Question

What is the best way to follow-up for recurrence of brain metastases?

Recommendation

Standard 3-monthly screening using MRI of the brain for recurrence of brain metastases is recommended in patients who are primarily treated with SRS or neurosurgical resection, without WBRT, if detection of a possible recurrence of brain metastases would lead to specific treatment.

In patients primarily treated with systemic chemotherapy, it is recommended that the systemic effect as well as the effect of chemotherapy on the brain metastases is evaluated, for example after 3 courses.

In most cases, MRI of the brain will only be performed with symptomatic brain metastases if treatment options are available. The neurological follow-up should be determined on an individual basis.

The issue of which healthcare provider is responsible the follow-up needs to be agreed upon per centre (and per situation). In most cases after SRS, the radiotherapist will coordinate the follow-up, in consultation with the primary physician (usually the pulmonologist or medical oncologist).

Conclusions

In prospective studies in which SRS or neurosurgical resection is not followed by WBRT, 3-monthly MRI monitoring is continued in order to detect and treat new brain metastases.
Andrews, 2004 (2);Kocher, 2011 (3)

Literature summary

The frequency of neurological and radiological follow-up of patients with brain metastases depends on various factors. The frequency of the follow-up is mainly determined by the clinical status of the patient, the presence of neurological deficits and/or epileptic seizures and the availability of individual treatment options in case of progression or recurrence of brain metastases (Ammirati, 2010 (1)).

Three-monthly screening with MRI for new (asymptomatic) brain metastases is often performed as a standard in patients treated with SRS (Andrews, 2004 (2)). New brain metastases are then treated again with SRS or WBRT. This treatment plan was also followed in the recent EORTC trial 22952: there was no difference in survival between patients treated with adjuvant WBRT after SRS or resection and a salvage treatment with recurring brain metastases (Kocher, 2011 (3)). If the decision is made not to administer adjuvant WBRT after local treatment of brain metastasis, 3-monthly screening is indicated, so that a recurrence may still be treated with WBRT or SRS (Kocher, 2011 (3)). Also see related module SRS / neurosurgical resection with or without WBRT. Research regarding the screening interval of 3 months has not been performed.

Patients with brain metastases, who are primarily treated with chemotherapy because of progressive systemic disease, are usually evaluated systemically after 3 courses of chemotherapy. One may then also evaluate the brain metastases and, if chemotherapy has no effect on the brain metastases, to treat the patient with WBRT or SRS. This also depends, of course, on the clinical status of the patient and the systemic response.

After patients have been treated with WBRT, standard screening for a recurrence of brain metastases is not indicated. Screening may be worthwhile in patients in whom the primary tumour is under control or may be kept under control for a longer period of time, and as long as SRS is still a treatment option for recurrent brain metastasis. This only concerns a small group of patients, usually with a breast carcinoma. There is no literature available on the interval and frequency with which screening should be performed.

Even in case of new and/or recurring neurological complaints, MRI is only indicated if there treatment possibilities are available. If this is not the case, symptomatic treatment with dexamethasone is often the only meaningful option. Whether neurological follow-up is of added value in this situation needs to be determined on an individual basis.

Neurosurgical resection of a symptomatic recurrence of brain metastasis may be considered in selected patients after WBRT or SRS (Ammirati, 2010 (1)).

WBRT is rarely repeated, only with symptomatic brain metastases for which no other treatment option is available and after a time interval of at least 6 months (Ammirati, 2010 (1)). There are no prospective studies on the effects of repeated WBRT.

References

  1. 1 - Ammirati M, Cobbs CS, Linskey ME, Paleologos NA, Ryken TC, Burri SH, et al. The role of retreatment in the management of recurrent/progressive brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010 Jan;96(1):85-96.
  2. 2 - 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 May 22;363(9422):1665-72.
  3. 3 - Kocher M, Soffietti R, Abacioglu U, Villa S, Fauchon F, Baumert BG, et al. Adjuvant whole-brain radiotherapy versus observationa after radiosurgery or surgical resectionof one to three cerebral metastases: results of the EORTC 22952-26001 study.J Clin Oncol 2011 Jan 10;29(2):134-41.

Considerations

There are no studies on the time interval of screening for new asymptomatic brain metastases that are still eligible for treatment. Since studies generally follow 3-monthly screening and the outcomes of the studies are partly based on salvage treatment of new (asymptomatic) brain metastases, there is no evidence so far to adhere to a different time interval.

Authorization date and validity

Last review : 01-07-2011

Last authorization : 01-07-2011

The period of validity of the guideline (maximum of 5 years) is being monitored by IKNL. For various reasons, it may be necessary to revise the guideline earlier than intended. Sections of the guideline will be amended in the interim, when required.

Initiative and authorization

Initiative : Nederlandse Vereniging voor Neurologie

Authorized by:
  • Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose
  • Nederlandse Vereniging voor Medische Oncologie
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Neurologie
  • Nederlandse Vereniging voor Radiotherapie en Oncologie
  • Verpleegkundigen en Verzorgenden Nederland
  • Nederlandse Vereniging voor Psychosociale Oncologie
  • Nederlands Instituut van Psychologen

Scope and target group

Objective

The guideline covers the processes of diagnosis, treatment, information provision and guidance of adult patients with metastases in the brain originating from solid tumours, thereby focusing on topical clinical problems encountered in daily practice. The guideline's recommendations aim to aid practitioners in their decision-making support when facing these problems. The recommendations are based on the highest available grade of scientific evidence and on consensus within the guideline development group. The guideline provides information on how the recommendations have been reached from the evidence.

 

The guideline may be used to provide information to patients and offers points of reference for transmural agreements or local protocols to facilitate implementation.

Users

The guideline is intended for all professionals involved in the diagnostics, treatment and guidance of adult patients with brain metastases of solid tumours. These professionals include:

  • Primary specialists: neurologists, neurosurgeons, radiotherapists, medical oncologists, pulmonologists, (oncology) nurses, general practitioners, specialists (working) in palliative care
  • Supporting specialists: radiologists, pathologists
  • Healthcare providers specialised in psychosocial care: social workers, psychologists, psychiatrists and geriatric medicine specialists

 

Samenstelling werkgroep

2011:

Chair:

mw. dr. J.M.M. Gijtenbeek, neuroloog, Universitair Medisch Centrum St Radboud, Nijmegen

Other members:

dr. L.V. Beerepoot, medisch oncoloog, St. Elisabeth Ziekenhuis, Tilburg

dr. W. Boogerd, neuroloog, Nederlands Kanker Instituut / Antoni van Leeuwenhoekziekenhuis, Slotervaartziekenhuis, Amsterdam

mw. S. Bossmann, nurse practitioner, Universitair Medisch Centrum St Radboud Nijmegen

mw. dr. M. van Dijk, internist-oncoloog, Maastricht Universitair Medisch Centrum, Maastricht

mw. dr. A.C. Dingemans, longarts, Maastricht Universitair Medisch Centrum, Maastricht

mw. dr. C. van Es, radiotherapeut-oncoloog, Utrecht Universitair Medisch Centrum, Utrecht, niet actief betrokken (is betrokken geweest bij het initiëren van de werkgroep maar kon vanwege onvoorziene omstandigheden niet aan de totstandkoming van de richtlijn meewerken)

dr. A. de Graeff, medisch oncoloog, Utrecht Universitair Medisch Centrum, Utrecht

dr. P.E.J. Hanssens, radiotherapeut-oncoloog, Gamma Knife Centrum, Tilburg

dr. H.F.M. van der Heijden, longarts, Universitair Medisch Centrum St Radboud, Nijmegen

dr. M.A.A.M. Heesters, radiotherapeut-oncoloog Universitair Medisch Centrum Groningen, Groningen

dr. P.A. M. Hofman, neuroradioloog, Maastricht Universitair Medisch Centrum, Maastricht

dr. R.L.H. Jansen, medisch oncoloog, Maastricht Universitair Medisch Centrum, Maastricht, niet actief betrokken

drs. E. Kurt, neurochirurg, Medisch Centrum Alkmaar

dr. F. J. Lagerwaard, radiotherapeut-oncoloog, Vrije Universiteit Medisch Centrum, Amsterdam

mw. prof.dr. J.B. Prins, klinisch psycholoog, Universitair Medisch Centrum St Radboud, Nijmegen

drs. J.H.C. Voormolen, neurochirurg, Leids Universitair Medisch Centrum, Leiden

drs. V.K.Y. Ho, epidemioloog/procesbegeleider, Integraal Kankercentrum Nederland (IKNL), locatie Utrecht

mw. M.L. van de Kar, ambtelijk secretaris, Landelijke Werkgroep Neuro-Oncologie (LWNO), Bussum

Ondersteuning methodologie

mw. dr. M. Brink, epidemioloog, IKNL, locatie Utrecht

drs. J.M. van der Zwan, MSc, epidemiologisch onderzoeker, IKNL, locatie Enschede

 

Leden werkgroep voorgaande revisie (2004)

dr. R.H. Boerman, neuroloog, Rijnstate Ziekenhuis, Arnhem (voorzitter)

dr. W. Boogerd, neuroloog, Nederlands Kanker Instituut / Antoni van Leeuwenhoekziekenhuis, Slotervaartziekenhuis, Amsterdam

mw. dr. W.M.H. Eijkenboom, radiotherapeut-oncoloog, Daniel den Hoed Kliniek, Rotterdam

dr. P.E.J. Hanssens, radiotherapeut-oncoloog, Dr. Bernard Verbeeten Instituut, Tilburg

dr. R.L.H. Jansen, medisch oncoloog, Academisch Ziekenhuis Maastricht

dr. F. J. Lagerwaard, radiotherapeut-oncoloog, Vrije Universiteit Medisch Centrum, Amsterdam

prof.dr. C.J.A. Punt, inetrnist-oncoloog, Academisch Ziekenhuis Nijmegen

drs. J.H.C. Voormolen, neurochirurg, Leids Universitair Medisch Centrum, Leiden

prof.dr. J.T. Wilmink, neuroradioloog, Academisch Ziekenhuis Maastricht

dr. J.G. Wolbers, neurochirurg, Academisch Ziekenhuis Dijkzigt, Rotterdam

 

 

Declaration of interest

All guideline working group members were asked to fill in a conflict of interest declaration, in which they stated ties with the medical industry at the start and completing the guideline process. An overview of these conflict of interest declarations can be found below. The remaining guideline working group members have declared that at this moment or in the last three years they have not performed any activities on invitation or with subsidy/sponsoring by the medical industry.
   

Lid

Firma

Activiteit

Overig

Dr. L.V. Beerepoot

Pfizer

Merck

Cephalon

consultatie / advisering

congres

congres

congres

Dr. W. Boogerd

Mundipharma

 

congres

Dr. M. van Dijk

Schering Plough

 

congres

Dr. A.C. Dingemans

Roche

 

Lilly

Astra Zeneca

 

Glaxo

consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek

consultatie / advisering / wetenschappelijk onderzoek

congres

 

cursus

Dr. C.A. van Es

Elektra

 

congres

Dr. A. de Graeff

 

Nycomed

Wyeth

consultatie / advisering

consultatie / advisering

 

Dr. P.A.M. Hofman

Strijker NL B.V.

Medtronics Spinal

Bayer Health Care

Johnson & Johnson

 

congres

congres

congres

congres

Dr. H.F.M. van der Heijden

Astra Zeneca

Sanofi Aventis

Lilly

 

Roche

consultatie / advisering

consultatie / advisering

consultatie / advisering / wetenschappelijk onderzoek

 

congres

congres

congres

 

congres

Dr. R.L.H. Jansen

Pfizer

Roche

Sanofi Aventis

Diverse firma's

 

 

wetenschappelijk onderzoek

studies

congres

congres

congres

Dr. F.J. Lagerwaard

Roche Nederland

Roche NL-longadviesraad

Brain Lab

Varian Medical Systems

wetenschappelijk onderzoek

consultatie / advisering

 

 

 

congres

congres

   

Method of development

Evidence based

Implementation

Considerations concerning the implementation of the guideline as well as the feasibility of recommendations have been taken into account as much as possible in drafting the revised guideline.

 

The guideline is summarised and may be consulted in its entirety on http://www.oncoline.nl/. The guideline has been brought to the attention of members of the LWNO, hospitals in the Netherlands, oncology commissions, as well as the scientific and professional associations involved. To further stimulate awareness and implementation of the guideline, regional tumour working groups on neuro-oncology of IKNL were invited to discuss its recommendations.

 

Given the highly progressive and unfavourable course of the disease, the guideline development group decided not to develop care indicators to measure the level of guideline implementation.