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Role of Induction and Adjuvant Therapy in Regionally Advanced / Resectable NSCLC. Rodney J. Landreneau M.D. Professor of Surgery Department of CardioThoracic Surgery University of Pittsburgh Medical Center Pittsburgh, Pennsylvania. Stage IIIA Non Small Cell Lung Cancer. - PowerPoint PPT Presentation
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Role of Induction and Adjuvant Role of Induction and Adjuvant Therapy in Regionally Advanced / Therapy in Regionally Advanced /
Resectable NSCLCResectable NSCLC
Rodney J. Landreneau M.D.Professor of Surgery
Department of CardioThoracic SurgeryUniversity of Pittsburgh Medical Center
Pittsburgh, Pennsylvania
Stage IIIA Non Small Cell Lung Stage IIIA Non Small Cell Lung CancerCancer
A “heterogeneous” anatomic stage
classification with difficult to interpret responses to
therapy
Stage IIIa Non-Small Cell Lung Stage IIIa Non-Small Cell Lung Cancer HeterogeneityCancer Heterogeneity
• Microscopic mediastinal disease prognosis compared to macroscopic disease.
• Single station mediastinal node involvement compared to multiple station involvement
• Minimal clinical nodal involvement vs. Bulky mediastinal node involvement
Stage IIIa – “Bulky”Stage IIIa – “Bulky”
Stage IIIa – “Minimal Involvement”Stage IIIa – “Minimal Involvement”
Single Station IIIa DiseaseSingle Station IIIa Disease
Induction Chemo-radiotherapy for Stage III-a non-small cell
lung cancer
Standard of Care ???
Intergroup Trial 0139Chemo-radiation vs Chemo-radiation
followed by surgical resection of Stage
IIIa NSCLC
Kathy Albain et al.
Lancet. 2009 Aug 1;374:379-86
LUNG INTERGROUP TRIAL 0139 STUDY DESIGN IIIA(PN2)
STRATIFY
KPS 70-80 vs 90-100T1 vs T2 vs T3
RANDOMIZE
RE-EVALUATE RE-EVALUATE 2-4 weeks after 7 days before completion of RT completion of RT
Induction CT/RT
Cisplatin, 50 mg/m2 IV d1, 8, 29, 36Etoposide, 50 mg/m2 IV d1-5, 29-33
Thoracic RT, 45 Gy (1.8 Gy/d), begin d1
LUNG INTERGROUP TRIAL 0139 STUDY DESIGN
No progression at re-evaluation
Surgical Resection
Continue RT to 61 Gy without interruption
CONSOLIDATIONcisplatin plus etoposide
X 2 cycles
INTERGROUP 0139/RTOG 9309PROGRESSION-FREE SURVIVAL BY
TREATMENT ARMS
CT/RT/S 159/202 CT/RT 172/194
Logrank p = 0.017Hazard ratio = 0.77 (0.62, 0.96)%
Aliv
e w
ithou
t Pro
gres
sion
0
25
50
75
100
0 12 24 36 48 60
/
/ /// / // / / / // / // / / / / / / // / /
Months from Randomization
Failed/Total
Criteria for Patient Criteria for Patient Eligibility for O139 Eligibility for O139
Trial?Trial?
“Any mediastinal node positive status by any means? No systemic sampling/ recording” – Kathy
Albain - personal communication
Adjuvant ChemotherapyAdjuvant Chemotherapy in NSCLC: in NSCLC:
A new standard of care?A new standard of care?
N Engl J Med 2004;350:351-60N Engl J Med 2004;350:351-60
New Engl J Med 2004;350:351-60New Engl J Med 2004;350:351-60
4%
NEJM 2004;350:351-60
Chemotherapy better
935 775 619 520 447 372 282 208 125
932 780 650 550 487 399 300 208 133
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6 7 8 years
chemotherapy: 578 deaths
- 495 deaths before 5 years
- 83 deaths after 5 years
control 590 deaths - 534 deaths before 5 years - 56 deaths after 5 years
HR: 0.91 (0.81-1.02, P = 0.10)
Le Chevalier T, et al. J Clin Oncol. 2008(May 20 suppl). Abstract 7507.
"Fading" Benefit ?"Fading" Benefit ?IALT: 7.5-Year Median Follow-UpIALT: 7.5-Year Median Follow-Up
ASCO 2004ASCO 2004
CALGB 9633CALGB 9633
0 20 40 60 80
Survival Time (Months)
0.0
0.2
0.4
0.6
0.8
1.0
Pro
bab
ility
Chemotherapy
Observation
71%59% HR 0.62
p=0.028
SUMMARY STATISTICS:Log-Rank test for equality of groups: p=0.0164Wilcoxon test for equality of groups: p=0.0100Survival rate at 5 years for Observation: 54% - % C.I. ( 48%, 61%)Survival rate at 5 years for Vinorelbine: 69% - % C.I. ( 62%, 75%)
Observation Vinorelbine
Perc
enta
ge
0
20
40
60
80
100
Time (years) # At Risk(Observation) # At Risk(Vinorelbine)
0.0239243
2.0182193
4.094
121
6.04751
8.01310
10.000
NCIC BR 10
Chemotherapy
Observation
69%54%
HR 0.7p=0.012
YRS
5yrs 4yrs
ChemotherapyChemotherapy ObservationObservation
MOSMOS 95 months95 months 78 months78 months
P valueP value 0.100.10
HR (90% CI)HR (90% CI) 0.80 (0.60-1.07)0.80 (0.60-1.07)
0 2 4 6 8
Survival Time (Years)
0.0
0.2
0.4
0.6
0.8
1.0
Pro
bab
ility
ObservationChemo
0 1 2 3 4 5 6 7 8 9
ASCO 2006 (137/155 of Total Events) ASCO 2006 (137/155 of Total Events) ABSTR #7007ABSTR #7007
CALGB 9633CALGB 9633 - - OVERALL SURVIVALOVERALL SURVIVAL
ASCO 2005 ANITA : OSASCO 2005 ANITA : OS
months
Su
rviv
al D
istr
ibu
tion
Fu
nct
ion
1.00
0.75
0.50
0.25
00 20 40 60 80 100 120
0.79 [0.66 - 0.95]0.79 [0.66 - 0.95]Hazard RatioHazard Ratio
0.0130.013P-valueP-value
65.865.843.843.8Median monthsMedian months
NVB + CDDPNVB + CDDPOBS.OBS.
Obs
NVB + CDDP
Review of Adjuvant Review of Adjuvant ChemotherapyChemotherapy
Adjuvant Platinum-Based Adjuvant Platinum-Based ChemotherapyChemotherapy
Study Design Stage N Chemo
ALPI RCT I-III 1209 Cis / Mito / Vindesine
IALT RCT I-III 1867Cis / Vinca or
Etoposide
BLT RCT I-IIIA 488* Cis regimen (1 of 4)
JBR.10 RCT IB-II 482 Cis / Vinorelbine
CALGB RCT IB 344* Carbo / Paclitaxel
ANITA RCT I-IIIA 840 Cis / Vinorelbine
*Failed to complete goal enrollment.Negative trial resultPositive trial resultInitial positive result, later follow-up negative
Perception or Reality???
Adjuvant Chemotherapy for NSCLCAdjuvant Chemotherapy for NSCLCLung Adjuvant Cisplatin Evaluation (LACE)Lung Adjuvant Cisplatin Evaluation (LACE)
• Meta-analysis of adjuvant cisplatin trials performed since 1995
• BLT, ALPI, IALT, JBR.10, ANITA
• Pooled individual patient data
• 4584 resected patients, 5 randomized trials– 7% Stage IA
– 30% Stage IB
– 36% Stage II
– 27% Stage III
Pignon JP, et al. J Clin Oncol. 2008;26:3552-3559.
Adjuvant Chemotherapy for NSCLCAdjuvant Chemotherapy for NSCLCLACE: Overall SurvivalLACE: Overall Survival
No Deaths Hazard Ratio
ALPI 569 / 1088 0.95 [0.81;1.12]
ANITA 458 / 840 0.82 [0.68;0.98]
BLT 186 / 307 [0.71;1.27]
IALT 980 / 1867 0.91 [0.80;1.04]
JBR10 197 / 482 0.71 [0.54;0.94]
Total 2390 / 4584
Trial / No Entered HR [95% CI]
P = 0.005
0.89 [0.82;0.96]
Chemotherapy better | Control better0.0 0.5 1.0 1.5 2.0
569 / 1088 0.95 [0.81;1.12]
458 / 840 0.82 [0.68;0.98]
0.95
980 / 1867 0.91
197 / 482 0.71 [0.54;0.94]
Total
Trial Entered (Chemotherapy / Control) (95% CI)
Chemotherapy effect
0.89 (0.82;0.96]
0.0 0.5 1.0 1.5 2.0
Pignon JP, et al. J Clin Oncol. 2008;26:3552-3559.
Adjuvant Chemotherapy for NSCLCAdjuvant Chemotherapy for NSCLCLACE: Pooled Data Overall SurvivalLACE: Pooled Data Overall Survival
5.4% survival advantage at 5 years
HR = 0.89
95% CI 0.82-0.96
P = 0.005
Su
rviv
al (
%)
0
20
40
60
80
100
Time from Randomization (Years)0 1 2 3 4 5
61.0
48.857.1
43.5
ChemotherapyNo chemotherapy
Su
rviv
al (
%)
0
20
40
60
80
100
0 1 2 3 4 5 ≥ 6
61.0
48.857.1
43.5
Pignon JP, et al. J Clin Oncol. 2008;26:3552-3559.
Adjuvant Chemotherapy for NSCLCAdjuvant Chemotherapy for NSCLCLACE Analysis by StageLACE Analysis by Stage
Adjuvant chemo has greatest benefit for stage II
and III and may be detrimental for stage IA
Stage IA 104 / 347 1.41 [0.96;2.09]
Stage IB 515 / 1371 0.92 [0.78;1.10]
Stage II 893 / 1616 0.83 [0.73;0.95]
Stage III 878 / 1247 0.83 [0.73;0.95]
CategoryNo. Deaths
/ No. EnteredHazard Ratio
(Chemotherapy / Control) HR [95% CI]
0.5 1.0 1.5 2.0 2.5
Stage IA 1.41 [0.96;2.09]
Stage IB 0.92 [0.78;1.10]
Stage II 0.83 [0.73;0.95]
Stage III 0.83 [0.73;0.95]
CategoryNo Deaths
/ No EnteredHazard
(Chemotherapy / Control) HR [95% CI]
Test for trend: P = 0.051Chemotherapy better Control better
0.5 1.0 1.5 2.0 2.5
Pignon JP, et al. J Clin Oncol. 2008;26:3552-3559.
Based on HR from LACE meta-analysis and 5YS from ANITA trialChemotherapy = 4 months of cisplatin + vinorelbine
Stage IB
Stage II
Stage III
Adjuvant Chemo for Stage IB – III NSCLCAdjuvant Chemo for Stage IB – III NSCLCAbsolute Benefit in 5-Year SurvivalAbsolute Benefit in 5-Year Survival
Alive dueto surgery
Alive dueto chemo
Die despitechemo
Pignon JP et al. J Clin Oncol. 2006;24(18S). Abstract 7008; Douillard JY et al. Lancet Oncol. 2006:7;719-727.
““NATCH” TrialNATCH” Trial
Induction Chemotherapy for NSCLCInduction Chemotherapy for NSCLCOngoing TrialOngoing Trial
“(Neo)adjuvant Taxol Carboplatin Hope” (NATCH) “(Neo)adjuvant Taxol Carboplatin Hope” (NATCH)
Stages I and II (T3N1) NSCLCGoal = 600 patients
Accrual complete - 624
Randomize
Surgery
Surgery - 211
Carboplatin/Paclitaxel x 3 (65%)
Surgery - 212Carboplatin/
Paclitaxel x 3 - 201 (93%)
Rosell R, et al. Lung Cancer. 2001;34(suppl 3):S63-S74.
““No” Differences 5 yr No” Differences 5 yr Disease Free SurvivalDisease Free Survival
Surgery – 39%Induction/Surgery – 41%
Surgery/ Adjuvant – 39%
Felip E., et al. - ASC0 (abst #7500) -2009
Adjuvant ChemotherapyAdjuvant Chemotherapy in NSCLC: in NSCLC:
A new standard of care?A new standard of care?
Breaking the Sound Barrier
Adjuvant ChemotherapyAdjuvant Chemotherapy
Standard of CareStandard of Care
Good performanceGood performance status patients with status patients with “R0” Anatomic Resection “R0” Anatomic Resection
– Stages IIA-BStages IIA-B
– IIIA NSCLCIIIA NSCLC
– Maybe Larger IBMaybe Larger IB ??????
Future Directions
0102030405060708090
100
1 2 3 4 5 6 7 8 9 10
YEARS
PE
RC
EN
T S
UR
VIV
AL
AD ChemotxEmperic ChemotxObservation
Patients with micrometastisisResponders to Chemotx
STD
Empiric therapy
Assay directed?
? Study Concept ?? Study Concept ?““Single Station IIIa NSCLC”Single Station IIIa NSCLC”
Is There a Role for Surgery for N2 NSCLC?Is There a Role for Surgery for N2 NSCLC?
““Surprise” N2 DiseaseSurprise” N2 Disease
Specific Clinical Frequency of Specific Clinical Frequency of ““Single StationSingle Station” IIIa NSCLC” IIIa NSCLC
Historically – 33% to 50% of patients in “IIIa” surgical series
Mithos P - Ann Thor Surg 2008
Rae F – Lung Cancer 2004
Kang HC – Ann Thor Surg 2008
““Single Station” Stage IIIa ProposalSingle Station” Stage IIIa Proposal
• Randomized trial: Induction Chemotherapy followed by anatomic resection “less than” pneumonectomy compared to anatomic resection “less than” pneumonectomy with Adjuvant Chemotherapy [mediastinal staging accuracy evaluation]
Small T1 Right Upper Lobe Small T1 Right Upper Lobe CancerCancer
Small T1 Right Upper Lobe Cancer- Small T1 Right Upper Lobe Cancer- Paratracheal Nodes Clinical NegativeParatracheal Nodes Clinical Negative
Small T1 Right Upper Lobe Cancer- Small T1 Right Upper Lobe Cancer- PET Positive Single Station PET Positive Single Station
Paratracheal Nodes Paratracheal Nodes
Phase III Randomized Study DesignPhase III Randomized Study Design
SINGLE
STATION
N2
R
A
N
D
O
M
I
Z
E
Platinum based Chemotherapy
x3 cycles
SURGERY
SURGERY Platinum based chemotherapy
x3 cycles
●Clinical Stage T1-3, N2 Single Station
● Staging Procedures: Mediastinoscopy, EBUS, EUS, PET
●RO anatomic resection (segmentectomy or lobectomy)
●Mediastinal node dissection (including 4R, 10, 7 pockets on right and 5, 6, 10L, 7 on left)
●Tissue acquisition for correlative studies
Surgical ManagementSurgical Management
Single Station IIIa ProposalSingle Station IIIa Proposal
Study ObjectivesStudy Objectives
• The primary endpoint – evaluation of the progression-free survival and overall survival surgery with induction vs adjuvant therapy single station IIIa disease
• Secondary endpoints
Response rate
Relative toxicity and complications.• To evaluate the utility of modern staging techniques of
mediastinoscopy, PET imaging and endoscopic ultrasound guided biopsy techniques in accurately identifying single station IIIa disease.
Correlative StudiesCorrelative Studies
Collaborative StudiesCollaborative Studies
• Chemoresponse assay analysis – observational study – tissues at mediastinoscopy and also at time of resections.
• Genotypic / mutational analysis of “excision / repair enzyme” profiles to assess such biomarker utility in determining individual response to platinum agents.
• Quality of life determinations related to induction therapy and adjuvant therapy for “single station” IIIa disease.
Companion / Integrated Companion / Integrated StudiesStudies
?Induction Radiation Therapy with Chemotherapy for multistation disease ( low volume (less 3cm dia
nodes) ?
?Adjuvant PORT with Chemotherapy for multi-station microscopic disease found at resection?
Nothing happens unless you try!Nothing happens unless you try!
City of PittsburghCity of PittsburghPennsylvaniaPennsylvania
Thank Thank YouYou
Case PresentationCase Presentation““Sublobar Resection” vs. Sublobar Resection” vs. “Lobectomy” for Stage I “Lobectomy” for Stage I
NSCLCNSCLC
Case Study Case Study
• An asymptomatic, well nourished, 77 year old man, 80 pk/year active cigarette smoker participating in the National Lung Screening Trial (NLST) is found to have a 1.4 cm non-calcified lung nodule in the posterior segment of his right upper lobe without mediastinal or hilar lymph node enlargement on first “incidence” scan in 2005.
Case StudyCase Study
• No history of previous cancer and no complaints of urinary or bowel problems. Screening colonoscopy performed 7 years ago normal without any polpys.
• Chest pain 4 years ago was evaluated with coronary angiography and ventriculogram demonstrating diffuse mild (less than 30%) narrowing and a left ventricular ejection fraction of 55%.
• No complaint of dyspnea on exertion. – Walks the 2 miles a day through the hills around home in Pittsburgh.
Case StudyCase Study
• PET/CT performed which demonstrated solitary nodule in Right upper lobe with SUV – 3. No other abnormal activity noted on fusion scan.
• Pulmonary function studies were performed demonstrating:– FEV-1 = 70% of predicted– FVC = 85% of predicted – FEF 25-75 = 55% of predicted– DLCO% = 60% of predicted– Normal ABG
Question #1Question #1• What diagnostic / therapeutic decisions would you make for this
patient?– A) percutaneous CT directed biopsy. If negative for malignant cells, further
follow-up scan in 6 months
– B) posterolateral thoracotomy and lobectomy with lymph node dissection
– C) VATS lobectomy with full nodal sampling
– D) Anatomic Segmentectomy with full nodal sampling
– E) VATS wedge resection with clear surgical margins
– F) B,C, or D
Question #1 answerQuestion #1 answer• What diagnostic / therapeutic decisions would you make for this patient?
– A) percutaneous CT directed biopsy. False negatives important issue. ? Influence of “lead time bias” and “over diagnosis” but generally not accepted.
– B) posterolateral thoracotomy and lobectomy with lymph node dissection – C) VATS lobectomy with full nodal sampling – D) Anatomic Segmentectomy with full nodal sampling – E) VATS wedge resection with clear surgical margins. Local recurrence (~20%) and
overall survival major negative influence on using this for primary therapy– F) B,C or D
Question #2Question #2• Which statement / statements are false regarding the clinical
outcome following sublobar resection?– A) wedge resection of stage I lung cancer has equivalent clinical success to that of anatomic
resection.– B) Anatomic segmentectomy has comparable survival to lobectomy for stage 1a nsclc – C) Pulmonary function is preserved relative to lobectomy
following anatomic segmentectomy for stage I nsclc– D) Visceral pleural involvement does affect survival for clinical 1a, node negative lung cancers
undergoing segmentectomy – E) VATS segmentectomy as equivalent clinical results to open segmentectomy for stage 1a nsclc
Question #2 answerQuestion #2 answer• Which statement / statements are false regarding the clinical
outcome following sublobar resection?– A) wedge resection of stage I lung cancer has equivalent clinical success to that of anatomic
resection.– B) Anatomic segmentectomy has comparable survival to lobectomy for stage 1a nsclc – C) Pulmonary function is preserved relative to lobectomy
following anatomic segmentectomy for stage I nsclc– D) Visceral pleural involvement does affect survival for clinical 1a, node negative lung cancers
undergoing segmentectomy – E) VATS segmentectomy as equivalent clinical results to open segmentectomy for stage 1a nsclc
Case StudyCase Study• VATS anatomic posterior segmentectomy of the right upper lobe
with comprehensive mediastinal nodal sampling (4R, 3,10,11, 7) in 2005. Uneventful 4 day hospital course.
• Typical adenocarcinoma (T1N0) – 1.5 cm dia. with 2.3 cm surgical margins. No evidence of neurovascular invasion or visceral pleural invasion.
• No evidence of local or systemic recurrence now 6 years from surgical resection.
Breaking the Sound BarrierBreaking the Sound Barrier
“Tragedies of Emperic Therapy”
SophoclesGreek Tragedian
497-405 BC
SophoclesGreek Tragedian
497-405 BC
Cancer – “The Crab” Cancer – “The Crab”
NSCLC StagingNSCLC Staging
Importance of Surgical StagingImportance of Surgical StagingImportance of Surgical StagingImportance of Surgical Staging
Lopez-Encuentra A et al. Ann Thorac Surg 2005; 79: 974-9
* Poor concordance between clinical and pathologic staging
"Fading" Benefit ?"Fading" Benefit ?IALT: Cisplatin + a Vinca or EtoposideIALT: Cisplatin + a Vinca or Etoposide
Arriagada R, et al. N Engl J Med. 2004;350:351-360.
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5
Surgery
Surgery + chemo
Pro
po
rtio
n S
urv
ivin
g
Years
HR = 0.86; 95% CI 0.76-0.98; P < 0.03
N = 1867
935 775 619 520 447 372 282 208 125
932 780 650 550 487 399 300 208 133
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6 7 8 years
chemotherapy: 578 deaths
- 495 deaths before 5 years
- 83 deaths after 5 years
control 590 deaths - 534 deaths before 5 years - 56 deaths after 5 years
HR: 0.91 (0.81-1.02, P = 0.10)
Le Chevalier T, et al. J Clin Oncol. 2008(May 20 suppl). Abstract 7507.
"Fading" Benefit ?"Fading" Benefit ?IALT: 7.5-Year Median Follow-UpIALT: 7.5-Year Median Follow-Up
Multimodality therapy of Multimodality therapy of Stage IIIa NSCLC ?Stage IIIa NSCLC ?
The Evolution of Treatment Outcomes for Resected Stage IIIA Non-Small Cell
Lung Cancer Over 15 Years at a Single Institution
Linda Martin, Arlene Correa, Wayne Hofstetter, Waun Ki Linda Martin, Arlene Correa, Wayne Hofstetter, Waun Ki Hong, Ritsuko Komaki, Joe Putnam, Jr., David Rice, Roy Hong, Ritsuko Komaki, Joe Putnam, Jr., David Rice, Roy
Smythe, Stephen Swisher, Ara Vaporciyan, Garrett Walsh, and Smythe, Stephen Swisher, Ara Vaporciyan, Garrett Walsh, and Jack RothJack Roth
The Department of Thoracic and Cardiovascular SurgeryThe Department of Thoracic and Cardiovascular Surgery
MD Anderson Cancer CenterMD Anderson Cancer Center
Houston, TexasHouston, Texas
MethodsMethods
• 1986-2001 – retrospectively 1986-2001 – retrospectively reviewed all NSCLC patients who reviewed all NSCLC patients who had surgery at UT MDACC (n= had surgery at UT MDACC (n= 2861, 2861, 353 IIIa patients353 IIIa patients))• identified pathologically confirmed N2 identified pathologically confirmed N2
metastasesmetastases• Included all T1-3, N2 casesIncluded all T1-3, N2 cases
1 30 2
Hazard Ratios - SurvivalHazard Ratios - Survival
Male vs. Female
Low/Mid vs. Upper Lobe
Multimodality Rx vs. Surgery
R1/R2 vs. R0
2 N2 Stations
>2 N2 Stations
Protective Increased Risk
0.003
<0.001
0.002
<0.001
<0.001
0.007
p-value
Survival by Lymph Node Survival by Lymph Node Stations InvolvedStations Involved
Cu
mu
lati
ve S
urv
ival
Pro
bab
ility
Cu
mu
lati
ve S
urv
ival
Pro
bab
ility
0 10 20 30 40 50 60
0.0
0.2
0.4
0.6
0.8
1.0
1 Station1 Station
2 Stations2 Stations
>2 Stations>2 StationsP<0.001P<0.001
Time (months)Time (months)
Median SurvivalMedian Survival
25.325.3
16.816.8
15.515.5
Survival -Treatment GroupSurvival -Treatment GroupC
um
ula
tive
Su
rviv
al P
rob
abili
tyC
um
ula
tive
Su
rviv
al P
rob
abili
ty
Time (months)Time (months)0 10 20 30 40 50 60
0.0
0.2
0.4
0.6
0.8
1.0
P=0.004P=0.004
Multimodality Multimodality TreatmentTreatment
Surgery Surgery AloneAlone
Median survivalMedian survival
15.9 months15.9 months
25.3 months25.3 months
ConclusionsConclusions
• Survival for pIIIA (N2) NSCLC has significantly Survival for pIIIA (N2) NSCLC has significantly improved over timeimproved over time
• Use of multimodality treatment has increased over Use of multimodality treatment has increased over timetime
• Prognostic factors associated improved survival:Prognostic factors associated improved survival: Female genderFemale gender Upper lobe tumor locationUpper lobe tumor location Single N2 station involvementSingle N2 station involvement R0 resectionR0 resection
• Multimodality therapy is a modifiable factor Multimodality therapy is a modifiable factor significantly associated with improved survivalsignificantly associated with improved survival
?? Accuracy of Preoperative ?? Accuracy of Preoperative Staging in Identifying Staging in Identifying
“Single Station” IIIa Non-“Single Station” IIIa Non-Small Cell Lung Cancer ??Small Cell Lung Cancer ??
NSCLC StagingNSCLC Staging
Radiographic AssessmentRadiographic AssessmentRadiographic AssessmentRadiographic Assessment
• CT Scan
• PET Scan
- Good at primary tumor assessment - LN sensitivity and specificity: 65-80%
NSCLC StagingNSCLC Staging
Radiographic AssessmentRadiographic AssessmentRadiographic AssessmentRadiographic Assessment
• CT Scan
• PET Scan
- Superior to CT in detecting mediastinal LN involvement (90%) and mets
- Good NPV, poor PPV- Unclear whether cost-effective
NSCLC StagingNSCLC Staging
PET/CT
- Excellent sensitivity- Limited PPV- False positives common- Better than CT or PET alone in detecting LN involvement or mets
Gonzalez-Stawinsky GV et al. JTCVS 2003; 126: 1900-5
- n=202 with CA
- PET neither confirms or excludes involvement of the mediastinum- Cervical mediastinoscopy with biopsy remains the gold standard
NSCLC StagingNSCLC Staging
Invasive Staging TechniquesInvasive Staging TechniquesInvasive Staging TechniquesInvasive Staging Techniques
• Cervical Mediastinoscopy
• Chamberlain Procedure
• Thoracoscopy
• EBUS/EUS
EBUS for Station 7EBUS for Station 7
Herth FJ et al. Endobronchial Ultrasound-guided Transbronchial Needle Aspiration. J Bronchol 2006; 13(2): 84-91
Surgical Resection Associated Surgical Resection Associated with “with “InductionInduction” or “” or “AdjuvantAdjuvant” ” Systemic Therapy for “Single Systemic Therapy for “Single
Station” IIIa NSCLCStation” IIIa NSCLC