THESIS-STUDY OF EPIDEMIOLOGY AND TREATMENT OUTCOME USING BARTHEL’S INDEX IN METASTATIC BRAIN TUMORS

1. STUDY OF EPIDEMIOLOGY AND
TREATMENT OUTCOME USING
BARTHEL’S INDEX IN METASTATIC
BRAIN TUMORS
PATRO K.C,SOY.L.M, KAKKAR.S, PADHI.S,
SENAPATI S.N, SINGH D.N

2. WHY THIS STUDY
In recent years there have been important
advances in the diagnosis and management of
brain metastasis. As a result most patients receive
effective palliation and the majorities do not die due
to complication of brain metastases.
Controversy still exists regarding the demographic
profile, radiotherapeutic dose fractionation in brain
secondaries, which requires further evaluation.
In view of the challenging role of radiotherapy in
management of intracranial neoplasms, the aim of
present study is to analyze the epidemiology and
treatment outcome in metastatic brain tumors.

3. AIMS & OBJECTIVES OF STUDY
To study various epidemiological aspects i.e. age,
sex, single vs. multiple, primary site distribution,
controlled vs. uncontrolled primary, sign and
symptoms,
Analysis of symptomatic improvement after
treatment using Barthel’s index.
To assess any survival advantage by using two
radiation protocols (ARM-A 300cGy/# X10# ,ARM-
B 400cGy/# x5#)

4. STUDY DETAILS
PLACE OF STUDY
---REGIONAL CANCER CENTRE
CUTTACK
PERIOD OF STUDY
---October 2003-Octeber 2005
TOTAL NO OF PATIENTS
---51

5. MATERIAL & METHODS
INCLUSION CRITERIAS FOR TREATMENT
1. Brain secondaries diagnosed on the basis of
CT/MRI scan with multiple metastasis.
2. Patients having ECOG performance status
0, 1, 2
3. Life expectancy >3 month
4. No prior RT to brain

6. EXCLUSION CRITERIAS FOR
TREATMENT
1. Brain secondaries diagnosed on the basis
of CT/MRI scan with single metastasis.
2. Patients having ECOG performance status
>2
3. Life expectancy <3 months
4. Prior RT to brain

7. TREATMENT DETAILS
Machine  Cobalt—60
Portal  As for whole brain RT
Technique  Bilateral opposing
Dose ARM—A300cGy/# x10# over 2week
ARM—B400cGy/# x5# over 1week
Medications Low dose steroids, antiematics,
anticonvulsants as needed and supportive care.

8. END POINTS & STATISTICAL ANALYSIS;
Distribution of age
Distribution of Sex
Site of lesion in brain:
Type of lesion: (single vs. Multiple)
Site of primary giving rise to metastasis:
Clinical features
Controlled primary vs. uncontrolled primary
Symptomatic improvement analysis just after
treatment using Barthel’s index.
Response rate on CT scan after 3 month:
Treatment morbidity
Median survival following RT
Stastical analysis was done on SPSS version 11.0

9. EPIDEMIOLOGICAL
ANALYSIS

10. AGE DISTRIBUTION
C
A
S
E
S
0
1 1
8
18
22
1
0
5
10
15
20
25
0-10
yrs
11-20
yrs
21-30
yrs
31-40
yrs
41-50
yrs
51-60
yrs
61-70
yrs
AGE GROUP
0-10
YRS
11-20
YRS
21-30
YRS
31-40
YRS
41-50
YRS
50-60
YRS
60-70
YRS
NO. OF CASES 0 1 1 8 18 22 1
TOTAL-51=100% 0% 2% 2% 15% 35% 43% 2%

11. SEX DISTRIBUTION
49%
51%
MALE FEMALE
Patients Male Female
51 26 25
100% 51% 49%

12. DISTRIBUTION OF PRIMARY
37%
35%
4%
4%
2%
2%
2%
2% 10%
2%
Lungs
Breast
Esophagus
Renal cell carcinoma
Lymphoma
Ewings sarcoma
Ovary
Choriocarcinoma
Urinary bladder
Unknown primary

13. SOLITARY VS MULTIPLE
C
A
S
E
S
35%
65%
0%
10%
20%
30%
40%
50%
60%
70%
SINGLE
METASTASIS
MULTIPLE
METASTASIS
Total cases Single metastasis Multiple metastasis
51 18 33
100% 35% 65%

14. LESION SITES IN BRAIN
54%
23%
3%
17%
2% 1%
PARIETAL
FRONTAL
TEMPORAL
OCCIPITAL
CEREBELLAR
OTHER
Total
Lesion
Frontal Parietal Temporal Occipital Cerebellar Other
94 22 50 3 16 2 1
100% 23% 54% 3% 17% 2% 1%

15. SYMPTOMATIC PRESENTATION
28
18
12
2
9
32
HEADACHE VOMITING
NEUROLOGCAL DEFICIT SEIZURE
CEREBELLAR SIGNS VISUAL SUMPOM
Sl.
No
Symptoms No. of
Cases
Percent
age
1 Headache 32 62%
2 Vomiting 28 55%
3 Neurological
deficit
18 35%
4 Seizures 12 24%
5 Cerebellar
signs
2 4%
6 Visual
symptoms
9 18%

16. CONTROLLED PRIMARY VS
UNCONTROLLED PRIMARY
12
39
0
5
10
15
20
25
30
35
40
controlled primary
uncontrolled primary
C
A
S
E
S
Cases Controlled
Primary
Uncontrolled
Primary
51 12 39
100% 24% 76%

17. DISTRIBUTION OF PATIENTS IN
DIFFRERENT TREATMENT ARMS
18 15
0
3
6
9
12
15
18
ARM-A ARM-B
LESION ARM Patient Dose/# TTD NO. OF #
Multiple A 18 300cGy 30 10
Multiple B 15 400cGy 20 5

18. ANALYSIS OF
SYMPTOMATIC
IMPROVEMENT USING
BARTHEL’S INDEX

19. BARTHEL INDEX)
No. Activity 0 1 2
1 Bowel Incontinent Occasional Accident Continent
2 Bladder Incontinent Occasional Accident Continent
3 Feeding Unable Can manage with some help Independent
4 Grooming Unable Can manage with some help Independent
5. Dressing Unable Can manage with some help Independent
6 Transfer Unable Can manage with some help Independent
7 Toilet use Unable Can manage with some help Independent
8 Walking Unable Can manage with some help Independent
9 Stairs Unable Can manage with some help Independent
10 Bathing Unable Can manage with some help Independent
Adjustment Daily Life (ADL) SCORE
Maximum Score - 20
Dependant - <10
Semi dependant - 10-14

20. ASSESSMENT OF SYMPTOMATIC IMPROVEMENT
AFTER RADIOTHERAPY USING BARTHEL’S
ADJUSTMENT DAILY LIFE (ADL) SCORE IN ARM-A
0
2
4
6
8
10
12
14
16
PRE TT JUST AFT.TT AT 6WK
0--10 11--14 15--20
ADL SCORE PRE TREATMENT ARM-
A
POST TREATMENT
ARM-A JUST AFTER TT
POST TREATMENT
ARM-A AT 6WK
0 – 10 0 0 0
11 – 14 8 2 3
15 – 20 10 16 13

21. ASSESSMENT OF SYMPTOMATIC IMPROVEMENT
AFTER RADIOTHERAPY USING BARTHEL’S
ADJUSTMENT DAILY LIFE (ADL) SCORE IN ARM-B
0
2
4
6
8
10
12
PRE TT JUST AFT.TT AT 6WK
0--10 11--14 15--20
ADL
SCORE
PRE TREATMENT
ARM-B
POST TREATMENT ARM-B
JUST AFTER TT
POST TREATMENT
ARM-B AT 6WK
0 – 10 0 0 0
11 – 14 9 3 4
15 – 20 6 12 11

22. TREATMENT MORBIDITY ARM-A
0
15
3
0 0
4
11
3
0 0
8
4
4
2
0
0
2
4
6
8
10
12
14
16
Skin GI CNS
Grade-0 Grade-1 Grade-2
Grade-3 Grade-4
Acute Morbidity RTOG
Grade-0
(n)
RTOG
Grade-1
(n)
RTOG
Grade-2
(n)
RTOG
Grade-3
(n)
RTOG
Grade-4 (n)
Skin Changes 0 15 3 0 0
Up.Gi Changes 4 11 3 0 0
Cns Changes 8 4 4 2 0

23. TREATMENT MORBIDITY ARM-B
0
13
2
0 0
8
6
1
0 0
4
9
2
0
0
0
2
4
6
8
10
12
14
Skin GI CNS
Grade-0 Grade-1 Grade-2
Grade-3 Grade-4
Acute Morbidity RTOG
Grade-0 (n)
RTOG
Grade-1 (n)
RTOG
Grade-2 (n)
RTOG
Grade-3
(n)
RTOG
Grade-4 (n)
Skin Changes 0 13 2 0 0
UP.GI changes 4 9 2 0 0
CNS Changes 8 6 1 0 0

24. RESPONSE RATE(%)
62
53
28
20
5
20
5 7
0
10
20
30
40
50
60
70
CR PR SD PD
ARM-A ARM-B
Response
Criteria
Arm A Arm B
Complete
response
(CR)
62% 53%
Partial response
(PR) 28% 20%
Stable disease
(SD) 5% 20%
Progressive
disease (PD) 5% 7%

25. CT scan picture of multiple brain secondaries before treatment and CT scan picture
of same patient 3 months after treatment showing complete response
COMPLETE RESPONSE
PRE RT POST RT(AT 3M)

26. CT scan picture of multiple brain secondaries before treatment and CT scan picture
of same patient 3 months after treatment showing progressive disease
PROGRESSIVE DISEASE
PRE RT POST RT(AT 3M)

27. CT scan picture of multiple brain secondaries before treatment and CT scan picture
of same patient 3 months after treatment showing stable disease
STABLE DISEASE
PRE RT POST RT(AT 3M)

28. MEDIAN SURVIVAL
S
U
R
V
I
V
A
L
(WKs)
24
27.43
0
4
8
12
16
20
24
28
ARM A ARM B
ARM Median Survival (wks)
ARM-A-WBRT 30Gy IN 10# 24
ARM-B-WBRT 20Gy IN 5# 27.43

29. Survival Function
SURVIVAL
400
300
200
100
0
1.0
.8
.6
.4
.2
0.0
GROUP
Survival Function
SURVIVAL
400
300
200
100
0
Cum
Survival
1.0
.8
.6
.4
.2
0.0
GROUP
20 GY
30 GY
KAPLAN-MEIERSURVIVAL ANALYSIS

30. Survival Functions
SURVIVAL
400
300
200
100
0
1.0
.8
.6
.4
.2
0.0
GROUP
20 Gy
30 Gy
Survival Analysis for 30 Gy
Survival Time Standard Error 95% Confidence Interval
Mean: 165.78 23.04 ( 120.63, 210.93 )
Median: 168.00 20.03 ( 128.75, 207.25 )
Survival Analysis for 20 Gy
Survival Time Standard Error 95% Confidence Interval
Mean: 180.47 20.63 ( 140.03, 220.91 )
Median: 192.00 50.24 ( 93.54, 290.46 )
Survival Analysis for 30 Gy vs 20Gy
Total Number
Events Censored
GROUP 30 Gy 18 18
GROUP 20 Gy 15 15
Overall 33 33
Test Statistics for Equality of Survival Distributions for GROUP
Statistics df significance
Log Rank .25 1 .6190(P value) not significant

31. REVIEW OF LITERATURE
Distribution of primary
Author Lung Breast GIT Renal Mela-
noma
unknown Oth.
Zimm
et.al
1981
64% 15% 4% 2% 4% 8% 3%
Nussabau
m
et.al.
1996
39% 17% 6% 6% 11% 5% 16%
Present
study
37% 35% 4% 2% 0% 10% 12%

32. Symptomatic presentation
Author HEAD
ACHE
VOMITING NEUROL
OGICAL
DEFICIT
SEIZURE CEREBELL
AR SIGNS
VISUAL
SYMPTOMS
Posnere
t.al.
1980
53% -- 66% 15% 20% ---
Posnere
t.al.
1995
49% -- 59% 18% 21% 6%
Present
study
62% 55% 35% 24% 4% 18%

33. Median survival
Author Patients TOTAL DOSE NUMBER OF # MEDIAN
SURVIVAL
(MO)
Broglet et.al
1973
910 30Gy 10 5.2
Broglet et.al
1976
902 20Gy 5 4.0
kurtz et.al
1979
255 30Gy
50Gy
10
20
4.5
4.2
Philips et.al
1993
72 37.5Gy 15 6.1
Present
study
18
15
30Gy
20Gy
10
5
6
6.6

34. SUMMARY :
The present work conducted in a span of two years
It is an uncontrolled prospective study of patients with brain
secondaries, their incidence and response to radiotherapy. 51 eligible
patients enrolled during the study.
It is more common in male and occurred in 6th decade of life mostly
Headache was the commonest presenting symptom.
Carcinoma lung was the commonest primary giving rise to brain
metastasis followed by breast.
Multiple metastases were more common than the single group.
Supratentorial lesions were commoner than infratentorial lesions.
Among them parietal lobe was the commonest site of involvement.
Whole brain irradiation remains the most effective means for treating
the patients with brain metastases with symptoms relief occurring in
70-90% of patients.
In multiple secondaries in brain the median survival for external
radiotherapy 30 Gy in 10 fractions is equally effective as 20 Gy in 5
fractions.

35. CONCLUSION
The present study highlights that the incidence of brain metastasis is
common in elderly population and mostly due to primary lung
majority of lesions that has been observed at parietal lobe.
Radiotherapy is the mainstay of treatment to relieve the symptoms
which was observed through the ADL score. There is definite
improvement in the relief of symptoms and quality of life in addition
of radiotherapy
20Gy in 5# is equally effective with that of the 30Gy in 10#. So we
can opt for 20Gy in 5# to palliate the symptoms as there is no
change in overall survival in two arms.
In a palliative setting short duration of treatment with minimum
discomfort to the patient is desirable. So with accrual of more
number of patients we can also further confirm of that can we opt
for 20Gy in 5# than 30Gy in 10# ?