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MACQUARIE NEUROSURGERY
Evidence Based Surgery
Dr Michael Mulcahy
25th of August, 2016
Radiation-Induced Meningiomas
Case 1- JH
Case - JH
Case 2 - MM
Searchable Question (PICO)
P - Radiation-induced meningiomas
I - Nil
C - Spontaneous meningiomas
O - grade, brain invasion, proliferation index, recurrence, multiplicity
Q: Are radiation-induced meningiomas more aggressive?
Search Strategy
Search for all studies that could provide surgical and pathologic data on
radiation-induced meningiomas
Search: medline, embase
Scopus review
Reference check
Include case series, cohort studies.
Exclude case reports and review articles.
Medline
Medline
Embase
PRISMA
Results
Radiation
Type
Cases Grade MIB-1 Multiple
Meningiomas
Recurrence
Morgenstern
2016
Previous
malignancy
30
21 surgical
12/21 (57%) G1
9/21 (43%) G2
Mean 5.4% for
grade 1
10/30 (33%) 4/21 (20%)(mean follow up 6yrs)
Felicetti
2015
Previous
malignancy
15
10 surgical
5/9 (56%) G1
4/9 (44%) G2 -
4/15 (27%) 5/9 (56%)
(unknown follow-up)
Godlewski
2012
Previous
malignancy
26
20 surgical
20/23 (87%) G1
3/23 (13%) G2 -
10/26 (38%) 4/23 (17%)
(follow up 6months - 16yrs)
Lillehei
2008
Mixed 20
15 surgical
10/15 (67%) G1
3/15 (20%) G2
2/15 (13%) G3
-
6/20 (30%) 6/15 (38%)
2 had a second recurrence
(unknown follow-up)
Goshen
2007
Previous
malignancy
16
12 surgical
11/12 (92%) G1
1/12 (8%) G2 -
3/16 (19%) 1/12 (8%)
(unknown follow-up)
Al-Mefty
2004
Previous
malignancy
16 surgical 10/16 (63%)
5/16 (31%)
1/16 (6%)
-
5/16 (31%) 13/16 (81%) (mean F/U 6 years)
8 had a second recurrence
2 had a third recurrence
3 not followed up
Sadetzki
2002
Tinea capitis
cohort
253
220 surgical - -
40/253 (16%) 46/220 (18%) (mean follow up 10 years)
Salvati
1997
Previous
malignancy
10 surgical 6/10 G1
4/10 G2 -
0 1/10 (unknown follow-up)
Musa
1995
Previous
malignancy
10 surgical 8/10 G1
2/10 G3 -
1/10 (10%) 1/10 (had 4 recurrences)
(unknown follow-up)
Rubenstein
1984
Tinea capitis
cohort
43 surgical 1 “malignant”
-
2/43 (5%) 11/43 (26%)
5 (12%) had a second recurrence
Soffer
1983
Tinea capitis
cohort
42 surgical 6 “malignant” 6/42 (14%) 6/42 (14%)
2 had a second recurrence
1 had a third recurrence
Results
Radiation
Type
Cases Grade MIB-1 Multiple
Meningiomas
Recurrence
Morgenstern
2016
Previous
malignancy
30
21 surgical
12/21 (57%) G1
9/21 (43%) G2
Mean 5.4% for
grade 1
10/30 (33%) 4/21 (20%)(mean follow up 6yrs)
Felicetti
2015
Previous
malignancy
15
10 surgical
5/9 (56%) G1
4/9 (44%) G2 -
4/15 (27%) 5/9 (56%)
(unknown follow-up)
Godlewski
2012
Previous
malignancy
26
20 surgical
20/23 (87%) G1
3/23 (13%) G2 -
10/26 (38%) 4/23 (17%)
(follow up 6months - 16yrs)
Lillehei
2008
Mixed 20
15 surgical
10/15 (67%) G1
3/15 (20%) G2
2/15 (13%) G3
-
6/20 (30%) 6/15 (38%)
2 had a second recurrence
(unknown follow-up)
Goshen
2007
Previous
malignancy
16
12 surgical
11/12 (92%) G1
1/12 (8%) G2 -
3/16 (19%) 1/12 (8%)
(unknown follow-up)
Al-Mefty
2004
Previous
malignancy
16 surgical 10/16 (63%)
5/16 (31%)
1/16 (6%)
-
5/16 (31%) 13/16 (81%) (mean F/U 6 years)
8 had a second recurrence
2 had a third recurrence
3 not followed up
Sadetzki
2002
Tinea capitis
cohort
253
220 surgical - -
40/253 (16%) 46/220 (18%) (mean follow up 10 years)
Salvati
1997
Previous
malignancy
10 surgical 6/10 G1
4/10 G2 -
0 1/10 (unknown follow-up)
Musa
1995
Previous
malignancy
10 surgical 8/10 G1
2/10 G3 -
1/10 (10%) 1/10 (had 4 recurrences)
(unknown follow-up)
Rubenstein
1984
Tinea capitis
cohort
43 surgical 1 “malignant”
-
2/43 (5%) 11/43 (26%)
5 (12%) had a second recurrence
Soffer
1983
Tinea capitis
cohort
42 surgical 6 “malignant” 6/42 (14%) 6/42 (14%)
2 had a second recurrence
1 had a third recurrence
Results
Grade 1 - 68/96 (71%) or 82/106 (77%)
Grade 2 - 25/96 (26%) or 29/106 (27%)
Grade 3 - 3/96 (3%) or 5/106 (5%)
WHO 2016:
20-25% grade 2
1-6% grade 3
Results
Multiple meningiomas:
87/481 (18%)
Recurrence:
98/422 (23%)
Summary and Conclusions
•More likely to be multiple
•More likely to recur
•Can’t say more likely to have higher grade
•Surveillance for irradiated children, and patient’s with RIM, unanswered
•Further studies would be beneficial
References
Morgenstern PF, Shah K, Dunkel IJ, et al. Meningioma after radiotherapy for malignancy. J Clin Neurosci. 2016;30:93-7.
Felicetti F, Fortunati N, Garbossa D, et al. Meningiomas after cranial radiotherapy for childhood cancer: a single
institution experience. J Cancer Res Clin Oncol. 2015;141:1277-82.
Godlewski B, Drummond KJ, Kaye AH. Radiation-induced meningiomas after high-dose cranial irradiation. J Clin
Neurosci. 2012;19:1627-35.
Lillehei KO, Donson AM, Kleinschmidt-DeMasters BK. Radiation-induced meningiomas: clinical, cytogenetic, and
microarray features. Acta Neuropathol. 2008;116:289-301.
Goshen Y, Stark B, Kornreich L, et al. High incidence of meningioma in cranial irradiated survivors of childhood acute
lymphoblastic leukemia. Pediatr Blood Cancer. 2007;49:294-7.
Al-Mefty O, Topsakal C, Pravdenkova S, et al. Radiation-induced meningiomas: clinical, pathological, cytokinetic, and
cytogenetic characteristics. J Neurosurg. 2004;100:1002-13.
Sadetzki S, Flint-Richter P, Ben-Tal T, et al. Radiation-induced meningioma: a descriptive study of 253 cases. J
Neurosurg. 2002;97:1078-82.
Salvati M, Cervoni L, Puzzilli F, et al. High-dose radiation-induced meningiomas. Surg Neurol. 1997;47:435-41.
Musa BS, Pople IK, Cummins BH. Intracranial meningiomas following irradiation--a growing problem? Br J Neurosurg.
1995;9:629-37.
Rubinstein AB, Shalit MN, Cohen ML, et al. Radiation-induced cerebral meningioma: a recognizable entity. J Neurosurg.
1984;61:966-71.
Soffer D, Pittaluga S, Feiner M, et al. Intracranial meningiomas following low-dose irradiation to the head. J Neurosurg.
1983;59:1048-53.

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Neurosurgery - Evidence Based Surgery

  • 1. MACQUARIE NEUROSURGERY Evidence Based Surgery Dr Michael Mulcahy 25th of August, 2016
  • 3.
  • 6. Case 2 - MM
  • 7. Searchable Question (PICO) P - Radiation-induced meningiomas I - Nil C - Spontaneous meningiomas O - grade, brain invasion, proliferation index, recurrence, multiplicity Q: Are radiation-induced meningiomas more aggressive?
  • 8. Search Strategy Search for all studies that could provide surgical and pathologic data on radiation-induced meningiomas Search: medline, embase Scopus review Reference check Include case series, cohort studies. Exclude case reports and review articles.
  • 13. Results Radiation Type Cases Grade MIB-1 Multiple Meningiomas Recurrence Morgenstern 2016 Previous malignancy 30 21 surgical 12/21 (57%) G1 9/21 (43%) G2 Mean 5.4% for grade 1 10/30 (33%) 4/21 (20%)(mean follow up 6yrs) Felicetti 2015 Previous malignancy 15 10 surgical 5/9 (56%) G1 4/9 (44%) G2 - 4/15 (27%) 5/9 (56%) (unknown follow-up) Godlewski 2012 Previous malignancy 26 20 surgical 20/23 (87%) G1 3/23 (13%) G2 - 10/26 (38%) 4/23 (17%) (follow up 6months - 16yrs) Lillehei 2008 Mixed 20 15 surgical 10/15 (67%) G1 3/15 (20%) G2 2/15 (13%) G3 - 6/20 (30%) 6/15 (38%) 2 had a second recurrence (unknown follow-up) Goshen 2007 Previous malignancy 16 12 surgical 11/12 (92%) G1 1/12 (8%) G2 - 3/16 (19%) 1/12 (8%) (unknown follow-up) Al-Mefty 2004 Previous malignancy 16 surgical 10/16 (63%) 5/16 (31%) 1/16 (6%) - 5/16 (31%) 13/16 (81%) (mean F/U 6 years) 8 had a second recurrence 2 had a third recurrence 3 not followed up Sadetzki 2002 Tinea capitis cohort 253 220 surgical - - 40/253 (16%) 46/220 (18%) (mean follow up 10 years) Salvati 1997 Previous malignancy 10 surgical 6/10 G1 4/10 G2 - 0 1/10 (unknown follow-up) Musa 1995 Previous malignancy 10 surgical 8/10 G1 2/10 G3 - 1/10 (10%) 1/10 (had 4 recurrences) (unknown follow-up) Rubenstein 1984 Tinea capitis cohort 43 surgical 1 “malignant” - 2/43 (5%) 11/43 (26%) 5 (12%) had a second recurrence Soffer 1983 Tinea capitis cohort 42 surgical 6 “malignant” 6/42 (14%) 6/42 (14%) 2 had a second recurrence 1 had a third recurrence
  • 14. Results Radiation Type Cases Grade MIB-1 Multiple Meningiomas Recurrence Morgenstern 2016 Previous malignancy 30 21 surgical 12/21 (57%) G1 9/21 (43%) G2 Mean 5.4% for grade 1 10/30 (33%) 4/21 (20%)(mean follow up 6yrs) Felicetti 2015 Previous malignancy 15 10 surgical 5/9 (56%) G1 4/9 (44%) G2 - 4/15 (27%) 5/9 (56%) (unknown follow-up) Godlewski 2012 Previous malignancy 26 20 surgical 20/23 (87%) G1 3/23 (13%) G2 - 10/26 (38%) 4/23 (17%) (follow up 6months - 16yrs) Lillehei 2008 Mixed 20 15 surgical 10/15 (67%) G1 3/15 (20%) G2 2/15 (13%) G3 - 6/20 (30%) 6/15 (38%) 2 had a second recurrence (unknown follow-up) Goshen 2007 Previous malignancy 16 12 surgical 11/12 (92%) G1 1/12 (8%) G2 - 3/16 (19%) 1/12 (8%) (unknown follow-up) Al-Mefty 2004 Previous malignancy 16 surgical 10/16 (63%) 5/16 (31%) 1/16 (6%) - 5/16 (31%) 13/16 (81%) (mean F/U 6 years) 8 had a second recurrence 2 had a third recurrence 3 not followed up Sadetzki 2002 Tinea capitis cohort 253 220 surgical - - 40/253 (16%) 46/220 (18%) (mean follow up 10 years) Salvati 1997 Previous malignancy 10 surgical 6/10 G1 4/10 G2 - 0 1/10 (unknown follow-up) Musa 1995 Previous malignancy 10 surgical 8/10 G1 2/10 G3 - 1/10 (10%) 1/10 (had 4 recurrences) (unknown follow-up) Rubenstein 1984 Tinea capitis cohort 43 surgical 1 “malignant” - 2/43 (5%) 11/43 (26%) 5 (12%) had a second recurrence Soffer 1983 Tinea capitis cohort 42 surgical 6 “malignant” 6/42 (14%) 6/42 (14%) 2 had a second recurrence 1 had a third recurrence
  • 15. Results Grade 1 - 68/96 (71%) or 82/106 (77%) Grade 2 - 25/96 (26%) or 29/106 (27%) Grade 3 - 3/96 (3%) or 5/106 (5%) WHO 2016: 20-25% grade 2 1-6% grade 3
  • 17. Summary and Conclusions •More likely to be multiple •More likely to recur •Can’t say more likely to have higher grade •Surveillance for irradiated children, and patient’s with RIM, unanswered •Further studies would be beneficial
  • 18. References Morgenstern PF, Shah K, Dunkel IJ, et al. Meningioma after radiotherapy for malignancy. J Clin Neurosci. 2016;30:93-7. Felicetti F, Fortunati N, Garbossa D, et al. Meningiomas after cranial radiotherapy for childhood cancer: a single institution experience. J Cancer Res Clin Oncol. 2015;141:1277-82. Godlewski B, Drummond KJ, Kaye AH. Radiation-induced meningiomas after high-dose cranial irradiation. J Clin Neurosci. 2012;19:1627-35. Lillehei KO, Donson AM, Kleinschmidt-DeMasters BK. Radiation-induced meningiomas: clinical, cytogenetic, and microarray features. Acta Neuropathol. 2008;116:289-301. Goshen Y, Stark B, Kornreich L, et al. High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2007;49:294-7. Al-Mefty O, Topsakal C, Pravdenkova S, et al. Radiation-induced meningiomas: clinical, pathological, cytokinetic, and cytogenetic characteristics. J Neurosurg. 2004;100:1002-13. Sadetzki S, Flint-Richter P, Ben-Tal T, et al. Radiation-induced meningioma: a descriptive study of 253 cases. J Neurosurg. 2002;97:1078-82. Salvati M, Cervoni L, Puzzilli F, et al. High-dose radiation-induced meningiomas. Surg Neurol. 1997;47:435-41. Musa BS, Pople IK, Cummins BH. Intracranial meningiomas following irradiation--a growing problem? Br J Neurosurg. 1995;9:629-37. Rubinstein AB, Shalit MN, Cohen ML, et al. Radiation-induced cerebral meningioma: a recognizable entity. J Neurosurg. 1984;61:966-71. Soffer D, Pittaluga S, Feiner M, et al. Intracranial meningiomas following low-dose irradiation to the head. J Neurosurg. 1983;59:1048-53.

Editor's Notes

  1. Well established from the Israeli tinea capitis cohort and the Japanese atomic bomb survivors that radiation increases the risk of meningiomas Case reports of RIM have been published since the 50s, (mann et al.;Clin. Radiol. (1969) RADIATION INDUCED INTRACRANIAL MENINGIOMAS. Munk et al.)
  2. Published in Lancet 1974, showed there was an increased risk of benign and malignant brain and neck tumours (Prior to this only case reports) (RR 9.5 for meningioma). Further supported by: - US and british childhood cancer survivor study Data on incidence of radiation induced tumours, but what is less well established: ?more likely to be higher grade ?more likely to recur ?natural history ?should be followed/managed differently
  3. 63 y.o. female R G1 cav sinus meningioma debulked 2005 Brisbane, then SRS 2006 B/G: smoker, post-op dvt, hypercholesterolaemia 2015: appearance of new convexity meningioma at craniotomy site 2016: enlarged OT: adherent to brain, multiple small meningiomas along dura towards floor of middle cranial fossa Path: transitional meningioma
  4. 63 y.o. female R G1 cav sinus meningioma debulked 2005 Brisbane, then SRS 2006 B/G: smoker, post-op dvt, hypercholesterolaemia 2015: appearance of new convexity meningioma at craniotomy site 2016: enlarged OT: adherent to brain, multiple small meningiomas along dura towards floor of middle cranial fossa Path: transitional meningioma
  5. MM 41 male RTx age 7 for acute lymphoblastic leukaemia 2014 seizure Resection of meningioma: grade 1 with brain invasion Advised RTx in MDT, currently under surveillance Also has 5 cavernous malformations
  6. define tumour aggressiveness (describes a tumour that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual) no intervention, just comparing the groups
  7. at least 10 cases
  8. Original search - radiation induced meningioma: 61 Mostly case reports and review articles but a few relevant case series from which alternative names to RIM were found, hence no.2
  9. Then looked at keywords and MESH terms and found additional terms Also found some papers in reference checks so knew I wasn’t getting everything Esp older papers had different referencing
  10. 316 total of the 245: - radiation treatment for meningioma or RIM - genetic studies - case reports and reviews - epidemiology studies (cause, prevalence)
  11. note on grading: prior to 1993 and second WHO grading there was no universal grading system so bottom two I have just put as malignant and non malignant even the first WHO grading was vague (first was 1979) no paper mentioned brain invasion
  12. scalp irradiation lower dose than treatment for tumours Morgenstern - high rate of G2. a large cohort had MIB-1 of 3.28% for grade 1 meningiomas (Roser et al. 2004) Felicetti - one death during anaesthetic induction (cardiac arrhythmia). high rate of G2 and recurrence Godlewski - missed on medline Lillehei - two G3 Goshen - lower rates Al-mefty - 100% recurrence of followed up patients. mostly referred from other institutes, so more aggressive by bias perhaps Sadetzki - nearly half had missing histopath data, mixture of grading schemes Rubenstein - no grading, classified based on russell and rubinstein. grading introduced? Soffer- grading based on rubinstein, zulch and kennel (characterized by loss of typical architecture, high cellularity, pleomorphism, increased mitotic rate, focal necrosis, and brain infiltration accompanied by marked glial proliferation)
  13. First number is from 2000 criteria (i.e.defined grade 2 and 3 meningioma), second number includes 2 studies from 1993 when WHO grading more defined could be an underestimate as large numbers are from pre-brain invasion criteria. also, don’t have grades from the largest study
  14. multiple SM - 1-5% (Multiple meningiomas: a clinical, surgical, and cytogenetic analysis. Butti et al. Surgical neurology, 1989) recurrence of SM up to 20% at 20 years (Seemingly complete removal of histologically benign intracranial meningioma: late recurrence rate and factors predicting recurrence in 657 patients. A multivariate analysis. Jääskeläinen J. 1986) But remember these were all unknown or less than 10 yrs follow-up
  15. All retrospective data, but good numbers Difficult to comment on grade as not only has grading changed between papers, even changed within some papers no consensus in the literature as to how to approach RIM (regarding surveillance, treatment and follow-up) Would take a long time to get numbers in a prospective study…grading might change again