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Erschienen in: Journal of Neuro-Oncology 1/2016

05.03.2016 | Clinical Study

Pencil beam scanning proton therapy for pediatric intracranial ependymoma

verfasst von: Carmen Ares, Francesca Albertini, Martina Frei-Welte, Alessandra Bolsi, Michael A. Grotzer, Gudrun Goitein, Damien C. Weber

Erschienen in: Journal of Neuro-Oncology | Ausgabe 1/2016

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Abstract

To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n = 46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6 years (range 1.1–15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5 cc and 9 with >1.5 cc residual tumor respectively). Forty-three (86 %) patients received post-operative chemotherapy before PT according to protocols; 44 (88 %) patients younger than 5 years required general anesthesia. Median prescribed dose was 59.4 Gy (RBE) (range 54–60) delivered in 1.8–2 Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4 months (range 8.5–113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5 cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78 ± 7.5 % and 5-year OS rates were 84 ± 6.8 %. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5 years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92 % of the patients and the number of patients with residual tumor ≥1.5 cc. The rates of late effects compare favorably with published photon-treated cohorts.
Literatur
1.
Zurück zum Zitat Central brain tumor registry of the United States. CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2008 (March 23, 2012 Revision). Hinsdale Author; 2012 Central brain tumor registry of the United States. CBTRUS Statistical Report: primary brain and central nervous system tumors diagnosed in the United States in 2004–2008 (March 23, 2012 Revision). Hinsdale Author; 2012
2.
Zurück zum Zitat Perilongo G, Massimino M, Sotti G et al (1997) Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group. Med Pediatr Oncol 29(2):79–85CrossRefPubMed Perilongo G, Massimino M, Sotti G et al (1997) Analyses of prognostic factors in a retrospective review of 92 children with ependymoma: Italian Pediatric Neuro-oncology Group. Med Pediatr Oncol 29(2):79–85CrossRefPubMed
3.
Zurück zum Zitat Merchant TE, Haida T, Wang MH, Finlay JL, Leibel SA (1997) Anaplastic ependymoma: treatment of pediatric patients with or without craniospinal radiation therapy. J Neurosurg 86(6):943–949CrossRefPubMed Merchant TE, Haida T, Wang MH, Finlay JL, Leibel SA (1997) Anaplastic ependymoma: treatment of pediatric patients with or without craniospinal radiation therapy. J Neurosurg 86(6):943–949CrossRefPubMed
4.
Zurück zum Zitat Schild SE, Nisi K, Scheithauer BW et al (1998) The results of radiotherapy for ependymomas: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 42(5):953–958CrossRefPubMed Schild SE, Nisi K, Scheithauer BW et al (1998) The results of radiotherapy for ependymomas: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 42(5):953–958CrossRefPubMed
5.
Zurück zum Zitat Timmermann B, Kortmann RD, Kuhl J et al (2000) Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials HIT 88/89 and HIT 91. Int J Radiat Oncol Biol Phys 46(2):287–295CrossRefPubMed Timmermann B, Kortmann RD, Kuhl J et al (2000) Combined postoperative irradiation and chemotherapy for anaplastic ependymomas in childhood: results of the German prospective trials HIT 88/89 and HIT 91. Int J Radiat Oncol Biol Phys 46(2):287–295CrossRefPubMed
6.
Zurück zum Zitat Oya N, Shibamoto Y, Nagata Y, Negoro Y, Hiraoka M (2002) Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neurooncol 56(1):87–94CrossRefPubMed Oya N, Shibamoto Y, Nagata Y, Negoro Y, Hiraoka M (2002) Postoperative radiotherapy for intracranial ependymoma: analysis of prognostic factors and patterns of failure. J Neurooncol 56(1):87–94CrossRefPubMed
7.
Zurück zum Zitat Mansur DB, Perry A, Rajaram V et al (2005) Postoperative radiation therapy for grade II and III intracranial ependymoma. Int J Radiat Oncol Biol Phys 61(2):387–391CrossRefPubMed Mansur DB, Perry A, Rajaram V et al (2005) Postoperative radiation therapy for grade II and III intracranial ependymoma. Int J Radiat Oncol Biol Phys 61(2):387–391CrossRefPubMed
8.
Zurück zum Zitat Shu HK, Sall WF, Maity A et al (2007) Childhood intracranial ependymoma: twenty-year experience from a single institution. Cancer 110(2):432–441CrossRefPubMed Shu HK, Sall WF, Maity A et al (2007) Childhood intracranial ependymoma: twenty-year experience from a single institution. Cancer 110(2):432–441CrossRefPubMed
9.
Zurück zum Zitat Merchant TE (2009) Three-dimensional conformal radiation therapy for ependymoma. Childs Nerv Syst 25(10):1261–1268CrossRefPubMed Merchant TE (2009) Three-dimensional conformal radiation therapy for ependymoma. Childs Nerv Syst 25(10):1261–1268CrossRefPubMed
10.
Zurück zum Zitat Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10(3):258–266CrossRefPubMedPubMedCentral Merchant TE, Li C, Xiong X, Kun LE, Boop FA, Sanford RA (2009) Conformal radiotherapy after surgery for paediatric ependymoma: a prospective study. Lancet Oncol 10(3):258–266CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Koshy M, Rich S, Merchant TE, Mahmood U, Regine WF, Kwok Y (2011) Post-operative radiation improves survival in children younger than 3 years with intracranial ependymoma. J Neurooncol 105(3):583–590CrossRefPubMed Koshy M, Rich S, Merchant TE, Mahmood U, Regine WF, Kwok Y (2011) Post-operative radiation improves survival in children younger than 3 years with intracranial ependymoma. J Neurooncol 105(3):583–590CrossRefPubMed
12.
Zurück zum Zitat Phi JH, Wang KC, Park SH et al (2012) Pediatric infratentorial ependymoma: prognostic significance of anaplastic histology. J Neurooncol 106(3):619–626CrossRefPubMed Phi JH, Wang KC, Park SH et al (2012) Pediatric infratentorial ependymoma: prognostic significance of anaplastic histology. J Neurooncol 106(3):619–626CrossRefPubMed
13.
Zurück zum Zitat Needle MN, Molloy PT, Geyer JR et al (1997) Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. Med Pediatr Oncol 29(1):28–32CrossRefPubMed Needle MN, Molloy PT, Geyer JR et al (1997) Phase II study of daily oral etoposide in children with recurrent brain tumors and other solid tumors. Med Pediatr Oncol 29(1):28–32CrossRefPubMed
14.
Zurück zum Zitat Merchant TE, Fouladi M (2005) Ependymoma: new therapeutic approaches including radiation and chemotherapy. J Neurooncol 75(3):287–299CrossRefPubMed Merchant TE, Fouladi M (2005) Ependymoma: new therapeutic approaches including radiation and chemotherapy. J Neurooncol 75(3):287–299CrossRefPubMed
15.
Zurück zum Zitat Timmermann B, Kortmann RD, Kuhl J et al (2005) Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: results of the prospective German brain tumor trials HIT-SKK 87 and 92. Radiother Oncol 77(3):278–285CrossRefPubMed Timmermann B, Kortmann RD, Kuhl J et al (2005) Role of radiotherapy in anaplastic ependymoma in children under age of 3 years: results of the prospective German brain tumor trials HIT-SKK 87 and 92. Radiother Oncol 77(3):278–285CrossRefPubMed
16.
Zurück zum Zitat Zacharoulis S, Levy A, Chi SN et al (2007) Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 49(1):34–40CrossRefPubMed Zacharoulis S, Levy A, Chi SN et al (2007) Outcome for young children newly diagnosed with ependymoma, treated with intensive induction chemotherapy followed by myeloablative chemotherapy and autologous stem cell rescue. Pediatr Blood Cancer 49(1):34–40CrossRefPubMed
17.
Zurück zum Zitat MacDonald SM, Safai S, Trofimov A et al (2008) Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. Int J Radiat Oncol Biol Phys 71(4):979–986CrossRefPubMed MacDonald SM, Safai S, Trofimov A et al (2008) Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose comparisons. Int J Radiat Oncol Biol Phys 71(4):979–986CrossRefPubMed
18.
Zurück zum Zitat Koehler AM, Schneider RJ, Sisterson JM (1977) Flattening of proton dose distributions for large-field radiotherapy. Med Phys 4:297–301CrossRefPubMed Koehler AM, Schneider RJ, Sisterson JM (1977) Flattening of proton dose distributions for large-field radiotherapy. Med Phys 4:297–301CrossRefPubMed
19.
Zurück zum Zitat Kanai T, Kawachi K, Kumamoto Y et al (1980) Spot scanning system for proton radiotherapy. Med Phys 7:365–369CrossRefPubMed Kanai T, Kawachi K, Kumamoto Y et al (1980) Spot scanning system for proton radiotherapy. Med Phys 7:365–369CrossRefPubMed
20.
Zurück zum Zitat Pedroni E, Bacher R, Blattmann H et al (1995) The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization. Med Phys 22:37–53CrossRefPubMed Pedroni E, Bacher R, Blattmann H et al (1995) The 200-MeV proton therapy project at the Paul Scherrer Institute: conceptual design and practical realization. Med Phys 22:37–53CrossRefPubMed
21.
22.
Zurück zum Zitat Lomax AJ, Boehringer T, Coray A et al (2001) Intensity modulated proton therapy: a clinical example. Med Phys 28:317–324CrossRefPubMed Lomax AJ, Boehringer T, Coray A et al (2001) Intensity modulated proton therapy: a clinical example. Med Phys 28:317–324CrossRefPubMed
23.
Zurück zum Zitat Lomax AJ, Pedroni E, Rutz H, Goitein G (2004) The clinical potential of intensity modulated proton therapy. Z Med Phys 14:147–152CrossRefPubMed Lomax AJ, Pedroni E, Rutz H, Goitein G (2004) The clinical potential of intensity modulated proton therapy. Z Med Phys 14:147–152CrossRefPubMed
24.
Zurück zum Zitat Frei-Welte M, Weiss M, Neuhaus D et al (2012) Pediatric anesthesia for proton radiotherapy : medicine remote from the medical centre. Anaesthesist 61(10):906–914CrossRefPubMed Frei-Welte M, Weiss M, Neuhaus D et al (2012) Pediatric anesthesia for proton radiotherapy : medicine remote from the medical centre. Anaesthesist 61(10):906–914CrossRefPubMed
25.
Zurück zum Zitat Weber DC, Rutz HP, Pedroni ES et al (2005) Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys 63:401–409CrossRefPubMed Weber DC, Rutz HP, Pedroni ES et al (2005) Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys 63:401–409CrossRefPubMed
26.
Zurück zum Zitat Paganetti H, Niemierko A, Ancukiewicz M et al (2002) Relative biological effectiveness values for proton beam therapy. Int J Radiat Oncol Biol Phys 53:407–421CrossRefPubMed Paganetti H, Niemierko A, Ancukiewicz M et al (2002) Relative biological effectiveness values for proton beam therapy. Int J Radiat Oncol Biol Phys 53:407–421CrossRefPubMed
27.
Zurück zum Zitat Lomax AJ, Boehringer T, Bolsi A et al (2004) Treatment planning and verification of proton therapy using spot scanning: initial experiences. Med Phys 337:3150–3157CrossRef Lomax AJ, Boehringer T, Bolsi A et al (2004) Treatment planning and verification of proton therapy using spot scanning: initial experiences. Med Phys 337:3150–3157CrossRef
28.
Zurück zum Zitat Lomax AJ, Pedroni E, Schaffner B, Tourovski A et al. (1996) 3D treatmnet planning for conformal proton therapy by spot scanning. Proceedings of 19th LH Gray conference (BIR Publishing London) 67–71 Lomax AJ, Pedroni E, Schaffner B, Tourovski A et al. (1996) 3D treatmnet planning for conformal proton therapy by spot scanning. Proceedings of 19th LH Gray conference (BIR Publishing London) 67–71
29.
Zurück zum Zitat Lomax AJ (2008) Intensity modulated proton therapy. In: Delaney T, Kooy H (eds) Proton and charged particle radiotherapy. Lippincott Williams & Wilkin, Boston Lomax AJ (2008) Intensity modulated proton therapy. In: Delaney T, Kooy H (eds) Proton and charged particle radiotherapy. Lippincott Williams & Wilkin, Boston
31.
Zurück zum Zitat Jaing TH, Wang HS, Tsay PK et al (2004) Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas. J Neurooncol 68(3):255–261CrossRefPubMed Jaing TH, Wang HS, Tsay PK et al (2004) Multivariate analysis of clinical prognostic factors in children with intracranial ependymomas. J Neurooncol 68(3):255–261CrossRefPubMed
32.
Zurück zum Zitat MacDonald SM, Sethi R, Lavally B et al (2013) Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients. Neuro Oncol 15(11):1552–1559CrossRefPubMedPubMedCentral MacDonald SM, Sethi R, Lavally B et al (2013) Proton radiotherapy for pediatric central nervous system ependymoma: clinical outcomes for 70 patients. Neuro Oncol 15(11):1552–1559CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Concato J, Peduzzi P, Holford T et al (1995) Importance of events per independent variable in proportional hazards analysis I. Background, goals, and general strategy. J Clin Epidemiol 48:1495–1501CrossRefPubMed Concato J, Peduzzi P, Holford T et al (1995) Importance of events per independent variable in proportional hazards analysis I. Background, goals, and general strategy. J Clin Epidemiol 48:1495–1501CrossRefPubMed
34.
Zurück zum Zitat Morris EB, Li C, Khan RB et al (2009) Evolution of neurological impairment in pediatric infratentorial ependymoma patients. J Neurooncol 94(3):391–398CrossRefPubMedPubMedCentral Morris EB, Li C, Khan RB et al (2009) Evolution of neurological impairment in pediatric infratentorial ependymoma patients. J Neurooncol 94(3):391–398CrossRefPubMedPubMedCentral
35.
Zurück zum Zitat Goldwein JW, Leahy JM, Packer RJ et al (1990) Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19(6):1497–1502CrossRefPubMed Goldwein JW, Leahy JM, Packer RJ et al (1990) Intracranial ependymomas in children. Int J Radiat Oncol Biol Phys 19(6):1497–1502CrossRefPubMed
36.
Zurück zum Zitat Mack SC, Taylor MD (2009) The genetic and epigenetic basis of ependymoma. Childs Nerv Syst 25(10):1195–1201CrossRefPubMed Mack SC, Taylor MD (2009) The genetic and epigenetic basis of ependymoma. Childs Nerv Syst 25(10):1195–1201CrossRefPubMed
37.
Zurück zum Zitat Rappaport R, Brauner R (1989) Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 25(6):561–567CrossRefPubMed Rappaport R, Brauner R (1989) Growth and endocrine disorders secondary to cranial irradiation. Pediatr Res 25(6):561–567CrossRefPubMed
38.
Zurück zum Zitat Hancock SL, McDougall IR, Constine LS (1995) Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys 31(5):1165–1170CrossRefPubMed Hancock SL, McDougall IR, Constine LS (1995) Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys 31(5):1165–1170CrossRefPubMed
39.
Zurück zum Zitat Merchant TE, Goloubeva O, Pritchard DL et al (2002) Radiation dose-volume effects on growth hormone secretion. Int J Radiat Oncol Biol Phys 52(5):1264–1270CrossRefPubMed Merchant TE, Goloubeva O, Pritchard DL et al (2002) Radiation dose-volume effects on growth hormone secretion. Int J Radiat Oncol Biol Phys 52(5):1264–1270CrossRefPubMed
40.
Zurück zum Zitat Merchant TE, Rose SR, Bosley C, Wu S, Xiong X, Lustig RH (2011) Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol 29(36):4776–4780CrossRefPubMedPubMedCentral Merchant TE, Rose SR, Bosley C, Wu S, Xiong X, Lustig RH (2011) Growth hormone secretion after conformal radiation therapy in pediatric patients with localized brain tumors. J Clin Oncol 29(36):4776–4780CrossRefPubMedPubMedCentral
41.
Zurück zum Zitat Merchant TE, Mulhern RK, Krasin MJ et al (2004) Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 22(15):3156–3162CrossRefPubMed Merchant TE, Mulhern RK, Krasin MJ et al (2004) Preliminary results from a phase II trial of conformal radiation therapy and evaluation of radiation-related CNS effects for pediatric patients with localized ependymoma. J Clin Oncol 22(15):3156–3162CrossRefPubMed
42.
Zurück zum Zitat Conklin HM, Li C, Xiong X, Ogg RJ, Merchant TE (2008) Predicting change in academic abilities after conformal radiation therapy for localized ependymoma. J Clin Oncol 26(24):3965–3970CrossRefPubMedPubMedCentral Conklin HM, Li C, Xiong X, Ogg RJ, Merchant TE (2008) Predicting change in academic abilities after conformal radiation therapy for localized ependymoma. J Clin Oncol 26(24):3965–3970CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Di Pinto M, Conklin HM, Li C, Xiong X, Merchant TE (2010) Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma. Int J Radiat Oncol Biol Phys 77(4):1002–1008CrossRefPubMedPubMedCentral Di Pinto M, Conklin HM, Li C, Xiong X, Merchant TE (2010) Investigating verbal and visual auditory learning after conformal radiation therapy for childhood ependymoma. Int J Radiat Oncol Biol Phys 77(4):1002–1008CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Merchant TE, Kiehna EN, Li C, Xiong X, Mulhern RK (2005) Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma. Int J Radiat Oncol Biol Phys 63(5):1546–1554CrossRefPubMed Merchant TE, Kiehna EN, Li C, Xiong X, Mulhern RK (2005) Radiation dosimetry predicts IQ after conformal radiation therapy in pediatric patients with localized ependymoma. Int J Radiat Oncol Biol Phys 63(5):1546–1554CrossRefPubMed
45.
Zurück zum Zitat Debus J, Hug EB, Liebsch NJ et al (1997) Brainstem tolerance to conformal radiotherapy of skull base tumors. Int J Radiat Oncol Biol Phys 39:967–975CrossRefPubMed Debus J, Hug EB, Liebsch NJ et al (1997) Brainstem tolerance to conformal radiotherapy of skull base tumors. Int J Radiat Oncol Biol Phys 39:967–975CrossRefPubMed
46.
Zurück zum Zitat Santoni R, Liebsch N, Finkelstein DM et al (1998) Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull. Int J Radiat Oncol Biol Phys 41:59–68CrossRefPubMed Santoni R, Liebsch N, Finkelstein DM et al (1998) Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull. Int J Radiat Oncol Biol Phys 41:59–68CrossRefPubMed
47.
Zurück zum Zitat Miyawaki D, Murakami M, Demizu Y et al (2009) Brain injury after proton therapy or carbon ion therapy for head-and-neck cancer and skull base tumors. Int J Radiat Oncol Biol Phys 75:378–384CrossRefPubMed Miyawaki D, Murakami M, Demizu Y et al (2009) Brain injury after proton therapy or carbon ion therapy for head-and-neck cancer and skull base tumors. Int J Radiat Oncol Biol Phys 75:378–384CrossRefPubMed
48.
Zurück zum Zitat Pehlivan B, Ares C, Lomax AJ et al (2012) Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors. Int J Radiat Oncol Biol Phys 83(5):1432–1440CrossRefPubMed Pehlivan B, Ares C, Lomax AJ et al (2012) Temporal lobe toxicity analysis after proton radiation therapy for skull base tumors. Int J Radiat Oncol Biol Phys 83(5):1432–1440CrossRefPubMed
49.
Zurück zum Zitat Sabin ND, Merchant TE, Harreld JH et al (2013) Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy. AJNR Am J Neuroradiol 34(2):446–450CrossRefPubMedPubMedCentral Sabin ND, Merchant TE, Harreld JH et al (2013) Imaging changes in very young children with brain tumors treated with proton therapy and chemotherapy. AJNR Am J Neuroradiol 34(2):446–450CrossRefPubMedPubMedCentral
Metadaten
Titel
Pencil beam scanning proton therapy for pediatric intracranial ependymoma
verfasst von
Carmen Ares
Francesca Albertini
Martina Frei-Welte
Alessandra Bolsi
Michael A. Grotzer
Gudrun Goitein
Damien C. Weber
Publikationsdatum
05.03.2016
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 1/2016
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-016-2090-4

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