Brain Metastasases Clinical Trial
Official title:
Evaluation of Repeated Whole Brain Radiotherapy Versus Best Supportive Care for Multiple Brain Metastases - the Randomized Trial ERASER.
Whole Brain Radiotherapy (WBRT) has been established as the treatment standard in patients
with multiple cerebral metastases from solid tumors. However, intracerebral recurrence is
possible and a repeated WBRT may be indicated to improve intracerebral tumor control. Each
institutsion offers different dosing regimens, which have all been published to be safe and
effective. Some favor best supportive care only.
The current study protocol is aimed at evaluating primarily the toxicity as well as
secondarily the local and loco-regional tumor control, overall survival and QoL after
repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to
BSC.
According to Nussbaum et al., 24-45% of cancer patients develop cerebral metastases during
the course of the disease. Brain metastases are generally associated with a poor prognosis
and high morbidity. Published median survival rates after WBRT are between 2 and 7 months.
Standard of care in multiple BM is WBRT delivered as 30 Gy in 10 fractions, leading to modest
palliation with a median survival of 3 to 5 months. Prognostic factors include the
RPA-classification, performance status, response to steroids and evidence of systemic
disease.
Unfortunately, intracerebral recurrence happens. For example, in the cohort of Meyners et
al.(2010) on WBRT in relatively radioresistant tumors, median time to recurrence was
4.5months and the local control rates at 6 and 12 months post radiationem were 37% and 15%,
respectively. Furthermore, the treatment of intracerebral recurrence after previous WBRT is
challenging. In case of </= 3 recurrent BM, surgery or radiosurgery (RS) are options. One
other option, especially in case of >3 recurrent BM is repeated WBRT. In this setting, one of
the first reports on repeated WBRT was published by Cooper et al. in 1990. The authors
reported on repeated WBRT (n=52) consisting of 25 Gy in 10 fractions. Response to
reirradiation was seen in 42% of the patients. Furthermore, the patients improved by at least
one level in their neurologic function status. Survival after second therapy averaged 5
months. In the report by Wong et al. (1996) median dose of retreatment (n=86) was 20 Gy.
Resolution of symptoms was achieved in 27% of patients, partial improvement in 43% and no
improvement or worsening of symptoms was seen in 29% of patients. The majority of patients
had no significant toxicity secondary to re-irradiation. Five patients had radiographic
abnormalities of their brain consistent with radiation-related changes. One patient had
symptoms of dementia that was thought to be caused by radiotherapy. Sadikov et al. (2007)
reported on 72 patients who underwent repeated WBRT for recurrent or progressive BM. The
median survival after re-irradiation was 4.1 months. One patient was reported as having
memory impairment and pituitary insufficiency after 5 months of progression-free survival.
In the report by Mayer et al. on re-irradiation tolerance of the human brain -in this
analysis focused on recurrent glioma-, the authors concluded that radiation-induced brain
tissue necrosis is found to occur at normalized tolerance doses of cumulative > 100 Gy.
The current study protocol is aimed at evaluating primarily the toxicity as well as
secondarily the local and loco-regional tumor control, overall survival and QoL after
repeated WBRT using 2 different dose concepts (20 Gy in 10 Fx vs. 30 Gy in 15 Fx) compared to
BSC.
In the present trial, the primary endpoint toxicity as well as the secondary endpoints QoL,
loco-regional progression-free survival, overall survival and imaging response in patients
previously treated with WBRT requiring repeated WBRT for intracerebral tumor progression will
be evaluated.
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