CrossRefPubMed

12.

Martínez-Carrillo M, Tovar-Martín I, Zurita-Herrera M, Del Moral-Ávila R, Guerrero-Tejada R, Saura-Rojas E, Osorio-Ceballos JL, Arrebola-Moreno JP, Expósito-Hernández J (2014) Salvage radiosurgery for selected patients with recurrent malignant gliomas. Biomed Res Int 2:657953

13.

National Comprehensive Cancer Network (2022) Central Nervous System Cancers. https://www.nccn.org/professionals/physician_gls/pdf/cns_blocks.pdf. Accessed 1 Feb 2023

14.

Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, Berger MS, Parsa AT (2012) Impact of extent of resection for recurrent glioblastoma on overall survival: clinical article. J Neurosurg 117:1032–1038. https://doi.org/10.3171/2012.9.JNS12504CrossRefPubMed

15.

Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R et al (2009) Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 27:4733–4740. https://doi.org/10.1200/JCO.2008.19.8721CrossRefPubMed

16.

Lombardi G, De Salvo GL, Brandes AA, Eoli M, Rudà R, Faedi M, Lolli I, Pace A, Daniele B, Pasqualetti F et al (2019) Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): A multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 20:110–119. https://doi.org/10.1016/S1470-2045(18)30675-2CrossRefPubMed

17.

Navarria P, Minniti G, Clerici E, Tomatis S, Pinzi V, Ciammella P, Galaverni M, Amelio D, Scartoni D, Scoccianti S et al (2019) Re-irradiation for recurrent glioma: Outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO). J Neurooncol 142:59–67. https://doi.org/10.1007/s11060-018-03059-xCrossRefPubMed

18.

Mazzola R, Corradini S, Gregucci F, Figlia V, Fiorentino A, Alongi F (2019) Role of radiosurgery/stereotactic radiotherapy in oligometastatic disease: brain oligometastases. Front Oncol 9:206. https://doi.org/10.3389/fonc.2019.00206CrossRefPubMedPubMedCentral

19.

Meduri B, Gregucci F, D’Angelo E, Alitto AR, Ciurlia E, Desideri I, Marino L, Borghetti P, Fiore M, Fiorentino A, AIRO Giovani -Italian Association of Radiation Oncology-Young Members (2020) Volume de-escalation in radiation therapy: state of the art and new perspectives. J Cancer Res Clin Oncol 146:909–924. https://doi.org/10.1007/s00432-020-03152-7CrossRefPubMed

20.

Gregucci F, Surgo A, Carbonara R, Laera L, Ciliberti MP, Gentile MA et al (2022) Radiosurgery and stereotactic brain radiotherapy with systemic therapy in recurrent high-grade gliomas: is it feasible? Therapeutic strategies in recurrent high-grade Gliomas. J Pers Med 12(8):1336. https://doi.org/10.3390/jpm12081336CrossRefPubMedPubMedCentral

21.

Fogh SE, Andrews DW, Glass J, Curran W, Glass C, Champ C, Evans JJ, Hyslop T, Pequignot E, Downes B et al (2010) Hypofractionated stereotactic radiation therapy: An effective therapy for recurrent high-grade gliomas. J Clin Oncol 28:3048–3053. https://doi.org/10.1200/JCO.2009.25.6941CrossRefPubMedPubMedCentral

22.

Holt DE, Bernard ME, Quan K, Clump DA, Engh JA, Burton SA, Heron DE (2016) Salvage stereotactic radiosurgery for recurrent glioblastoma multiforme with prior radiation therapy. J Cancer Res Ther 12:1243–1248. https://doi.org/10.4103/0973-1482.199537CrossRefPubMed

23.

Martínez-Garcia M, Álvarez-Linera J, Carrato C, Ley L, Luque R, Maldonado X, Martínez-Aguillo M, Navarro LM, Vaz-Salgado MA, Gil-Gil M (2018) SEOM clinical guidelines for diagnosis and treatment of glioblastoma. Clin Transl Oncol 20:22–28. https://doi.org/10.1007/s12094-017-1763-6CrossRefPubMed

24.

Torok JA, Wegner RE, Mintz AH, Heron DE, Burton SA (2011) Re-irradiation with radiosurgery for recurrent glioblastoma multiforme. Technol Cancer Res Treat 10:253–258. https://doi.org/10.7785/tcrt.2012.500200CrossRefPubMed

25.

Gigliotti MJ, Hasan S, Karlovits SM, Ranjan T, Wegner RE Re-irradiation with stereotactic radiosurgery/radiotherapy for recurrent high-grade gliomas: Improved survival in the modern era. Stereotact Funct Neurosurg 96:289–295. https://doi.org/10.1159/000493545

26.

Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216. https://doi.org/10.1093/jnci/92.3.205CrossRefPubMed

27.

Alongi F, Fiorentino A, Gregucci F, Corradini S, Giaj-Levra N, Romano L, Rigo M, Ricchetti F, Beltramello A, Lunardi G et al (2019) First experience and clinical results using a new non-coplanar mono-isocenter technique (HyperArc™) for Linac-based VMAT radiosurgery in brain metastases. J Cancer Res Clin Oncol 145:193–200. https://doi.org/10.1007/s00432-018-2781-7CrossRefPubMed

28.

Gregucci F, Bonaparte I, Surgo A, Caliandro M, Carbonara R, Ciliberti MP, Aga A, Berloco F, De Masi M, De Pascali C et al (2021) Brain linac-based radiation therapy: “test drive” of new immobilization solution and surface guided radiation therapy. J Pers Med 11:1351. https://doi.org/10.3390/jpm11121351CrossRefPubMedPubMedCentral

29.

Gregucci F, Surgo A, Bonaparte I, Laera L, Ciliberti MP, Carbonara R, Gentile MA, Giraldi D, Calbi R, Caliandro M et al (2021) Poor-prognosis patients affected by glioblastoma: retrospective study of hypofractionated radiotherapy with simultaneous integrated boost and concurrent/Adjuvant Temozolomide. J Pers Med 11:1145. https://doi.org/10.3390/jpm11111145CrossRefPubMedPubMedCentral

30.

Stiefel I, Schröder C, Tanadini-Lang S, Pytko I, Vu E, Klement RJ, Guckenberger M, Andratschke N et al (2021) High-dose re-irradiation of intracranial lesions—Efficacy and safety including dosimetric analysis based on accumulated EQD2Gy dose EQD calculation. Clin Transl Radiat Oncol 27:132–138. https://doi.org/10.1016/j.ctro.2021.01.011CrossRefPubMedPubMedCentral

31.

Weller M, van den Bent M, Preusser M, Le Rhun E, Tonn JC, Minniti G, Bendszus M, Balana C, Chinot O, Dirven L et al (2021) EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol 18(3):170–186. https://doi.org/10.1038/s41571-020-00447-zCrossRefPubMed

32.

Hau P, Baumgart U, Pfeifer K, Bock A, Jauch T, Dietrich J, Fabel K, Grauer O, Wismeth C, Klinkhammer-Schalke M et al (2003) Salvage therapy in patients with glioblastoma: Is there any benefit? Cancer 98:2678–2686. https://doi.org/10.1002/cncr.11845CrossRefPubMed

33.

Kondziolka D, Flickinger JC, Bissonette DJ, Bozik M, Lunsford LD (1997) Survival benefit of stereotactic radiosurgery for patients with malignant glial neoplasms. Neurosurgery 41:776–783. https://doi.org/10.1097/00006123-199710000-00004 (discussion 783–5)CrossRefPubMed

34.

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 75:156–163. https://doi.org/10.1016/j.ijrobp.2008.10.043CrossRefPubMedPubMedCentral

35.

Vordermark D, Kölbl O, Ruprecht K, Vince GH, Bratengeier K, Flentje M (2005) Hypofractionated stereotactic re-irradiation: treatment option in recurrent malignant glioma. BMC Cancer 5:55. https://doi.org/10.1186/1471-2407-5-55CrossRefPubMedPubMedCentral

36.

Yaprak G, Isık N, Gemici C, Pekyurek M, Ceylaner Bıcakcı B, Demircioglu F, Tatarlı N (2020) Stereotactic radiotherapy in recurrent Glioblastoma: a valid salvage treatment option. Stereotact Funct Neurosurg 98:167–175. https://doi.org/10.1159/000505706CrossRefPubMed

37.

Conti A, Pontoriero A, Arpa D, Siragusa C, Tomasello C, Romanelli P, Cardali S, Granata F, De Renzis C, Tomasello F (2012) Efficacy and toxicity of CyberKnife re-irradiation and “dose dense” temozolomide for recurrent gliomas. Acta Neurochir 154:203–209. https://doi.org/10.1186/s40064-015-0804-2CrossRefPubMed

38.

Flieger M, Ganswindt U, Schwarz SB, Kreth FW, Tonn JC, la Fougère C, Ertl L, Linn J, Herrlinger U, Belka C et al (2014) Re-irradiation and bevacizumab in recurrent high grade glioma: An effective treatment option. J Neurooncol 117:337–345. https://doi.org/10.1007/s11060-014-1394-5CrossRefPubMed

39.

Tsien CI, Pugh SL, Dicker AP, Raizer JJ, Matuszak MM, Lallana EC, Huang J, Algan O, Deb N, Portelance L, Villano JL, Hamm JT, Oh KS, Ali AN, Kim MM, Lindhorst SM, Mehta MP (2023) NRG oncology/RTOG1205: a randomized phase II trial of concurrent bevacizumab and reirradiation versus bevacizumab alone as treatment for recurrent Glioblastoma. J Clin Oncol 41(6):1285–1295. https://doi.org/10.1200/JCO.22.00164CrossRefPubMed

40.

Navarria P, Pessina F, Clerici E, Bellu L, Franzese C, Franzini A, Simonelli M, Bello L, Santoro A, Politi LS et al (2022) Re-irradiation for recurrent high-grade glioma (HGG) patients: results of a single arm prospective phase 2 study. Radiother Oncol 167:89–96. https://doi.org/10.1016/j.radonc.2021.12.019CrossRefPubMed

41.

Balducci M, Chiesa S, Diletto B, D’Agostino GR, Mangiola A, Manfrida S, Mantini G, Albanese A, Fiorentino A, Frascino V, De Bari B, Micciche’ F, De Rose F, Morganti AG, Anile C, Valentini V (2012) Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study. Neuro Oncol 14(1):79–86. https://doi.org/10.1093/neuonc/nor173CrossRefPubMed

42.

Song CW, Cho LC, Yuan J et al (2013) Radiobiology of stereotactic body radiation therapy/stereotactic radiosurgery and the linear-quadratic model. Int J Radiat Oncol Biol Phys 87(1):18–19. https://doi.org/10.1016/j.ijrobp.2013.03.013CrossRefPubMed

43.

Wilhelm SM, Dumas J, Adnane L et al (2011) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 129:245–255. https://doi.org/10.1002/ijc.25864CrossRefPubMed

44.

Daudigeos-Dubus E, Le Dret L, Lanvers-Kaminsky C et al (2015) Regorafenib: antitumor activity upon mono and combination therapy in preclinical pediatric malignancy models. PLoS ONE 10:e142612. https://doi.org/10.1371/journal.pone.0142612CrossRefPubMedPubMedCentral

Titel: Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma
verfasst von: Fabiana Gregucci, M.D.
Fiorella Cristina Di Guglielmo
Alessia Surgo
Roberta Carbonara
Letizia Laera
Maria Paola Ciliberti
Maria Annunziata Gentile
Roberto Calbi
Morena Caliandro
Nicola Sasso
Valerio Davi’
Ilaria Bonaparte
Vincenzo Fanelli
David Giraldi
Romina Tortora
Valeria Internò
Francesco Giuliani
Giammarco Surico
Francesco Signorelli
Giuseppe Lombardi
Alba Fiorentino
Publikationsdatum: 21.11.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-023-02172-9

Springer Medizin

Reirradiation with radiosurgery or stereotactic fractionated radiotherapy in association with regorafenib in recurrent glioblastoma

Abstract

Purpose

Methods

Results

Conclusion

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Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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Neu im Fachgebiet Onkologie

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Viel pflanzliche Nahrung, seltener Prostata-Ca.-Progression

Update Onkologie