Top

Published in:

01-03-2019 | Original Article

Linac-based radiosurgery or fractionated stereotactic radiotherapy with flattening filter-free volumetric modulated arc therapy in elderly patients

A mono-institutional experience on 110 brain metastases

Authors: Fabiana Gregucci, MD, Alba Fiorentino, Stefanie Corradini, Vanessa Figlia, Rosario Mazzola, Francesco Ricchetti, Ruggero Ruggieri, Filippo Alongi

Published in: Strahlentherapie und Onkologie | Issue 3/2019

Abstract

Aim

The aim of this study was to analyze the feasibility and clinical results of linear accelerator (linac-)based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SFRT) with flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) in elderly patients affected by brain metastases (BMs).

Patients and methods

Patients selected for the present analysis were ≥65 years old with a life expectancy of >3 months, a controlled or synchronous primary tumor, and <10 BMs with a diameter <3 cm. All patients were treated with FFF linac-based SRS/SFRT. The prescribed total dose (15–30 Gy/1–5 fractions) was based on BM size and proximity to organs at risk (OAR). Toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. MedCalc v18.2 (MedCalc Software, Ostend, Belgium) was used for statistical analysis.

Results

From April 2014 to December 2017, 40 elderly patients with 110 BMs were treated by FFF linac-based SRS/SFRT. With a median follow-up of 28 months (range 6–50 months), median and 1‑year overall survival were 9 months and 39%, respectively; median intracranial progression-free survival was 6 months. At the time of the analysis, local control was reported in 109/110 BMs (99.1%): 12 BMs had a complete response; 51 a partial response; 46 showed stable disease. One BM (0.9%) progressed after 2 months. BM volume (<1 cc) and higher SRS/SFRT dose correlated to treatment response (p = 0.01 and p = 0.0017, respectively). No adverse events higher than grade 2 were observed.

Conclusion

The present findings highlight the feasibility, safety, and effectiveness of FFF linac-based SRS/SFRT in elderly patients with BMs.

Mehta MP, Tsao MN, Whelan TJ et al (2005) The American society for therapeutic radiology and oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastasis. Int J Radiat Oncol Biol Phys 63:37–46CrossRefPubMed

Patchell RA (2003) The management of brain metastases. Cancer Treat Rev 29:533–540CrossRefPubMed

Lin X, DeAngelis LM (2015) Treatment of brain metastases. J Clin Oncol 33:3475–3484CrossRefPubMedPubMedCentral

Yancik R, Ries LA (2004) Cancer in older persons: an international issue in an aging world. Semin Oncol 31:128–136CrossRefPubMed

Rowland JH, Yancik R (2006) Cancer survivorship: The interface of aging, comorbidity, and quality care. J Natl Cancer Inst 98:504–505CrossRefPubMed

Gaspar L, Scott C, Rotman M et al (1997) Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745–751CrossRefPubMed

Lutterbach J, Bartelt S, Stancu E et al (2002) Patients with brain metastases: hope for recursive partitioning analysis (RPA) class 3. Radiother Oncol 63:339–345CrossRefPubMed

Rades D, Evers JN, Veninga T et al (2011) Shorter-course whole-brain radiotherapy for brain metastases in elderly patients. Int J Radiat Oncol Biol Phys 81:e469–e473CrossRefPubMed

Sperduto PW, Kased N, Roberge D et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30(4):419–425CrossRefPubMed

10.

NCCN (2018) NCCN guidelines. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp

11.

Kocher M, Wittig A, Piroth MD et al (2014) Stereotactic radio-surgery for treatment of brain metastases. A report of the DEGRO Working Group on Stereotactic Radiotherapy. Strahlenther Onkol 190(6):521–532CrossRefPubMed

12.

Scoccianti S, Ricardi U (2012) Treatment of brain metastases: review of phase III randomized controlled trials. Radiother Oncol 102:168–179CrossRefPubMed

13.

Andrews DW, Scott CB, Sperduto PW et al (2004) 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 363:1665–1672CrossRefPubMed

14.

Aoyama H, Shirato H, Tago M et al (2006) Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:2483–2491CrossRefPubMed

15.

Yamamoto M, Serizawa T, Shuto T et al (2014) Results of stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective study. Lancet Oncol 15:387–395CrossRefPubMed

16.

DeAngelis LM, Delattre JY, Posner JB (1989) Radiation-induced dementia in patients cured of brain metastases. Baillieres Clin Neurol 39:789–796

17.

Crossen JR, Garwood D, Glatstein E et al (1994) Neurobehavioral sequelae of cranial irradiation in adults: a review of radiation-induced encephalopathy. J Clin Oncol 12:627–642CrossRefPubMed

18.

Fiorentino A, Tebano U et al (2017) Stereotactic ablative radiation therapy for brain metastases with volumetric modulated arc therapy and flattening filter free delivery: feasibility and early clinical results. Radiol Med 122(9):676–682CrossRefPubMed

19.

Ruggieri R, Naccarato S, Mazzola R et al (2018) Linac-based VMAT radiosurgery for multiple brain lesions: comparison between a conventional multi-isocenter approach and a new dedicated mono-isocenter technique. Radiat Oncol 13(1):38CrossRefPubMedPubMedCentral

20.

Noel G, Bollet MA, Noel S et al (2005) Linac stereotactic radiosurgery: an effective and safe treatment for elderly patients with brain metastases. Int J Radiat Oncol Biol Phys 63(5):1555–1561CrossRefPubMed

21.

Kim SH, Weil RJ, Chao ST et al (2008) Stereotactic radiosurgical treatment of brain metastases in older patients. Cancer 113(4):834–840CrossRefPubMed

22.

Minniti G, Esposito V, Clarke E et al (2013) Stereotactic radiosurgery in elderly patients with brain metastases. J Neurooncol 111(3):319–325CrossRefPubMed

23.

Watanabe S, Yamamoto M, Sato Y et al (2014) Stereotactic radiosurgery for brain metastases: a case-matched study comparing treatment results for patients 80 years of age or older versus patients 65–79 years of age. J Neurosurg 121(5):1148–1157CrossRefPubMed

24.

Park JY, Moon KS, Lee KH et al (2015) Gamma knife radiosurgery for elderly patients with brain metastases: evaluation of scoring systems that predict survival. BMC Cancer 15:54CrossRefPubMedPubMedCentral

25.

Yomo S, Hayashi M et al (2016) Is upfront stereotactic radiosurgery a rational treatment option for very elderly patients with brain metastases? A retrospective analysis of 106 consecutive patients age 80 years and older. BMC Cancer 16(1):948CrossRefPubMedPubMedCentral

26.

Roh TH, Choi MS, You N et al (2018) Identifying candidates for gamma knife radiosurgery among elderly patients with brain metastases. J Neurooncol 137(3):559–565CrossRefPubMed

27.

Wiggenraad R, Verbeek-de Kanter A, Kal HB et al (2011) Dose-effect relation in stereotactic radiotherapy for brain metastases. A systematic review. Radiother Oncol 98(3):292–297CrossRefPubMed

28.

Koay E, Sulman EP (2012) Management of brain metastasis: past lessons, modern management, and future considerations. Curr Oncol Rep 14(1):70–78CrossRefPubMed

29.

Maclean J, Fersht N, Singhera M et al (2013) Multi-disciplinary management for patients with oligometastases to the brain: results of a 5 years cohort study. Radiat Oncol 8:156CrossRefPubMedPubMedCentral

30.

D’Agostino GR, Autorino R, Pompucci A et al (2011) Whole-brain radiotherapy combined with surgery or stereotactic radiotherapy in patients with brain oligometastases: long-term analysis. Strahlenther Onkol 187(7):421–425CrossRefPubMed

31.

Balducci M, Autorino R, Chiesa S et al (2015) Radiosurgery or fractionated stereotactic radiotherapy plus whole-brain radioherapy in brain oligometastases: a long-term analysis. Anticancer Res 35(5):3055–3059PubMed

32.

Franco P, De Bari B, Ciammella P et al (2014) The role of stereotactic ablative radiotherapy in oncological and non-oncological clinical settings: highlights from the 7th Meeting of AIRO—Young Members Working Group (AIRO Giovani). Tumori 100(6):e214–e219CrossRefPubMed

33.

Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of radiosurgery alone vs radiosurgery with whole brain radiation therapy on cognitive function in patients with 1 to 3 brain metastases: a randomized clinical trial. JAMA 316(4):401–409CrossRefPubMedPubMedCentral

34.

Sahgal A, Aoyama H, Kocher M et al (2015) Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. Int J Radiat Oncol Biol 91(4):710–717CrossRef

35.

Robin TP, Camidge DR, Stuhr K et al (2018) Excellent outcomes with radiosurgery for multiple brain metastases in ALK and EGFR driven non-small cell lung cancer. J Thorac Oncol 13(5):715–720CrossRefPubMed

36.

Lutterbach J, Bartelt S, Momm F et al (2005) Is older age associated with a worse prognosis due to different patterns of care? A long-term study of 1346 patients with glioblastomas or brain metastases. Cancer 103(6):1234–1244CrossRefPubMed

37.

Alongi F, Fiorentino A, Gregucci F (2018) 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. https://doi.org/10.1007/s00432-018-2781-7 CrossRefPubMed

38.

Kubicek GJ, Turtz A, Xue J et al (2016) Stereotactic radiosurgery for poor performance status patients. Int J Radiat Oncol Biol Phys 95(3):956–959CrossRefPubMed

39.

Fiorentino A, Mazzola R, Giaj Levra N et al (2018) Comorbidities and intensity-modulated radiotherapy with simultaneous integrated boost in elderly breast cancer patients. Aging Clin Exp Res 30(5):533–538CrossRefPubMed

40.

Fiorentino A, Gregucci F, Mazzola R et al (2018) Intensity modulated radiotherapy and hypofractionated volumetric modulated arc therapy for elderly patients with breast cancer: comparison of acute and late toxicities. Radiol Med. In press

41.

Fiorentino A, Balducci M, De Bonis P et al (2015) Can elderly patients with newly diagnosed glioblastoma be enrolled in radiochemotherapy trials? Am J Clin Oncol 38(1):23–27CrossRefPubMed

42.

Sneed PK, Suh JH, Goetsch SJ et al (2002) A multi-institutional review of radiosurgery alone vs. radiosurgery with whole brain radiotherapy as the initial management of brain metastases. Int J Radiat Oncol Biol Phys 53:519–526CrossRefPubMed

43.

Manon R, O’Neill A, Knisely J et al (2005) Eastern Cooperative Oncology Group. Phase II trial of radiosurgery for one to three newly diagnosed brain metastases from renal cell carcinoma, melanoma, and sarcoma: an Eastern Cooperative Oncology Group study (E 6397). J Clin Oncol 23:8870–8876CrossRefPubMed

44.

Kocher M, Soffietti R, Abacioglu U et al (2006) 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 29:134–141CrossRef

45.

Rieber J, Tonndorf-Martini E, Schramm O et al (2016) Radiosurgery with flattening-filter-free techniques in the treatment of brain metastases: plan comparison and early clinical evaluation. Strahlenther Onkol 192(11):789–796CrossRefPubMed

46.

Stieler F, Simeonova A, Lohr F (2013) Intensity modulated radiosurgery of brain metastases with flattening filter-free beams. Radiother Oncol 109(3):448–451CrossRefPubMed

47.

Navarria P, Ascolese AM, Mancosu P et al (2013) Volumetric modulated arc therapy with flattening filter free (FFF) beams for stereotactic body radiation therapy (SBRT) in patients with medically inoperable early stage non small cell lung cancer (NSCLC). Radiother Oncol 107:414–418CrossRefPubMed

48.

Reggiori G, Mancosu P, Castiglioni S et al (2012) Can volumetric modulated arc therapy with flattening filter free beams play a role in stereotactic body radiotherapy for liver lesions? A volume-based analysis. Med Phys 39:1112–1118CrossRefPubMed

49.

Scorsetti M, Alongi F, Castiglioni S et al (2011) Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments. Radiat Oncol 6:113CrossRefPubMedPubMedCentral

50.

Alongi F, Fogliata A, Clerici E et al (2012) Volumetric modulated arc therapy with flattening filter free beams for isolated abdominal/pelvic lymph nodes: report of dosimetric and early clinical results in oligometastatic patients. Radiat Oncol 7:204CrossRefPubMedPubMedCentral

51.

Terem I, Ni WW, Goubran M et al (2018) Revealing sub-voxel motions of brain tissue using phase-based amplified MRI (aMRI). Magn Reson Med. https://doi.org/10.1002/mrm.27236 CrossRefPubMed

Title: Linac-based radiosurgery or fractionated stereotactic radiotherapy with flattening filter-free volumetric modulated arc therapy in elderly patients
A mono-institutional experience on 110 brain metastases
Authors: Fabiana Gregucci, MD
Alba Fiorentino
Stefanie Corradini
Vanessa Figlia
Rosario Mazzola
Francesco Ricchetti
Ruggero Ruggieri
Filippo Alongi
Publication date: 01-03-2019
Publisher: Springer Berlin Heidelberg
Published in: Strahlentherapie und Onkologie / Issue 3/2019
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-018-1405-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Linac-based radiosurgery or fractionated stereotactic radiotherapy with flattening filter-free volumetric modulated arc therapy in elderly patients

A mono-institutional experience on 110 brain metastases

Abstract

Aim

Patients and methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Aim

Patients and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2019

Reduzierte strahleninduzierte Hirnnekrose bei Patienten mit Nasopharynxkarzinom durch Bevacizumab-Monotherapie

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors

SBRT planning for spinal metastasis: indications from a large multicentric study

ICRU report 91 on prescribing, recording, and reporting of stereotactic treatments with small photon beams

Das Ende der TPF-Induktion bei lokoregionär fortgeschrittenen HNO-Karzinomen? Induktionschemotherapie gefolgt von Cetuximab und Bestrahlung nicht effektiver als simultane Radiochemotherapie

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries