CARE PATHS FOR ADULT
CNS TUMOURS
November 2012
Care Paths for Adult CNS Tumours
Page
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18-20
October 2010
Site
LG Astrocytoma, Mixed Oligoastrocytoma, Glioneurocytoma & DNET
LG Oligodendroglioma
Anaplastic Oligodendroglioma
Anaplastic Astrocytoma, Mixed Oligoastrocytoma and Atypical Glioneurocytoma
GBM
Recurrent GBM & Glioma
Meningioma & Vestibular Schwannoma
Chordoma/Chondrosarcoma, Pituitary Adenoma and Craniopharyngioma
CNS Lymphoma & Medulloblastoma/PNET
Brain Metastases: Solitary & 2-3 Metastases
Brain Metastases: Multiple & Retreat Metastases
Brain Stem Glioma, Ependymoma & Anaplastic Ependymoma
Pineal Tumours & Spine Tumours
Haemangioblastoma, Haemangiopericytoma & Germ Cell Tumours
Appendix A- Radiation Tolerance Doses
Appendix B: Chemotherapy Regimes
Note: These apply to patients treated off a study – where possible patients should be
offered participation in a study.
2
LOW GRADE ASTROCYTOMA, MIXED OLIGOASTROCYTOMA,
GLIONEUROCYTOMA & DNET: (EXCLUDING GEMISTOCYTIC
ASTROCYTOMA)
Tissue confirmation of a tumour and molecular markers (for 1p, 19q LOH) is
recommended in all cases with an abnormal MRI suggestive of a low-grade brain tumour.
A. Patients with high-risk features will be offered post-operative radiation as described
below. These features are at least three of the following: age 40 years or greater; largest
preoperative diameter of tumour of 6 cm. or greater; tumour crossing midline; tumour
subtype of astrocytoma or astrocytoma dominant; preoperative Neurological Function
Status (NFS) greater than 1.
B. All other patients will be treated as follows:
(a). Patients without symptoms (except seizures) and no evidence of progression on
MRI will be followed with regular imaging.
(b). Patients with new symptoms and / or progressive disease will have maximum
safe surgical resection and molecular markers performed if not already available.
Further management then depends on extent of surgical resection:
(1). Gross total resection
Age < 40 years - follow with regular imaging
Age > 40 years - radiation as described below
Any age and pilocytic astrocytoma or DNET - follow with regular imaging
(2). Residual disease
Pilocytic astrocytoma or DNET with subtotal resection - follow with regular
imaging
Others - radiation as described below
Target volume (CTV) - surgical defect and any flair abnormality plus 1.0 cm. margin
on postop flair MRI
Dose - 5040 cGy in 28# to isocentre
RT to start < 5 weeks post surgery
References Pilocytic +DNET
3
[1] Brown PD et al. Adult patients with Supratentorial Pilocytic Astrocytomas: A
Prospective Multicentre clinical trial. RED2004Mar 15; 58(4): 1153-60.
[2] Hallemeier CL et al. Stereotactic Radiosurgery for Recurrent or Unresectable
Pilocytic Astrocytoma. RED 2012; 83(1): 107-112.
4
LOW GRADE OLIGODENDROGLIOMA: (80% 5 year OS)
Tissue confirmation of a tumour and molecular markers (for 1p, 19q LOH) is
recommended in all cases with an abnormal MRI suggestive of a low-grade brain tumour.
A. Patients with high-risk features will be offered post-operative radiation or
chemotherapy as described below. These features are at least three of the following: age
40 years or greater; largest preoperative diameter of tumour of 6 cm. or greater; tumour
crossing midline; tumour subtype of astrocytoma or astrocytoma dominant; preoperative
Neurological Function Status (NFS) greater than 1.
B. All other patients will be treated as follows:
(a). Patients without symptoms (except seizures) and no evidence of progression on
MRI will be followed with regular imaging.
(b). Patients with new symptoms and / or progressive disease will have maximum
safe surgical resection and molecular markers performed if not already available.
Further management then depends on extent of surgical resection.
(1). Gross total resection
Age < 40 years - follow with regular imaging
Age > 40 years - manage as described below
(2). Residual disease - favourable markers: (LOH for 1p, 19q)
- chemotherapy with temozolomide or PCV (see appendix B)
Drug
Temozolomide
Dose
150 – 200 mg/m2 once
daily for 5 days
repeated every 4 weeks
for 12 cycles
Administration
oral
(3). Residual disease – unfavourable markers
-
radiation as described below
Target volume (CTV) - surgical defect and any flair abnormality plus 1.0 cm. margin
on postop flair MRI
Dose - 5040 cGy in 28# to isocentre
RT to start < 5 weeks post surgery
5
References Grade II Astrocytoma/Oligodentroglioma
[1] Jenkens RB et al. Translocation 1p19q predicts better prognosis of patients
With Oligodendroglioma. Cancer Res. 2006 Oct 15; 66(20) 9852-61.
[2] Karim AB et al. A randomized trial on dose-response in radiation therapy
Of low grade cerebral glioma EORTC 22844. RED 1996 Oct 1;36(3):549-56.
[3] Shaw E et al. Prospective Randomized trial of low- versus high dose
Radiation therapy in adults with supratentorial low grade glioma. Intergroup.
JCO 2002 May 1; 20(9): 2267-76
[4]van den Bent MJ et al. Long-term efficacy of early vs delayed radiotherapy
For low grade astrocytoma and oligodendroglioma in adults: the EORTC 22845
The Lancet September 2005 366(94900: 985-90.
[5] Pignatti F et al. Prognostic factors for survival in adults with low grade
Glioma. JCO 2002 Apr 15;20(8): 2076-84
6
ANAPLASTIC OLIGODENDROGLIOMA: (50% 5 year OS)
Patients will receive maximum safe surgical resection. Radiation treatment is
recommended except for patients aged > or = 65 years with poor Karnofsky. Patients
aged under 65 will be offered concomitant and adjuvant chemotherapy with
temozolomide (see appendix B). Adjuvant temozolomide will continue for six cycles if
no measurable disease at start or to maximal response plus two cycles if disease
measurable.
(a). Age 65 or older
(1). K < 50
Supportive care only
(2). K > or = 50
Target volume (CTV) - surgical defect, any enhancing and any flair abnormality plus
1.5 cm. margin on postop MRI
Dose – 4005 cGy in 15# to isocentre
(b). Age under 65
Target volume (CTV) - surgical defect, any enhancing and any flair abnormality plus
1.5 cm. margin on postop MRI
Dose - 5940 cGy in 33# to isocentre
Drug
TMZ
Dose
75 mg/m2 once daily x 42 consecutive days
concomitantly with fractionated radiation
followed by temozolomide monotherapy 200
mg/m2 x 5 days, every 28 days for six cycles if
no measurable disease at start or to maximal
response plus two cycles up to twelve cycles
total if disease measurable.
Administration
oral
RT to start < 5 weeks post surgery
7
ANAPLASTIC ASTROCYTOMA, MIXED OLIGOASTROCYTOMA,
ATYPICAL GLIONEUROCYTOMA AND GEMISTOCYTIC
OLIGOASTROCYTOMA:
Patients will receive maximum safe surgical resection. Radiation treatment is
recommended except for patients aged > or = 65 years with poor Karnofsky. Patients
aged under 65 with anaplastic astrocytoma or mixed oligoastrocytoma will be offered
concomitant and adjuvant chemotherapy with temozolomide (see appendix B). Adjuvant
temozolomide will continue for six cycles if no measurable disease at start or to maximal
response plus two cycles if disease measurable.
(a). Age 65 or older
(1). K < 50
Supportive care only
(2). K > or = 50
Target volume (CTV) - surgical defect, any enhancing and any flair abnormality plus
1.5 cm. margin on postop MRI
Dose – 4005 cGy in 15# to isocentre
(b). Age under 65
Target volume (CTV) - surgical defect, any enhancing and any flair abnormality plus
1.5 cm. margin on postop MRI
Dose - 5940 cGy in 33# to isocentre if Anaplastic or
5400cGy in 30# if high risk low grade tumour e.g. grade II to III.
Drug
TMZ
Dose
75 mg/m2 once daily x 42 consecutive days
concomitantly with fractionated radiation
followed by temozolomide monotherapy 200
mg/m2 x 5 days, every 28 days for six cycles if
no measurable disease at start or to maximal
response plus two cycles up to twelve cycles
total if disease measurable.
Administration
oral
RT to start < 5 weeks post surgery
8
GLIOBLASTOMA MULTIFORME: (10% 5 year OS; 30% if favorable factors)
Patients will receive maximum safe surgical resection. Treatment is recommended except
for patients aged > or = 65 years with poor Karnofsky. Patients aged under 65 will be
offered concomitant and adjuvant chemotherapy with temozolomide (see appendix B).
Adjuvant temozolomide will continue for six cycles if no measurable disease at start or to
maximal response plus two cycles if disease measurable.
(a). Age 65 or older
(1). K < 50
Supportive care only
(2). K > or = 50
Target volume (CTV) - surgical defect and any enhancing abnormality plus 1.5 cm.
margin on postop T1 + gad MRI
Dose – 4005 cGy in 15# to isocentre
(b). Age under 65
Target volume (CTV) - surgical defect and any enhancing abnormality plus 2.0 cm.
margin on postop T1 + gad MRI
Dose - 6000 cGy in 30# to isocentre
Drug
TMZ
Dose
75 mg/m2 once daily x 42 consecutive days
concomitantly with fractionated radiation
followed by temozolomide monotherapy 200
mg/m2 x 5 days, every 28 days for six cycles if
no measurable disease at start or to maximal
response plus two cycles up to twelve cycles
total if disease measurable.
Administration
oral
RT to start < 5 weeks post surgery
9
RECURRENT GBM:
Patients with recurrent GBM will be offered temozolomide (see appendix B) unless aged
> 65 years and Karnofsky < 50.
Small lesions can receive fractionated SRT
PTV=GTV+1mm, where GTV is enhancing lesion on T1+gad MRI
PTV < 20 mm
3500 cGy in 5#
PTV 21-60 mm
3000 cGy in 5#
Large lesions can be reirradiated if > 2 years from original treatment.
Consider 4500 cGy/25# if original RT was 6000 cGy/30#.
Otherwise keep BED < 200
References High Grade/GBM
[1]Roa W et al. Abbreviated course of radiation therapy in older patients with
glioblastoma multiforme: a prospective randomized clinical trial. JCO 2004 May
1;22(9): 1583-8.
[2] Stupp R et al. Effects of radiotherapy with concominant and adjuvant
temozolomide versus radiotherapy alone on survival in glioblastoma in a
randomized phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet
Oncology 2009 May; 10(5): 459-66
[3] Stupp R et al. Radiotherapy plus Concominant and Adjuvant Temozolomide for
Glioblastoma. NEJM 2005; 352(10):987-996.
[4] Wick W et al. NOA-04 randomized phase III trial of sequential
radiochemotherapy for anaplastic glioma with procarbazine, lomustine and
vincristine or temozolomide. JCO 2009 Dec 10; 27(35): 5874-80.
[5] Van den Bent MJ et al. Adjuvant procarbazine, lomustine and vincristine
improves progression-free survival but not overall survival in newly diagnosed
anaplastic oligodendrogliomas and oligoastrocytomas: A randomized EORTC phase
III trial. JCO 2006 June 20;24(18): 2715-22.
[6] Fogh et al. Hypofractionated Stereotactic Radiation Therapy: An Effective
Therapy for Recurrent High-Grade Gliomas. JCO 2010 June 20; 28:3048-53
[7]Easaw et al. Canadian recommendations for the treatment of recurrent or
progressive glioblastoma multiforme. Current Oncology 2011; 18(3): e126-e136.
[8] Greenspoon JN et al. Fractionated Stereotactic Radiosurgery with concurrent
temozolomide for recurrent glioblastoma multiforme: A prospective study. GREEN
2011 CARS/ASTRO/RSS (ABSTRACT)
10
MENINGIOMA: (Grade II 80% and Grade III 60% 5 year OS)
Patients will receive maximum safe surgical resection. The patient will be observed with
regular imaging unless there is concern regarding location; the meningioma has atypical /
malignant features (grades II & III), irrespective of the extent of resection; or the tumour
is recurrent when radiation is recommended. Radiosurgery is an option for small lesions.
(a). Low risk – new grade I will be observed post surgery unless there is concern
regarding location
(b). Intermediate risk - new GTR grade II and recurrent grade I
Target volume (CTV) - surgical defect and any enhancing abnormality on postop T1
+ gad MRI with margin of 1.0 cm.
Dose – 5400 cGy in 30# to isocentre
(c). High risk - new STR or recurrent grade II; and new or recurrent grade III
Target volume (CTV1) – surgical defect and any enhancing abnormality on postop
T1 + gad MRI with margin of 2.0cm.
Target volume (CTV2) – surgical defect and any enhancing abnormality on postop
T1 + Gad MRI with margin of 1.0cm.
Dose – 5400 cGy to CTV1 and 6000 cGy to CTV2 in same 30# to isocenter
Radiosurgery
Meningioma
PTV<3cm
16Gy/1 or 24Gy/3 if Grade II or III
PTV 3.0-3.9cm 18Gy/3
PTV >=4.0cm
25Gy/5
References Meningioma
[1] Rogers LC et al. Observation or Radiation Therapy in Treating Patients with
Grade I, Grade II or Grade III meningioma.RTOG 0539. Accessed clinicaltrials.gov
[2] Kullova et al. Gamma Knife Surgery for Benign Meningoma. J Neurosurg 2007;
107:325-336.
[3] Choi CYH et al. Cyberknife Stereotactic Radiosurgery for Treatment of
Atypical (Who Grade II) Cranial Meningiomas. Neurosurgery 2010; 67:1180-1188.
11
VESTIBULAR SCHWANNOMA:
Radiation treatment is recommended for surgically inoperable lesions. Depending on the
size of the lesion, SRS may be an option.
Target volume (CTV) – tumour plus 0.5 cm. margin on T1+gad MRI
Dose – 5400 cGy in 30# to isocentre
Radiosurgery: (favour RT if significant brain stem compression). PTV=GTV+1mm
PTV < 30 mm
PTV 31-40 mm
1800 cGy in 3#
2500 cGy in 5#
References Vestibular Schwannoma
[1] Combs SE et al. Management of Acoustic Neuroma with FSRT: Long-Term
Results in 106 patients. RED 2006; 63(1): 75-81
[2] Combs SE et al. Differences in Clinical Results After Linac-Based Single Dose
Radiosurgery vs FSRT for patients with vestibular schwannoma. RED 2010; 76(1):
193-200.
CHORDOMA / CHONDROSARCOMA : (75% 5 year OS)
Patients will receive maximum safe surgical resection with postop radiation treatment in
all cases.
Target volume (CTV) – surgical defect and any enhancing abnormality plus 0.5
cm. on postop T1 + gad MRI
Dose – 7600 cGy in 38# to isocentre (chordoma)
7000 cGy in 35# to isocentre (chondrosarcoma)
Limit surface of brain stem to 6500 cGy, within brain stem to 6000 cGy by 0.5
cm. Chiasm limit of 5400 cGy. Avoid hot spots in carotids and middle cerebral
arteries.
Radiosurgery is an option in small lesions. PTV=GTV+1mm
PTV
PTV
PTV
PTV
< 20 mm
21-30 mm
31-40 mm
> 40 mm
1800-2400 cGy in 1#
1500-1800 cGy in 1#
1200-1500 cGy in 1# or 1800 cGy in 3#
2500 cGy in 5#
References Chordoma/Chondrosarcoma
12
[1] Koga T et at. Treatment with high marginal dose is mandatory to achieve long
term control of skull base chordomas and chondrosarcomas by means of SRS. J
Neurooncol 2010. Jun;90(2): 233-8.
[2] Martin JJ et al. Radiosurgery for chordomas and chondrosarcomas of the skull
base. J Neurosurg 2007. Oct;107(4): 758-64.
[3] Kano H et al. Stereotactic radiosurgery for chordoma: a report from the North
American Gamma Knife Consortium. 2011 Neurosurgery Feb;68(2):379-89.
PITUITARY ADENOMA & CRANIOPHARYNGIOMA:
Patients with pituitary adenoma will receive surgery by a trans-sphenoidal resection. If
there is a gross total resection or minimal residual without elevated prolactin or growth
hormone, observation with regular imaging is recommended. Radiation treatment is
recommended in cases that have gross residual tumour post-resection or elevated
hormone and medical management is not feasible. Radiation is also recommended in
recurrent cases.
Patients with craniopharyngioma will receive surgery. Radiation is recommended in
cases with residual disease or in recurrent cases.
Target volume (CTV) – pituitary fossa / cyst and any residual tumour plus
0.3 cm. margin on postop MRI
Dose – 5010 cGy in 30# to isocentre if gross residual pituitary adenoma
4509 cGy in 27# if minimal residual pituitary adenoma
5400 cGy in 30# to isocentre if residual craniopharyngioma
Radiosurgery is preferred for functioning adenoma if < 30 mm and optic apparatus dose
constraint respected. Dose 2500 cGy in 5#. PTV=GTV.
References Pituitary Adenoma/Craniopharyngioma
[1] Jagannathan J et al. Stereotactic Radiosurgery for pituitary adenomas: a
comprehensive review of indications, techniques and long term results using
Gamma Knife. 2009 J Neurooncol May;92(3):345-56.
[2] Niranjan A et al. Radiosurgery for craniopharyngioma. 2010 RED. Sep 1;78(1):
64-71.
13
CNS LYMPHOMA: (50% 3 year OS)
Patients receive a biopsy or surgical resection (when needed) and are then treated
following the last RTOG study 93-10, receiving chemotherapy for 10 weeks (MTX x 5
cycles) and then cranial radiation with further post-RT chemotherapy.
Target volume (CTV) – whole brain and meninges
Dose – if residual tumour post-chemo. 4500 cGy in 25# to MPD
if no residual tumour
3600 cGy in 30# bid to MPD
Following chemotherapy SRS can be considered to treat residual imaging abnormalities
in patients who cannot tolerate or refuse WBRT
PTV=GTV+1mm
PTV <20mm MED
20-60mm MED
3000cGy in 5 #
2500cGy in 5#
MEDULLOBLASTOMA / PNET:
Patients will receive maximum safe surgical resection and will then be treated according
to risk categories (supratentorial PNET & anaplastic medullo will be high risk):
(a). Average Risk – minimal residual (< 1.5 cm3), no dissemination on neuraxis MRI and
CSF negative
Target volume (CTV) – whole brain and meninges and spine to ~S2/3
posterior fossa for boost
Dose – 3600 cGy in 20# to MPD of cranium
3600 cGy in 20# to anterior spinal canal
1980 cGy in 11# posterior fossa boost
(b). High Risk – all others, radiation and chemotherapy
(cisplatinum/etoposide/vincristine/cyclophosphamide)
Target volume (CTV) – whole brain and meninges and spine to ~S2/3
posterior fossa for boost
or surgical defect and any enhancing abnormality plus 1.5
cm. margin on postop T1 + gad MRI if supratentorial
(i). No dissemination and CSF negative:
Dose – 3600 cGy in 20# to MPD of cranium
3600 cGy in 20# to anterior spinal canal
1980 cGy in 11# posterior fossa or supratentorial boost
14
(ii). Dissemination or positive CSF:
Dose – 3960 cGy in 22# to MPD of cranium
3960 cGy in 22# to anterior spinal canal
1620 cGy in 9# posterior foosa or supratentorial boost
540 cGy in 3# boost to metastases
BRAIN METASTASES: (RTOG 0671; CEC.3; RTOG 0933; CK v T)
A survival advantage has been demonstrated with the addition of radiosurgery to whole
brain radiotherapy if one of the following applies:
1.
single metastasis;
2.
age < 50 years;
3.
RPA class I – controlled primary, no systemic mets, age < 65 years and KPS >60;
or
4.
NSCLC and any squamous cell carcinoma.
Consider radiosurgery with WBRT in these and selected other cases in patients with
stable or not yet treated primary and systemic disease:
(i).
(ii).
(iii).
(iv).
(v).
Small solitary met not requiring surgery for diagnosis or reduction of mass effect;
Solitary met post surgery if residual disease;
1-3 mets < 3 cm;
1-3 mets previously treated with WBRT with incomplete response;
Recurrent 1-3 mets.
(a). Solitary brain metastasis:
Surgery or radiosurgery (if no mass effect and < 3 cm. lesion) is recommended if K > 50,
stable (or not yet treated) primary disease and other systemic disease. Survival advantage
demonstrated in RTOG study irrespective of pathology.
(i). Post-surgery
Target volume – whole brain
Dose – 3000 cGy in 10# to MPD
(ii). Radiosurgery
Target volume – Phase 1 – SRS to enhancing lesion + 1mm (PTV=GTV+1mm)
Phase 2 – whole brain
Dose – Phase 1 – 2200 cGy in 1# (PTV <20 mm)
1800 cGy in 1# (PTV 21-30 mm)
2100 cGy in 3# (PTV 31-40 mm)
2200 cGy in 5# (PTV > 40 mm)
15
Phase 2 – 3000 cGy in 10# to MPD
16
If patient refuses or not well enough for WBRT,or WBRT was completed > 3 months
ago, can do SRS alone (PTV=GTV+1mm):
Dose – 2400 cGy in 1# (PTV <20 mm)
2000 cGy in 1# (PTV 21-30 mm)
2400 cGy in 3# (PTV 31-40 mm)
2500 cGy in 5# (PTV >40 mm)
For lesions in brain stem, can give SRS alone (PTV=GTV):
Dose – 1800 cGy in 1# or 2400 cGy in 3# (PTV <20 mm)
1500 cGy in 1# or 2100 cGy in 3# (PTV 21-30 mm)
1200 cGy in 1# or 1800 cGy in 3# (PTV 31-40 mm)
Following WBRT, SRS can be given to lesions in the brainstem (PTV=GTV)
Dose- 1600cGy in 1# or 2100 in 3# (PTV<20mm)
1800cGy in 3# (PTV 21-30mm)
2200cGy in 5# (PTV 31-40mm)
(b). 2 – 3 brain metastases:
If one of metastases is large and symptomatic or life threatening, refer to neurosurgery
for debulking of lesion prior to radiotherapy.
Whole brain RT and radiosurgery or radiosurgery alone as for solitary metastasis
(c). Multiple brain metastases:
If one of metastases is large and symptomatic or life threatening, refer to neurosurgery
for debulking of lesion prior to whole brain radiotherapy.
Otherwise, give whole brain radiotherapy unless patient age and condition prevents.
Dose – 3000 cGy in 10# to MPD
(d). Retreat brain metastases:
After 3000 cGy in 10#, give 2500 cGy in 10# WBRT or radiosurgery
After 2000 cGy in 5#, give 2100 cGy in 7# WBRT or radiosurgery
(e). Postop to surgical bed (without whole brain RT) (NCIC CEC.3)
PTV=surgical bed and any residual + 2mm
17
Dose - < 4.2 ml
4.2-7.9 ml
8.0-14.3 ml
14.4-19.9 ml
20.0-29.9 ml
> 30.0 ml
2000 cGy in 1#
1800 cGy in 1#
1700 cGy in 1#
1500 cGy in 1#
1400 cGy in 1#
1200 cGy in 1# (but < 50 cm max. diameter)
References Brain Metastases
[1] Andrews D et al. Whole Brain Radiation with or without SRS boost for patients
with 1-3 mets: phase III results of the RTOG 9508. 2004 Lancet; May 363: 1665-72.
[2] Muacevic A et al. Microsurgery plus whole brain irradiation versus Gamma
Knife surgery alone for treatment of single brain mets: an RCT. 2008 J Neurooncol
87:299-307.
[3]Aoyama H et al. Stereotactic Radiosurgery Plus WBRT v SRS alone for brain
mets. 2006 JAMA295:2483-91.
[4]Kocher M et al. Adjuvant WBRT vs OBS after SRS or Sx for 1-3 brain mets:
EORTC 22952-26001. JCO 2011. 29:134-41.
[5] Sperduto P et al. DSGPA and outcomes for patients with newly diagnosed brain
mets: A multi-institutional analysis of 4259 Patients. 2010 RED. 77(3): 655-61.
[6]Blonigen et al. Irradiated volume as a predictor of Necrosis after SRS. 2010
RED: 77(4); 996-1001.
[7] Soltys S et al. SRS of the postoperative resection cavity for brain mets, 2008
RED: 70(1); 187-93.
[8]Koyfman S et al. SRS for single brainstem mets: The Cleveland Clinic
Experience. 2010 RED: 78(2); 409-414.
[9] Scoccianti S et al. Treatment of brain mets: Review of phase III RCT. 2012
GREEN:102; 168-79.
[10]Linskey M et al. The role of SRS in the management of newly diagnosed brain
mets: guideline. 2010 J Neurooncol: 96:45-68.
[11] Ammirati et al. The role of retreatment in the management of
recurrent/progressive brain mets: guideline. 2010 J Neurooncol 96:85-96.
18
BRAIN STEM GLIOMA:
No biopsy is recommended if glioma is a diffuse pontine type. If exophytic, a biopsy or
debulking surgery may be possible. Radiation treatment is recommended and adjuvant
chemotherapy with BCNU or temozolomide (see appendix A) may be offered in selected
cases.
Target volume (CTV) – surgical defect and any T2 abnormality plus 1.5 cm. margin
on postop T2 MRI
Dose – 5400 cGy in 30# to isocentre
RT to start urgently
EPENDYMOMA & ANAPLASTIC EPENDYMOMA:
Patients will receive maximum safe surgical resection with a gross total resection
attempted where possible. Postop radiation treatment is recommended in all cases after
staging with neuraxis MRI and LP for cytology.
(a). No dissemination on neuraxis MRI and CSF negative
Target volume (CTV) – surgical defect and any enhancing abnormality plus 1.0
cm. margin on postop T1 + gad MRI
Dose – 5940 cGy in 33# to isocentre
(b). Dissemination or positive CSF
Target volume (CTV) – whole brain and meninges and spine to ~S2/3
posterior fossa for boost
or surgical defect and any enhancing abnormality plus 1.5
cm. margin on postop T1 + gad MRI if supratentorial
Dose – 3960 cGy in 22# to MPD of cranium
3960 cGy in 22# to anterior spinal canal
1620 cGy in 9# to posterior fossa or supratentorial boost
540 cGy in 3# boost to metastases
19
PINEAL TUMOURS :
Pineocytoma :
Patients will receive maximum safe surgical resection with a gross total resection
attempted where possible. Postop radiation treatment is recommended in all cases after
staging with neuraxis MRI.
Target volume (CTV) – surgical defect and any enhancing abnormality plus 1.0
cm. margin on postop T1 + gad MRI
Dose – 5400 cGy in 30# to isocentre
Reference Pineal Gland:
[1] Kano H et al. Roleof SRS in the management of pineal parenchymal tumours.
2009 Prog Neurol Surg; 23:45-58.
Pineoblastoma :
Patients will receive maximum safe surgical resection with a gross total resection
attempted where possible. Postop radiation treatment and chemotherapy is recommended
in all cases after staging with neuraxis MRI and LP for cytology. Craniospinal dose /
fractionation as for PNET.
SPINE TUMOURS :
Patients will receive maximum safe surgical resection with a gross total resection
attempted where possible. Postop radiation treatment is recommended in all cases unless
a gross total resection is achieved (when patients can be observed with regular MRI
imaging). Patients with ependymoma should have a cranial MRI performed. For high
grade astrocytomas, consider more extensive radiation volumes and concurrent and
adjuvant TMZ.
Dose given is 5000cGy in 30# to anterior extent of tumour if using a direct
posterior field. Margin depends on tumour type – refer to appropriate section.
20
HAEMANGIOBLASTOMA & HAEMANGIOPERICYTOMA
Haemangioblastoma will be resected surgically or have radiosurgery if surgery
contraindicated. Check for Von Hippel Lindau Disease.
Haemangiopericytoma patients will receive maximum safe surgical resection followed by
postop radiation treatment.
Target volume (CTV) – surgical defect and any enhancing abnormality plus 1.0
cm. margin on postop T1 + gad MRI
Dose – 5400 cGy in 30# to isocentre
Radiosurgery is an option for small haemangioblastomas
PTV < 20 mm
PTV 21-30 mm
PTV 31-40 mm
2000 cGy
1800 cGy
1500 cGy
For small haemagiopericytomas
PTV <40 mm
1400-1600 cGy
References Haemangioblastoma
[1] Asthagiri et al. Prospective evaluation of radiosurgery for hemangioblastomas
in VHL. 2010 Neuro-Oncology: 12(1):80-86.
[2] Veeravagu et al. Cyberknife Stereotactic Radiosurgery for Recurrent,
Metastatic and Residual Hemangiopericytomas. 2011 J Heamatol Oncol;
4(26):online.
21
GERM CELL TUMOURS:
Germinoma: (80% 5 year OS)
Radiation treatment is recommended for all patients. See COG ACNS0232 protocol for
details.
Volume – ventricles with boost to involved field unless disseminated when CSI
Dose – 2400 cGy at 150 cGy per fraction to ventricles or CSI
2100 cGy at 150 cGy per fraction to involved field
Non-germinomatous germ cell tumour (NGGCT): (20-45% 5 year OS)
Radiation treatment is recommended for all patients. See COG ACNS0122 protocol for
details.
Volume – CSI with boost to involved field
Dose – 3600 cGy in 20 # CSI
1800 cGy in 10# to involved field
22
APPENDIX A – RADIATION TOLERANCE DOSES
The following structures should have the maximum dose limited to the prescribed dose or
tolerance dose shown (whichever is lower) unless that would require shielding CTV or
GTV. Daily fraction size is 180-200 cGy.
Optic chiasm & nerves
5500 cGy (or 5000 cGy for benign tumours)
Retina
5000 cGy
Pituitary
5500 cGy
Brain stem
6000 cGy
Lens
1000 cGy (700 cGy on RTOG study)
Cervical spine
5000 cGy
Whole spine
4000 cGy
Partial spine
5000 cGy
Cochlea
4500 cGy
Lacrimal gland
5000 cGy
Hippocampus
D100% <= 1000 cGy and max point dose <17Gy
RADIOSURGERY (Max point dose) Timmerman Seminars in Radiation Oncology
Oct 2008
Optic chiasm & nerves
1000 cGy
Brain stem
1500 cGy
Eloquent cortex
1500 cGy
Cochlea & other cranial nerves
1200 cGy
Lens
100 cGy
Brachial plexus
1600 cGy
Hippocampus
1000 cGy
23
APPENDIX B – CHEMOTHERAPY REGIMES
1. TEMOZOLOMIDE:
Indications:


Recurrent anaplastic astrocytoma, glioblastoma multiforme or anaplastic
oligodendroglioma
Low grade oligodendroglioma (selected cases)
Premedications:


Ondansetron 8 mg po starting 30 minutes prior to temozolomide, then
prochlorperazine 10 mg po q 6h prn
Granisetron 1 mg po q12h can be used instead of ondansetron
Treatment Schedule:
Drug
Temozolomide


Dose
150 mg/m2 once daily
for 5 days
Administration
oral
Dose may start at 200 mg/m2 for chemo-naïve patients
Dose may be increased to 200 mg/m2 for second and subsequent cycle if no
significant toxicity with 150 mg/m2
Cycle Frequency:
Recurrent anaplastic astrocytoma, glioblastoma multiforme or anaplastic
oligodendroglioma
 Repeat every 4 weeks x 12 cycles, to a maximum of 24 cycles
Low grade oligodendroglioma
 Repeat cycles every 4 weeks x 12 cycles
24
2. LOMUSTINE (CCNU):
Indications:
Recurrent anaplastic astrocytoma, glioblastoma multiforme or anaplastic
oligodendroglioma
Premedications:



Ondansetron 8 mg po starting 30 minutes prior to lomustine then prochlorperazine
10 mg po q 6h prn
Granisetron 1 mg po q12h can be used instead of ondansetron
Dexamethasone 12 mg po starting 30 minutes prior to lomustine, then 4 mg q12h
for 48 to 72 hours
Treatment Schedule:
Day
1
Drug
Lomustine (CCNU)
Dose
130 mg/m2 at bedtime
Administration
oral
Cycle Frequency:
Repeat cycles every 6 – 8 weeks x 6 cycles
25
3. CONCOMITANT WITH RADIATION AND ADJUVANT TEMOZOLOMIDE
Indications:
Newly diagnosed glioblastoma multiforme, anaplastic astrocytoma and anaplastic
oligodendroglioma in patients aged <65 years.
Premedications:



Prochlorperazine 10 mg po q6h prn for concomitant temozolomide and radiation
Ondansetron 8 mg po starting 30 minutes prior to temozolomide for adjuvant
temozolomide monotherapy
Granisetron 1 mg po q12h can be used instead of ondansetron
Treatment Schedule:
Drug
Temozolomide
Dose
Administration
75 mg/m2 once daily x 42 consecutive days
oral
concomitantly with fractionated radiation
followed by temozolomide monotherapy 200
mg/m2 x 5 days, every 28 days for 6 cycles if no
measurable disease at start or to maximal
response plus two cycles up to twelve cycles
total if disease measurable.
Antibiotic prophylaxis:
Consider the use of TMP / SMX prophylaxis during concurrent TMZ administration.
26
APPENDIX C: NEURO-ONCOLOGY DRIVING GUIDANCE
No driving during and after therapy for time period specified. At that point, patient
can be reviewed and allowed to drive if brain tumour is stable. Submit form as
specified to MOT and code K035 to OHIP.
Condition
Submit form to MOT
Time period
Seizure
Yes
1 year seizure free
Visual field defect
No
refer to ophtho
Significant neuro deficits
Yes
or refer to neuro
Brain metastases
Single posterior fossa
Single supratentorial
Others
No
No
Yes
1 month
3 months
1 year
Glioma (grade I&II)
Yes
1 year
Glioma (grade III&IV) / PNET
Yes
2 years
Pituitary adenoma
No
1 month
Schwannoma
No
1 month
Craniopharyngioma
No
1 month
Meningioma (grade 1)
No
1 month
Meningioma (grade 2 / 3)
Yes
1 year
27
APPENDIX D: KPS/ECOG PERFORMANCE SCALES
28