Question

Which patients are eligible for total cranial irradiation?

Recommendation

 WBRT as sole treatment is recommended for patients with >3 brain metastases and RPA class 1. With RPA class 2, patient- and tumour-specific factors (especially tumour type and monitoring of extracranial disease) are the decisive factors whether or not to treat with WBRT. In general, conservative management is recommended for patients in RPA class 3 (see Related Appendix 1 for RPA classification).

If WBRT is the treatment of choice, fractionation schedules of 5x4 or 10x3 Gy are recommended.

Conclusions

No conclusion can be drawn about the influence of WBRT on the survival of patients with brain metastases.
Tsao, 2006 (5);Horton, 1971 (1)

The median survival of patients with multiple brain metastases treated with WBRT varies in most studies from 2 to 6 months.
Lagerwaard, 1999 (2);Pease, 2005 (3);Tsao, 2003 (4);Tsao, 2006 (5);Wong, 2008 (6)

No conclusion can be drawn about the influence of WBRT on the quality of life of patients with brain metastases.
Wong, 2008 (6)

There is a correlation between (changes in) the quality of life of patients with brain metastases and survival time.
Corn, 2008 (15);Pan, 2008 (21);Scott, 2007 (23);Sehlen, 2003 (24);Wong, 2009 (25)

There are indications of a decline in cognitive functioning in patients with brain metastases after WBRT. This decline is partly related to progression of the metastases, but should also in part be considered a side effect of WBRT.
Aoyama, 2007 (32);Corn, 2008 (15);DeAngelis, 1989 (30);Li, 2007 (35);Regine, 2002 (31);Chang, 2009 (13)

Variation in dosis and fractionation schedule for WBRT as reported in the literature does not appear to make a difference in survival or in the neurological functioning of patients with brain metastases.
Gaspar, 2010 (34);Tsao, 2006 (5)

Literature summary

Whole Brain Radiotherapy (WBRT) refers to irradiation of the brain tissue as a whole. This is considered the standard treatment of brain metastases that is commonly applied. A limited number of selected patients are eligible for operative removal of a (often) solitary metastasis. Stereotactic radiotherapy is a form of radiotherapy in which a brain metastasis is irradiated with high precision. This may be performed with a single high dose, in which case it is referred to as Radiosurgery (Stereotactic Radiosurgery; SRS). Until recently, SRS was only possible in a limited number of centres. Nowadays, most radiotherapy centres have the ability to perform SRS. Stereotactic precision irradiation with multiple fractions may also be applied, and this is referred to as Stereotactic Radiotherapy (SRT or FSRT (fractionated SRT)). SRT is generally applied with larger metastases, or instead of SRS in some centres. Current evidence for stereotactic irradiation is entirely based on studies on SRS, and this guideline therefore only discusses SRS as treatment modality. There are currently no results available of prospective studies comparing SRS and SRT in the treatment of brain metastases, but SRT series show outcomes that are comparable to results achieved with SRS.

Neurosurgical resection, WBRT and SRS can be applied as single modalities or in different combinations. The treatment of brain metastases from germ cell tumours and SCLC is discussed separately given the more prominent place of systemic therapy here.

WBRT and survival
Although considered standard treatment, the value of WBRT compared to best supportive care has not been well researched. Only one randomised study (Horton, 1971 (1)) has compared WBRT+best supportive care (including corticosteroids) with best supportive care alone. This concerns a study with only 48 patients, which was conducted before the advent of CT. The median survival was 10 weeks in the best supportive care arm and 14 weeks in the WBRT+corticosteroid arm. The duration of the remission of complaints was longer in the WBRT arm. No statistical analyses were performed so that evidence regarding the influence of WBRT compared to best supportive care on survival is still lacking.

The median survival reported by most studies with patients treated with WBRT varies from 2-6 months (Lagerwaard, 1999 (2);Pease, 2005 (3);Tsao, 2003 (4);Tsao, 2006 (5);Wong, 2008 (6)). It should be noted that, due to patient selection, survival rates obtained within a trial context are generally higher than those of patients who do not participate in a study, and the abovementioned numbers assumedly overestimate the actual survival for patients with brain metastases.

WBRT and quality of life
Symptomatic response was reported in 64-85% of patients with brain metastases in older studies with WBRT (Borgelt, 1980 (7);Cairncross, 1980 (8);Katz, 1981 (9);Sneed, 1996 (10)). However, symptom response and quality of life were not the primary endpoints in these studies. Furthermore, response was generally not clearly defined, and no standardised and validated measuring instruments were applied to assess the response. Lastly, many studies did not distinguish effects due to treatment with corticosteroids from those of radiotherapy.

A number of studies, some of which were recently published, report on the effect of radiotherapy on patients' quality of life as primary endpoint in case of multiple brain metastases. This concerned either their general quality of life or specific aspects such as (neurological) symptoms, neurological or neurocognitive functioning and/or performance status. (Addeo, 2007 (11);Bezjak, 2002 (12);Chang, 2009 (13);Chow, 2005 (14);Corn 2008 (15);Doyle, 2007 (16);Gerrard, 2003 (17);Hird 2010 (18);Kondziolka, 2005 (19);Murray, 2000 (20);Pan, 2008 (21);Pease, 2005 (3);Regine, 2004 (22);Scott, 2007 (23);Sehlen, 2003 (24);Wong, 2008 (6);Wong, 2009 (25);Yaneva, 2006 (26)). Various measuring instruments have been used in these studies (Functional Assessment of Cancer Therapy-General (FACT-G) and Brain subscale instrument (FACT-BR), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), sometimes in combination with the EORTC Brain Module (BM), Edmonton Symptom Assessment Scale (ESAS), Spitzer Quality of Life Index (SQLI), Profile of Moods States-Short Form (POMS), Karnofsky Performance Scale (KPS), ECOG/WHO performance status and other quality of life instruments specifically developed for a particular study).

The heterogeneity of the studies with respect to inclusion criteria (patient selection, differences in treatment regimens, different endpoints and measuring instruments as well as the sometimes high dropout rate) makes it difficult to draw conclusions on the effect of WBRT with respect to quality of life. Again, many studies did not differentiate between the effect due to treatment with corticosteroids and those brought about by radiotherapy. The available results suggest that WBRT only modestly impact neurological symptoms and quality of life.

The RPA classification (Gaspar, 1997 (27);Gaspar, 2000 (28);Nieder, 2000 (29), (see Related Appendix 1) is correlated with quality of life both before and after treatment (Wong, 2009). Changes in quality of life are correlated to survival (Corn, 2008 (15);Pan, 2008 (21);Scott, 2007 (23);Sehlen 2003 (24);Wong, 2009 (25)).

Side effects of WBRT
Aside from the (usually temporary) short term side effects such as alopecia, nausea, headache and fatigue (Tsao, 2006 (5)), it is mainly the potential late effects on patients' cognitive functioning that make treatment with WBRT subject of debate. The frequently cited publication by DeAngelis (DeAngelis 1989 (30)), which described 12 patients with progressive dementia after WBRT, is of limited significance not only because the study is outdated, but also because the populations studied were not clearly described and given the high fraction radiotherapy dose administered.

Effects on neurocognition in patients with brain metastases after WBRT, measured with the global MMSE test (see Related Appendix 1), were described in the RTOG 91-04 study. The MMSE score dropped as a result of progression of the metastases (Regine, 2002 (31)). In the randomised prospective trial in which SRS+WBRT was compared to SRS, control of tumour activity in the brain was also found to be the most important factor in stabilising the MMSE score. However, after a follow-up of 3 years, the patients in the SRS+WBRT arm were more likely to have a >3 point decrease in MMSE (stabilisation ≤3 point MMSE 14.7% SRS+WBRT versus 51.9% SRS only), possibly due to the long-term effects of WBRT (Aoyama, 2007 (32)).

Specific cognitive domains were studied using more extensive neurocognitive tests in a few studies. In a prospective study (Li, 2007 (33)), neurocognitive function after WBRT remained stable after radiological regression of the metastases and decreased with tumour progression.

There is only one prospective randomised study on cognitive functioning after WBRT with a control group without WBRT. This study randomised patients with 1-3 brain metastases between SRS and SRS+WBRT. The trial was stopped with 58 patients and a 96% probability that SRS+WBRT patients had a greater cognitive decline in the memory domain despite better intracranial tumour monitoring (Chang, 2009 (13)).

WBRT with other dose/fractionation schedules
In patients with good prognostic factors, prospective studies have been performed to improve treatment results with WBRT. A Cochrane review summarised nine prospective randomised studies which evaluated different dose/fractionation schedules. No schedule was found to be superior (Tsao, 2006 (5)), which was confirmed again recently in an extensive systematic review (Gaspar, 2010 (34)). The most commonly used fractionating schedules are 5x4 Gy or 10x3 Gy.

References

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  2. 2 - Lagerwaard FJ, Levendag PC, Nowak PJ, Eijkenboom WM, Hanssens PE, Schmitz PI. Identification of prognostic factors in patients with brain metastases: a review of 1292 patients. Int J Radiat Oncol Biol Phys 1999 Mar 1;43(4):795-803.
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  6. 6 - Wong J, Hird A, Kirou-Mauro A, Napolskikh J, Chow E. Quality of life in brain metastases radiation trials: a literature review. Curr Oncol 2008 Oct;15(5):25-45.
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  8. 8 - Cairncross JG, Kim JH, Posner JB. Radiation therapy for brain metastases. Ann Neurol 1980 Jun;7(6):529-41.
  9. 9 - Katz HR. The relative effectiveness of radiation therapy, corticosteroids, and surgery in the management of melanoma metastatic to the central nervous system. Int J Radiat Oncol Biol Phys 1981 Jul;7(7):897-906.
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  12. 12 - Bezjak A, Adam J, Barton R, Panzarella T, Laperriere N, Wong CS, et al. Symptom response after palliative radiotherapy for patients with brain metastases. Eur J Cancer 2002 Mar;38(4):487-96.
  13. 13 - Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 2009 Nov;10(11):1037-44.
  14. 14 - Chow E, Davis L, Holden L, Tsao M, Danjoux C. Prospective assessment of patient-rated symptoms following whole brain radiotherapy for brain metastases. J Pain Symptom Manage 2005 Jul;30(1):18-23.
  15. 15 - Corn BW, Moughan J, Knisely JP, Fox SW, Chakravarti A, Yung WK, et al. Prospective evaluation of quality of life and neurocognitive effects in patients with multiple brain metastases receiving whole-brain radiotherapy with or without thalidomide on Radiation Therapy Oncology Group (RTOG) trial 0118. Int J Radiat Oncol Biol Phys 2008 May 1;71(1):71-8.
  16. 16 - Doyle M, Bradley NM, Li K, Sinclair E, Lam K, Chan G, et al. Quality of life in patients with brain metastases treated with a palliative course of whole-brain radiotherapy. J Palliat Med 2007 Apr;10(2):367-74.
  17. 17 - Gerrard GE, Prestwich RJ, Edwards A, Russon LJ, Richards F, Johnston CF, et al. Investigating the palliative efficacy of whole-brain radiotherapy for patients with multiple-brain metastases and poor prognostic features. Clin Oncol (R Coll Radiol ) 2003 Oct;15(7):422-8.
  18. 18 - Hird A, Wong J, Zhang L, Tsao M, Barnes E, Danjoux C, et al. Exploration of symptoms clusters within cancer patients with brain metastases using the Spitzer Quality of Life Index. Support Care Cancer 2010 Mar;18(3):335-42.
  19. 19 - Kondziolka D, Niranjan A, Flickinger JC, Lunsford LD. Radiosurgery with or without whole-brain radiotherapy for brain metastases: the patients' perspective regarding complications. Am J Clin Oncol 2005 Apr;28(2):173-9.
  20. 20 - Murray KJ, Scott C, Zachariah B, Michalski JM, Demas W, Vora NL, et al. Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the Radiation Therapy Oncology Group protocol 91-04. Int J Radiat Oncol Biol Phys 2000 Aug 1;48(1):59-64.
  21. 21 - Pan HC, Sun MH, Chen CC, Chen CJ, Lee CH, Sheehan J. Neuroimaging and quality-of-life outcomes in patients with brain metastasis and peritumoral edema who undergo Gamma Knife surgery. J Neurosurg 2008 Dec;109 Suppl:90-8.
  22. 22 - Regine WF, Schmitt FA, Scott CB, Dearth C, Patchell RA, Nichols RC, Jr., et al. Feasibility of neurocognitive outcome evaluations in patients with brain metastases in a multi-institutional cooperative group setting: results of Radiation Therapy Oncology Group trial BR-0018. Int J Radiat Oncol Biol Phys 2004 Apr 1;58(5):1346-52.
  23. 23 - Scott C, Suh J, Stea B, Nabid A, Hackman J. Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases. Am J Clin Oncol 2007 Dec;30(6):580-7.
  24. 24 - Sehlen S, Lenk M, Hollenhorst H, Schymura B, Aydemir U, Herschbach P, et al. Quality of life (QoL) as predictive mediator variable for survival in patients with intracerebral neoplasma during radiotherapy. Onkologie 2003 Feb;26(1):38-43.
  25. 25 - Wong J, Hird A, Zhang L, Tsao M, Sinclair E, Barnes E, et al. Symptoms and quality of life in cancer patients with brain metastases following palliative radiotherapy. Int J Radiat Oncol Biol Phys 2009 Nov 15;75(4):1125-31.
  26. 26 - Yaneva MP, Semerdjieva MA. Assessment of the effect of palliative radiotherapy for cancer patients with intracranial metastases using EORTC-QOL-C30 questionnaire. Folia Med (Plovdiv ) 2006;48(2):23-9.
  27. 27 - Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys 1997 Mar 1;37(4):745-51.
  28. 28 - Gaspar LE, Scott C, Murray K, Curran W. Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys 2000 Jul 1;47(4):1001-6.
  29. 29 - Nieder C, Nestle U, Motaref B, Walter K, Niewald M, Schnabel K. Prognostic factors in brain metastases: should patients be selected for aggressive treatment according to recursive partitioning analysis (RPA) classes? Int J Radiat Oncol Biol Phys 2000 Jan 15;46(2):297-302.
  30. 30 - DeAngelis LM, Delattre JY, Posner JB. Radiation-induced dementia in patients cured of brain metastases. Neurology 1989 Jun;39(6):789-96.
  31. 31 - Regine WF, Huhn JL, Patchell RA, St Clair WH, Strottmann J, Meigooni A, 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 Feb 1;52(2):333-8.
  32. 32 - Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, et al. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys 2007 Aug 1;68(5):1388-95.
  33. 33 - Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol 2007 Apr 1;25(10):1260-6.
  34. 34 - Gaspar LE, Mehta MP, Patchell RA, Burri SH, Robinson PD, Morris RE, et al. The role of whole brain radiation therapy in the management of newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010 Jan;96(1):17-32.
  35. 35 - Lin NU, Winer EP. Brain metastases: the HER2 paradigm. Clin Cancer Res 2007 Mar 15;13(6):1648-55.

Considerations

No univocal conclusions can be drawn from the literature. While WBRT is considered the standard treatment for multiple brain metastases, the actual value of WBRT compared to supportive treatment with steroids has not been well assessed.

In daily practice, patient and tumour-specific factors appear to inform the decision whether or not to provide treatment with WBRT. The RPA classification may be used for this purpose (see Whether or not treatment should be performed).

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

 

Members of the guideline panel

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.