Top

Journal of Cancer Research and Clinical Oncology

Published in:

Open Access 01-09-2021 | Metastasis | Original Article – Clinical Oncology

Cyberknife^® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases

Authors: Sergej Telentschak, Daniel Ruess, Stefan Grau, Roland Goldbrunner, Niklas von Spreckelsen, Karolina Jablonska, Harald Treuer, Martin Kocher, Maximilian Ruge

Published in: Journal of Cancer Research and Clinical Oncology | Issue 9/2021

Abstract

Purpose

The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife^® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature.

Methods

All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE).

Results

We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%.

The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively.

Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%.

Conclusion

Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care.

Aoki M, Abe Y, Hatayama Y et al (2006) Clinical outcome of hypofractionated conventional conformation radiotherapy for patients with single and no more than three metastatic brain tumors, with noninvasive fixation of the skull without whole brain irradiation. Int J Radiat Oncol 64:414–418. https://doi.org/10.1016/j.ijrobp.2005.03.017CrossRef

Aoyama H, Shirato H, Onimaru R et al (2003) Hypofractionated stereotactic radiotherapy alone without whole-brain irradiation for patients with solitary and oligo brain metastasis using noninvasive fixation of the skull. Int J Radiat Oncol 56:793–800. https://doi.org/10.1016/S0360-3016(03)00014-2CrossRef

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. JAMA 295:2483. https://doi.org/10.1001/jama.295.21.2483CrossRefPubMed

Ayas AW, Grau S, Jablonska K et al (2018) Postoperative local fractionated radiotherapy for resected single brain metastases. Strahlenther Onkol 194:1163–1170. https://doi.org/10.1007/s00066-018-1368-1CrossRefPubMed

Baliga S, Garg MK, Fox J et al (2017) Fractionated stereotactic radiation therapy for brain metastases: a systematic review with tumour control probability modelling. Br J Radiol 90:20160666. https://doi.org/10.1259/bjr.20160666CrossRefPubMedPubMedCentral

Brenner DJ, Martel MK, Hall EJ (1991) Fractionated regimens for stereotactic radiotherapy of recurrent tumors in the brain. Int J Radiat Oncol 21:819–824. https://doi.org/10.1016/0360-3016(91)90703-7CrossRef

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. JAMA 316:401. https://doi.org/10.1001/jama.2016.9839CrossRefPubMedPubMedCentral

Ernst-Stecken A, Ganslandt O, Lambrecht U et al (2006) Phase II trial of hypofractionated stereotactic radiotherapy for brain metastases: results and toxicity. Radiother Oncol 81:18–24. https://doi.org/10.1016/j.radonc.2006.08.024CrossRefPubMed

Feuvret L, Vinchon S, Martin V et al (2014) Stereotactic radiotherapy for large solitary brain metastases. Cancer/Radiothérapie 18:97–106. https://doi.org/10.1016/j.canrad.2013.12.003CrossRef

Flickinger JC, Kondziolka D, Dade Lunsford L et al (1994) A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis. Int J Radiat Oncol 28:797–802. https://doi.org/10.1016/0360-3016(94)90098-1CrossRef

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 37:745–751. https://doi.org/10.1016/S0360-3016(96)00619-0CrossRef

Guan Y, Wang C, Zhu H et al (2020) Hypofractionated radiosurgery plus bevacizumab for locally recurrent brain metastasis with previously high-dose irradiation. World Neurosurg 133:e252–e258. https://doi.org/10.1016/j.wneu.2019.08.233CrossRefPubMed

Hashimoto K, Narita Y, Miyakita Y et al (2011) Comparison of clinical outcomes of surgery followed by local brain radiotherapy and surgery followed by whole brain radiotherapy in patients with single brain metastasis: single-center retrospective analysis. Int J Radiat Oncol 81:e475–e480. https://doi.org/10.1016/j.ijrobp.2011.02.016CrossRef

Hoffman R, Sneed PK, McDermott MW et al (2001) Radiosurgery for brain metastases from primary lung carcinoma. Cancer J 7:121–131PubMed

Igaki H, Harada K, Umezawa R et al (2017) Outcomes of surgery followed by local brain radiotherapy compared with surgery followed by whole brain radiotherapy for single brain metastasis. Tumori J 103:367–373. https://doi.org/10.5301/tj.5000657CrossRef

Inoue HK, Sato H, Suzuki Y et al (2014) Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study. Radiat Oncol 9:231. https://doi.org/10.1186/s13014-014-0231-5CrossRefPubMedPubMedCentral

Johung KL, Yeh N, Desai NB et al (2016) Extended survival and prognostic factors for patients with ALK—rearranged non–small-cell lung cancer and brain metastasis. J Clin Oncol 34:123–129. https://doi.org/10.1200/JCO.2015.62.0138CrossRefPubMed

Kim Y-J, Cho KH, Kim J-Y et al (2011) Single-dose versus fractionated stereotactic radiotherapy for brain metastases. Int J Radiat Oncol 81:483–489. https://doi.org/10.1016/j.ijrobp.2010.05.033CrossRef

Kocher M, Soffietti R, Abacioglu U et al (2011) 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 29:134–141. https://doi.org/10.1200/JCO.2010.30.1655CrossRefPubMed

Kwon AK, DiBiase SJ, Wang B et al (2009) Hypofractionated stereotactic radiotherapy for the treatment of brain metastases. Cancer 115:890–898. https://doi.org/10.1002/cncr.24082CrossRefPubMed

Lehrer EJ, Peterson JL, Zaorsky NG et al (2019) Single versus multifraction stereotactic radiosurgery for large brain metastases: an international meta-analysis of 24 trials. Int J Radiat Oncol 103:618–630. https://doi.org/10.1016/j.ijrobp.2018.10.038CrossRef

Lesueur P, Lequesne J, Barraux V et al (2018) Radiosurgery or hypofractionated stereotactic radiotherapy for brain metastases from radioresistant primaries (melanoma and renal cancer). Radiat Oncol 13:138. https://doi.org/10.1186/s13014-018-1083-1CrossRefPubMedPubMedCentral

Li B, Yu J, Suntharalingam M et al (2000) Comparison of three treatment options for single brain metastasis from lung cancer. Int J Cancer 90:37–45. https://doi.org/10.1002/(SICI)1097-0215(20000220)90:1%3c37::AID-IJC5%3e3.0.CO;2-7CrossRefPubMed

Lin NU, Lee EQ, Aoyama H et al (2015) Response assessment criteria for brain metastases: proposal from the RANO group. Lancet Oncol 16:e270–e278. https://doi.org/10.1016/S1470-2045(15)70057-4CrossRefPubMed

Manning MA, Cardinale RM, Benedict SH et al (2000) Hypofractionated stereotactic radiotherapy as an alternative to radiosurgery for the treatment of patients with brain metastases. Int J Radiat Oncol 47:603–608. https://doi.org/10.1016/S0360-3016(00)00475-2CrossRef

Mengue L, Bertaut A, Ngo Mbus L et al (2020) Brain metastases treated with hypofractionated stereotactic radiotherapy: 8 years experience after Cyberknife installation. Radiat Oncol 15:82. https://doi.org/10.1186/s13014-020-01517-3CrossRefPubMedPubMedCentral

Minniti G, D’Angelillo RM, Scaringi C et al (2014) Fractionated stereotactic radiosurgery for patients with brain metastases. J Neurooncol 117:295–301. https://doi.org/10.1007/s11060-014-1388-3CrossRefPubMed

Murai T, Ogino H, Manabe Y et al (2014) Fractionated stereotactic radiotherapy using cyberknife for the treatment of large brain metastases: a dose escalation study. Clin Oncol 26:151–158. https://doi.org/10.1016/j.clon.2013.11.027CrossRef

Murovic J, Ding V, Han SS et al (2017) Impact of cyberknife radiosurgery on overall survival and various parameters of patients with 1–3 versus ≥ 4 brain metastases. Cureus 9:1–19. https://doi.org/10.7759/cureus.1798CrossRef

Nakamura M, Nishimura H, Mayahara H et al (2017) Investigation of the efficacy and safety of CyberKnife hypofractionated stereotactic radiotherapy for brainstem metastases using a new evaluation criterion: ‘symptomatic control.’ J Radiat Res 58:834–839. https://doi.org/10.1093/jrr/rrx042CrossRefPubMedPubMedCentral

Narayana A, Chang J, Yenice K et al (2007) Hypofractionated stereotactic radiotherapy using intensity-modulated radiotherapy in patients with one or two brain metastases. Stereotact Funct Neurosurg 85:82–87. https://doi.org/10.1159/000097923CrossRefPubMed

Rades D, Janssen S, Dziggel L et al (2017) A matched-pair study comparing whole-brain irradiation alone to radiosurgery or fractionated stereotactic radiotherapy alone in patients irradiated for up to three brain metastases. BMC Cancer 17:30. https://doi.org/10.1186/s12885-016-2989-3CrossRefPubMedPubMedCentral

Rajakesari S, Arvold ND, Jimenez RB et al (2014) Local control after fractionated stereotactic radiation therapy for brain metastases. J Neurooncol 120:339–346. https://doi.org/10.1007/s11060-014-1556-5CrossRefPubMed

Royer P, Salleron J, Vogin G et al (2017) Radiothérapie stéréotaxique hypofractionnée des métastases cérébrales : bénéfice de l’irradiation encéphalique totale ? Cancer/Radiothérapie 21:731–740. https://doi.org/10.1016/j.canrad.2017.02.005CrossRef

Saitoh I, Saito Y, Kazumoto T et al (2010) Therapeutic effect of linac-based stereotactic radiotherapy with a micro-multileaf collimator for the treatment of patients with brain metastases from lung cancer. Jpn J Clin Oncol 40:119–124. https://doi.org/10.1093/jjco/hyp128CrossRefPubMed

Salles AAF, Hariz M, Bajada CL et al (1993) Comparison between radiosurgery and stereotactic fractionated radiation for the treatment of brain metastases. Advances in stereotactic and functional neurosurgery 10. Springer Vienna, Vienna, pp 115–118CrossRef

Shin SM, Vatner RE, Tam M et al (2015) Resection followed by involved-field fractionated radiotherapy in the management of single brain metastasis. Front Oncol 5:12–13. https://doi.org/10.3389/fonc.2015.00206CrossRef

Title: Cyberknife® hypofractionated stereotactic radiosurgery (CK-hSRS) as salvage treatment for brain metastases
Authors: Sergej Telentschak
Daniel Ruess
Stefan Grau
Roland Goldbrunner
Niklas von Spreckelsen
Karolina Jablonska
Harald Treuer
Martin Kocher
Maximilian Ruge
Publication date: 01-09-2021
Publisher: Springer Berlin Heidelberg
Keyword: Metastasis
Published in: Journal of Cancer Research and Clinical Oncology / Issue 9/2021
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-021-03564-z

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 9/2021

One-stitch method vs. traditional method of protective loop ileostomy for rectal cancer: the impact of BMI obesity

Improved oncologic outcomes by ablative radiotherapy in patients with bone metastasis from hepatocellular carcinoma

Cytoplasmic LXR expression is an independent marker of poor prognosis for patients with early stage primary breast cancer

Do proton pump inhibitors prevent Barrett’s esophagus progression to high-grade dysplasia and esophageal adenocarcinoma? An updated meta-analysis

Colonoscopy and polypectomy: beside age, size of polyps main factor for long-term risk of colorectal cancer in a screening population

Why so few Nobel Prizes for cancer researchers? An analysis of Nobel Prize nominations for German physicians with a focus on Ernst von Leyden and Karl Heinrich Bauer

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage