Prophylactic cranial irradiation for extensive stage small cell lung cancer Jiraporn Setakornnukul, MD

1. Prophylactic Cranial
Irradiation in Extensive
Stage Small Cell Lung Cancer
Jiraporn Setakornnukul, MD.
Division of Radiation Oncology, Department of Radiology
Faculty of Medicine Siriraj Hospital, Mahidol University

2. Outline
 Significance of brain metastases in SCLC
 PCI in ED with complete response:
evidence from IPD-metaanalyses
 Two major RCTs : EORTC & Japanese trials
 Worse prognosis in asymptomatic BM ?
 Significant neurocognitive toxicity ?

3. Introduction
 Worldwide, lung cancer occurred in
approximately 1.8 million patients in 2012
and caused an estimated 1.6 million
deaths
 95 % of all lung cancers are classified as
either small cell lung cancer (SCLC) or
non-small cell lung cancer (NSCLC)

4. Introduction
 SCLC represents about 15% of all lung
cancers
– Proportion of SCLC/Total lung cancer
 NCI Thailand (2011): 21/336 (6.25%)
 Siriraj Hospital (2009): 29/592 (4.9%)
 Nature: rapid doubling time, high growth
fraction, and the early development of
metastases
– 70% Extensive stage
– 30% Limited stage

5. Staging SCLC
Staging SCLC by Veterans' Affairs Lung
Study Group (VALSG)
 Limited stage: disease confine to one
hemithorax or radiotherapy portal field
 Extensive stage: tumor beyond the
boundaries of limited disease
– distant metastases
– malignant pericardial/pleural effusions
– contralateral supraclavicular and contralateral
hilar involvement

6. Treatment: ED-SCLC
 ED-SCLC is a disseminated disease
 Thus systemic chemotherapy is the initial
treatment

7. Background: Treatment outcomes
Response rate after combination CMT
 Complete response: usually around 10%
 Partial response: 33-45%
Survival rate after combination CMT
 Median survival: 6.9-11.5 mo.
 1yr-OS: 21-42%
 2yr-OS: usually less than 5%
Data from 2,580 patient SWOG data base
Kathy S., JCO 1990

8. Why PCI is the interesting role in
SCLC?
 Incidence of brain metastasis
– At diagnosis: 10-15%
– From autopsy: 35-55%
Elliott JA, JCO 1987
Bunn PA, Seminars in Oncology 1978
Pattern of failure
– Most common failure site: intrathoracic and
CNS

9. Outline
 Significance of brain metastases in SCLC
 PCI in ED with complete response:
evidence from IPD-metaanalyses
 Two major RCTs : EORTC & Japanese trials
 Worse prognosis in asymptomatic BM ?
 Significant neuocognitive toxicity ?

10. PCI for complete response ED-SCLC
 RR of death: 0.77 (0.54-1.11)
 RR of brain met: 0.38 (0.23-0.64)
 Cumulative incidence of BM at 3 yr (whole group)
33.3% for PCI and 58.6% for no PCI
(Absolute decrease 25.3%)

11. PCI for any response ED-SCLC
EORTC study
from Slotman; Published in
NEJM 2007
 Published study
 Pragmatic study
– Inhomogeneous
patients
– Clinical follow up
Japanese study
from Seto; Presented at ASCO
2014
 Abstract only
 Efficacy study
– Homogeneous
patients
– Need MRI brain
follow up
2014

12. ED-SCLC
Combination CMT
With any response
PCI: 20 Gy/5F,
25 Gy/8-10F, 30 Gy/10F
No PCI
Median time between diagnosis and randomization: 4.2 months

13. Primary end point: the development of symptomatic
brain metastases
BM 16.8% (PCI) VS 41.3% (no PCI)
Absolute reduction 24.5%
Relative reduction 2.46
MS 6.7 mo (PCI) VS 5.4 mo (no PCI)

15. Primary end point: Overall Survival
BM 32.4% (PCI) VS 58% (no PCI)
Absolute reduction 25.6%
Relative reduction 1.79

16. EORTC VS Japanese trial
EORTC Japanese study
Population Exclude symptomatic BM Exclude both symptomatic
& asymptomatic BM
F/U, CNS Clinical F/U
Symptomatic BM
MRI F/U
Mixed symptomatic &
asymptomatic BM
BM Absolute reduction 24.5% Absolute reduction 25.6%
PFS 14.7 wk (~3.67 mo) , PCI
12 wk (~3 mo), no PCI
2.2 mo, PCI
2.4 mo, no PCI
Salvage Rx
outside CNS
68% in PCI
45.1% in no PCI
81% in PCI
89% in no PCI
MS 6.7 mo in PCI
5.4 mo in no PCI
10.1 mo in PCI
15.1 mo in no PCI

17. Asymptomatic brain metastasis
Asymptomatic BM response rate
(CMT: cyclophosphamide, doxolubicine, and etoposide)
 Response rate: 27%
 CR rate 2/22 (9%) and PR rate 4/22 (18%)
 Median duration to symptomatic BM: 2.3 mo
(range, 0.5-5 mo)
 Median survival: 8.3 mo (1.3-43.4 mo)

18. Summary from two studies
 PCI can be omitted if patient get a good
follow up protocol such as MRI brain
every 3 months to early detect
asymptomatic BM
 Symptomatic BM may cause deteriorate
patient performance and cannot receive
salvage chemotherapy, so the survival
could decrease

19. Neurocognitive disorder
EORTC trial
 Role functioning, Cognitive functioning, and
Emotional functioning did not different between
PCI and no PCI
Grosshans et al.
 Persistent declines in cognitive function were not
observed after PCI (25Gy in 10F) in SCLC
 Do not favor omission PCI due to fears of
neurotoxic effects
Grosshans DR, Cancer 2008

20. Conclusion (1)
ED-SCLC: Complete response after
combination chemotherapy
 Should get PCI after CMT
 Data from Meta-analysis in 1999
– Gain survival benefit 5.4%
– Reduce BM 25.3%

21. Conclusion (2)
ED-SCLC: Any response (Partial response)
after combination chemotherapy
 Good Prognosis such as single metastasis
with complete systemic response
– Single metastasis: better prognosis
Foster NR, Cancer 2009
 PCI is the standard treatment in both
arms in ongoing RCT (EORTC and RTOG)
– role of thoracic radiotherapy after
chemotherapy

22. Conclusion (3)
ED-SCLC: Any response (Partial response)
after combination chemotherapy
 Moderate to poor prognosis such as
multiple metastases and partial response
of systemic metastasis
 Should receive PCI when patient cannot
do regular MRI F/U