Role of Hyperbaric Oxygenation Plus Hypofractionated Stereotactic Radiotherapy in Recurrent High-Grade Glioma

Donatella Arpa, Elisabetta Parisi, Giulia Ghigi, Annalisa Cortesi, Pasquale Longobardi, Patrizia Cenni, Martina Pieri, Luca Tontini, Elisa Neri, Simona Micheletti, Francesca Ghetti, Manuela Monti, Flavia Foca, Anna Tesei, Chiara Arienti, Anna Sarnelli, Giovanni Martinelli, Antonio Romeo, Donatella Arpa, Elisabetta Parisi, Giulia Ghigi, Annalisa Cortesi, Pasquale Longobardi, Patrizia Cenni, Martina Pieri, Luca Tontini, Elisa Neri, Simona Micheletti, Francesca Ghetti, Manuela Monti, Flavia Foca, Anna Tesei, Chiara Arienti, Anna Sarnelli, Giovanni Martinelli, Antonio Romeo

Abstract

Background: The presence of hypoxic cells in high-grade glioma (HGG) is one of major reasons for failure of local tumour control with radiotherapy (RT). The use of hyperbaric oxygen therapy (HBO) could help to overcome the problem of oxygen deficiency in poorly oxygenated regions of the tumour. We propose an innovative approach to improve the efficacy of hypofractionated stereotactic radiotherapy (HSRT) after HBO (HBO-RT) for the treatment of recurrent HGG (rHGG) and herein report the results of an ad interim analysis.

Methods: We enrolled a preliminary cohort of 9 adult patients (aged >18 years) with a diagnosis of rHGG. HSRT was administered in daily 5-Gy fractions for 3-5 consecutive days a week. Each fraction was delivered up to maximum of 60 minutes after HBO.

Results: Median follow-up from re-irradiation was 11.6 months (range: 3.2-11.6 months). The disease control rate (DCR) 3 months after HBO-RT was 55.5% (5 patients). Median progression-free survival (mPFS) for all patients was 5.2 months (95%CI: 1.34-NE), while 3-month and 6-month PFS was 55.5% (95%CI: 20.4-80.4) and 27.7% (95%CI: 4.4-59.1), respectively. Median overall survival (mOS) of HBO-RT was 10.7 months (95% CI: 7.7-NE). No acute or late neurologic toxicity >grade (G)2 was observed in 88.88% of patients. One patient developed G3 radionecrosis.

Conclusions: HSRT delivered after HBO appears to be effective for the treatment of rHGG, it could represent an alternative, with low toxicity, to systemic therapies for patients who cannot or refuse to undergo such treatments.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT03411408.

Keywords: TomoTherapy; hyperbaric oxygenation; hypofractionated stereotactic radiotherapy; re-irradiation; recurrent high-grade glioma.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Arpa, Parisi, Ghigi, Cortesi, Longobardi, Cenni, Pieri, Tontini, Neri, Micheletti, Ghetti, Monti, Foca, Tesei, Arienti, Sarnelli, Martinelli and Romeo.

Figures

Figure 1
Figure 1
Examples of (A) dose distribution and (B) typical dose volume histogram (DVH) for a prescription dose of 15 Gy in 3 fractions to PTV1 and 12 Gy in 3 fractions to PTV FLAIR.
Figure 2
Figure 2
Progression-free survival (PFS) after HBO-RT.
Figure 3
Figure 3
Overall survival (OS) after HBO-RT.

References

    1. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. . 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 (2009) 10:459–66. 10.1016/S1470-2045(09)70025-7
    1. Niyazi M, Siefert A, Schwarz SB, Ganswindt U, Kreth F-W, Tonn J-C, et al. . Therapeutic options for recurrent malignant glioma. Radiother Oncol (2011) 98:1–14. 10.1016/j.radonc.2010.11.006
    1. Wick W, Gorlia T, Bendszus M, Taphoorn M, Sahm F, Harting I, et al. . Lomustine and Bevacizumab in Progressive Glioblastoma. N Engl J Med (2017) 377:1954–63. 10.1056/nejmoa1707358
    1. Taal W, Oosterkamp HM, Walenkamp AME, Dubbink HJ, Beerepoot LV, Hanse MCJ, et al. . Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): A randomised controlled phase 2 trial. Lancet Oncol (2014) 15:943–53. 10.1016/S1470-2045(14)70314-6
    1. Reardon DA, Brandes AA, Omuro A, Mulholland P, Lim M, Wick A, et al. . Effect of Nivolumab vs Bevacizumab in Patients with Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial. JAMA Oncol (2020) 6:1003–10. 10.1001/jamaoncol.2020.1024
    1. Tsien C, Pugh S, Dicker AP, Raizer JJ, Matuszak MM, Lallana E, et al. . Randomized Phase II Trial of Re-Irradiation and Concurrent Bevacizumab versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma (NRG Oncology/RTOG 1205): Initial Outcomes and RT Plan Quality Report. Int J Radiat Oncol (2019) 105:S78. 10.1016/j.ijrobp.2019.06.539
    1. Seystahl K, Wick W, Weller M. Therapeutic options in recurrent glioblastoma–An update. Crit Rev Oncol Hematol (2016) 99:389–408. 10.1016/j.critrevonc.2016.01.018
    1. Jensen RL. Hypoxia in the tumorigenesis of gliomas and as a potential target for therapeutic measures. Neurosurg Focus (2006) 20:E24. 10.3171/foc.2006.20.4.16
    1. Jensen RL. Brain tumor hypoxia: Tumorigenesis, angiogenesis, imaging, pseudoprogression, and as a therapeutic target. J Neurooncol (2009) 92:317–35. 10.1007/s11060-009-9827-2
    1. Kaynar MY, Sanus GZ, Hnimoglu H, Kacira T, Kemerdere R, Atukeren P, et al. . Expression of hypoxia inducible factor-1α in tumors of patients with glioblastoma multiforme and transitional meningioma. J Clin Neurosci (2008) 15:1036–42. 10.1016/j.jocn.2007.07.080
    1. Fischer I, Gagner J-P, Law M, Newcomb EW, Zagzag D. Angiogenesis in Gliomas: Biology and Molecular Pathophysiology. Brain Pathol (2006) 15:297–310. 10.1111/j.1750-3639.2005.tb00115.x
    1. Onishi M, Ichikawa T, Kurozumi K, Date I. Angiogenesis and invasion in glioma. Brain Tumor Pathol (2011) 28:13–24. 10.1007/s10014-010-0007-z
    1. Tate MC, Aghi MK. Biology of Angiogenesis and Invasion in Glioma. Neurotherapeutics (2009) 6:447–57. 10.1016/j.nurt.2009.04.001
    1. Nakabayashi H, Yawata T, Shimizu K. Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells. BMC Cancer (2010) 10:339. 10.1186/1471-2407-10-339
    1. Chi A, Norden AD, Wen PY. Inhibition of angiogenesis and invasion in malignant gliomas. Expert Rev Anticancer Ther (2007) 7:1537–60. 10.1586/14737140.7.11.1537
    1. Lally BE, Rockwell S, Fischer DB, Collingridge DR, Piepmeier JM, Knisely JPS. The interactions of polarographic measurements of oxygen tension and histological grade in human glioma. Cancer J (2006) 12:461–6. 10.1097/00130404-200611000-00005
    1. Beppu T, Kamada K, Yoshida Y, Arai H, Ogasawara K, Ogawa A. Change of oxygen pressure in glioblastoma tissue under various conditions. J Neurooncol (2002) 58:47–52. 10.1023/A:1015832726054
    1. Kayama T, Yoshimoto T, Fujimoto S, Sakurai Y. Intratumoral oxygen pressure in malignant brain tumor. J Neurosurg (1991) 74:55–9. 10.3171/jns.1991.74.1.0055
    1. Collingridge DR, Piepmeier JM, Rockwell S, Knisely JPS. Polarographic measurements of oxygen tension in human glioma and surrounding peritumoural brain tissue. Radiother Oncol (1999) 53:127–31. 10.1016/S0167-8140(99)00121-8
    1. Kohshi K, Beppu T, Tanaka K, Ogawa K, Inoue O, Kukita I, et al. . Potential roles of hyperbaric oxygenation in the treatments of brain tumors. Undersea Hyperb Med (2013) 40:351–62.
    1. Stępień K, Ostrowski RP, Matyja E. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours. Med Oncol (2016) 33:101. 10.1007/s12032-016-0814-0
    1. Moen I, Stuhr LEB. Hyperbaric oxygen therapy and cancer - A review. Target Oncol (2012) 7:233–42. 10.1007/s11523-012-0233-x
    1. Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C. Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev (2016) 4:CD005005. 10.1002/14651858.CD005005.pub4
    1. Bennett MH, Feldmeier J, Smee R, Milross C. Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Cochrane Database Syst Rev (2012) 5:CD005005. 10.1002/14651858.CD005005.pub3
    1. Huang L, Boling W, Zhang J. Hyperbaric oxygen therapy as adjunctive strategy in treatment of glioblastoma multiforme. Med Gas Res (2018) 8:24–8. 10.4103/2045-9912.229600
    1. Kunugita N, Kohshi K, Kinoshita Y, Katoh T, Abe H, Tosaki T, et al. . Radiotherapy after hyperbaric oxygenation improves radioresponse in experimental tumor models. Cancer Lett (2001) 164:149–54. 10.1016/S0304-3835(00)00721-7
    1. Kinoshita Y, Kohshi K, Kunugita N, Tosaki T, Yokota A. Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging. Br J Cancer (2000) 82:88–92. 10.1054/bjoc.1999.0882
    1. Wise RJ, Bernardi S, Frackowiak RS, Jones T, Legg NJ, Lenzi GL. Measurement of regional cerebral blood flow, oxygen extraction ratio and oxygen utilization in stroke patients using positron emission tomography. Exp Brain Res (1982) Suppl 5:182–86. 10.1007/978-3-642-68507-1_25
    1. Tyler JL, Diksic M, Villemure JG, Evans AC, Meyer E, Yamamoto YL, et al. . Metabolic and hemodynamic evaluation of gliomas using positron emission tomography. J Nucl Med (1987) 28:1123–33.
    1. Chen JR, Xu HZ, Ding JB, Qin ZY. Radiotherapy after hyperbaric oxygenation in malignant gliomas. Curr Med Res Opin (2015) 31:1977–84. 10.1185/03007995.2015.1082988
    1. Ogawa K, Kohshi K, Ishiuchi S, Matsushita M, Yoshimi N, Murayama S. Old but new methods in radiation oncology: Hyperbaric oxygen therapy. Int J Clin Oncol (2013) 18:364–70. 10.1007/s10147-013-0537-6
    1. Kohshi K, Yamamoto H, Nakahara A, Katoh T, Takagi M. Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas. J Neurooncol (2007) 82:297–303. 10.1007/s11060-006-9283-1
    1. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, et al. . Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. J Clin Oncol (2010) 28:1963–72. 10.1200/JCO.2009.26.3541
    1. Cancer Institute N . Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (2009). Available at: (Accessed May 23, 2020).
    1. Simon R. Optimal Two-Stage Designs for Phase II Clinical Trials. Control Clin Trials (1989) 10:1–10. 10.1016/0197-2456(89)90015-9
    1. Carson KA, Grossman SA, Fisher JD, Shaw EG. Prognostic factors for survival in adult patients with recurrent glioma enrolled onto the new approaches to brain tumor therapy CNS Consortium phase I and II clinical trials. J Clin Oncol (2007) 25:2601–6. 10.1200/JCO.2006.08.1661
    1. Minniti G, Amelio D, Amichetti M, Salvati M, Muni R, Bozzao A, et al. . Patterns of failure and comparison of different target volume delineations in patients with glioblastoma treated with conformal radiotherapy plus concomitant and adjuvant temozolomide. Radiother Oncol (2010) 97:377–81. 10.1016/j.radonc.2010.08.020
    1. Kim H. Appraisal of re-irradiation for the recurrent glioblastoma in the era of MGMT promotor methylation. Radiat Oncol J (2019) 37:1–12. 10.3857/roj.2019.00171
    1. Shanker M, Chua B, Bettington C, Foote MC, Pinkham MB. Re-irradiation for recurrent high-grade gliomas: A systematic review and analysis of treatment technique with respect to survival and risk of radionecrosis. Neuro Oncol Pract (2019) 6:144–55. 10.1093/nop/npy019
    1. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol (1953) 26:638–48. 10.1259/0007-1285-26-312-638
    1. Overgaard J. Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck - A systematic review and meta-analysis. Radiother Oncol (2011) 100:22–32. 10.1016/j.radonc.2011.03.004
    1. Horsman MR, Overgaard J. The impact of hypoxia and its modification of the outcome of radiotherapy. J Radiat Res (2016) 57 Suppl 1:i90–8. 10.1093/jrr/rrw007
    1. Bennett MH, Feldmeier J, Smee R, Milross C. Hyperbaric oxygenation for tumour sensitisation to radiotherapy. Diving Hyperb Med (2018) 48:116–7. 10.1002/14651858.CD005007.pub4
    1. Gill AL, Bell CNA. Hyperbaric oxygen: Its uses, mechanisms of action and outcomes. QJM - Mon J Assoc Physicians (2004) 97:385–95. 10.1093/qjmed/hch074
    1. Al-Waili NS. Hyperbaric oxygen and malignancies: a potential role in radiotherapy, chemotherapy, tumor surgery and phototherapy. Med Sci Monit (2005) 11(9):RA279–89.
    1. Beppu T, Kamada K, Nakamura R, Oikawa H, Takeda M, Fukuda T, et al. . A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas. J Neurooncol (2003) 61:161–70. 10.1023/A:1022169107872
    1. Ogawa K, Ishiuchi S, Inoue O, Yoshii Y, Saito A, Watanabe T, et al. . Phase II trial of radiotherapy after hyperbaric oxygenation with multiagent chemotherapy (procarbazine, nimustine, and vincristine) for high-grade gliomas: Long-term results. Int J Radiat Oncol Biol Phys (2012) 82:732–8. 10.1016/j.ijrobp.2010.12.070
    1. Kohshi K, Kinoshita Y, Imada H, Kunugita N, Abe H, Terashima H, et al. . Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas. Br J Cancer (1999) 80:236–41. 10.1038/sj.bjc.6690345
    1. Yahara K, Ohguri T, Udono H, Yamamoto J, Tomura K, Onoda T, et al. . Radiotherapy using IMRT boosts after hyperbaric oxygen therapy with chemotherapy for glioblastoma. J Radiat Res (2017) 58:351–6. 10.1093/jrr/rrw105
    1. Vordermark D, Kölbl O, Ruprecht K, Vince GH, Bratengeier K, Flentje M. Hypofractionated stereotactic re-irradiation: Treatment option in recurrent malignant glioma. BMC Cancer (2005) 5:1–7. 10.1186/1471-2407-5-55
    1. Ernst-Stecken A, Ganslandt O, Lambrecht U, Sauer R, Grabenbauer G. Survival and quality of life after hypofractionated stereotactic radiotherapy for recurrent malignant glioma. J Neurooncol (2007) 81:287–94. 10.1007/s11060-006-9231-0
    1. Fokas E, Wacker U, Gross MW, Henzel M, Encheva E, Engenhart-Cabillic R. Hypofractionated Stereotactic Reirradiation of Recurrent Glioblastomas. Strahlentherapie und Onkol (2009) 185:235–40. 10.1007/s00066-009-1753-x
    1. Kim B, Soisson E, Duma C, Chen P, Hafer R, Cox C, et al. . Treatment of recurrent high grade gliomas with hypofractionated stereotactic image-guided helical tomotherapy. Clin Neurol Neurosurg (2011) 113:509–12. 10.1016/j.clineuro.2011.02.001
    1. Minniti G, Scaringi C, De Sanctis V, Lanzetta G, Falco T, Di Stefano D, et al. . Hypofractionated stereotactic radiotherapy and continuous low-dose temozolomide in patients with recurrent or progressive malignant gliomas. J Neurooncol (2013) 111:187–94. 10.1007/s11060-012-0999-9
    1. Shapiro LQ, Beal K, Goenka A, Karimi S, Iwamoto FM, Yamada Y, et al. . Patterns of Failure After Concurrent Bevacizumab and Hypofractionated Stereotactic Radiation Therapy for Recurrent High-Grade Glioma. Int J Radiat Oncol (2013) 85:636–42. 10.1016/j.ijrobp.2012.05.031
    1. Yazici G, Cengiz M, Ozyigit G, Eren G, Yildiz F, Akyol F, et al. . Hypofractionated stereotactic reirradiation for recurrent glioblastoma. J Neurooncol (2014) 120:117–23. 10.1007/s11060-014-1524-0
    1. Minniti G, Agolli L, Falco T, Scaringi C, Lanzetta G, Caporello P, et al. . Hypofractionated stereotactic radiotherapy in combination with bevacizumab or fotemustine for patients with progressive malignant gliomas. J Neurooncol (2015) 122:559–66. 10.1007/s11060-015-1745-x
    1. Navarria P, Ascolese AM, Tomatis S, Reggiori G, Clerici E, et al. . Hypofractionated Stereotactic Radiation Therapy in Recurrent High-Grade Glioma: A New Challenge. Cancer Res Treat (2016) 48:37–44. 10.4143/crt.2014.259
    1. Combs SE, Niyazi M, Adeberg S, Bougatf N, Kaul D, Fleischmann DF, et al. . Re-irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score—report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK). Cancer Med (2018) 7:1742–9. 10.1002/cam4.1425
    1. Navarria P, Minniti G, Clerici E, Tomatis S, Pinzi V, Ciammella P, et al. . Re-irradiation for recurrent glioma: outcome evaluation, toxicity and prognostic factors assessment. A multicenter study of the Radiation Oncology Italian Association (AIRO). J Neurooncol (2019) 142:59–67. 10.1007/s11060-018-03059-x
    1. Arpa D, Parisi E, Ghigi G, Savini A, Colangione SP, Tontini L, et al. . Re-irradiation of recurrent glioblastoma using helical TomoTherapy with simultaneous integrated boost: preliminary considerations of treatment efficacy. Sci Rep (2020) 10:19321. 10.1038/s41598-020-75671-9
    1. Chapman CH, Hara JH, Molinaro AM, Clarke JL, Oberheim Bush NA, Taylor JW, et al. . Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival. Neuro Oncol Pract (2019) 6:364–74. 10.1093/nop/npz017

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다