1.

INTRODUCTION
Each year in the United States, more than 228,000 people are diagnosed with lung cancer
and nearly 160,000 die of the disease. Lung cancer takes more lives than breast, prostate
and colon cancers combined which accounts for about 27% of all cancer deaths. The rate
of lung cancer death is higher among veterans than non-veterans. Smoking is a significant
problem in the U.S. military. The smoking rates of military personnel, particularly
deployed personnel, are 50% greater than in the civilian population, according to an
Institute of Medicine (IoM) report in 2009.Beyond smoking, other inhaled exposures are
elevated among military personnel including radon, asbestos, depleted uranium used in
weapons and armor shielding, beryllium, fuel exhaust, and other battlefield emissions.
Lung cancer is a disease in which the cells of the lung tissues grow uncontrollably
and form tumors. Lung cancer is classified into two major groups: non-small cell lung
cancer (NSCLC), and small cell lung cancer (SCLC). According to the American
Cancer Society, approximately 85-90 percent of lung cancer cases are NSCLC and it is
further divided into three tumor histologic subtypes: adenocarcinoma (40%), squamous
cell carcinoma (25%-30%) and large cell carcinoma (10%-15%) whilst SCLC consist of
only one subtype; small cell (10%-15%).
Different types of treatments are available for lung cancer patients. Some
treatments are standard (the currently used treatment), and some are being tested in
clinical trials. A clinical trial is a research study meant to help improve current treatments
or obtain information on new treatments for patients with cancer.
A patients performance status also dictates the type of treatment regime
employed. Performance status can be assessed using a variety of assessment including
Karnofsky Performance Status (KPS) scale. The KPS scores range from 0 to 100. A
higher score means the patient is better able to carry out daily activities.

This report was mainly concerned with a study and analysis an estimation of the
survivorship time. The trial includes 137 advanced lung cancer patients collected by
Veterans Administration Lung Cancer Study Group (VALCSG). It focus on the
population of male veterans, in which patients aged 34 and above who have diagnosed
with advanced or inoperable lung cancer were treated with chemotherapy. Chemotherapy
is a treatment of cancer-killing drugs used to kill lung cancer cells. Patients were
randomized to one of the two chemotherapeutic agents; standard and test.The censored
time-to-event outcome is the lung cancer survival time ranging from 1 to 999 days. The
data set also contains the values of six other variables namely treatment type, tumor cell
type, performance status, months from diagnosis, age and prior therapy which were
recorded for each patient.
The objectives of this report are to identify important prognostic factors that
influence the survival of male patients with inoperable lung cancer among currently
living veterans. The primary purpose of the study was to compare patient survival for the
two treatment group i.e. patients who received standard treatment (the currently used
treatment) and test treatment (clinical trial). Besides that we want to study the main
covariates that influence the survival of lung cancer patients. The analysis is to determine
whether or not there exists a difference in types of tumor cells (adeno, squamous, large,
or smallcell), performance status (KPS score), patients age, and prior therapy attempted
have different survival rates. Furthermore we also want to look for the best model of any
variables that most influence the survival time of patients with inoperable lung cancer.

2.

LITERATURE REVIEW
This assignment presents a report of an investigation of lung cancer for two treatments of
standard and test with other factors affect. The study was about role of chemotherapy in
improving survival of patients with inoperable small lung cancer. Shajeem et al. (2003)
had taken the data of 82 patients with operable lung cancer which were treated under
Institute of Medical Education & Research in India for a period of January to June 2001.
There were divided into two groups based on treatment received which were
chemotherapy group and best supportive care group.
The survival was the main outcome of the study. Survival time was calculated
from the date of diagnosis. There were predictors of age, sex, histology, stage and
performance status (Karnofsky scale) were included to compare between two groups.
Method of Log-rank test was used for the differences between two groups and then
presented in a table. Kaplan Meier was used to represent in survival curve for all patients,
chemotherapy group and supportive care group from the trend of survival of patients
which is more patients were survived in chemotherapy group. The median survival for
chemotherapy group was higher as compared to supportive care group. There was
showed a significant improvement in survival in patients with inoperable lung cancer
with chemotherapy group as compared with best supportive care group.
A study of conducted by Schiller et al. (2002) to compare four chemotherapy
regimens for advanced non-small cell lung cancer with total of 1207 patients. The
patients were randomly assigned to a reference regimen of cisplatin and paclitaxel or
another three experimental regimes which were cisplatin and gemcitabine, cisplatin and
docetaxel or carboplatin and paclitaxel.
Survival was calculated from date of enrollment to date of death or date of patient
still alive. The variables that included in study were performance status, disease stage,
survival time and response of disease. Two-sided long rank test is used for comparison
between each survival distributions for three experimental regimens with control3

reference regimen. All survival distributions were estimated by Kaplan-Meier method. Pvalues are two-sided and were adjusted according to OBrien-Fleming method. As a
conclusion, there was no significant difference in survival among four chemotherapy
regimens of advanced non-small cell lung cancer.
Leah et al.(2013) examined the association between race and receipt of timely
non-small cell lung cancer care and survival among Veteran Affairs health care system
patients. Patients with late stage disease which are stage 3 and 4 have five-year survival
rates of 2%-15%. Receipt of timely was stage of appropriate care for non-small cell lung
cancer patients can increase length of survival. There were total of 2200 patients which
were including African American and Caucasian patients. The variables were included
demographic characteristics (age at diagnosis, marital status, and geographic region) and
clinical factors (stage at diagnosis and performance status) associated with timeliness of
care.
The Kaplan-Meier method was used to estimate time-to-event curves for racial
distribution of key variables for stage at diagnosis, performance stage and age. Then, the
comparison between African American and Caucasian patients was measured by log-rank
and Wilcoxon tests. Multivariate Cox proportional hazard models were used to test the
association between race and time to event after controlling the variables. Veteran Affairs
health care system provides racially equitable care but future work need for longer
periods of follow-up in other veteran groups.
Lee (2012) had compared the survival rate in patients with non-small cell lung
cancer among elderly patients that treated with radiofrequency ablation, surgery, or
chemotherapy according to staging of lung cancer. There are 77 patients meeting criteria
which were between year 2000 and 2004 that approved by Institutional Ethics
Committee. The comparison for long-term survival of patients was compared between
radiofrequency ablation and other treatments such as surgery and chemotherapy.

The demographic factors were age, sex, WHO performance status, clinical stage,
median of follow up interval and histology of cell. Chi-square test was used to compare
radiofrequency ablation group with comparison group for sex and age, WHO
performance status, clinical stage, follow-up interval, cell type and tumour size according
to staging of lung cancer. Deaths would be events of lung cancer. Kaplan Meier method
and log-rank test were used to calculate survival curves in patients treated with different
treatment and show differences between survival curves. Gehan-Breslow-Wilcoxon test
was used to make comparisons for different therapeutic modality (radiofrequency
ablation, chemotherapy and surgery). It could be concluded that radiofrequency ablation
can be used as an alternative treatment to surgery for elderly patients with stage I to II
inoperable cancer and therapy with chemotherapy was suitable for patients with stage III
to IV lung cancer.
The review of journal showed that Kaplan Meier method was used to show the
survival distributions with survival curve and median value for patients of lung cancer.
Log-rank test was then used for comparison between two different groups for different
study for lung cancer. Then, proportional hazard model was approach modeling for
survival data for different study to cure lung cancer. From the review of journal, the
survival time for the death as outcome of study which can be shown through Kaplan
Meier method by survival curve for different groups of treatment. Then, proportional
hazard model is built for other factors included.

3.

MATERIAL AND METHOD

3.1

Clinical Trial
This dataset is originated obtained from the book of The Statistical Analysis Of
Failure Time Data by J.D. Kalbfleisch and R.L. Prentice (1980) which construct a clinical
trial of inoperable lung cancer patients that taking almost 3 years. Usually for inoperable
or advanced lung cancer patient, there are two main treatment that can be used which is
chemotherapy and radiotherapy because these treatment can either reduce or stop the
cancer so that the symptoms of lung cancer will be reduced and prolong the patients
lifespan. For this study, Kalbfleisch and Prentice (1980) focused on treatment based on
chemotherapy. The primary endpoint for therapy comparison was time to death.

There are 137 male patients that suffered from inoperable lung cancer were
taking into this clinical trial. Out of 137 male patients, there only 9 of them were
censored. They were assigned into two main treatment group which is one of them is
standard treatment (treatment 1). This treatment referred to patient that received
chemotherapy of any routine for lung cancer disease and actually was currently used
treatment. According to Curtis L. Meinert (2012), standard treatment is a treatment that
widely practiced and routinely applied for a specified disease. Meanwhile the other one
treatment is test treatment (treatment 2) which basically used for clinical trial which is
best known as new treatment. According to Pigeot et al.(2003) in Modern Clinical Trial
Analysis by Wan Tang and Xin Tu (2012), test treatment is actually treatment that used to
compare with standard treatment which is its efficacy is clinically relevant. The dataset
6

shows that about 69 male patients within age (34-81 years old) were assigned in treatment
1 and treatment 2 consists of 68 male patients with age between (35 -81 years old).
There are six variables in this dataset that can be linked to the survival times of a

60 and

60

patient which is month from diagnosis to randomization., age in years

treatment that consists of standard and test treatment which had been explained above,
cell type that consists of 4 type (squamous, small, adeno and large), patients performance
score (Karnofsky Score) that had been randomized (10-30 completely hospitalized, 40-60
partial confinement, 70-90 able to care for self) and prior therapy (0 = no, 10 = yes).
Refer to Table 1 for brief explanation about Karnofsky Score. Adjustments were made for
several demographic and clinical factors, including age in years, Karnofsky Score and
time in months from diagnosis to randomization.

Score (%)
0
10
20

Definition
Dead
Moribund; fatal processes progressing rapidly.
Very sick; hospital admission necessary; Active supportive treatment

30

necessary.
Severely disabled; hospital admission is indicated although death not

40
50
60

imminent.
Disabled; requires special care and assistance.
Requires considerable assistance and frequent medical care.
Requires occasional assistance, but is able to care for most of his personal

70
80
90
100

needs.
Cares for self; unable to carry on normal activity or to do active work
Normal activity with efforts; some signs or symptoms of disease.
Able to carry on normal activity; Minor signs or symptoms of disease
Normal no complaints; no evidence of disease
Table 1 : Karnofsky Performance Status Scale Definitions Rating (%) Criteria.
7

(Source : Oxford Textbook of Palliative Medicine, Oxford University Press. 1993;109)

For the cell types, there are 2 major types of lung cancer which is small cell lung
cancer (SCLC) that consists of only one subtype of SCLC which is small cell
undifferentiated carcinoma and the other one is non-small cell lung cancer (NSCLC) that
consists of 3 subtypes of NSCLC which is adenocarcinoma, squamous cell carcinoma
and large cell carcinoma. For this study, these two major types are included. The dataset
shows that 31 male patients from both treatment suffered from squamous cell (celltype 1),
45 of them suffered from small cell (celltype 2), 26 of them suffered from adeno cell
(celltype 3) and the balance of 26 patients suffered from large cell (celltype 4). The more
brief explanation will be shown in next chapter.

Most important variables in this clinical data trial is absolutely survival time of all
patients in days. The survival times started to record from the moment the patients
entered this study and end whenever the patients died or lost to follow up in the 3 years
this data was studied. As was mentioned above, there were 9 out of 137 male patients
were diagnosed as censored data which means either the patients were survived until the
end of study or lost to follow up.

3.2

Statistical Analysis

For the analysis data, survival time was measured since the beginning of diagnosis
until the date of death or follow up of a patient was occured. Since the censored data was
present when this study was conducted, the best method that will be used is
nonparametric method that consists of Kaplan-Meier method and Actuarial method. As
for this study, survival analysis was performed using the well-known Kaplan-Meier
method. The main reason was using this method is because it is applicable either to small,
moderate and large samples. Kaplan-Meier method also is based on survival times of an
individual which means the time of a patient starting from certain point until the
occurence of the given event. Kaplan and Meier (1958) develop a product-limit (PL)
method of estimating the survivorship function.

d
S t 1 i
ni
ti t

ti

Where

di

is duration of study at point i,

ni

is the number of deaths up to the point i and

ti

is number of individuals at risk just prior to

. According to Kaplan and Meier (1958), if

ti

a subject is last to followed up at time

ti

and then leaves the study for any reason,

is

counted as their censoring time. Based on the assumptions, censored data can not be
tested to avoid bias in the data that as well reduces S.

Furthermore, according to Mantel, 1996; Peto & Peto, 1972, the most commonly
used for treatment differences with censored survival data is the log-rank test. The logrank test actually used to compare two or more group of survival times and also test the
null hypothesis of group that come from the same population. It is also known that if the
survival time t conditional on treatment assignment x follows the proportional hazards

model that was proposed by Cox (1972);

hi t | x h0 t exp ' x

,
or equivalently to;
hi t | x h0 t exp 1 xi1 2 xi 2 ......... k xik hi t

hi t | x

Where

denotes the conditional hazard rate of failing at time t given treatment

X=x for x = 0,1 respectively, the log-rank test is optimal for testing for treatment
H0 : 0

difference, for example to test null hypothesis

. For this clinical trial,

differences between two treatments were assessed by using log-rank test.

Even though this log-rank test was used to test the differences between two
treatment but does not mean that the other explanatory variables could be taken into
account also. So, for the other explanatory variables to be tested, cox proportional
hazards models were used. According to John Fox (2002), this model is semi parametric
because while the baseline hazard can take any form, the covariates enter the model
10

linearly. Besides that, cox proportional hazards model also used to identify association
between explanatory variables and survival times. Statistical significance that had been
p 0.05
considered to use in this study is at

. All the statistical analysis were performed

by using MINITAB 16.0.

4.

RESULT
A total of 137 patients who suffered from inoperable lung cancer were screened and 9
patients is lost to follow up. Among the rest, patients was divided into two group of
treatment ; standard teratment and test treatment and were follow up for a period of 3
years or until death. Out of these, for each treatment, 64 patiens received a standard
treatment and test treatment. Baseline characteristics of the two groups are shown in
Table 1.
Treatment

Celltype
1Squamous
2Smallcell
3Adeno
4Large
Age in Years ;mean (SD)
Month from Diagnosis
Prior Therapy
Yes = 10
No = 0
Karnofsky Score

Standard

Test

Treatment 1 (n=64)

Treatment 2 (n=64)

13 (41.9%)
28 (62.1%)
9 (34.6%)
14 (53.9%)
57 11 (54-60)
8.9 9.0 (6.9-11.1)

18 (58.1%)
17 (37.9%)
17 (65.4%)
12 (46.3%)
60 10 (57-62)
8.9 12.5 (5.7-12.0)

20 (54.1%)
44 (48.4%)
58.20 18.68
Table 2 : Characteristic of Patients

17 (45.9%)
47 (51.6%)
56.88 21.17

11

From Table 2, the patients with Squamous celltype was 13 patients (41.9%) and 18
patients (58.1%) for standard and test treatment respectively. For the Smallcell celltpe,
there was about 28 patients (62.1%) for standard treatment and 17 patients (37.9%) for
test treatment. Meanwhile, for patients with Adeno celltype, there was 9 and 17 patients
for standard and test treatment respectively. From the Large celltype, there was 14
patients and 12 patients for standard and test treatment respectively.
The mean (SD) age for standard treatment is 57 years (range, 55-60), whereas for test
treatment is 60 years (range, 57-62). The standard and test treatment was conducted from
an average 8.9 months from the diagnosis with (range, 6.9-11.1). and (range, 5.7-12.0),
respectively. Among the patients, 20 patients for standard treatment and 17 patients for
test treatment has a prior therapy history.
Figure 1 below, shows the Kaplan-Meier survival curve of all patients. The overall
median survival when both groups were taken together was 80 days.

Survival Plot for Survival in Days

Kaplan-Meier Method
Censoring Column in Status
100

Table of Statistics
Mean
132.777
Median
80
I QR
137

Percent

80

60

40

20

200

400
600
Survival in Days

800

1000

Figure 1 : Kaplan-Meier for both treatments

12

Figure 2 below, shows the median survival in the standard treatment group was 103 days
and in test treatment group, it was 52 days. The difference was not statistically significant
(p=0.928>0.05, log rank test). Both group were comparable for each celltype, age,
duration of diagnosis and previous treatment of the disease.
Survival Plot for Survival in Days
Kaplan-Meier Method
Censoring Column in Status
100

Treatment
1
2

Percent

80

Table of Statistics
Mean Median I QR
123.928
103 135
142.061
52 116

60

40

20

200

400
600
Survival in Days

800

1000

Figure 2 : Kaplan Meier survival analysis by treatment groups

13

Survival Plot for Survival in Days (CI)

Kaplan-Meier Method
Censoring Column in Status (C1)
100

Treatment
1
2

Percent

80

Table of Statistics
Mean Median I QR
136.790
110 102
293.362
201 359

60

40

20

200

400
600
Survival in Days (CI)

800

1000

Figure 3 : Kaplan Meier survival analysis for Squamous (C1) vs treatment group (p=0.117)
Figure 3 shows that the median survival for patients with Squamous celltype (C1) for
standard treatment group (T1) was 110 days and for test treatment group (T2) is 201
days. Survival difference between the two groups for Squamous celltype (C1) was
statistically not significant (p=0.117<0.05, log rank test).

14

Survival Plot for Survival in Days C2

Kaplan-Meier Method
Censoring Column in Status C2
100

Treatment
1
2

Percent

80

Table of Statistics
Mean Median I QR
99.2565
80 95
39.0397
24 43

60

40

20

100

200
300
Survival in Days C2

400

Figure 4 :Kaplan Meier survival analysis for Smallcell (C2) vs treatment group (p=0.006)
Meanwhile, from Figure 4, the median survival time was 80 days (T1) and 24 days(T2)
for Smallcell (C2) celltype. The survival difference between the two treatment groups
was statistically significant (p=0.006<0.05, log rank test).

15

Survival Plot for Survival in Days C3

Kaplan-Meier Method
Censoring Column in Status C3
100

Treatment
1
2

Percent

80

Table of Statistics
Mean Median I QR
72.8889
92 105
62.0556
48 60

60

40

20

50

100
Survival in Days C3

150

200

Figure 5 : Kaplan Meier survival analysis for Adeno (C3) vs treatment group (p=0.288)

Survival Plot for Survival in Days C4

Kaplan-Meier Method
Censoring Column in Status C4
100

Treatment
1
2

Percent

80

Table of Statistics
Mean Median I QR
200.522
177 145
132.333
53 121

60

40

20

100

200
300
400
Survival in Days C4

500

600

Figure 6 : Kaplan Meier survival analysis for Large (C4) vs treatment group (p=0.629)

16

From Figure 5 and Figure 6, the median survival for the Adeno (C3) celltype, was 92
days and 48 days for standard treatment (T1) and test treatment (T2) respectively. Finally,
for the Large (C4) celltype, the median survival was 177 days (T1) and 53 days (T2).
Survival difference between the two groups was not statistically significant
(p=0.629>0.05, log rank test) and (p=0.288>0.05, log rank test) for Adeno (C3) and
Large (C4) celltype respectively.

Survival Plot for Survival in Days T1

Kaplan-Meier Method
Censoring Column in Status 1
100

Age in
Years
60
>60

Percent

80

Table of Statistics
Mean Median I Q R
127.966
100 182
105.914
72 126

60

40

20

100

200
300
400
Survival in Days 1

500

600

Figure 7 : Kaplan Meier survival analysis for Age according to standard treatment (T1)
(p=0.610)
Figure 7 shows that, the median survival time for standard treatment (T1) patients with
age less and equal 60 years is 100 days. Meanwhile the median survival time for patients
with age more than to 60 years is 72 days. Survival difference between the age was
statistically not significant (p=0.610>0.05, log rank test).

17

Survival Plot for Survival in Days T2

Kaplan-Meier Method
Censoring Column in Status 2
100

Age in
Years
60
>60

Percent

80

Table of Statistics
Mean Median I QR
172.080
51 166
100.308
53 86

60

40

20

200

400
600
Survival in Days 2

800

1000

Figure 8 : Kaplan Meier survival analysis for Age according to test treatment (T2)
(p=0.412)
Meawhile for test treatment, Figure 8 shows that, the median survival time for patients
with age less and equal than 60 years is 51 days. Meanwhile the median survival time for
patients with age more than to 60 years is 53 days. Survival difference between the two
groups was statistically not significant (p=0.412>0.05, log rank test).

18

Survival Plot for Survival in Days T1

Kaplan-Meier Method
Censoring Column in Status 1
100

Karnofsky
Score
10-30
40-60
70-90

Percent

80

Table of Statistics
Mean Median I QR
32.889
18 10
114.379
63 156
146.346
117 70

60

40

20

100

200
300
400
Survival in Days 1

500

600

Figure 9 : Kaplan Meier survival analysis for KPS according to standard treatment (T1)
(p=0.001)
Patients were divided into 3 groups based on their Karnofsky performance score (KPS) ;
Group 1 (10-30), Group 2 (40-60), Group 3 (70-90). 9 patients belong to Group 1, 29
patients and 26 patients belong to Group 2 and 3 respectively. Figure 9 shows that,
according to standard treatment (T1), the median survival time for KPS (10-30) was 18
days, 63 days for KPS (40-60) and 117 days for KPS (70-90). Survival difference
between the KPS scores was statistically significant (p=0.001<0.05, log rank test).

19

Survival Plot for Survival in days T2

Kaplan-Meier Method
Censoring Column in Status 2
100

Karnofsky
Score
10-30
40-60
70-90

Percent

80

Table of Statistics
Mean Median I QR
25.154
21 18
73.480
45 61
232.692
133 256

60

40

20

200

400
600
Survival in days 2

800

1000

Figure 10 : Kaplan Meier survival analysis for KPS according to test treatment (T2)
(p=0.000)
Meanwhile, for test treatment, the median survival time for KPS (10-30) was 21 days, 45
days for KPS (40-60) and 133 days for KPS (70-90). The Figure 10 also shows that the
survival difference between the KPS scores was statistically significant (p=0.000<0.05,
log rank test).

20

Survival Plot for Survival in Days T1

Kaplan-Meier Method
Censoring Column in Status
100

Prior
Therapy
No
Yes

Percent

80

Table of Statistics
Mean Median I QR
120.591
95 121
105.600
56 141

60

40

20

100

200

300
400
Survival in Days

500

600

Figure 11 : Kaplan Meier survival analysis for Prior Therapy according to standard
treatment (p=0.700)
For standard treatment, the median survival time for patients with prior therapy is 56 days
(Figure 11). Meanwhile the median survival time for patients with no prior thearpy is 95
days. Survival difference between the two groups was statistically not significant
(p=0.700>0.05, log rank test).

21

Survival Plot for Survival in Days T2

Kaplan-Meier Method
Censoring Column in Status 2
100

Prior
Therapy
No
Yes

Percent

80

Table of Statistics
Mean Median I QR
104.277
52 86
194.882
51 182

60

40

20

200

400
600
Survival in Days 2

800

1000

Figure 12 : Kaplan Meier survival analysis for Prior Therapy according to test treatment
(p=0.348)
Figure 12 shows that for test treatment, the median survival time for patients with prior
therapy is 51 days. Meanwhile the median survival time for patients with no prior thearpy
is 52 days. Survival difference between the two groups was statistically not significant
(p=0.348>0.05, log rank test).

22

Regression with Life Data: S.D versus treat, C.T, K.S, M.D, Age, prior
Response Variable: S.D
Censoring Information Count
Uncensored value
128
Right censored value
9
Censoring value: Status = 0
Estimation Method: Maximum Likelihood
Distribution: Exponential

Regression Table
Standard
95.0% Normal CI
Predictor
Coef
Error
Z
P
Lower
Upper
Intercept
3.14891 0.710360 4.43 0.000
1.75664 4.54119
treat
-0.184342 0.182451 -1.01 0.312 -0.541940 0.173257
C.T
-0.136463 0.0747321 -1.83 0.068 -0.282936 0.0100087
K.S
0.0353214 0.0049785 7.09 0.000 0.0255636 0.0450792
M.D
-0.0029654 0.0089507 -0.33 0.740 -0.0205085 0.0145776
Age
0.0010820 0.0090893 0.12 0.905 -0.0167327 0.0188968
prior
0.0111529 0.0218412 0.51 0.610 -0.0316551 0.0539610
Shape
1

Figure
Log-Likelihood = -724.014

13: Cox Proportional Hazard

Figure 13 above shows the result of testing the prognostic factor that influence the risk of death
in the VA lung cancer using Cox Proportional Hazard Model.
The proportional hazards regression model for the ith individual of male patients are then
1Treatmenti 2Celltype2i 3 Karnofsky Score3i

hi t exp 4 Months from Diagnosis4i 5 Age in Years5i h0 t

Prior Therapy

6
6i

Where the subscript i on an explanatory variables represents the value of that variable for ith
individual.
From the result that obtained in MINITAB above, it can be concluded that K.S referred to
Karnofsky Score has p-value (p=0.000) that have big influence on the hazard of death or survival
times of a patients. Based on this output also, we can performed our new model with the known
parameters obtained from the result.

23

 0.184342 Treatmenti 0.136463 Celltypei 0.0353214 Karnofsky Scorei

hi t exp 0.0029654 Months from Diagnosisi 0.0010820 Age in Yearsi

h0 t
0.0111529 Prior Therapy

5.

DISCUSSION
This study was planned to evaluate whether there is significant difference between
standard treatment (the currently used treatment) and test chemotherapy treatment
(clinical trial) for inoperable lung cancer and to study the factors involved.
The study first compared the patients who received standard treatment (the
currently used treatment) and test chemotherapy treatment (clinical trial). The main
outcome measure was survival. As to compare both treatments, Kaplan Meier survival
analysis has been done. For standard treatment, the median survival is 103 days while for
test chemotherapy treatment, the median survival is 52 days. Although there is a wide
difference between the median survival, the comparison (p=0.928>0.05, log rank test)
shows that there is no significant difference between them.
As we know, cancer does not have any perfect cure and the ending for the patients
is always death.The introduction of test chemotherapy treatment has given the hope of
prolonging survival in such patients. Since the treatments types show that there is no
significant difference, we assume that the standard treatment and test chemotherapy
treatment is equally likely the same.
However in order to further the study, we then test each of the treatment types and
compare the result within each factor that exist in this study which is cell type, month of
diagnosis, prior therapy and Karnofsky score. As we can see the result for cell types in
treatment 1 and treatment 2, C1 and C2 are significant. By using chemotherapy test
treatment for the celltype Squamous (C1) and Smallcell (C2) the result on prolonging the
survival period is increase. This is maybe because the cancer is still in a lower stage.
However for Adeno (C3) and Large (C4) they are not significant. Meaning that for

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serious case as Adeno and Large, the chemotherapy does not affect the patients and result
as same as standard treatment.
Based on the study, for the age factor, there is no significant different to show that
age plays an important role in determine the survival time. Cancer survivors basically
survive longer if they have higher spirit to survive. Age factor is not really the best factor
to compare as different patient may have their own inspirations. However, based on the
survival median there is a little difference compare to patients with age less than 60 and
age more than 60.
For standard treatment, patients with age less than 60 survive longer than patients
with age more than 60 while for test chemotherapy treatment, patients with age more than
60 survive longer than patients with age less than 60. Psychology of patients with age
more than 60 for standard treatment is probably down as they feel that they will have no
chance to live as compared to patients with age less than 60, while the psychology for the
patients with age more than 60 for test chemotherapy treatment is high as they believe on
the test chemotherapy treatment.
For Karnofsky performance score, results for treatment 1 and treatment 2 shows
that there is a significant different between the three groups. As we know, Karnofsky
score is used to measure the patients quality life. It also used to measure how many dose
of chemotherapy and how the treatment being perform to the patients. The result show
that, the higher the Karnofsky performance score, the higher survival rate. The evidence
assembled in the study indicates that the performance status base on the Karnofsky
performance score. As we can see the definition of the Karnofsky performance score 70
and above the patients able to carry on normal activity and able to work. There also no
need of special care. Doctor should focus on the patients with the lowest performance
score.
For prior therapy, the test shows that it is not statistically significant to conclude
that there is a difference between both prior and no prior therapy. This concludes that
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either the patient went or not for the prior therapy the result are the still same. Prior
therapy means patient received therapy prior to the start of the study.
The Cox Proportional Hazard Model show that, the Karnofsky Score has p-value
(p=0.000), it can be conclude that it have big influence on the hazard of death or survival
times of a patients. Basically, the one that use the Karnofsky score is doctor.
As chances of being survive are very important to patients, newer technology and
formula should be used to increase the performance of test chemotherapy treatment.
Stopping smoking can also reduce the risk of having a lung cancer. Therefore it is
important to take preventive measures against lung cancer such as campaign to avoid
smoking. Other than that, patient also should be advised to exercise most days in a week
and have a diet full of fruits and vegetables.

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6.

CONCLUSION
With the Kaplan-Meier survival analysis procedure, we have examined the distribution of
time to effect for two different treatment groups. The comparison tests show that there is
nosignificant difference in survival times (p >0.05, log rank test) between standard and
test treatment.This study cannot prove that test treatment can provide better results that
the standard.
The attention was then focused on the evaluation of the prognostic effect of other
variables. The result for tumor cells types showed that there is a statistically significant
difference in survival times between standard and test treatment for small cell and
squamous cell. Both cell types seem to affect the relationship between treatments groups
with the occurance of lung cancer deaths. While foradeno cell and large cell, the
treatmentdifference (standard versus test) was shown to be statistically not significant.
Therefore both cell types seem to have no effect on the relationship between treatment
groups and the occurance of lung cancer deaths.
In the analysis for the age factor, the patient survival difference between two age
groups (less than or equal to 60 years old versus more than 60 years old) did not reach
statistical significance. Age was not associated with better survival forthe patients.
For Karnofsky Performance Status (KPS), survival difference between the
Karnofsky score 10-30, Karnofsky score 40-60 and Karnofsky score 70-90 is statistically
significant. In general, the higher the score performance status, the occurrence of lung
cancer deaths is getting smaller. However, there is no significant difference on the total
score Karnofsky Performance Status in the test group and the standard group.

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Further, data on the patients who had received prior therapycompared with patient
without prior therapy does not differ significantly. The study suggests that the survival
time distribution may be the same for individuals with or without prior therapy.
The analysis proceeds to identify important prognostic factors and to model the
expected survival in days. By using the Cox Proportional Hazard Model, we are able to
assess the importance of various covariates that influence the risk of death in the Veterans
Administration lung cancer trial. From the Regression Table, we found that only
KarnofskyScore (p = 0.000) has an influence on the hazard of death. The model obtained
can be expressed mathematically as follows:

0.184342 Treatmenti 0.136463 Celltypei 0.0353214 Karnofsky Scorei

hi t exp 0.0029654 Months from Diagnosisi 0.0010820 Age in Yearsi

h0 t
0.0111529 Prior Therapy

In conclusion, this analysis would indicate that patient survival does not differ
significantly between treatment groups after taking account of the prognostic effect of
other variables.The poor survival of these veterans is due to performance status (KPS
rating) and cell type, rather than to their treatment received. Karnofsky Performance
Status score has the most influence on the hazard of death or survival times of the
patients.

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REFERENCES
American Cancer Society.Cancer Facts and Figures 2013. Atlanta: American Cancer Society;
2013.
A Study of Cancer in the Military Beneficiary Population, Guarantor: Raymond Shelton
Crawford III, MD MBA, Contributors: Raymond Shelton Crawford III, MD MBA; Julian Wu,
MD MPH; Dae Park, MD; Galen Lane Barbour, MD; Military Medicine, Vol. 172, October 2007
U.S. Medicine, The voice of federal medicine
Repercussions of High Military Smoking Rates Affect Health Systems. Retrieved from
http://www.usmedicine.com/clinical-topics/copd/repercussions-of-high-military-smoking-ratesaffect-health-systems/
What is non-small cell lung cancer? (2013, July 12). American Cancer Society.Retrieved January
25, 2014 from http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-smallcell-lung-cancer-what-is-non-small-cell-lung-cancer
Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In:
MacLeod CM (Ed), Evaluation of chemotherapeutic agents. Columbia Univ Press.1949: 196
Buccheri G, Ferrigno D, Tamburin M. Karnofsky and ECOG performance status scoring in lung
cancer: a prospective, longitudinal study of 536 patients from a single institution. Eur J Cancer.
1996; Jun; 32A(7): 1135-41
Leah, L. Z., William, R. C., Dawn, T. P., Morris, W., Bryce, B. R., Christina, D. W. & George, L.
J. (2013). The association of race with timeliness of care and survival among Veteran Affairs

29

health care system patients with late-stage non-small cell lung cancer. Cancer Management and
Research, 2.Retrieved from http://dx.doi.org/10.2147/CMAR.546688.
Lee, H., Jin, G. Y., Han, Y. M., Chung, G. H., Lee, Y. C., Kwon, K. S. & Lynch, D. (2012)
Comparison of survival rate in primary non-small-cell lung cancer among elderly patients treated
with radiofrequency ablation, surgery, or chemotherapy. CardiovascInterventRadiol, 35, 343350.
Schiller, J. H., Harrington, D., Belani, C. P., Langer, C., Sandler, A., Krook, J., Zhu, J. &
Johnson, D. H. (2002). Comparison of four chemotherapy regimens for advanced non-small-cell
lung cancer. The New England Journal of Medicine, 346(2), 92-98.
Shajeem, O. Behera, D. & Aggarwal, A. N. (2003).Chemotherapy versus best supportive care in
management of lung cancer. Journal of Association of Physicians of India, 51, 261-264.
Kalbfleisch, J.D. and Prentice, R.L. (2002).The Statistical Analysis Of Failure Time Data. Wiley
New York, 2nd Edition
Meinert, C.L. (2012). Clinical Trials Handbook : Design And Conduct.John Wiley and Sons. Pp.
80-81
W. Tang and Xin Tu (2012). Modern Clinical Trial Analysis.Applied Bioinformatics and
Biostatistics in Cancer Research.Springer. Pp.167-172
John R.Seffrin (1913, May 23). American Cancer Society. Retreived from
http://www.cancer.org/cancer/lungcancer/
Oxford Textbook of Palliative Medicine, Oxford University Press. 1993;109

30

Harpal Kumar (CEO) (2002, February 22). Cancer Research UK . Retreived from
http://www.cancerresearchuk.org/about-cancer/type/lungcancer/treatment/advanced/whichtreatment-for-advanced-lung-cancer
Prof. Lain E. Buchan (2000) .Stats Direct. Retreived from
http://www.statsdirect.com/help/default.htm#survival_analysis/kaplan_meier.html
Viv Bewick et. al (2004). Articles aboutStatistics Review 12 : Survival Analysis, US Natinal
Library of Medicine National Institutes of Health, Critical Care, Volume 8(5). Pp. 389-394.
John Fox (2002). Cox Proportional Hazards Regression for Survival Data.
X. Lu and Tsiatis, A.A (2008). Improving The Efficiency Of The Log-Rank Test Using Auxiliary
Covariates, Oxford Journal, Science& Mathematics, Biometrika, Volume 95, Issue 3. Pp. 679694.

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