AccScience Publishing / EJMO / Volume 5 / Issue 4 / DOI: 10.14744/ejmo.2021.29249
SYSTEMATIC REVIEW

Treatment Protocols and Outcomes of Intraoperative Radiotherapy for Brain Metastases: A Systematic Review

Juan Silvestre G. Pascual1 Ella Mae D. Cruz-Lim2 Aveline Marie D. Ylanan2 Katrina Hannah D. Ignacio3 Johanna Patricia A. Cañal2 Kathleen Joy O. Khu1
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1 Department of Neurosciences, Division of Neurosurgery, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Philippines
2 Department of Radiology, Division of Radiation Oncology, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Philippines
3 Department of Neurosciences, Division of Adult Neurology, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Philippines
EJMO 2021, 5(4), 281–290; https://doi.org/10.14744/ejmo.2021.29249
Submitted: 29 July 2021 | Accepted: 30 August 2021 | Published: 1 December 2021
© 2021 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Objectives: Intraoperative radiotherapy (IORT) is the delivery of ionizing radiation to the tumor or tumor bed during surgery. It is being explored as a treatment modality for brain metastases (BrMs). We aimed to determine the safety and efficacy of IORT for BrMs by reviewing the current evidence.

Methods: We performed a systematic review of the online databases for studies on IORT for BrMs. Data on clinical features, treatment modalities, and outcomes were collected.

Results: Five studies (n=179) were included. Mean age was 60.4 years, 43% were women. The most common etiology of BrMs were lung, melanoma, breast, and renal cancer. Ninety-five patients underwent IORT with the Photon Radiosurgery System (PRS) while 84 were treated with the INTRABEAM system. Follow-up ranged from 5 days to 94 months. The most frequent complication was radiation necrosis. Local recurrence and distal progression were seen in 11-77% and 0-82%, respectively. The 6- and 12-month overall survival ranged from 60-86% and 34-73%, respectively.

Conclusion: The results of the systematic review on the safety and efficacy of IORT on BrMs were inconclusive, due to heterogeneity of the studies. Larger prospective studies are needed to determine the optimal dose, efficacy, and safety of IORT for BrMs.

Conflict of interest
None declared.
References

1.Paunesku T, Woloschak GE. Future directions of intraoperative radiation therapy: A brief review. Front Oncol 2017;7:300.

2. Calvo FA. Intraoperative irradiation: Precision medicine for quality cancer control promotion. Radiat Oncol 2017;12:36.

3. Herskind C, Wenz F, Giordano FA. Immunotherapy combined with large fractions of radiotherapy: Stereotactic radiosurgery for brain metastases—implications for intraoperative radiotherapy after resection. Front Oncol 2017;7:147.

4. Prott FJ, Willich N, Palkovic S, Horch C, Wassmann H. A new method for treatment planning and quality control in IORT of brain tumors. Front Radiat Ther Oncol 1997;31:97–101.

5. Corica T, Joseph D, Saunders C, Bulsara M, Nowak AK. Intraoperative radiotherapy for early breast cancer: Do health professionals choose convenience or risk? Radiat Oncol 2014;9:33.

6. Pilar A, Gupta M, Laskar SG, Laskar S. Intraoperative radiotherapy: Review of techniques and results. Ecancermedicalscience 2017;11:750.

7. Tom MC, Joshi N, Vicini F, Chang AJ, Hong TS, Showalter TN, et al. The American brachytherapy society consensus statement on intraoperative radiation therapy. Brachytherapy 2019;18:242–57.

8. Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep 2012;14:48–54.

9. Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: A randomized trial. J Am Med Assoc 1998;280:1485–9.

10. Moravan MJ, Fecci PE, Anders CK, Clarke JM, Salama AKS, Ad-amson JD, et al. Current multidisciplinary management of brain metastases. Cancer 2020;126:1390–406.

11. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al. A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 1990;322:494– 500.

12. Goldson AL, Streeter OE, Ashayeri E, Collier-Manning J, Barber JB, Fan KJ. lntraoperative radiotherapy for lntracranial malignancies: A pilot study. Cancer 1984;54:2807–13.

13. Rich TA. Intraoperative radiotherapy. Radiother Oncol 1986;6:207–21.

14. Stoll A, van Oepen A, Friebe M. Intraoperative delivery of cell-killing boost radiation – a review of current and future methods. Minim Invasive Ther Allied Technol 2016;25:176–87.

15. Mahase SS, Navrazhina K, Schwartz TH, Parashar B, Wernicke AG. Intraoperative brachytherapy for resected brain metastases. Brachytherapy 2019;18:258–70.

16. Usychkin S, Calvo F, Dos Santos MA, Samblás J, De Urbina DO, Bustos JC, et al. Intra-operative electron beam radiotherapy for newly diagnosed and recurrent malignant gliomas: Feasibility and long-term outcomes. Clin Transl Oncol 2013;15:33– 8.

17. Curry WT, Cosgrove GR, Hochberg FH, Loeffler J, Zervas NT. Stereotactic interstitial radiosurgery for cerebral metastases. J Neurosurg 2005;103:630–5.

18. Pantazis G, Trippel M, Birg W, Ostertag CB, Nikkhah G. Stereotactic interstitial radiosurgery with the photon radiosurgery system (PRS) for metastatic brain tumors: A prospective single-center clinical trial. Int J Radiat Oncol Biol Phys 2009;75:1392–400.

19. Weil RJ, Mavinkurve GG, Chao ST, Vogelbaum MA, Suh JH, Kolar M, et al. Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: Initial experience and longterm outcomes. J Neurosurg 2015;122:825–32.

20. Vargo JA, Sparks KM, Singh R, Jacobson GM, Hack JD, Cifarelli CP. Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery. J Neurooncol 2018;140:413–20. 

21. Cifarelli CP, Brehmer S, Vargo JA, Hack JD, Kahl KH, Sarria-Vargas G, et al. Intraoperative radiotherapy (IORT) for surgically resected brain metastases: Outcome analysis of an international cooperative study. J Neurooncol 2019;145:391–7.

22. Sethi A, Emami B, Small W, Thomas TO, Thomas TO. Intraoperative radiotherapy with intrabeam: Technical and dosimetric considerations. Front Oncol 2018;8:74.

23. Cox JD. Evolution and accomplishments of the radiation therapy oncology group. Int J Radiat Oncol Biol Phys 1995;33:747– 54.

24. Matsutani M, Nakamura O, Nagashima T, Asai A, Fujimaki T, Tanaka H, et al. Intra-operative radiation therapy for malignant brain tumours: Rationale, method, and treatment results of cerebral glioblastomas. Acta Neurochir (Wien) 1994;131:80– 90.

25. Ueki K, Matsutani M, Nakamura O, Tanaka Y. Comparison of whole brain radiation therapy and locally limited radiation therapy in the treatment of solitary brain metastases from non- small cell lung cancer. Neurol Med Chir (Tokyo) 1996;36:364–9.

26. Nemoto K, Ogawa Y, Matsushita H, Takeda K, Takai Y, Yamada S, et al. Intraoperative radiation therapy (IORT) for previously untreated malignant gliomas. BMC Cancer 2002;2:1.

27. Krivoshapkin A, Gaytan A, Salim N, Abdullaev O, Sergeev G, Marmazeev I, et al. Repeat resection and intraoperative radiotherapy for malignant gliomas of the brain: A history and review of current techniques. World Neurosurg 2019;132:356– 62.

28. Cosgrove GR, Hochberg FH, Zervas NT, Pardo FS, Valenzuela RF, Chapman P. Interstitial irradiation of brain tumors, using a miniature radiosurgery device: Initial experience. Neurosurgery 1997;40:518–23.

29. Hakim R, Zervas NT, Hakim F, Butler WE, Beatty J, Yanch JC, et al. Initial characterization of the dosimetry and radiology of a device for administering interstitial stereotactic radiosurgery. Neurosurgery 1997;40:510–6.

30. Shaw E, Scott C, Souhami L, Dinapoli R, Kline R, Loeffler J, et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: Final report of RTOG protocol 90- 05. Int J Radiat Oncol Biol Phys 2000;47:291–8.

31. Douglas RM, Beatty J, Gall K, Valenzuela RF, Biggs P, Okunieff P, et al. Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases. Int J Radiat Oncol Biol Phys 1996;36:443–50.

32. Giordano FA, Brehmer S, Mürle B, Welzel G, Sperk E, Keller A, et al. Intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO): An open-label, dose-escalation phase I/II trial. Clin Neurosurg 2019;84:41–9.

33. Giordano FA, Brehmer S, Abo-Madyan Y, Welzel G, Sperk E, Keller A, et al. INTRAGO: Intraoperative radiotherapy in glioblastoma multiforme - a phase I/II dose escalation study. BMC Cancer 2014;14:992.

34. Herskind C, Steil V, Kraus-Tiefenbacher U, Wenz F. Radiobiological aspects of intraoperative radiotherapy (IORT) with isotropic low-energy X rays for early-stage breast cancer. Radiat Res 2005;163:208–15.

35. Milano MT, Usuki KY, Walter KA, Clark D, Schell MC. Stereotactic radiosurgery and hypofractionated stereotactic radiotherapy: Normal tissue dose constraints of the central nervous system. Cancer Treat Rev 2011;37:567–78.

36. Rogers LR, Rock JP, Sills AK, Vogelbaum MA, Suh JH, Ellis TL, et al. Results of a phase II trial of the GliaSite radiation therapy system for the treatment of newly diagnosed, resected single brain metastases. J Neurosurg 2006;105:375–84.

37. Schueller P, Micke O, Palkovic S, Schroeder J, Moustakis C, Bruns F, et al. 12 Years’ experience with intraoperative radiotherapy (IORT) of malignant gliomas. Strahlenther Onkol 2005;181:500–6.

38. Vellayappan B, Tan CL, Yong C, Khor LK, Koh WY, Yeo TT, et al. Diagnosis and management of radiation necrosis in patients with brain metastases. Front Oncol 2018;8:395.

39. Roberge D, Petrecca K, El Refae M, Souhami L. Whole-brain radiotherapy and tumor bed radiosurgery following resection of solitary brain metastases. J Neurooncol 2009;95:95–9.

40. Minniti G, Scaringi C, Paolini S, Lanzetta G, Romano A, Cicone F, et al. Single-fraction versus multifraction (3 × 9 gy) stereotactic radiosurgery for large (>2 cm) brain metastases: A comparative analysis of local control and risk of radiation-induced brain necrosis. Int J Radiat Oncol Biol Phys 2016;95:1142–8.

41. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, et al. Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: Phase III results of the RTOG 9508 randomised trial. Lancet 2004;363:1665–72.

42. Culberson WS, Davis SD, Gwe-Ya Kim G, Lowenstein JR, Ouhib Z, Popovic M, et al. Dose-rate considerations for the INTRABEAM electronic brachytherapy system: Report from the American association of physicists in medicine task group no. 292. Med Phys 2020;47:913–9.

43. Noh T, Walbert T. Brain metastasis: Clinical manifestations, symptom management, and palliative care. 1st ed. Handbook of Clinical Neurology. Elsevier B.V; 2018. p 75–88.

44. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: Results of the EORTC 22952-26001 study. J Clin Oncol 2011;29:134–41.

45. Mahajan A, Ahmed S, McAleer MF, Weinberg JS, Li J, Brown P, et al. Post-operative stereotactic radiosurgery versus observation for completely resected brain metastases: A single-centre, randomised, controlled, phase 3 trial. Lancet Oncol 2017;18:1040–8.

46. Brehmer S, Welsch M, Karakoyun A, Forster A, Seiz-Rosenhagen M, Clausen S, et al. P05.35 Intraoperative radiotherapy after resection of brain metastases (INTRAMET) - initial safety/ efficacy analysis of a prospective phase II study. Neuro Oncol 2018;20:310–1.

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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing