CNS IV Brain Mets Flashcards
Management of Brain Metastases
- about 10-20% of all cancer patients develop brain metastases
-> incidence is increasing with refinement in diagnostic tools and improvements in primary treatments increase survival - tumours that metastasise frequently to the brain include: SCLC, RCC, Colorectal, Breast, Pancreas, Malignant Melanoma
-> incidence varies with different histologies e.g. at diagnosis 25% of malignant melanoma and metastatic lung adenocarcinoma patients have brain metastases, while this drops to 10% in RCC (Cagney et al., 2017) - usually multiple lesions. ‘single’ = one brain met, other sites of disease. ‘solitary’ = one brain met, only site of disease
- most frequent in frontal and parietal lobes
presenting signs and symptoms
- headaches - constant and can be worse at night or early in the morning
- seizures
- ataxia
- memory loss
- aphasia
- weakness in extremities
personalised approach
- brain mets are complex to treat
- shared decision-making is extremely important, patients need to be informed about the potential benefits and harms of each option
- specific patient context has to be considered - physical: number of metastases, frailty index etc, psychosocial: home
general management of brain metastases
steroid administration improves both headaches and neurologic function in symptomatic patients
- no impact on survival however
- dexamethasone dose should be tapered gradually
treatment options for brain mets
- whole brain radiation therapy
- stereotactic radiosurgery (SRS), stereotactic radiation therapy (SRT)
- surgery
- systemic therapies - these can be considered alone or in combination
supportive care if no active treatment is appropriate
whole brain RT: immobilisation
supine neutral position, 3 point mask
whole brain RT: scanning
not appropriate to have very small thickness. 2-2.5cm
whole brain RT: borders
posterior - clear posterior skull
superior - clear superior skull
inferior - C1/C2. German helmet - whole brain + more inferior border to C2/C3
anterior - worried about orbits. use half beam block and put isocentre at posterior orbits
you can do a clinical set-up for patients that are very unwell - not often done. 30-40deg up on teh collimator. Reid’s plane goes from supraorbital ridge to tragus of ear. Diagonal. Inferiorly as close to clearing skull as possible. Typically start with field size 20cm width x 15cm length. This might have to be adjusted
evidence for treatment options
WBRT and SRS verses WBRT alone
3 RCTs have assessed the combination of WBRT and SRS compared to WBRT only (Andrews et al., 2004, El Gantery et al., 2014, Kondziolka et al., 1999)
- no study reported a survival benefit or fewer deaths caused by brain mets with the combination treatment compared to WBRT only
- however, on subgroup analysis, Andrews et al. (RTOG 9508 trial) reported a survival benefit in a subgroup of patients with a single brain metastasis with teh combined SRS and WBRT as well as an increase in KPS
- Kondziolka et al. reported better local control in the combined treatment group (p = 0.002)
Evidence for treatment options
WBRT and surgery vs WBRT alone
3 RCTs have assessed the combination of WBRT and surgery compared to WBRT only (Mintz et al. 1996, Vecht et al. 1993, Noordijk et al., 1994)
- no study reported a benefit in OS when surgery was combined with WBRT compared to WBRT alone
Evidence for treatment options
WBRT with radiosensitisers vs WBRT alone
5 RCTs have assessed the combination of WBRT with radiosensitisers compared to WBRT only (Philips et al. 1995, Mehta et al., 2009, Rojas-Puentas et al., 2013, El-Hamamsy et al., 2016 and Mehta et al., 2003)
- no study reported a benefit in OS when surgery was combined with radiosensitisers compared to WBRT alone
Evidence for treatment options
WBRT fractionation schedules and techniques
6 RCTs compared different doses
- Chatani et al., 1994: 30Gy in 10# over 2 weeks vs. 50Gy in 20# over 4 weeks, 30Gy in 10# over 2 weeks vs. 20Gy in 5# over 1 week
- Davey et al., 2008: 40Gy in 20# of 2Gy bidaily vs. 20Gy in 5# over 1 week
- Graham et al., 2010: 20Gy in 4# within 1 week vs. 40Gy in 20# bidaily
- Murray et al., (RTOG 9104) 1997: 32Gy in 20# bidaily (1.6Gy/fraction) with a boost of 22.4Gy in 14# vs30Gy in 10#
- Priestman et al., 1996: 30Gy in 10# over 2 weeks vs. 12Gy in 2# on consecutive days
- Saha et al., 2014: 30Gy in 10# over 2 weeks vs. 20Gy in 5# over 1 week
no dose-response effect for OS, DFS or deaths due to brain metastases is found when data from all trials are combined in meta-analysis
Evidence for treatment options
WBRT with neuroprotection
1 RCT (RTOG 0614, Brown et al., 2013) has assessed the effect of memantine to WBRT
- Memantine is a N-methyl-D-Aspartate receptor antagonist
- it is used to treat moderate to severe dementia in Alzheimer’s Disease
-> trial illustrated that memantine delayed the risk of cognitive decline and reduced rates of decline in memory, executive function and processing speed, relative to WBRT alone
3 RCTs (Hauswald et al., 2019, Yang et al., 2019, Brown et al., 2020) have compared hippocampal avoidance WBRT compared to conventional WBRT
- Yang et al. found that hippocampal-avoidance WBRT resulted in better preservation of late verbal memory but not in verbal fluency or executive funtion
- Hippocampal avoidance WBRT combined with memantine resulted in a lower risk of cognitive failure, less deterioration of executive function and learning and memory in Brown et al. study relative to WBRT and memantine alone
ASCO-SNO-ASTRO guideline for treatment of Brain Metastases
1. Value of Surgery
- Panel agreed that surgery may be offered to patients with limited brain metastases, but it must be on a case-by-case basis
- Patients who have large tumours with mass effect may benefit from surgery
ASCO-SNO-ASTRO guideline for treatment of Brain Metastases
2. Value of Systemic Therapies
- evidence is limited
- panel consensus was that Temezolomide could not be recommended
- panel reviewed different agents for different brain metastases histologies (Melanoma, breast, lung)
