CNS III Low Grade Glioma Flashcards
what percentage of LGG transform into high grade glioma
45%-74%
LGG presentation
- most patients present with seizures. Other presentations include personality changes, nausea, headache and lethargy
-> location and size of the tumour dictates symptoms - usually present in the frontal or temporal lobes, grow along white matter tracts and can traverse into contralateral hemisphere
- incidence peaks in adulthood with increased prevalence in Caucasians and those who were assigned male gender at birth
- LGG consist of both WHO Grade 1 tumours (pilocytic - mainly children) and WHO Grade 2 tumours
- presents as non-enhancing lesion with limited associated oedema
Initial Management of LGG
- based on symptoms of patient
-> high prevalence of seizures so ant-epileptic drugs are used for early seizure control but about half of patients are refractory (drug doesn’t work on you) to these
-> in cases with oedema, steroids can be administered - surgery is the first line treatment
-> provides tissue to confirm the diagnosis
-> extent of resection is associated with (in retrospective analyses): - prolonged survival
- greater seizure control
- reduced risk of transformation to a higher grade
RT Management of LGG
Goals of management
- to prolong OS
- to prolong PFS
- minimise morbidity
to achieve this we must:
- prevent tumour enlargement
- prevent transformation from LGG to HGG
- minimise treatment-related complications (chronic condition)
treatment-related complication from RT
RT causes:
- oedema from breakdown of blood-brain barrier
- a general pro-inflammatory state in the brain, further sustained by microglial activation and proliferation
- reactive gliosis (a change in glial cells in response to damage)
These manifest in patients as:
- headache, dizziness, nausea, vomiting, seizures, altered levels of alertness, personality change in the acute setting
- neurocognitive decline (correlated to specific structural cerebral changes), leukoencephalopthy, tissue necrosis in the late setting
RT management of LGG
Main area of controversy:
role and timing of RT (adjuvant vs delayed until evidence of clinical progression, given potential treatment-related complications
RT Management of LGG
EORTC 22845 trial (2002: Karim et al, and 2005 follow up: van den Bent et al)
- 311 patients from 24 institutions in Europe were randomised to receive either immediate RT post surgical resection to 54Gy in 1.8Gy fractions or to receive no RT until progression. 154 were in the intervention arm and 157 in the control arm
- had to have a WHO PS of 0-2 or a KPS of at least 60
- median age in the intervention arm was 36.5 years and was 41 years in the control arm
- median follow up was 8 years. immediate RT group had a significantly prolonged PFS (median 5.4 vs 3.7 years) but there was no difference in OS (7.4 vs 7.2 years)
- intervention arm patients had slightly better PS as seizures were better controlled
=> this trial tells us: absence of OS benefit illustrates that RT slows progression but does not prevent transformation into HGG
what characteristics of grade 2 LGG patients signify a poorer prognosis than in others, which can help clinicians and patients to decide on how to proceed:
- > 40 years old
- incomplete surgical resection
- large pre-operative tumour size (> 4cms)
- tumours crossing midline
- adverse tissue molecular characteristics (IDH wildtype, lack of 1p/19q deletion)
RT management of LGG: positioning & immobilisation
Supine, 3 point mask, shimms but should not have same issue with oedema as with GBM, knee rest for comfort, neutral. Take out hearing aids, if patient wants to keep in dentures they can because you are treating brain. Sometimes safety feature to remove dentures. If patient was claustrophobic open face mask if chin and forehead are very well immobilised with SGRT setup relative to a mark based setup on masks evidence behind thermoplastic masks, other types of thermoplastic masks, how to make masks well Consider claustrophobia. Do not consider medication straight away consider other options first (xanax). FALLS risk
RT management of LGG: Simulation / CT
Clear vertex of the skull to C2. with LGG you are unlikely to come through with vertex field. Lipid based contrast if not contraindicated. Slice thickness of 1-2.5cm. discuss pros & cons of slice thickness - treatment planning thinner / thicker slices Consider dose length produce (DLP) when selecting pre-sets. A vendor will always up everything and do not really care about the DLP.
RT management of LGG: Treatment Planning
IMRT/VMAT with avoidance sectors to reduce dose to OARs. Inverse optimised and priority to target coverage. GTV = gross demonstrable tumour on imaging. No GTV if R0 resection. CTV = microscopic spread. Follow white matter tract. GTV + 1-1.5cm. PTV = CTV + IM + setup margin. OARs: brainstem, cochlea, optic apparatus, hypothalamus, lacrimal gland, pituitary, hippocampus, orbits, lens, spinal cord, inner ear, normal brain parenchyma. Because of the chronic nature of LGG, if you breach the DVCs, the effects of it have the time to manifest in these patients. *when listing OARs you must give the metric** 54Gy/30#s 1.8Gy/#
RT management of LGG: Treatment Verification
1) Daily online imaging (CBCTs or KVs) make reference to equipment
2) Offline imaging eNAL (days 1-4, shifts and then verifying weekly) expand on this
Mostly bony matches. Should be a relatively straight forward verification - little oedema
Can reduce dose to lenses while taking verification images through use of imaging
Verification dose should be considered in your plan and should be incorporated into your plan. This is always done in the Dutch centres
RT management of LGG: on treatment supportive, side effect and psychosocial care
Headaches (steroid situation), fatigue, nausea, balance issues and vision issues. Falls risk. Gentle exercise. Potential hair loss - very delicate conversation chronic disease. Pain management. Anti-sickness (zofran - loperamide). Checking support network. Check that patient can afford the drugs needed. Check understanding of prognosis
RT management of LGG: dosing
standard EBRT total dose for LGG is 54Gy in 1.8Gy dose/# in 30#s but a range from 45Gy to 60Gy can be observed
- GTV:
-> region of high signal intensity on T2 weighted MRI scan (pre-op) or FLAIR sequences corresponding to the hypodense area on CT images
-> GTV (post-op) = operative cavity and residual tumour based on post-operative imaging - CTV:
-> GTV + 1-1.5cm
-> anatomical boundaries should be respected e.g tentorium, flax, bone - PTV:
-> CTV + 0.3-0.5cm
-> smaller margins may be used if departmental set up error has been appropriately quantified
Current trials in LGG
1608-EORTC-BTG[I-WOT]) is a phase III trial currently recruiting patients with LGG
Aim: to investigate whether early post-op RT of IDH-mutated 1p/19q intact astrocytoma patients combined with chemotherapy would improve outcome and improve QoL
