This document discusses the role of radiotherapy in treating acute leukemia in the central nervous system. It notes that intrathecal drugs do not evenly distribute throughout the brain and spinal cord, so cranial radiotherapy is used along with intrathecal chemotherapy to more fully treat the entire central nervous system. Studies from the 1960s showed that cranial radiotherapy reduced CNS relapse rates in pediatric ALL patients from 65% to 4%. More recent trials have aimed to reduce radiation doses to decrease side effects, focusing cranial radiotherapy only on high-risk patients. Doses as low as 12Gy have proven effective in some studies while maintaining low CNS relapse rates below 5%. Therapeutic radiotherapy is also discussed for treating isolated CNS

1. ROLE OF RADIOTHERAPY IN ACUTE LEUKEMIA
• Intrathecal (IT) drugs distribute unevenly , throughout the
subarachnoid space.
• IT therapy undertreat the ventricular spaces & cerebral/
cerebellar sulci as well as any gross disease extending into
the brain substance.
• This concept has lead to combining of cranial R.T with
IT C.T later to cover the spinal subarachnoid space.
• When CSI is needed to treat higher burden of CNS
leukemia , IT therapy allows spine to be treated with lower
dose.

2. CNS PROPHYLAXIS OF ACUTE LEUKEMIA & ROLE
OF CRANIAL R.T :-
• Previously It was considered that CNS is a site , protected from
chemotherapy by BBB.
• CNS disease was capable of reseeding the blood & marrow.
• Overall only 15-20% of paediatric ALL pt with high risk feature
require Cranial RT .
• Studies 5 & 6 in 1962-1967 from SJCRH established that CSI to 24gy in
15-16 # reduce CNS relapse rate from 65% to 4%.
• SJRCH study 8, std maintenance with oral MTX and mercaptopurine
following cranial RT along with IT MTX to treat spinal subarachnoid
have lowest CNS relapse & least toxicity.

3. • Cranial irradiation & IT MTX proved to be superior with
respect to both CNS and systemic relapse rate.
• Regarding present day use of prophylactic Cranial RT, pt
who are at highest risk of CNS relapse are been focussed.
• Use of cranial R.t in paediatric ALL has been to use it in
high risk pt ,at the same time reducing radiation doses to
decrease the late effect which includes learning disabilities,
cognitive defects, growth retardation , hypopituitarism,
secondary malignancies & leukoencephalopathy.
• COG has followed with reduction in cranial radiation dose
in its current ALL trials.

4. • To reduce the toxicity of prophylactic cranial R.T,
reduction in radiation dose is been suggested by
investigators.
• Pt being T/td with BFM type chemotherapy may be t/td
with lower dose of cranial R.T of 12gy.
• ALL BFM 90 protocol stopped using cranial R.T in low or
std risk pt, but medium and high risk pr received 12gy
prophylactic cranial R.T result in CNS recurrence rate <5%.
• ALL BFM 90 protocol, which utilizes cranial rather than CSI
- avoid any RT < 1 year of age.
- 18gy for 1-2 year of age.
- 24gy for older patient.

5. THERAPEUTIC CNS R.T FOR MENINGEAL RELAPSE
• Experience within POG with isolated CNS relapse of ALL in
which RT used cranial dose 24gy and spine dose of 15gy,
the 4 year event free survival was 71%.
• Pt who presented with > 18 month DF interval prior to CNS
relapse has a 4yr event free survival of 83% compared to
46% for those with shorter remission duration.
• POG trial suggested to omit RT to spine if there is long DF
interval , but if DF interval is <18 months 24gy to brain
while 15gy is delivered to the spine.
• High dose Ara-C is been added to mx of CNS relapse ,
More et al reported 63% complete response rate.

6. • In case of testicular relapse both intensive C.T & local
RT is indicated.
• Dose of 24 to 26gy over 2.5 to 3.5 weeks is std.
• Data from CCG & POG studies suggests that local RT &
intensive systemic CT results in prolonged event free
survival in roughly 50-65% of pt.