Question

Is postoperative total cranial irradiation always necessary?

  • after resection?
  • after (stereotactic) biopsy?

Recommendation

The guideline development group is of the opinion that the treatment plan for patients with brain metastases should be discussed in a multidisciplinary oncology / neuro-oncology working group. The development group recommends involving a neurosurgeon in the case of a solitary brain metastasis.

Patients with a solitary brain metastasis and a KPS ≥70 are preferably treated with SRS unless neurosurgical resection is preferred (in case histological diagnosis is required, if decompression is considered worthwhile or if the metastasis is too large for SRS).

The development group recommends SRS in patients with a KPS ≥70 who have 2-3 brain metastases with a maximum diameter of 3.5-4cm, with treatable or limited extracranial tumour activity.

The development group does not recommend standard WBRT after complete resection or SRS. The development group does recommend monitoring patients every 3 months using MRI but only when results are anticipated to have therapeutic consequences.

Radiotherapy is recommended after incomplete resection. Radicality of the resection may be determined using MRI within 72 hours.

Conclusions

Level 3
There are indications that there is no difference in survival or local tumour control between neurosurgical resection+WBRT versus SRS in case of a solitary brain metastasis.
B: Muacevic, 2008 (29)

Level 1
It has been shown that for selected patients with a solitary brain metastasis and with a KPS ≥70, an improvement in survival can be achieved if WBRT is combined with resection or SRS.
A2: Patchell, 1990 (1);Noordijk, 1994 (39)
A2: Andrews, 2004 (19)

Level 3
There are indications that the combination WBRT and SRS improves the radiological response and the KPS, without a demonstrable influence on survival.
A2: Andrews, 2004 (19)

Level 1
It has been shown that in patients with a KPS ≥70, omitting WBRT after resection of a solitary brain metastasis or SRS of 1-3 brain metastases does not have a negative effect on the duration of patients' survival.
A2: Patchell, 1998 (5);Aoyama, 2006 (6);Kocher, 2011 (8)

Level 1
It has been shown that WBRT after resection of a solitary brain metastasis reduces the risk of intracranial recurrence.
A2: Patchell, 1998 (5);Kocher, 2011 (8)

Level 1
It has been shown that WBRT after SRS of 1-3 brain metastases reduces the risk of intracranial recurrence.
A2: Aoyama, 2006 (6);Kocher, 2011 (8)

Level 3
There are indications that WBRT increases the risk of cognitive decline in patients treated with SRS.
A2: Chang, 2009 (7)

Literature summary

A limited number of selected patients are eligible for operative removal of (a generally solitary) brain metastasis. Until recently, stereotactic single precision irradiation (Stereotactic Radiosurgery: SRS) or fractionated stereotactic irradiation (Stereotactic Radiotherapy; SRT or FSRT) was only possible in a limited number of centres. These days, most radiotherapy centres are able to perform SRS/SRT. SRT is generally applied with larger metastases, or instead of SRS in some centres. Current evidence for the value of stereotactic irradiation is entirely based on SRS, and this guideline therefore only considers the role of SRS as treatment modality. No results are available from prospective studies that compare SRS and SRT for brain metastases, but SRT series show outcomes that are comparable to results achieved with SRS.

Neurosurgical resection, WBRT and SRS may all be applied as either single treatment modality or in various combinations.

Neurosurgical resection

There is an indication for surgery in particular situations in patients with a solitary brain metastasis. Surgery is indicated for:

  • obtaining a histological diagnosis
  • a brain metastasis with a significant mass effect when the neurological situation is expected to worsen with application of radiotherapy while neurosurgery is expected to have a favourable effect
  • a solitary brain metastasis that is too large to expect an effect from SRS
  • progression of a symptomatic brain metastasis after earlier SRS

 

Neurosurgical resection followed by WBRT versus WBRT only
The effect of neurosurgical resection followed by WBRT compared to WBRT only was compared in three prospective randomised studies. In two studies, the patients treated with neurosurgical resection followed by WBRT had a significantly longer absolute survival and a longer survival with good performance (Patchell, 1990 (1);Vecht, 1993 (2)). In another study, there was no difference in survival compared to the patients in the WBRT arm; however, the latter study also included patients with performance <70 and those with extensive extracranial disease activity (Mintz, 1996 (3)). A meta-analysis of these three trials (Hart, 2005 (4)) concluded that resection followed by WBRT provided no survival advantage, although it may entail a possible advantage in functional independent survival and a reduction in death due to a neurological cause. However, it is questionable whether a reliable conclusion may be drawn on the basis of  only three studies that used different inclusion criteria.

Is WBRT standard treatment after neurosurgical resection?
Following neurosurgical resection, postoperative WBRT has been considered standard treatment, as advised by the previous guideline for brain metastases. Results from various recent and less recent studies (Patchell, 1998 (5); Aoyama, 2006 (6);Chang, 2009 (7)), as well as the results of the EORTC trial 22952-26001 (see below) (Kocher, 2011 (8)) put the role of WBRT after resection up for renewed discussion.

A randomised study examined outcomes after resection+WBRT versus resection only (Patchell, 1998 (5)). This study randomised 95 patients with a solitary brain metastasis and a KPS ≥70, after complete resection was determined by postoperative MRI. The primary endpoint was radiological control of tumour activity in the brain. With a median follow-up of 43 weeks, 82% had radiological tumour control in the resection+WBRT arm versus 30% in the arm with resection only. This concerned both control at the location of the original metastasis (10% local recurrences versus 46%) as well as metastasis elsewhere in the brain only (8% versus 24%). Secondary endpoints were absolute survival (no difference: RR 0.91 (0.59-1.4)), death from a neurological cause (surgery+WBRT 14% versus 44%), death due to extracranial tumour activity (surgery+WBRT 84% versus 46%) and survival with KPS ≥ 70 (no difference: RR 0.84 (0.61-1.17)). Neurotoxicity, quality of life (QoL) and possible salvage treatments after recurrence were not assessed.

The EORTC trial 22952-26001 is the most important study to date on the value of WBRT after both neurosurgical resection and SRS (Kocher, 2011 (8)). The study randomised 359 patients with 1-3 brain metastases between WBRT or no WBRT, with neurosurgical excision or SRS being primary treatment. The primary endpoint was survival with a performance WHO ≤2. There was no difference between the two arms (WBRT 9.5 months (7.8-11.9) versus 10 months (8.1-11.7) without WBRT). Secondary endpoints were progression-free survival (WBRT median 4.6 months (3.9-6.1) versus no WBRT 3.4 (3.1-3.9), with more frequent intracranial progression (and intracranial progression as the cause of death) in the arm without WBRT (78% versus 48% with WBRT). With a follow-up of 2 years after surgery, local recurrence percentage was 59% for the arm without WBRT and 27% with WBRT, while that of new metastases elsewhere in the brain was 42% versus 23%. Salvage treatment was more common in the arm without WBRT (51% versus 16%), and acute toxicity was somewhat more common in the WBRT arm. The quality of life study was published separately whereas cognitive functioning was not examined.

The preliminary conclusion on the basis of only these two prospective randomised studies is that postoperative WBRT entails no advantage in absolute survival and survival for patients with KPS ≥70. However, forgoing postoperative WBRT may lead to more recurrences at the location of the surgical area as well as new brain metastases.

As long as detection of progressive or new asymptomatic brain metastases is relevant for treatment, patients should be monitored every 3 months using MRI. In the case of progression or recurrence, SRS may be repeated or WBRT administered (see related Recurrence and Follow-up).

Recent developments
There are studies in which SRS of the surgical cavity is performed after resection of brain metastases (Do, 2009 (9)). This strategy is applied in different centres (Kalkanis, 2010 (10)). However, prospective studies are still lacking.

Recent publications also describe resection of multiple brain metastases in a single surgical session using neuronavigation techniques (Andrews, 2008 (11);Schackert, 2001 (12)) or the combination of resection of a metastasis with SRS/WBRT aimed at residual metastases (Limbrick, 2009 (13);Iwadate, 2002 (14)).

Stereotactic radiosurgery (SRS)
SRS is applied in a select group of patients in whom a longer survival is expected (RPA class I and II). Retrospective analyses and case series indicate that the number and volume of metastases are also prognostically significant (Weltman, 2000 (15)). Joseph (Joseph, 1996 (16)) found <3 brain metastases to be a significant prognostic factor for longer survival. Karlsson (Karlsson, 2009 (17)) showed that a solitary brain metastasis and the absence of extracranial tumour activity correlate with a longer survival. Varlotto ((Varlotto, 2003 (18)) showed a association between tumour volume (largest diameter 3.5-4 cm) and the risk of toxicity, with a decreasing risk of tumour control. There are no clinical trials which compare SRS to WBRT in case of more than 4 brain metastases. The indication for SRS is therefore currently limited to a maximum of 3-4 brain metastases with a maximum diameter of 3.5-4 cm in patients with a KPS ≥70 without rapidly progressive or untreatable extracranial tumour activity.

There is one published randomised trial (RTOG 9508) (Andrews, 2004 (19)) in which WBRT+SRS was compared with WBRT in patients with 1-3 brain metastases (n=333). Only patients from RPA class I and II were included, and stratification took place for the number of metastases and the status of the primary tumour. The average survival was significantly longer in the WBRT+SRS arm (6.5 months versus 4.9 months) for patients with a single brain metastasis. Post-hoc analysis showed a significant favourable effect of the combined treatment on a number of secondary endpoints; KPS after 6 months improved or remained stable (43% versus 27%), a reduction in or termination of dexamethasone use (54% versus 33 %) and radiological control after 1 year (82% versus 71%). Deaths from a neurological cause (28% versus 31%) or deaths from extracranial disease (50% versus 54%) were not significantly different.

The other published randomised trial, in patients with 2-4 brain metastases (Kondziolka, 1999 (20)), was stopped after interim analysis with 27 patients because of the large difference in local tumour control in both arms. Local control, defined as no increase in the size of the metastases and no increase in symptoms, was 92% after 1 year in the WBRT+SRS arm versus 0% in the WBRT arm. Due to the limited number of patients, no significant difference in survival was demonstrable (11 months for WBRT+SRS versus 7 months for WBRT).

Retrospective studies comparing WBRT and SRS report better survival and local control with SRS (Muller-Riemenschneider, 2009 (21);Linskey, 2010 (22)). Recently, Linskey (Linskey, 2010 (22)) published a systematic review and proposed evidence-based guidelines: this review cites studies in which a better survival is found for SRS (Li, 2000 (23);Wang 2002 (24);Lee, 2008 (25);Rades, 2007 (26)), better survival with SRS in RPA class I and II, but not in class III (Datta, 2004 (27)), and one study where no difference in survival was found (Kocher, 2004 (28)).

Is neurosurgical resection or SRS the treatment of choice with a solitary brain metastasis?
A randomised study on neurosurgical resection+WBRT versus SRS (Muacevic, 2008 (29)) (64 patients with a solitary operable brain metastasis with RPA class I or II) was stopped early as there were too few patients to participate in the study. No significant difference was found in functional outcome or median survival (9.5 months for neurosurgery+WBRT versus 10.3 months for SRS). Local control after 1 year was 82% versus 97% for SRS. New metastases elsewhere in the brain were found in 3% in the neurosurgery+WBRT arm versus 26% in the SRS arm.

There is no evidence so far whether neurosurgical resection or SRS should be the treatment of choice. Three randomised trials that have not yet been published (one of which is closed and one is still open) compare neurosurgical resection versus SRS (Kalkanis, 2010 (10)). In the EORTC-trial 22952-26001, there was a difference in local tumour control between neurosurgical resection without WBRT (59% local recurrence) and SRS without WBRT (31%) (Kocher, 2011 (8)). Until further results of these trials are available, SRS appears to be the preferred treatment since SRS is a non-invasive treatment, the risks of morbidity are considerably smaller, because it entails a better local tumour control (if WBRT is not administered) and clinical admission is not required. However, surgery is preferred in some situations, for instance when histopathological verification is to be obtained, if direct decompression is necessary (e.g. with closed hydrocephalus), and if the tumour is too large for SRS (larger than 3.5 to 4 cm). These factors are preferably considered in multidisciplinary consultation.

Is WBRT standard treatment after SRS?
SRS is followed by WBRT as a standard, especially in the USA; in centres in the Netherlands, patients are commonly monitored using MRI following SRS.

A randomised study evaluated SRS+WBRT versus SRS only (Aoyama, 2006 (6)) in patients with 1-4 brain metastases. The study was stopped after interim analysis with 132 patients since the primary endpoint, a difference in total survival, could not be achieved (805 patients needed). The median follow-up duration was 7.8 months. There was no difference in median or 1-year survival (SRS+WBRT 7.5 months, 39% (27%-50%) versus SRS 8.0 months, 28% (18%-39%). Secondary endpoints were radiological recurrence in the brain (47% after 1 year in the SRS+WBRT arm versus 76%), death due to a neurological cause (23% SRS+WBRT versus 19%), KPS ≥70 after 1 year (34% SRS+WBRT versus 27%) and no worsening in neurological status after 1 year (72% SRS+WBRT versus 70%). Neurotoxicity was also studied: there was no difference in late effects of radiotherapy, such as radionecrosis, leukoencephalopathy, lethargy and epilepsy (n=7 SRS+WBRT versus n=3). A follow-up MRI was performed every three months during the study. Salvage treatment (SRS or WBRT) was given in the event of radiological recurrence, and was applied more often in the SRS arm: 43% versus 15%. QoL was not studied.

Another prospective randomised study was closed due to an insufficient accrual. An analysis of 19 included patients with or without WBRT after SRS or resection did not show a difference in survival or quality of life (QoL); however, there were more intracranial recurrences in the arm without WBRT (Roos, 2006 (30)).

The EORTC trial 22952-26001 (Kocher, 2011 (8)) did not show a difference in survival with performance WHO ≤2 between the arms with and without WBRT. Again, more intracranial recurrences were observed in the SRS without WBRT arm within 2 years of follow-up, both locally (31% versus 19%) and with respect to new metastases elsewhere in the brain (48% versus 33%).

The randomised study by Chang (Chang, 2009 (7)), which demonstrated a decrease in neurocognitive functioning in the memory domain after WBRT, also showed more intracranial recurrences in the arm without WBRT (SRS+WBRT 73% recurrence-free after 1 year versus SRS only 27% recurrence-free after 1 year).

With respect to whether or not omitting WBRT, the same considerations are at play for SRS as for neurosurgical resection. Forgoing WBRT directly after SRS means less risk of cognitive loss in the memory domain while it does not have a negative effect on survival. However, the chance of intracranial recurrence does increase. Early detection of a recurrence using MRI monitoring followed by treatment before the recurrence becomes symptomatic is a commonly employed strategy in the Netherlands. Whether this strategy is relevant for each patient and for each moment in the follow-up has to be considered in each individual case. Also see Asymptomatic brain metastases, Recurrence of brain metastases and Follow-up.

Recent developments in radiotherapy for treatment of brain metastases
Non-randomised studies describe new approaches with radiotherapy.
Results achieved with stereotactic radiotherapy (SRT) or fractionated radiotherapy (FSRT) appear to be similar to those with SRS (Kim, 2010 (31)). By applying IMRT techniques, WBRT may be administered simultaneously with high dose precision irradiation of the metastases (Lagerwaard, 2009 (32)). In addition, it is possible to administer WBRT with selective sparing of the hippocampus region (to prevent cognitive disorders) (Gutierrez, 2007 (33)) and fractionated high dose irradiation at the location of the brain metastases (Fahrig, 2007 (34)). The combination of WBRT with targeted drugs and chemotherapy is currently being studied (Lind, 2009 (35);Olson, 2010 (36)). SRS for 4 or more brain metastases is described in retrospective studies (Karlsson, 2009 (17);Bhatnagar, 2006 (37)). It remains unclear what the role of these new approaches will be in the treatment of brain metastases.

SCLC
See the guideline on SCLC.
Prophylactic irradiation (PCI) is indicated in patients with both SCLC-LD as ED, who do not have disease progression after treatment but who do have a good KPS, because PCI significantly increases survival.

WBRT and chemotherapy are the standard treatment for SCLC patients with brain metastases.

There is no clear role for SRS in the treatment of brain metastases derived from SCLC. However, SRS is reported as treatment in retrospective series and in one prospective series (Bhatnagar, 2006 (37); Serizawa, 2002 (38);Li, 2000 (23)). In addition, SRS may have a role as salvage treatment in selected patients with a recurrence of brain metastasis after previous WBRT/PCI.

For the treatment of germ cell tumours, see Systemic therapy of symptomatic brain metastases under germ cell tumours.

Click here for the evidence table.

References

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  2. 2 - Vecht CJ, Haaxma-Reiche H, Noordijk EM, Padberg GW, Voormolen JH, Hoekstra FH, et al. Treatment of single brain metastasis: radiotherapy alone or combined with neurosurgery? Ann Neurol 1993 Jun;33(6):583-90.
  3. 3 - Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al. A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 1996 Oct 1;78(7):1470-6.
  4. 4 - Hart MG, Grant R, Walker M, Dickinson H. Surgical resection and whole brain radiation therapy versus whole brain radiation therapy alone for single brain metastases. Cochrane Database Syst Rev 2005;(1):CD003292.
  5. 5 - Patchell RA, Tibbs PA, Regine WF, Dempsey RJ, Mohiuddin M, Kryscio RJ, et al. Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial. JAMA 1998 Nov 4;280(17):1485-9.
  6. 6 - Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA 2006 Jun 7;295(21):2483-91.
  7. 7 - 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.
  8. 8 - 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.
  9. 9 - Do L, Pezner R, Radany E, Liu A, Staud C, Badie B. Resection followed by stereotactic radiosurgery to resection cavity for intracranial metastases. Int J Radiat Oncol Biol Phys 2009 Feb 1;73(2):486-91.
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  11. 11 - Andrews DW. Current neurosurgical management of brain metastases. Semin Oncol 2008 Apr;35(2):100-7.
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  13. 13 - Limbrick DD, Jr., Lusis EA, Chicoine MR, Rich KM, Dacey RG, Dowling JL, et al. Combined surgical resection and stereotactic radiosurgery for treatment of cerebral metastases. Surg Neurol 2009 Mar;71(3):280-8, disucssion.
  14. 14 - Iwadate Y, Namba H, Yamaura A. Whole-brain radiation therapy is not beneficial as an adjuvant therapy for brain metastases compared with localized irradiation. Anticancer Res 2002 Jan;22(1A):325-30.
  15. 15 - Weltman E, Salvajoli JV, Brandt RA, de Morais HR, Prisco FE, Cruz JC, et al. Radiosurgery for brain metastases: a score index for predicting prognosis. Int J Radiat Oncol Biol Phys 2000 Mar 15;46(5):1155-61.
  16. 16 - Joseph J, Adler JR, Cox RS, Hancock SL. Linear accelerator-based stereotaxic radiosurgery for brain metastases:the influence of number of lesions on survival. J Clin Oncol 1996 Apr;14(4):1085-92.
  17. 17 - Karlsson B, Hanssens P, Wolff R, Soderman M, Lindquist C, Beute G. Thirty years' experience with Gamma Knife surgery for metastases to the brain. J Neurosurg 2009 Sep;111(3):449-57.
  18. 18 - Varlotto JM, Flickinger JC, Niranjan A, Bhatnagar AK, Kondziolka D, Lunsford LD. Analysis of tumor control and toxicity in patients who have survived at least one year after radiosurgery for brain metastases. Int J Radiat Oncol Biol Phys 2003 Oct 1;57(2):452-64.
  19. 19 - 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.
  20. 20 - Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999 Sep 1;45(2):427-34.
  21. 21 - Muller-Riemenschneider F, Bockelbrink A, Ernst I, Schwarzbach C, Vauth C, von der Schulenburg JM, et al. Stereotactic radiosurgery for the treatment of brain metastases. Radiother Oncol 2009 Apr;91(1):67-74.
  22. 22 - Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, et al. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol 2010 Jan;96(1):45-68.
  23. 23 - Li B, Yu J, Suntharalingam M, Kennedy AS, Amin PP, Chen Z, et al. Comparison of three treatment options for single brain metastasis from lung cancer. Int J Cancer 2000 Feb 20;90(1):37-45.
  24. 24 - Wang LG, Guo Y, Zhang X, Song SJ, Xia JL, Fan FY, et al. Brain metastasis: experience of the Xi-Jing hospital. Stereotact Funct Neurosurg 2002;78(2):70-83.
  25. 25 - Lee DH, Han JY, Kim HT, Yoon SJ, Pyo HR, Cho KH, et al. Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study. Cancer 2008 Jul 1;113(1):143-9.
  26. 26 - Rades D, Pluemer A, Veninga T, Hanssens P, Dunst J, Schild SE. Whole-brain radiotherapy versus stereotactic radiosurgery for patients in recursive partitioning analysis classes 1 and 2 with 1 to 3 brain metastases. Cancer 2007 Nov 15;110(10):2285-92.
  27. 27 - Datta R, Jawahar A, Ampil FL, Shi R, Nanda A, D'Agostino H. Survival in relation to radiotherapeutic modality for brain metastasis: whole brain irradiation vs. gamma knife radiosurgery. Am J Clin Oncol 2004 Aug;27(4):420-4.
  28. 28 - Kocher M, Maarouf M, Bendel M, Voges J, Muller RP, Sturm V. Linac radiosurgery versus whole brain radiotherapy for brain metastases. A survival comparison based on the RTOG recursive partitioning analysis. Strahlenther Onkol 2004 May;180(5):263-7.
  29. 29 - Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW. Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the brain: a randomized controlled multicentre phase III trial. J Neurooncol 2008 May;87(3):299-307.
  30. 30 - Roos DE, Wirth A, Burmeister BH, Spry NA, Drummond KJ, Beresford JA, et al. Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05). Radiother Oncol 2006 Sep;80(3):318-22.
  31. 31 - Kim YJ, Cho KH, Kim JY, Lim YK, Min HS, Lee SH, et al. Single-Dose Versus Fractionated Stereotactic Radiotherapy for Brain Metastases. Int J Radiat Oncol Biol Phys 2010 Aug 26.
  32. 32 - Lagerwaard FJ, van der Hoorn EA, Verbakel WF, Haasbeek CJ, Slotman BJ, Senan S. Whole-brain radiotherapy with simultaneous integrated boost to multiple brain metastases using volumetric modulated arc therapy. Int J Radiat Oncol Biol Phys 2009 Sep 1;75(1):253-9.
  33. 33 - Gutierrez AN, Westerly DC, Tome WA, Jaradat HA, Mackie TR, Bentzen SM, et al. Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. Int J Radiat Oncol Biol Phys 2007 Oct 1;69(2):589-97.
  34. 34 - Fahrig A, Ganslandt O, Lambrecht U, Grabenbauer G, Kleinert G, Sauer R, et al. Hypofractionated stereotactic radiotherapy for brain metastases--results from three different dose concepts. Strahlenther Onkol 2007 Nov;183(11):625-30.
  35. 35 - Lind JS, Lagerwaard FJ, Smit EF, Senan S. Phase I study of concurrent whole brain radiotherapy and erlotinib for multiple brain metastases from non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2009 Aug 1;74(5):1391-6.
  36. 36 - Olson JJ, Paleologos NA, Gaspar LE, Robinson PD, Morris RE, Ammirati M, et al. The role of emerging and investigational therapies for metastatic brain tumors: a systematic review and evidence-based clinical practice guideline of selected topics. J Neurooncol 2010 Jan;96(1):115-42.
  37. 37 - Bhatnagar AK, Flickinger JC, Kondziolka D, Lunsford LD. Stereotactic radiosurgery for four or more intracranial metastases. Int J Radiat Oncol Biol Phys 2006 Mar 1;64(3):898-903.
  38. 39 - Noordijk EM, Vecht CJ, Haaxma-Reiche H, Padberg GW, Voormolen JH, Hoekstra FH, et al. The choice of treatment of single brain metastasis should be based on extracranial tumor activity and age. Int J Radiat Oncol Biol Phys 1994 Jul 1;29(4):711-7.

Considerations

No adequate randomised studies are available that have examined the added value of WBRT in comparison to supportive treatments (steroids) or WBRT in comparison to SRS or surgery. WBRT may be considered if SRS or surgery are not indicated.

With rapid progressive or untreatable extracranial tumour activity, SRS or surgery are generally no longer indicated.

An important consideration in deciding whether or not to apply WBRT after neurosurgical resection of a solitary brain metastasis, or after SRS of 1-3 brain metastases, is whether the side effects of WBRT weigh up against a reduction in the risk of intracranial recurrence.

There are no studies on the optimal time interval for MRI follow-up after local treatment of brain metastases.

SRT is also applied as alternative to SRS, especially with larger metastases.

Given the complexity of care for patients with brain metastases, all disciplines involved in the treatment are preferably consulted when determining the treatment plan.

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.