Elsevier

The Lancet Neurology

Volume 4, Issue 5, May 2005, Pages 289-298
The Lancet Neurology

Review
Therapeutic management of brain metastasis

https://doi.org/10.1016/S1474-4422(05)70072-7Get rights and content

Summary

This review focuses on the management of brain metastases. The four main modes of therapy are discussed: whole brain radiation therapy (WBRT), surgery, radiosurgery, and chemotherapy. Young patients with limited extracranial disease may benefit from surgical resection of a single brain metastasis, and from radiosurgery (or stereotactic radiotherapy) if two to four brain metastases are present. Whether WBRT after surgery or radiosurgery is beneficial is uncertain. Therefore, two approaches can be justified in patients with a good prognosis: WBRT after surgery or radiosurgery, or alternatively, observation with MRI follow-up after surgery or radiosurgery. A hyperfractionated radiation scheme is then to be preferred to limit late toxicity of WBRT. Patients with extensive extracranial tumour activity or impaired quality of life may benefit from radiosurgery (one to four brain metastases), or from shorter WBRT schedules. We propose a decision tree on the various ways to treat brain metastasis.

Section snippets

Prognostic factors

An adequate estimation of independent prognostic factors is required to enable the clinician to decide between invasive treatment and to avoid unnecessary treatment. Demographic and clinical variables that might be of prognostic significance for brain metastasis have been analysed extensively.5, 6 These variables include age, performance status (often determined by use of the Karnofsky performance status [KPS] score), type of primary tumour (eg, lung or breast), number of brain metastases

Treatment results

The effect of WBRT as symptomatic treatment for brain metastases has been investigated extensively. Fractionation schemes have included 30 Gy in 2 weeks, 50 Gy in 4 weeks, and accelerated hyperfractionated schemes.12, 13 None was superior over another. WBRT is often considered as the principal treatment for patients with multiple brain metastases to reverse neurological deficit and control progression in the brain. A commonly accepted fractionation scheme is 30 Gy in ten fractions over 2 weeks.

Prophylactic cranial irradiation

The method of prophylactic cranial irradiation (ie, irradiation of supposedly subclinical brain metastases) has now been under evaluation for over 30 years. Most studies have focused on small cell lung cancer (SCLC). The cumulative risk on intracranial relapse in SCLC treated with systemic chemotherapy approaches 50–80% by 2 years.21 Data from two meta-analyses show a increased overall survival advantage with a relative risk of death of between 0·82 and 0·84, and a reduction in rate of brain

Surgery

Improved imaging and localisation techniques have made surgery an accepted therapy, particularly in patients with good prognostic factors, and should be considered for patients with a single brain metastasis in an accessible location. With significant mass effects or obstructive hydrocephalus, surgery usually results in immediate relief of symptoms. In general, patients with limited or absent systemic disease are selected for surgery. However, patients with worse prognostic factors may also

Radiosurgery

Reports on radiosurgery (or stereotactic radiotherapy), which include the delivery of high doses of radiation, use of multiple cobalt sources (gamma knife), or a linear accelerator (linac), dominate the recent literature on brain metastases. The attention to radiosurgery is not without reason, since brain metastases are ideal targets for radiosurgery. The tumours are often spherical, with a diameter of less than 3 cm, and have radiographically distinct margins. Brain metastases are therefore

Chemotherapy

There is a substantial difference between the importance of chemotherapy in general oncology and in neuro-oncology. The brain has long been thought to be a sanctuary for metastases and as a less accessible site for chemotherapeutic drugs. This relative inaccessibility may be due to the inability of certain drugs to cross the BBB, although others argue that the BBB has already been disrupted if the brain metastases are detectable.53 The importance of the BBB for chemotherapeutic drugs has been

Management of brain metastasis

Our proposed decision tree for a therapeutic strategy for the main categories of patients with brain metastasis is shown in the figure. The chart starts at the diagnostic process, dividing patients according to their RPA class and subdividing class 1 and 2 in single or multiple brain metastases. Class 2 is further split into patients with or without active extracranial disease. Class 1 and 2 patients without active extracranial disease may be treated with surgery (single metastasis) or

Conclusion

Treatment options for brain metastasis have increased substantially during the past decades. Today, we know from randomised clinical studies that surgery or radiosurgery of a single metastasis in addition to WBRT in patients with a good prognosis results in improved survival.27, 31, 34 Whether additional WBRT after surgery or radiosurgery is beneficial in terms of quality of life or survival is currently under study. In the meantime, two approaches can be justified in good prognosis patients:

Search strategy and selection criteria

A PubMed search was performed for the words “brain” and “metastasis” or “metastases” using boolean search algorithms with a time limit of 3·5 years, which was last updated in February, 2005. Approximately 1400 references were retrieved and scanned for relevance. PubMed searches were done for each subject (eg, “radiosurgery” AND “brain” AND [“metastasis” OR “metastases”]) without a time limit. Cited publications were also analysed for other relevant references. To limit the total number of

References (77)

  • EF Vines et al.

    Prophylactic cranial irradiation in small cell lung cancer

    Semin Oncol

    (2003)
  • DW Andrews 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)
  • BP O'Neill et al.

    A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases

    Int J Radiat Oncol Biol Phys

    (2003)
  • RM Auchter et al.

    A multiinstitutional outcome and prognostic factor analysis of radiosurgery for resectable single brain metastasis

    Int J Radiat Oncol Biol Phys

    (1996)
  • JC Flickinger et al.

    A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis

    Int J Radiat Oncol Biol Phys

    (1994)
  • SN Sanghavi et al.

    Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method

    Int J Radiat Oncol Biol Phys

    (2001)
  • MA Chidel et al.

    Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases

    Int J Radiat Oncol Biol Phys

    (2000)
  • MK Shehata et al.

    Stereotatic radiosurgery of 468 brain metastases < or =2 cm: implications for SRS dose and whole brain radiation therapy

    Int J Radiat Oncol Biol Phys

    (2004)
  • WF Regine et al.

    Risk of symptomatic brain tumor recurrence and neurologic deficit after radiosurgery alone in patients with newly diagnosed brain metastases: results and implications

    Int J Radiat Oncol Biol Phys

    (2002)
  • PK Sneed et al.

    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

    (2002)
  • MJ van den Bent

    The role of chemotherapy in brain metastases

    Eur J Cancer

    (2003)
  • E Verger et al.

    Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial

    Int J Radiat Oncol Biol Phys

    (2005)
  • R Dziadziuszko et al.

    Temozolomide in patients with advanced non-small cell lung cancer with and without brain metastases. a phase II study of the EORTC Lung Cancer Group (08965)

    Eur J Cancer

    (2003)
  • CM Lima et al.

    Treatment of relapsed small-cell lung cancer: a focus on the evolving role of topotecan

    Lung Cancer

    (2003)
  • K Hotta et al.

    Effect of gefitinib (‘Iressa’, ZD1839) on brain metastases in patients with advanced non-small-cell lung cancer

    Lung Cancer

    (2004)
  • F Grossi et al.

    The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer

    Crit Rev Oncol Hematol

    (2001)
  • X Quantin et al.

    Concomitant brain radiotherapy and vinorelbine-ifosfamide-cisplatin chemotherapy in brain metastases of non-small cell lung cancer

    Lung Cancer

    (1999)
  • A Korfel et al.

    Response to topotecan of symptomatic brain metastases of small-cell lung cancer also after whole-brain irradiation. a multicentre phase II study

    Eur J Cancer

    (2002)
  • LE Abrey et al.

    Temozolomide for treating brain metastases

    Semin Oncol

    (2001)
  • C Christodoulou et al.

    Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases

    Ann Oncol

    (2001)
  • EE Lower et al.

    Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival

    Clin Breast Cancer

    (2003)
  • JY Delattre et al.

    Distribution of brain metastases

    Arch Neurol

    (1988)
  • MP Mehta et al.

    Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases

    J Clin Oncol

    (2003)
  • JC Bendell et al.

    Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma

    Cancer

    (2003)
  • J Lutterbach et al.

    Long-term survival in patients with brain metastases

    J Cancer Res Clin Oncol

    (2002)
  • WF Regine et al.

    Recursive partitioning analysis classifications I and II: applicability evaluated in a randomized trial for resected single brain metastases

    Am J Clin Oncol

    (2004)
  • LT Komarnicky et al.

    A randomized phase III protocol for the evaluation of misonidazole combined with radiation in the treatment of patients with brain metastases (RTOG-7916)

    Int J Radiat Oncol Biol Phys

    (1991)
  • E Shaw et al.

    RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group recursive partitioning analysis brain metastases database

    J Clin Oncol

    (2003)

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