Rodney J. Landreneau, MD Professor of Surgery Heart, Lung & Esophageal Surgery Institute University...
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Rodney J. Landreneau, MD Rodney J. Landreneau, MD Professor of Surgery Professor of Surgery Heart, Lung & Esophageal Surgery Heart, Lung & Esophageal Surgery Institute Institute University of Pittsburgh Medical Center University of Pittsburgh Medical Center Management of Non-Small Management of Non-Small Cell Lung Cancer Cell Lung Cancer St. Margaret Grand Rounds September 10,2009
Rodney J. Landreneau, MD Professor of Surgery Heart, Lung & Esophageal Surgery Institute University of Pittsburgh Medical Center Management of Non-Small
Rodney J. Landreneau, MD Professor of Surgery Heart, Lung &
Esophageal Surgery Institute University of Pittsburgh Medical
Center Management of Non-Small Cell Lung Cancer St. Margaret Grand
Rounds September 10,2009
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Management of Non-Small Cell Lung Cancer CT surveillance for
lung cancer Sublobar Resection vs. Lobectomy Role of surgical
resection for regionally advanced lung cancer Adjuvant Systemic
Therapy for regionally advanced resectable lung cancer CT
surveillance for lung cancer Sublobar Resection vs. Lobectomy Role
of surgical resection for regionally advanced lung cancer Adjuvant
Systemic Therapy for regionally advanced resectable lung
cancer
Slide 3
Lung Cancer Surveillance
Slide 4
Original Article Survival of Patients with Stage I Lung Cancer
Detected on CT Screening The International Early Lung Cancer Action
Program Investigators N Engl J Med Volume 355(17):1763-1771 October
26, 2006
Slide 5
Kaplan-Meier Survival Curves for 484 Participants with Lung
Cancer and 302 Participants with Clinical Stage I Cancer Resected
within 1 Month after Diagnosis The International Early Lung Cancer
Action Program Investigators. N Engl J Med 2006;355:1763-1771
Slide 6
Conclusion Annual spiral CT screening can detect lung cancer
that is curable Comparable screening efficacy as mammographic
screening for breast cancer (prevalence 1.6%; incidence 0.6%) Cost
effective - low energy, fast scanning about $200 Treatment of early
stage disease less expensive than advanced disease
Slide 7
Controversy
Slide 8
CT scans have radiation risks and sometimes detect cancers that
would not have progressed, leading to risky procedures like
biopsies and lung surgery when not needed. lung surgery lung
surgery
Slide 9
The National Cancer Institute started in 2002 the $200 million
National Lung Screening Trial comparing death rates among 55,000
people randomly assigned to have CT scans or chest X- rays. Results
are not expected until 2010.
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Sublobar Resection or Lobectomy for stage I lung cancer
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Standard of Care For Peripheral Nodules 1940s Pneumonectomy
1960s Lobectomy 1990s ?Segmentectomy/Wedge (and adjuvant
local/systemic Rx) Surgical Resection of the Lung
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Errett LE et al J Thorac Cardiovasc Surg. 1985 Nov;90(5):656-61
Sublobar Resection vs. Lobectomy for Stage 1 Non-Small Cell Lung
Cancer
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Randomized Trial of Lobectomy Versus Limited Resection for T1
N0 Non-Small Cell Lung Cancer (125 Lobectomy, 122 Limited
Resection) RJ Ginsberg, LV Rubinstein and Lung Cancer Study Group
Ann Thorac Surg 1995;60:615-23
Slide 25
Lobectomy vs Limited Resection Time to death (from any cause)
by treatment logrank p=0.088 (one-tailed) Ginsberg and Rubinstein
Ann Thorac Surg
Slide 26
Wedge Resection Versus Lobectomy for Stage I (T1 N0 M0)
Non-Small Lung Cancer Landreneau, et.al., J Thorac Cardiovasc Surg
1997;113:691-700
Slide 27
Wedge vs Lobectomy for Stage I NSCLC p=0.889 Landreneau,
et.al., J Thorac Cardiovasc Surg 1997;113:691-700
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Wedge vs Lobectomy for Stage I NSCLC Open WR VATS WR
Vs.LobeP< Op Mortality (%)00Vs.3.30.20* Postop Stay (days)
7.76.5Vs.10.10.0002* Local Recur (%) 1715 Vs. 5 0.08*
Local/Systemic Recurrence (%) 2423vs.170.43* *- all WR (n=95) vs.
Lobe (n=124) Statistical Methods: Life Table Analyses Obtained by
Log Rank and Wilcoxson Tests Landreneau, et.al., J Thorac
Cardiovasc Surg 1997;113:691-700
Slide 29
! Local Recurrence !
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Adjuvant Radiation Therapy External beam radiation therapy -
Potential risk of increased injury to surrounding pulmonary
parenchyma What is efficacy of intraoperative brachytherapy when
external beam radiation may otherwise be applied?
Slide 31
Intraoperative Brachytherapy Not a new concept for lung cancer
Mostly used for Stage IIIA disease - close or positive margins
Improved local control What is its role in high risk patients with
totally resectable disease where lobar resection is not feasible
and adjuvant radiotherapy is recommended?
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Comparison Between Sublobar Resection and 125Iodine
Brachytherapy After Sublobar Resection in High-Risk Patients with
Stage I NonSmall-Cell Lung Cancer Comparison Between Sublobar
Resection and 125Iodine Brachytherapy After Sublobar Resection in
High-Risk Patients with Stage I NonSmall-Cell Lung Cancer R.
Santos, A. Colonias, D. Parda, M. Trombetta, RH Maley, R. Macherey,
S. Bartley, T. Santucci, RJ Keenan, RJ Landreneau Surgery 2003,
Oct;134(4): 691-7
Slide 42
Sublobar Resection (n=102) Sublobar Resection With Brachy
(n=96) Local Recurrence19 (18.6%)1 (1%) p=.0001 Hospital Mortality0
(0%)3 (3%) p=ns Hospital Stay7 days8 days p=ns Survival % 1, 2, 3
and 4 year93, 73, 68, 60%96, 82, 70, 67% p=ns Systemic Recurrence
29 (28.4)22 (23%) p=ns Pre-op FEV 1% predicted 65%53% p=nsResults
The FEV 1 did not change postoperatively in the sublobar resection
with brachytherapy group in the interval of follow-up
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Lobectomy vs Sublobar Resection Effect of Tumor Size on
Prognosis in Patients with Non-Small Cell Lung Cancer: The Role of
Segmentectomy as a Type of Lesser Resection Effect of Tumor Size on
Prognosis in Patients with Non-Small Cell Lung Cancer: The Role of
Segmentectomy as a Type of Lesser Resection Okada M, Nishio W,
Sakamoto T, Uchino K, Yuki T, Nakagawa A, Tsubota N. J Thorac
Cardiovasc Surg. 2005 Jan;129(1):87-93 An evaluation of surgical
resection in 1272 NSCLC patients
Slide 45
TUMOR SIZE Segmental ResectionLobectomy Wedge Resection 20 mm
or less96.792.485.7 20-30 mm84.687.439.4 More than 30 mm 62.981.30
Lobectomy vs Sublobar Resection 5 Year Cancer Specific Survival
Stage I Okada, M, et al J Thorac Cardiovasc Surg. 2005
Jan;129(1):87-93
Slide 46
Efficacy of Anatomic Segmentectomy in the Treatment of Stage I
NSCLC Matthew J. Schuchert M.D., Brain L. Pettiford M.D., Samuel
Keeley M.D., Thomas A. DAmato M.D., Ph.D., Arman Kilic B.S., Hiran
C. Fernando M.D., John Close M.A., Ricardo Santos M.D., James R.
Landreneau, James D. Luketich M.D., Rodney J. Landreneau M.D.
Division of Thoracic Surgery Heart, Lung and Esophageal Surgery
Institute UPMC Health System Pittsburgh, Pennsylvania
Slide 47
Patient and Tumor Characteristics Stage IA Anatomic
Segmentectomy (n=182) Lobectomy (n=246) Stage IA109 (60%) 114 (46%)
Tumor Size Mean (cm) Range (cm) 1.71.9 Schuchert MJ., et. Al.; STS
2007
Slide 48
Stage IA Segmentectomy vs Lobectomy Cumulative Survival Time
(months) Lobectomy Segmentectomy log rank = 0.780 Schuchert MJ.,
et. Al.; STS 2007 Overall Survival
Slide 49
Recurrence Patterns - Stage IA Anatomic Segmentectomy (n=109)
Lobectomy (n=114) P Value NED 97 (89%) 102 (83.3%) NS Recurrence
Locoregional Distant 12 (11.0%) 5 (4.6%) 7 (6.4%) 12 (10.5 %) 6
(5.3%) NS Follow-Up (Mos)18.330.0
Anatomic Segmentectomy Favorable Criteria for Anatomic
Segmentectomy Peripheral location (outer 1/3) Small Tumors: < 2
cm in diameter Pathologic Margin > 1 cm (Margin/Tumor
ratio>1) Age >75 Marginal pulmonary function Ground glass
opacities Bronchoalveolar UPMC Experience 452 Anatomic
Segmentectomies - 224 Stage I NSCLC - 114 Stage II-III NSCLC - 31
Metastasectomies - 9 Benign Neoplasms - 53
Inflammatory/Granulomatous - 15 Bullous Disease - 5
Infection/Abscess - 1 Trauma ACOSOG Z0030: Mortality 3%;
Complications 46% UPMC: Mortality 1.1%; Complications 32%
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Sublobar Resection?
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Sublobar Resection vs. Lobectomy?
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Induction (pre-operative ) Chemo-radiotherapy for Stage III-a
non-small cell lung cancer Standard of Care ???
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Intergroup trial 0139 Chemo-radiation vs Chemo- radiation
followed by surgical resection of Stage IIIa NSCLC Kathy Albain et
al. ASCO 2005 Lancet 2009;374:379-86
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Adjuvant Chemotherapy in NSCLC: A new standard of care?
Progression-Free Survival by Treatment Arm 05/09/2005, median
F/U 31 mo Pisters, et. Al. ASCO 2005
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Overall Survival by Treatment Arm 05/09/2005, median F/U 31 mo
Pisters, et. Al. ASCO 2005
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CS (n=154)S Only (n=160) N=7* (.045)N=4 (.025) Lobectomy
Pneumonectomy 3 (.02) 4/24 (.17) Lobectomy Pneumonectomy 4 (.035)
0/26 [2R, 2L] *p=0.32 From: Eric Vallieries 2007 Randomized Trial
of Induction Chemotherapy Followed by Anatomic Lung Resection Stage
IIIA SWOG 9900
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Depierre Randomized Preop Trial Preop Trial N=355 eligible,
stages IB, II and IIIA (35% N2) MIP x2 Surgery (+2 adj: PR/path CR)
Surgery alone Median survival 37 vs 26 months, p=0.15 Depierre JCO
2002
Slide 94
Disease free survival 27 vs 13 mo, p=0.033 Risk of DM=0.54
[0.33-0.88], p=0.01 Stage I-II: Risk death= 0.68 [0.49-0.96],
p=0.027 Depierre Randomized Preop Trial Preop Trial Continued
Depierre JCO 2002
Slide 95
Results Overall Survival BLOTS9900Depierre
PreopControlPreopControl Median OS (months) 4347403726 1 year (%)
8482797773 2 year (%) 6869635952 Pisters, et. Al. - ASCO 2005; JCO
2002
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Management of Non-Small Management of Non-Small Cell Lung
Cancer Lung Cancer Survival
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Still Empiric Therapy Approach!!
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Dr. Henschke has asserted that allowing hundreds of thousands
of people to die in the meantime is unethical. Therefore, off study
CT screening should be approved by insurance for high risk
patients!