an analysis of clinicopathologicalprofile and of with lung ... · an analysis of...

An Analysis of Clinicopathological Profile and Survival of Patients with Lung Cancer

Dr. Prabhat S. Malik

Guide – Dr. V. RainaProf. &Head

Department of Medical Oncology

Co‐GuideDr N K Shukla

Co‐GuideD S V S D

Co‐GuideDr B K MohantiDr. N.K. Shukla

Prof. & HeadDept of Surgical Oncology

Dr. S.V.S. DeoAddl ProfessorDept of Surgical Oncology

Co‐Guide Co‐Guide

Dr. B.K. MohantiProfessorDept of Radiation Oncology

Co GuideDr. M.C.SharmaAddl ProfessorDept of Pathology

Co GuideDr. Anant MohanAssociate Prof.Dept. of Pulmonary Mrdicine

IntroductionIntroduction

• Lung cancer ranks among the most commonLung cancer ranks among the most common and most lethal malignancies worldwide

• The incidences of lung cancer vary id bl diff h iconsiderably among different ethnic

populations throught the world

Disease Burden :Global ScenarioDisease Burden :Global Scenario

• Worldwide‐• 12.7% of all new cancers • The most common cause of death from cancer, (18.2% of the total) GLOBOCAN 2008

• US –• 14% of new cancer cases in males and females each• 28% of cancer related deaths in males and 26% in females

CA Cancer J Clin. 2010

• Europe –• 12% of new cancer cases, and 19.7% of cancer‐related deathsdeaths Ann Oncol 2007;18:581

Indian ScenarioIndian Scenario

Males FemalesMales Females

GLOBOCAN 2008

Time Trends : WorldTime Trends : World


GLOBOCAN 2008

Time Trends (1982‐2005): IndiaTime Trends (1982 2005): India


Report from Indian Council of Medical Research 2009Report from Indian Council of Medical Research. 2009

Ten Leading SitesTen Leading Sites

Males Females

Delhi Cancer Registry 2006‐2007

Males Females

Lung

AAR/100,000

Breast

AAR/100,000

LarynxTongueProstate

Lung

Gall BladderOvary

Cervix UteriBreast

MouthBladder

NHLAAR

NHLThyroid

LungCorpus Uteri

AAR/100,000

Gall BladderOesophagus

Brain

BrainOesophagus

NHL

0 5 10 15 0 20 40

Geographical variations: HistologyGeographical variations: Histology

Behera et al Indian J Chest Dis Allied Sci 2004; 46 : 269‐281

Clinical Epidemiology 2011:3 139–148

Prognostic Relevance of HistologyPrognostic Relevance of HistologySEER databaseN=51,741

Clinical Epidemiology 2011:3 139–148

New Proposed Classification Of Adenocarcinoma lung

J Thorac Oncol 2011

Principles of Pathology ReviewPrinciples of Pathology Review• The diagnostic report should include the histological class, as described in

WHO classification

NCCN Guidelines ver 2.2012

WHO classification

• The generic term “NSCLC” should be avoided

• In small biopsies of poorly differentiated carcinoma following terms are acceptable‐– NSCLC favor adenocarcinoma– NSCLC favor squamous cell carcinoma

• Judicious use of ancillarry IHC studies in small bx

• Use of recent classification of adenocarcinoma

• Use of BAC term should be discouragedUse of BAC term should be discouraged

Principles of Pathology ReviewPrinciples of Pathology Review• IHC should be used to differentiate primary lung adenocarcinoma from

squamous or large cell ca from metastatic carcinoma and from

NCCN Guidelines ver 2.2012

squamous or large cell ca, from metastatic carcinoma and from mesothelioma

• Adenocarcinoma– TTF‐1 – 70‐100%– Napsin A ‐ >80%

l f d l f f• Pannel of TTF‐1 and p63 can classify most of NSCLC

• Neuroendocrine differentiation –CD 56 CG and synaptophysin– CD 56,CG and synaptophysin

• Mesothelioma– WT‐1, Calretinin, CK‐5/6, , /

Diagram illustrates the key changes to the T and M descriptors in the TNM‐7 system.

Nair A et al. Radiographics 2011;31:215‐238

©2011 by Radiological Society of North America

• 19% in USA • Age19% in USA • 33%in Australia • 37% in Scotland

Age• PS• Histology (NSCLC>SCLC)• 37% in Scotland

• 50% in Ireland• Histology (NSCLC>SCLC)• Social reasons

J Thorac Oncol 2010;5: 1025–1032J Thorac Oncol. 2010;5: 1025–1032

• 71% concordance • Factors responsible for71% concordance between guidelines and MDM recommendation

Factors responsible for not following guidelines (multivariate analysis)

• Discordance‐ – Age >70

• Physician’s decision ‐39%• Comorbidity ‐25%• Technical factors 22%

– PS>2– NSCLC stage III

• Technical factors‐ 22%

Journal of Oncology Practice 2010

Optimal Utilization of RT in Lung CaOptimal Utilization of RT in Lung Ca

Cancer EBM Guidelines (%) In Actual Practice(%)

All‐ New 52R R 15 20‐ Re‐Rx 15‐20

Lung 76 36‐71*g* Sweden, SEER, ACS

Personal beliefs rather than universal knowledge tend to g ide the treatment practicesguide the treatment practices.

Delaney G et al. Cancer 2005; 104: 1129‐37

S d P lStudy Protocol

Aims and ObjectivesAims and Objectives

• To study the clinical and pathological profile ofTo study the clinical and pathological profile of patients with lung cancer at our centre

• To analyze the treatment outcomes and i l f l isurvival of lung cancer patients

Material and MethodMaterial and Method• Data source – Case record files of lung cancer patients registered in

L C Ch th Cli i (M di l O l )Lung Cancer Chemotherapy Clinic (Medical Oncology)

• Search Criteria –ICD 10 d C 34– ICD 10 code C‐34

– LCCC no

• Study Period – July 2008‐June 2011 (3year)y y ( y )

• Follow Up period – till 31‐12‐11

• Follow up by‐• Telephone• Self addressed postcard

Material and MethodMaterial and Method• Inclusion Criteria

– Pathological diagnosis of lung cancer – Diagnosed between July 2008 till June 2011– Complete clinical, pathological, staging and treatment details in p p g g g

file– For treatment outcome and survival analysis

» Patient should have received at least one treatment modality i.e. surgery, RT (radical or palliative) chemotherapy (at least 1 # of chemotherapy) or TKI(radical or palliative) , chemotherapy (at least 1 # of chemotherapy) or TKI

• Exclusion CriteriaC ith i l t b li d t– Cases with incomplete baseline data.

– For treatment outcome and survival analysis• Who did not received any treatment• Who had received treatment outside before registration at IRCH• Who had received treatment outside, before registration at IRCH.

Pathology ReviewPathology Review

• Biopsy slides which were available inBiopsy slides which were available in pathology department, were retrieved and reviewed and reclassified according to WHOreviewed and reclassified according to WHO classification 2004, in major categories

• Slides were reviewed on the basis of• Slides were reviewed on the basis of morphology and available IHC (done at the time of reporting)time of reporting)

11‐126

Squamous Cell Carcinoma

11‐24100 Adenocarcinoma

MC TTF

09‐15035 CK7

CK 20 AB PAS

BAC

11‐23870

CG SYN

Small Cell Carcinoma

11‐23870 CKCD56

MIB TTF

StagingStaging

• Restaging was done on the basis of availableRestaging was done on the basis of available imaging modalities, according to new AJCC staging system (AJCC 7th edition)staging system (AJCC 7 edition)

C i h i l i k• Cases with incomplete metastatic workup were classified as Mx

Outcome EvaluationOutcome Evaluation

• Responses were ascertained clinically and radiologicaly and p y g ycoded according to standard criteria

• Follow up information were gathered as following– As per details entered in the case files– Contact with patient/family through telephoneContact with patient/family through telephone– Postal contact with help of a reply postcard

Study End PointsStudy End Points

• Patients were followed from the date of diagnosis to the date gof death and were censored at the date they were last known to be alive i.e. date of last follow up (if lost to follow‐up) or December 31 2011 whichever came firstDecember 31, 2011, whichever came first

– Overall Survival (OS): From date of registration to death due to any cause

– Progression Free Survival (PFS): From date of registration to occurrence of any one of the following ‐

• Progression of the disease• Death

Statistical AnalysisStatistical Analysis• The data was censored at 31st December 2011 or last follow up

d t (if LFU)date (if LFU)

• Descriptive statistics was used for describing demographic and clinical characteristicsclinical characteristics

• Survival was estimated by the Kaplan–Meier method and the Cox Regression Model (Univariate and multivariate) was used toCox Regression Model (Univariate and multivariate) was used to identify significant prognostic factors

• Analysis was done using the Stata software (Release 9.0, StataCorp.) and SPSS ver 15

Results

543 files screened109

434 Confirmed cases of

Excluded

434 Confirmed cases of lung cancer

NSCLCN=370 (85.2%)

SCLCN=64 (14.7%)No

T/TNo T/TT/T

109 TreatedN=261

TreatedN=49

T/T15

OS data available

PFS data available

OS data available

PFS data available

=66.67% (207/310

=84.19% (261/310)

=61.22% 30/49)

=81.63% (40/49)

AgeAge

Chart Title

Median age= 55 yrs (23‐84)

140

160

100

120

Title

40

60

80

Axis T

0

20

<40 41‐50 51‐60 61‐70 >70Female 10 22 25 12 8Male 30 79 134 92 22

GenderGender

GenderGenderMales Females

18%

82%

Residencees de ceDelhi Non Delhi

31%

69%

SmokingSmoking

300

350

200

250

300

Title

100

150Axis T

0

50

Male FemaleNon smoker 63 64Smoker 283 12

Type of smoking(%)

27%

Type of smoking(%)

55%

27%

Bidi55%

18%CigaretteUnknown

HistologyHistology

Histology ReviewHistology sto ogy e e

Squamous cell caAd

sto ogy

Squamous cell caAd i

25%17%15%

Adenoca

Large cell ca

26%21%15%

AdenocarcinomaLarge cell ca

39%

2%2%

caBAC

NSCLC NOS

34%

2%

caBAC

NSCLC NOS 2% NSCLC NOS

SCLC

2% NSCLC NOS

SCLC

Histopathology ReviewHistopathology Review

• Total Bx reports from Reported ReviewedTotal Bx reports from AIIMS = 228 NSCLC NOS =19 Adenocarcinoma=8

Squamous = 9Large cell = 2

• Slides reviewed = 178 Adenocarcinoma=1Squamous =1

NOS/Poorly diff

• Diagnosis changed =35(19.66%)

Squamous =9 Adenocarcinoma

Small Cell=1 Atypical Carcinoid( )Adeno=2Squamous =1

? Metastasis

Histology (Reviewed)‐M:FHistology (Reviewed) M:F

Chart Title

160

180

100

120

140

Title

40

60

80Axis T

0

20

Squamous Adeno Large cell BAC NOS SCLCFemale 9 47 1 6 8 6Male 100 121 6 4 68 58

Histology: SmokingHistology: Smoking

Chart Title

160

180

100

120

140

Title

40

60

80Axis T

0

20

Squamous Adeno Large cell BAC NOS SCLCNon smoker 12 83 3 8 13 8Smoker 92 81 3 2 61 56

Method of DiagnosisMethod of Diagnosis

Method of Diagnosis(%)Method of iagnosis(%)Method of Diagnosis(%)

66.13

25.12

Biopsy FNAC Fluid Cytology

Sputum BAL

25.125.07 0.46 3.24

Cytology

PSPSPS

71.40%

≤2 >2 NA

19.80%8.70%

≤2 >2 NA

Treatment TreatmentTreatment received Not received

29%

71%

Demographic Feature NSCLC, n= 370 SCLC, n=64Age Median(Range) 55 (23-84) 55.5 (25-76)

<40 33 (8.92%) 7 (10.94%)( ) ( )41-50 89 (24.05%) 12 (18.75%)51-60 136 (36.76%) 23 (35.94%)61-70 86 (23.24%) 18 (28.13%)>70 26 (7.03%) 4 (6.25%)( ) ( )

SexMale 299 (80.81%) 58 (90.63%)Female 71 (19.19%) 6 (9.38%)Female 71 (19.19%) 6 (9.38%)

ResidenceDelhi 118 (31.89%) 18 (28.13%)Non Delhi 252 (68 11%) 46 (71 88%)Non Delhi 252 (68.11%) 46 (71.88%)

SmokingSmoker 239 (64.59%) 56 (87.50%)Non Smoker 119 (32 16%) 8(12 50%)Non Smoker 119 (32.16%) 8(12.50%)

NA 12 (3.24%)

Type of smoking (239)Bidi 121(50 64%) 42 (75%)Bidi 121(50.64%) 42 (75%)Cigarette 50 (20.92%) 4 (7.15%)

Others/NA 68 (28.45%) 10 (17.85%)

NSCLC SCLCHistology (After Review)

Squamous cell carcinoma

109 (29.46%)

Adenocarcinoma 168 (45.41%)Large cell carcinoma 7 (1.89%)BAC 10 (2.70%)NOS 76 (20.54%)

Small Cell Ca 64 (100%)

Method of diagnosisBiopsy 239 (64.59%) 48 (75%)FNAC 94 (25.41%) 15(23.44%)Fluid cytology 22 (5.95%) 0Sputum 2 (0.54%) 0BAL 13 (3.51%) 1(1.56%)

Performance Status (ECOG)≤2 266 (71.89%) 44 (68.75%)>2 69 (17.83%) 17 (26.56%)NA 35 (9.45%) 3 (1.45%)

Treatment Yes 261 (70.54%) 49 (76.56%)No 109 (29.46%) 15 (23.44%)

Clinical FeaturesClinical FeaturesSymptom NSCLC n= 370 SCLC n=64

Cough 211 (57.03%) 37 (57.81%)Hemoptysis 112 (30.27%) 18 (28.13%)

Dyspnoea 146 (39 57%) 26 (40 63%)Dyspnoea 146 (39.57%) 26 (40.63%)Chest Pain 192 (51.89%) 31 (48.44%)

Wt Loss 124 (33.51%) 25 (39.06%)A i 116 (31 35%) 21(32 81%)Anorexia 116 (31.35%) 21(32.81%)

Voice Change 41 (11.08%) 10 (15.63%)Fever 76 (20.54%) 10(15.63%)

Signs NSCLC SCLC

SVCO 20 (5.42%) 16(25%)

Pancost 22 (5.95%) 0

Horner’s syndrome 5 (1.36%) 0

Pleural Effusion 99 (26.76%) 12 (18.75%)Pleural Effusion 99 (26.76%) 12 (18.75%)

Cytology = 99Positive

NegativeNA

51 (51.52%)08(8.08%)40 (40.40%)

2(16.6%)1(8.33%)9 (75%)

Metastatic SitesMetastatic SitesMetastatic Site NSCLC SCLC

Liver 56 (15.18%) 16 (25%)Bone 75 (20.33%) 12 (18.7%)

Adrenal 21 (5.69%) 8 (12.5%)Adrenal 21 (5.69%) 8 (12.5%)NR LN 22 (5.98%) 4 (6.25%)Brain 17 (4.61%) 4 (6.25%)Ski 5 (1 36%)Skin 5 (1.36%)

Others 1 (0.27%)Bone Marrow - 2 (3.13%)

Stage (AJCC 7th edition)Stage (AJCC 7 edition)Stage NSCLC SCLC

IA 1 (0.27%)

IB 9 (2.4%)

IIA 6 (1.6%)IIA 6 (1.6%)

IIB 24 (6.4%)

IIIA 53 (14.32%)

IIIB 4 (14 9%)IIIB 54 (14.59%)

IV 210 (56.75%)

L 15 (23.4%)

E 46 ( 71.87%)

NA 13(3.5%) 3 (4.6%)

Treatment : NSCLCTreatment Modality N (%)First treatment modality

Surgery 8 (3.07%)g y ( )RT 15 (5.75%)Chemotherapy 191 (73.18%)TKI 47(19.15%)

Surgery 14 (5.36%)

RT to primary site 102 (39.08%)Radical RT 30(29.4%)( )Palliative RT 66 (64.7%)PORT 6 (5.8%)

RT to metastatic site 36 (13.8%)( )Spine 14 (38.8%)Brain 17 (47.22%)Pelvis 2 (5.5%)Extremity bones 3 (8.3%)y ( )PCI 0Others 0

ChemotherapyN (%)

Chemotherapy 197 (75.47%)Palliative 166 (84.26%)NACT 27 (13.7%)Adjuvant 4 (2.03%)

Number of chemotherapy courses<2 43 (21.83%)2-3 80 (40.61%)4-6 74 (37.56%)

RegimenPaclitaxel-Carboplatin 163(82.74%)Docetaxel – Carboplatin 12 (6.1%)Gem-Cis 4 (2.03%)Gem-Carb 3 (1.52%)Pem –Cis 8 (4.06%)Pem- Carb 5 (2.53%)Vin- Cis 2 (1.02%)

Response to chemotherapyCR 8(4.06%)PR 62 (31.47%)

70(35.53%)

SD 44 (22.34%)PD 53 (26.90%)NA 30 (15.23%)

TKITKITKI use N=100

1st lineGeftinibErlotinib

50 45(90%)

5 (10%)

MaintenanceGeftinibErlotinib

3322(66.66%)11 (33 33%)Erlotinib 11 (33.33%)

Secondline or moreGeftinib

1612(75%)

Erlotinib( )

4 (25%)

Adjuvant 1

Survival Analysis: NSCLCSurvival Analysis: NSCLC• Median follow up – 8.2 months • Overall Survival‐

– OS data available ‐ 207/310 treated pts (66.77%)– Median OS ‐13.2 months ed a OS 3 o t s– 1 yr OS =55.2%– 2yr OS = 27.7%

• Progression Free Survival ‐– PFS data available ‐ 261/310 treated pts (84.19%)

M di PFS 7 8 th– Median PFS‐ 7.8 months – 1 yr PFS = 31.1%– 2yr PFS = 9.4%

Overall Survival :NSCLCOverall Survival :NSCLC

Survival FunctionSurvival Function

HISTGRP: 11.2

Median Survival :13.2months

1.0

.8

urvi

val

.6

.4

OSM

403020100-10

Cum

S

.2

Survival Function

Censored

OSM

PFS:NSCLCPFS:NSCLC


HISTGRP: 11.2

Median PFS :7.8 months

1.0

.8

urvi

val

.6

.4

2

PFSM

403020100-10

Cum

S .2

0.0

Survival Function

Censored

PFSM

U i i t C i d l fUnivariate Cox regression model for overall survival

Variable n Alive Died HR (95%CI) pAge <60 >60

183(70.1%)78(29.9%)

103 40

80 38

1(ref) 1.086(0.73‐1.598)

0.676

SexSex Female Male

58(22.2%) 203(77.8%)

33 110

25 93

1(ref) 0.936(0.602‐1.47)

0.771

Smoking No Yes

95(37.5%) 158(62.5%)

50 86

45 72

1(ref) 1.124(0.77‐1.632)

0.54

PS ≤2 >2

206(83.4%)41(16.6%)

116 17

90 24

1(ref) 2.61(1.65‐4.12)

<0.001

Stage 1‐3A 3B 4

68(26.3%) 34(13.1%) 157(60.6%)

45 20 78

23 14 79

1(ref) 1.19 (0.617‐2.33) 1.730 (1.08‐2.758)

0.59 0.021

Histology Squamous 75(28 7%) 46 29 1(ref)Squamous Adeno Large cell BAC NOS

75(28.7%)124(47.5%)5(1.9%) 9(3.4%) 48(18.4%)

4669 4 5 19

2955 1 4 29

1(ref) 1.193(0.76‐1.87) 0.43 (0.059‐3.19) 1.012(0.35‐2.88) 2.022 (1.20‐3.38)

0.44 0.41 0.98 0.008

Hemoglobin>12 ≤12

113(52.3%)103(47.7%)

65 52

48 51

1(ref) 1.65(1.114‐2.46)

0.013( ) ( )

Albumin >3.5 ≤3.5

136(75.6%)44(24.4%)

77 19

59 25

1(ref) 2.26(1.47‐3.63)

0.001

No.of chemotherapy #>4 3‐4 ≤2

74(37.6%) 80(40.6%) 43(21.8%)

46 42 22

28 38 21

1(ref) 1.637 (1.003‐2.67) 7.476 (4.132‐13.52)

0.048 <0.001

TKI Use Not used

100(38.3%)161(61.7%)

60 83

40 78

1(ref) 2.077(1.41‐3.06)

<0.001

TKI timing 2nd line or more 1st line Maintenance

16(16.2%) 50(50.5%) 33(33.33%)

9 23 27

7 27 6

1(ref) 2.018(0..87‐4.67) 0.351(0.118‐1.046)

0.10 0.06

Treatment modalitiesTreatment modalities used in 1st line 3 1 2

17(6.5%) 141(54%) 103(39.5%)

15 65 63

2 76 40

1(ref) 17.16(4.16‐70.73) 5.518(1.325‐22.981)

<0.001 0.019

Univariate Cox regression model for PFSUnivariate Cox regression model for PFS

Variable n Not Progressed

Progressed HR (95%CI) p

Age <60 >60

183(70.1%)78(29.9%)

55 22

128 56

1(ref) 0.974(0.711‐1.335)

0.871

Sex Female Male

58(22.2%) 203(77.8%)

20 57

38 146

1(ref) 1.002(0.70‐1.43)

0.99

Smoking No Yes

95(37.5%) 158(62.5%)

27 45

68 113

1(ref) 1.01(0.753‐1.377)

0.906

PS ≤2 >2

206(83.4%)41(16.6%)

61 9

145 32

1(ref) 2.068(1.40‐3.04)

<0.001

Stage 1‐3A 3B 4

68(26.3%) 34(13.1%) 157(60.6%)

30 8 39

38 26 118

1(ref) 1.454 (0.882‐2.39) 1.715 (1.18‐2.47)

0.142 0.004

HistologySquamous 75(28.7%) 23 52 1(ref)SquamousAdenocarcinoma Large cell BAC NOS

75(28.7%)124(47.5%)5(1.9%) 9(3.4%) 48(18.4%)

2338 3 3 10

5286 2 6 38

1(ref) 1.11(0.786‐1.566) 0.636(0.154‐2.61) 0.768(0.32‐1.791) 1.36(0.899‐2.083)

0.55 0.53 0.54 0.14

Hemoglobin>12 ≤12

113(52.3%)103(47.7%)

32 30

81 73

1(ref) 1.343(0.978‐1.846)

0.068

AlbuminAlbumin >3.5 ≤3.5

136(75.6%)44(24.4%)

41 12

95 32

1(ref) 1.55(1.035‐2.323)

0.033

No.of chemotherapy # >4 3‐4 ≤2

74(37.6%) 80(40.6%) 43(21.8%)

26 15 14

48 65 29

1(ref) 1.872 (1.287‐2.723) 5.072 (3.154‐8.155)

0.001 <0.001

TKITKI Use Not used

100(38.3%)161(61.7%)

32 45

68 116

1(ref) 1.575(1.164‐2.131)

0.003

TKI timing1st line Maintenance

50(50.5%) 33(33.33%)

15 16

35 17

1(ref) 0.335(0.185‐0.610)

<0.001

T t tTreatment modalities used in 1st line 3 1 2

17(6.5%) 141(54%) 103(39.5%)

9 36 32

8 105 71

1(ref) 6.842(3.24‐14.41) 2.734(1.3‐5.74)

<0.001 0.08

Multivariate (Cox Regression – Enter Method) analysis for OS and PFS:Method) analysis for OS and PFS:

NSCLC• OS –

– PS : • HR 10.02 (1.64‐61.30), p=0.013

– TKI Timing (2nd line Vs Maintenance): • HR 0.011 (0.001‐0.099), p= <0.001

• PFS –– PS

• HR 9.882 (1.61‐60.35) , p= 0.013– TKI Timing

• HR 0.064(0.018‐0.225), p <0.001– Treatment modalities used

• 3 modalities (ref)• 1 modality HR 9.176 (1.64‐51.29), p= 0.019• 2 modalities HR 1 74 (0 66 4 55) p 0 257• 2 modalities HR 1.74 (0.66‐4.55) , p=0.257

SCLC: Treatment Treatment Modality N= 49First treatment modality

SurgeryRT 3 (6.12%)Chemotherapy 46 (93.88%)

Surgery 1 (2.04%)RT to primary site 18 (36.7%)

Radical RT 5 (27.77%)Palliative RT 13 (72.22%)PORT 0

RT to metastatic site 13 (26 5%)RT to metastatic site 13 (26.5%)Spine 3(23.06%)Brain 4 (30.76%)Pelvis 1 (7.6%)Extremity bones 0PCI 4(30.76%)Others 1 (7.6%)

N 49N=49

Chemotherapy 49 (100%)Palliative 36 (73.47%)NACT 13 (26.53%)( %)Adjuvant 0

Number of chemotherapy<2 16(32.65%)3-4 12 (24.49%)3 ( 9%)5-6 21 (42.86%)

RegimenCisplatin Etoposide 30 (61.22%)Carboplatin- Etoposide 15 (30.61%)Carboplatin Etoposide 15 (30.61%)Oral Etoposide 2 (4.08%)

Others 2(4.08%)

Response to chemotherapyResponse to chemotherapyCR 7 (14.29%)PR 14 (28.57%)SD 5 (10.20%)PD 12 (24.49%)PD 12 (24.49%)NA 11 (22.45%)

• Median Follow up‐ 6.5 monthsp• Overall Survival‐

– OS data available ‐30/49 (61.22%) – Median OS – 9.9 months– 1 year OS = 40%

• Progression Free Survival ‐– PFS data available ‐ 40/49 treated pts(81.63%)– Median PFS – 6.1 months – 1 year PFS = 4.6%

OS:SCLCOS:SCLC


HISTGRP: 21.2

Median Survival :9.9 months

1.0

.8

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val

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.4

2

OSM

403020100-10

Cum

S .2

0.0

Survival Function

Censored

OSM

PFS SCLCPFS SCLC


HISTGRP: 21.2

Median PFS :6.1 months

1.0

.8

.6

urvi

val

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.2

PFSM

1614121086420

Cum

S 0.0

-.2

Survival Function

Censored

PFSM

U i i t C i d l fUnivariate Cox regression model for overall survival (SCLC)

Variable n Alive Died HR (95%CI) pAge ≤60 35(71.4%) 23 12 1(ref) 0.064>60

( )14(28.6%) 5 9

( )2.344(0.95‐5.78)

Sex Female Male

3(6.1%) 46(93.9%)

2 28

1 21

1 (ref) 1.29(0.162‐10.34)

0.808

SmokingSmoking No Yes

6(12.2%) 43(87.8%)

5 23

1 20

1 (ref) 4.76 (0.62‐36.3)

0.132

PS ≤2 >2

36(75%) 12(25%)

20 7

16 5

1 (ref) 1 439(0 5‐4 07)

0 49>2 12(25%) 7 5 1.439(0.5 4.07) 0.49

Stage Limited Extensive

12(25%) 36(75%)

7 20

5 16

1 (ref) 1.48(0.53‐4.13)

0.45

Hb >12 29(61 7%) 15 14 1(ref)>12 ≤12

29(61.7%)18(38.3%)

1511

147

1(ref) 0.63 (0.252‐1.60) 0.33

Albumin >3.5 ≤3.5

28(77.8%)8(22.2%)

15 4

13 4

1 5.63(1.38‐22.92)

0.016

No of Chemotherap #No. of Chemotherapy#>4 3‐4 ≤2

21(42.9%)12(24.5%)16(32.7%)

11 9 8

10 3 8

1 0.561 (0.149‐2.114) 47.355(5.498‐407.86)

0.39 <0.001

Treatment modalities 2 19(38 8%) 11 8 12 1

19(38.8%)30(61.2%)

1117

813

12.277(0.85‐6.049) 0.099

Univariate Cox regression model for PFSUnivariate Cox regression model for PFS

Variable n Not progressed

Progressed HR (95% CI) p

Age <60 35(71 4%) 11 24

1( f) 0 0 599<60

>60 35(71.4%)14(28.6%)

113

2411

1(ref) 0.823(0.398‐1.70)

0.0.599

Sex Female Male

3(6.1%) 46(93.9%)

2 12

1 34

1 (ref) 29.53(0.102‐8577)

0.242

SmokingSmoking No Yes

6(12.2%) 43(87.8%)

3 11

3 32

1 (ref) 4.19 (0.981‐17.9)

0.053

PS ≤2 >2

36(75%) 12(25%)

11 3

25 9

1 (ref) 1.286(0.566‐2.922)

0.549

Stage Limited Extensive

12(25%) 36(75%)

5 8

7 28

1 (ref) 2.555(0.972‐6.71)

0.057

Hb >12 ≤12

29(61.7%)18(38 3%)

8 4

21 14

1 (ref) 0 848 (0 423 1 70)

0 643≤12 18(38.3%) 4 14 0.848 (0.423‐1.70) 0.643

Albumin >3.5 ≤3.5

28(77.8%)8(22.2%)

5 3

23 5

1 (ref) 3.543(1.178‐10.65)

0.024

No. of Chemotherapy#

Chemotherapy# >4 3‐4 ≤2

21(42.9%)12(24.5%)16(32.7%)

3 4 7

18 8 9

1(ref) 1.167 (0.48‐2.826) 85.08(9.311‐777.47)

0.733 <0.001

Treatment modalities 19(38.8%) 3 16

1 (ref)

2 1

30(61.2%) 11 19 1.696(0.81‐3.55) 0.161

Multivariate (Cox Regression – Enter h d) l f dMethod) analysis for OS and PFS: SCLC

• OS –OS – No. of chemotherapy cycles

• >4 (ref)• 3‐4 HR= 0.924 (0.216‐3.94) p=0.915• ≤2 HR =74.9 (7.97‐703.96), p <0.001

• PFS –– No. of chemotherapy cycles

4 ( f)• >4 (ref)• 3‐4 HR= 6.77 (1.7‐26.89), p=0.007• ≤2 HR =153.14 (13.75‐1704.8), p <0.001≤2 HR 153.14 (13.75 1704.8), p <0.001

Radical RTN =35

Age 55 (30-73)

SexMale

Female34 (97.14%)1 (2.86%)

SmokingSmoker 30 (85.71%)

Non SmokerNA

( )3 (8.5%)2 (5.71%)

HistologySquamous 15 (42.86%)q

AdenoLarge cell

BACNSCLC NOS

( )6 (17.14%)1 (2.86%)08 (22.86%)

Small Cell ca( )

5 (14.29%)Stage

1-3A3B

12 (34.28%)7 (20%)

4LE

( )11 (31.43%)4 (11.43%)1 (2.86%)

Prior ChemotherapyNo chemotherapy

Palliative chemotherapyNACT

1 (2.86%)12 (34.29%)22 (62.86%)

RegimenCis-EtoCarb-EtoPacli-Carb

4 (11.76%)2 (5.88%)28 (82.35%)

No. of chemotherapy #≤2

3-45-6

015 (42.8%)20 (57.14%)

Response of ChemotherapyCRPRSD

8 (22.85%)17 (48.57%)9 (25.71%)

NA 1 (2.8%)

Dose40 Gy/4# 45 Gy/25#60 Gy/30#

2 (5.71%)6 (17.14%)27 (77 14%)60 Gy/30# 27 (77.14%)

RT responseNACR

8 (22.86%)4 (11.43%)

PRSDPD

2 (5.71%)13 (37.14%)8 (22.86%)

Second line treatmentSecond line treatmentNo treatment

ChemotherapyTKI

27 (77.14%)7 (20%)1 (2.86%)

Median OS = 24 4 months Median PFS = 12 57 monthsMedian OS = 24.4 months Median PFS = 12.57 months

Kaplan-Meier survival estimate Kaplan-Meier survival estimate

0.75

1.00

p

0.75

1.00

p

0.25

0.50

0.25

0.50

0.00

0 10 20 30 40analysis time

0.00

0 10 20 30analysis time

TKIs as first line treatmentN (%)

Age –Median (Range) 60 (23-80)

SexMaleFemale

19 (38%)31 (62%)

SmokingSmokerNon smoker

14 (28%)36 (72%)Non smoker

NA36 (72%)

HistologySquamous

AdenoBAC

2 (4%)35 (75%)6 ( 12%)BAC

Large cellNOS

6 ( 12%)07 (14%)

PS≤2 31 (62%)>2NA

18 (36%)1 (2%)

Stage1-3A

3B10 (20%)6 (12%)3B

4NA

6 (12%)33 (66%)1 (2%)

TKI usedGeftinibErlotinib

45 (90%)05(10%)

EGFR t ti t tEGFR mutation statusNA

PostiveNegative

43 (86%)3 (6%)4 (8%)

RResponseNA

CR+PRSDPD

6 (12%)10 (20%)17 (34%)17 (34%)

27 (54%)

PD 17 (34%)Toxicity

NASkinG t

40 (80%)7 (14%)3 (6%)Gut 3 (6%)

Toxicity GradeGrd 1&2Grd 3&4

91

S d li t t tSecond line treatmentNo treatment

ChemotherapyTKI

41 (82%)4 (8%)5 (10%)

First line TKIFirst line TKI

Overall Survival Progrssion free survivalOverall Survival Progrssion free survival

Kaplan-Meier survival estimate Kaplan-Meier survival estimate.1

1. .1

1.1. .1 .1 .1.1 .1.11.

.11..111

0.75

1.00

p

.11.

1.1.

1. 1

0.75

1.00

p

1.1.

1..1

.1 .1

1. .10.25

0.50

1. .1.1 1..1

1. .1

1. 1.

10.

250.

50

0.00


1.0.

00


Median OS =12.7 months Median PFS = 7.5 months

First line Chemotherapy vs TKIFirst line Chemotherapy vs TKI

Log rank (OS) p=0 21 Log rank (PFS) p= 0 46Log rank (OS) p=0.21 Log rank (PFS) p= 0.46

Kaplan-Meier survival estimates, by firsttt Kaplan-Meier survival estimates, by firsttt

00.

751.

00

p , y

00.

751.

00

p , y

000.

250.

50

000.

250.

50

0.


firsttt = 0 firsttt = 1

0.


firsttt = 0 firsttt = 1

First tt 0=ChemotherapyFirst tt 1= TKI

TKI MaintenanceTKI MaintenanceN=33

Age 50 (31‐73)g

SexMaleFemale

25(75.76%)8 (24.24%)

S kiSmokingSmokerNon smoker

NA

11 (33.33%)21 (63.63%)1 (3.03%)

Hi t lHistologySquamous

AdenoBAC

L ll

6 (18.18%)25 (75.76%)00Large cell

NOS02 (6.06%)

PS

≤2 31 (93 93%)≤2>2 NA

31 (93.93%)1 (3.03%)1(3.03%)

N=33Stage

1-3A3B

2 (6.06%)2(6.06%)

4NA

29 (87.88%)

TKI usedGeftinibErlotinib

22 (66.67%)11 (33.33%)

EGFR mutation statusNA

Postive29 (87.88%)2 (6.06%)

Negative 2 (6.06%)

Prior Chemotherapy (Regimen)

Pacli-Carb 23 (69.7%)Doce-Carb

Gem-CisGem-CarbPem- Cis

1 (3.03%)01 (3.03%)4 (12 12%)Pem Cis

Pem- Carb4 (12.12%)4 (12.12%)

Number of chemotherapy Cycles≤3 2 (6.06%)

4-6 31(93.94%)Response of chemotherapy

CRPR

1 (3.03%)20 (60 61%)PR

SD20 (60.61%)12 (36.36%)

Response of TKINA

CR+PR2 (6.06%)9 (27.27%)

SDPD

15 (45.45%)7 (21.21%)

ToxicityNA 28 (84 84%)NA

SkinGut

28 (84.84%)4 (12.12%)1(3.03%)

Toxicity GradeGrd 1&2Grd 3&4

4(12.12%)1(3.03%)

Second line treatmentNo treatment 25 (75 76%)No treatment

ChemotherapyTKI

25 (75.76%)8 (24.24%)0

Maintenance TKIMaintenance TKI

Overall Survival Progrssion free survivalOverall Survival Progrssion free survival

Kaplan-Meier survival estimate Kaplan-Meier survival estimate

0.75

1.00

p

0.75

1.00

p

0.25

0.50

0.25

0.50

0.00


0.00


Median OS =median not reached Median PFS = 14.7 months

Maintenance Vs No MaintenanceMaintenance Vs No Maintenance

L k (OS) 0 0026 Log rank (PFS) p=0 0014Log rank (OS) p=0.0026 Log rank (PFS) p=0.0014

Kaplan-Meier survival estimates, by tkimaintcat Kaplan-Meier survival estimates, by tkimaintcat

00.

751.

00

p , y

00.

751.

00

p , y

000.

250.

50

000.

250.

50

0.


tkimaintcat = 0 tkimaintcat = 1

0.


tkimaintcat = 0 tkimaintcat = 1

DiscussionDiscussion

• Main findings of this study are –Main findings of this study are • Adenocarcinoma is the commonest histology• Younger median age, as compared to westg g , p• Majority of the patients present in advanced stage • PS and adequacy of chemotherapy are the most important prognostic factors

• TKI use in maintenance (in clinically selected patients) may improve survivalmay improve survival

Authors TotalNo.

M:F Median Age

Sm:NS Squamous

Adenocarcinoma

Smallcell ca

Others

a

Prasad et al, Respirology

400 4.3:1 57 yrs 2.5:1 46.5% 18.5% 18.2% 16.8%

Respirology2004

Khan etl

321 11.3:1 30‐80 7.6:1 77.3% 5.3% 17.1% 0.3%al, Indian J Chest DisAllied Sci2006

yeas

Mohan A et al, Indian Journal of Cancer 2006

76 5.3:1 54.9 yrs 9:1 100%

Cancer 2006

Prasad et al, J

799 6:1 58 yrs 3:1 47% 18.2% 13.7% 21.1%

Cancer Res Ther, 2009

Authors TotalNo.

M:F Median Age

Sm:NS Squamous

Adenocarcino

Smallcell ca

Others

ma

Rawat et al, Lung I di 2009

203 8.2:1 55 yrs 4:1 44.3% 19.70% 16.75% 18.7%

India 2009

OUR STUDY

434 4.5:1 55 yrs 2.3:1 25% 39% 15% 21%

SEER data Clinical Epidemiology 2011

51,749 (NSCLC St IV)

1.5:1 65.6 yrs 18% 46% ‐ 9%

2011

F h 4669 5 2 1 64 5 11 5 1 47% 36% 17%French StudyLancet Oncol2007

4669 (NSCLC)

5.2:1 64.5 yrs 11.5:1 47% 36% ‐ 17%

Limitations 1. Inadequacy in facts recording in the files (e.g. PS, smoking

and pattern of smoking)

2. Inadequate toxicity reporting in files

3 Overall survival data was incomplete as the mortality data3. Overall survival data was incomplete as the mortality data was unavailable for some patients

…thank you

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