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

Clinical article

View More View Less
  • 1 Katsuta Hospital Mito GammaHouse, Hitachi-naka;
  • 2 Department of Neurosurgery, Faculty of Medicine, University of Tsukuba, Tsukuba;
  • 3 Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo;
  • 4 Clinical Research Center and
  • 6 Department of Neurosurgery, Chiba University Graduate School of Medicine, Chiba; and
  • 5 Department of Neurosurgery, Kyoto Prefectural University of Medicine Graduate School of Medical Sciences, Kyoto, Japan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00
Print or Print + Online

Object

Recently, an increasing number of patients with brain metastases, even patients over 80 years of age, have been treated with stereotactic radiosurgery (SRS). However, there is little information on SRS treatment results for patients with brain metastases 80 years of age and older. The authors undertook this study to reappraise whether SRS treatment results for patients 80 years of age or older differ from those of patients who are 65–79 years old.

Methods

This was an institutional review board–approved, retrospective cohort study. Among 2552 consecutive brain metastasis patients who underwent SRS during the 1998–2011 period, we studied 165 who were 80 years of age or older (Group A) and 1181 who were age 65–79 years old (Group B). Because of the remarkable disproportion in patient numbers between the 2 groups and considerable differences in pre-SRS clinical factors, the authors conducted a case-matched study using the propensity score matching method. Ultimately, 330 patients (165 from each group, A and B) were selected. For time-to-event outcomes, the Kaplan-Meier method was used to estimate overall survival and competing risk analysis was used to estimate other study end points, as appropriate.

Results

Although the case-matched study showed that post-SRS median survival time (MST, months) was shorter in Group A patients (5.3 months, 95% CI 3.9–7.0 months) than in Group B patients (6.9 months, 95% CI 5.0–8.1 months), this difference was not statistically significant (HR 1.147, 95% CI 0.921–1.429, p = 0.22). Incidences of neurological death and deterioration were slightly lower in Group A than in Group B patients (6.3% vs 11.8% and 8.5% vs 13.9%), but these differences did not reach statistical significance (p = 0.11 and p = 0.16). Furthermore, competing risk analyses showed that the 2 groups did not differ significantly in cumulative incidence of local recurrence (HR 0.830, 95% CI 0.268–2.573, p = 0.75), rates of repeat SRS (HR 0.738, 95% CI 0.438–1.242, p = 0.25), or incidence of SRS-related complications (HR 0.616, 95% CI 0.152–2.495, p = 0.49). Among the Group A patients, post-SRS MSTs were 11.6 months (95% CI 7.8–19.6 months), 7.9 months (95% CI 5.2–10.9 months), and 2.8 months (95% CI; 2.4–4.6 months) in patients whose disease status was modified–recursive partitioning analysis (RPA) Class(es) I+IIa, IIb, and IIc+III, respectively (p < 0.001).

Conclusions

Our results suggest that patients 80 years of age or older are not unfavorable candidates for SRS as compared with those 65–79 years old. Particularly, even among patients 80 years and older, those with modified-RPA Class I+IIa or IIb disease are considered to be favorable candidates for more aggressive treatment of brain metastases.

Abbreviations used in this paper:CI = confidence interval; HR = hazard ratio; KPS = Karnofsky Performance Status; MST = median survival time; PET = positron emission tomography; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group; SRS = stereotactic radiosurgery; WBRT = whole-brain radiotherapy.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $505.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $600.00

Contributor Notes

Address correspondence to: Masaaki Yamamoto, M.D., Katsuta Hospital Mito GammaHouse, 5125-2 Nakane, Hitachi-naka, Ibaraki 312-0011, Japan. email: bcd06275@nifty.com.

Please include this information when citing this paper: published online July 25, 2014; DOI: 10.3171/2014.6.JNS132790.

  • 1

    Aoyama H, , Shirato H, , Tago M, , Nakagawa K, , Toyoda T, & Hatano K, : Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 295:24832491, 2006

    • Search Google Scholar
    • Export Citation
  • 2

    Bakoyannis G, & Touloumi G: Practical methods for competing risks data: a review. Stat Methods Med Res 21:257272, 2012

  • 3

    Fine JP, & Gray RJ: A proportional hazards model for the sub-distribution of a competing risk. J Am Stat Assoc 94:496509, 1999

  • 4

    Gaspar L, , Scott C, , Rotman M, , Asbell S, , Phillips T, & Wasserman T, : Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 37:745751, 1997

    • Search Google Scholar
    • Export Citation
  • 5

    Gooley TA, , Leisenring W, , Crowley J, & Storer BE: Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:695706, 1999

    • Search Google Scholar
    • Export Citation
  • 6

    Gray RJ: A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16:11411154, 1988

  • 7

    Hanssens P, , Karlsson B, , Yeo TT, , Chou N, & Beute G: Detection of brain micrometastases by high-resolution stereotactic magnetic resonance imaging and its impact on the timing of and risk for distant recurrences. Clinical article. J Neurosurg 115:499504, 2011

    • Search Google Scholar
    • Export Citation
  • 8

    Hayashi M, , Yamamoto M, , Nishimura C, & Satoh H: Do recent advances in MR technologies contribute to better gamma knife radiosurgery treatment results for brain metastases?. Neuroradiol J 20:481490, 2007

    • Search Google Scholar
    • Export Citation
  • 9

    Hotta T, , Kohno H, , Taniguchi E, , Magaki T, , Hidaka T, & Nishimoto T: Treatment option for elderly patients with metastatic brain tumors. Jpn J Cancer Clin 45:11431148, 1999

    • Search Google Scholar
    • Export Citation
  • 10

    Kano H, , Kondziolka D, , Lobato-Polo J, , Zorro O, , Flickinger JC, & Lunsford LD: T1/T2 matching to differentiate tumor growth from radiation effects after stereotactic radiosurgery. Neurosurgery 66:486492, 2010

    • Search Google Scholar
    • Export Citation
  • 11

    Kaplan EL, & Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457481, 1958

  • 12

    Karnofsky DA, & Buechenal JH, The clinical evaluation of chemotherapeutic agents in cancer. MacLeod CM: Evaluation of Chemotherapeutic Agents New York, Columbia University Press, 1949. 191205

    • Search Google Scholar
    • Export Citation
  • 13

    Kim SH, , Weil RJ, , Chao ST, , Toms SA, , Angelov L, & Vogelbaum MA, : Stereotactic radiosurgical treatment of brain metastases in older patients. Cancer 113:834840, 2008

    • Search Google Scholar
    • Export Citation
  • 14

    Lorenzoni J, , Devriendt D, , Massager N, , David P, , Ruíz S, & Vanderlinden B, : Radiosurgery for treatment of brain metastases: estimation of patient eligibility using three stratification systems. Int J Radiat Oncol Biol Phys 60:218224, 2004

    • Search Google Scholar
    • Export Citation
  • 15

    Lutterbach J, , Bartelt S, , Momm F, , Becker G, , Frommhold H, & Ostertag C: 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 103:12341244, 2005

    • Search Google Scholar
    • Export Citation
  • 16

    Matsuo M, , Miwa K, , Shinoda J, , Kako N, , Nishibori H, & Sakurai K, : Target definition by C11-methionine-PET for the radiotherapy of brain metastases. Int J Radiat Oncol Biol Phys 74:714722, 2009

    • Search Google Scholar
    • Export Citation
  • 17

    Minniti G, , Esposito V, , Clarke E, , Scaringi C, , Bozzao A, & Lanzetta G, : Stereotactic radiosurgery in elderly patients with brain metastases. J Neurooncol 111:319325, 2013

    • Search Google Scholar
    • Export Citation
  • 18

    Nariai T, , Tanaka Y, , Wakimoto H, , Aoyagi M, , Tamaki M, & Ishiwata K, : Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma. J Neurosurg 103:498507, 2005

    • Search Google Scholar
    • Export Citation
  • 19

    Noel G, , Bollet MA, , Noel S, , Feuvret L, , Boisserie G, & Tep B, : Linac stereotactic radiosurgery: an effective and safe treatment for elderly patients with brain metastases. Int J Radiat Oncol Biol Phys 63:15551561, 2005

    • Search Google Scholar
    • Export Citation
  • 20

    Parsons LS: Reducing bias in a propensity score matched-pair sample using greedy matching techniques. SAS (http://www2.sas.com/proceedings/sugi26/p214-26.pdf) [Accessed June 18, 2014]

    • Search Google Scholar
    • Export Citation
  • 21

    Rades D, , Pluemer A, , Veninga T, & Schild SE: Comparison of different treatment approaches for one to two brain metastases in elderly patients. Strahlenther Onkol 184:565571, 2008

    • Search Google Scholar
    • Export Citation
  • 22

    Radiation Therapy Oncology Group: Cooperative Group Common Toxicity Criteria (http://www.rtog.org/ResearchAssociates/AdverseEventReporting/CooperativeGroupCommonToxicityCriteria.aspx) [Accessed June 18, 2014]

    • Search Google Scholar
    • Export Citation
  • 23

    Satagopan JM, , Ben-Porat L, , Berwick M, , Robson M, , Kutler D, & Auerbach AD: A note on competing risks in survival data analysis. Br J Cancer 91:12291235, 2004

    • Search Google Scholar
    • Export Citation
  • 24

    Sperduto PW, , Berkey B, , Gaspar LE, , Mehta M, & Curran W: A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys 70:510514, 2008

    • Search Google Scholar
    • Export Citation
  • 25

    Sperduto PW, , Chao ST, , Sneed PK, , Luo X, , Suh J, & Roberge D, : Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: a multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys 77:655661, 2010

    • Search Google Scholar
    • Export Citation
  • 26

    Tsao M, , Xu W, & Sahgal A: A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy, or both for patients presenting with a limited number of brain metastases. Cancer 118:24862493, 2012

    • Search Google Scholar
    • Export Citation
  • 27

    Tsuyuguchi N, , Sunada I, , Iwai Y, , Yamanaka K, , Tanaka K, & Takami T, : Methionine positron emission tomography of recurrent metastatic brain tumor and radiation necrosis after stereotactic radiosurgery: is a differential diagnosis possible?. J Neurosurg 98:10561064, 2003

    • Search Google Scholar
    • Export Citation
  • 28

    Weltman E, , Salvajoli JV, , Brandt RA, , de Morais Hanriot R, , Prisco FE, & Cruz JC, : Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 46:11551161, 2000

    • Search Google Scholar
    • Export Citation
  • 29

    Yamamoto M, , Ide M, , Nishio Si, & Urakawa Y: Gamma Knife radiosurgery for numerous brain metastases: is this a safe treatment?. Int J Radiat Oncol Biol Phys 53:12791283, 2002

    • Search Google Scholar
    • Export Citation
  • 30

    Yamamoto M, , Kawabe T, , Higuchi Y, , Sato Y, , Barfod BE, & Kasuya H, : Validity of three recently proposed prognostic grading indexes for breast cancer patients with radiosurgically treated brain metastases. Int J Radiat Oncol Biol Phys 84:11101115, 2012

    • Search Google Scholar
    • Export Citation
  • 31

    Yamamoto M, , Kawabe T, , Higuchi Y, , Sato Y, , Nariai T, & Barfod BE, : Delayed complications in patients surviving at least 3 years after stereotactic radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 85:5360, 2013

    • Search Google Scholar
    • Export Citation
  • 32

    Yamamoto M, , Kawabe T, , Sato Y, , Higuchi Y, , Nariai T, & Barfod BE, : A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1–4 vs ≥ 5 tumors. Clinical article. J Neurosurg 118:12581268, 2013

    • Search Google Scholar
    • Export Citation
  • 33

    Yamamoto M, , Sato Y, , Serizawa T, , Kawabe T, , Higuchi Y, & Nagano O, : Subclassification of recursive partitioning analysis Class II patients with brain metastases treated radiosurgically. Int J Radiat Oncol Biol Phys 83:13991405, 2012

    • Search Google Scholar
    • Export Citation
  • 34

    Yamamoto M, , Serizawa T, , Sato Y, , Kawabe T, , Higuchi Y, & Nagano O, : Validity of two recently-proposed prognostic grading indices for lung, gastro-intestinal, breast and renal cell cancer patients with radiosurgically-treated brain metastases. J Neurooncol 111:327335, 2013

    • Search Google Scholar
    • Export Citation
  • 35

    Yancik R, & Ries LAG: Cancer in older persons: an international issue in an aging world. Semin Oncol 31:128136, 2004

Metrics