New Proposals for Lung Cancer Staging

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New Proposals for Lung Cancer Staging

• Akif Turna, MD, PhD, FETCS
• Yedikule Teaching Hospital for Chest Diseases and
  Thoracic Surgery, Istanbul, Turkey

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Presentation Scheme
- Conventional Staging of Lung Cancer - New
Staging Proposals - Non-anatomical staging -
Histopathological Staging - Molecular Staging -
Pathologically tailored surgical therapy -
Genotypically tailored surgical therapy - Future
directions
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Lung Cancer
- The Number one cause of cancer deaths
worldwide - 162 460 deaths from NSCLC occured in
2006 in US - M1 and N2-3 indicated poorer
survival, futile surgery
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Conventional Staging (6th)
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Survival Rates in Resected Non-Small Cell Lung
Cancer
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Survival Curves of Patients with Thyroid
Carcinoma According to Stages
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Survivals in Melanoma Patients
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Staging in Melanoma
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New Staging Proposal
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n100869
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New T Definitions (T1)
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New T Definitions (T2-T4)
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Recursive Partitioning
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Sample Size in 7th Staging Proposal
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7th Staging Proposal- Lymph Nodes WHY IS THAT
NOT DIFFERENT?
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Survival According to N1 type
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Multiple N1 and Multiple N2 Involvement
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Anatomical Proposals
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New Proposals for Lymph Node Locations
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New Proposals for Lymph Node Locations

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Histopathological Staging
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Histopathological Factors

• Histological type
• Grade
• Lymphatic Invasion
• Blood vessel invasion
• Necrosis
• Cytokeratin expression

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Text
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Poncelet et al., 2008, EJCTS
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Molecular Staging
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Role of p53

• TP53 gene alterations are present in about 50
  of NSCLC and their prognostic implications have
  been evluated in diverse clinical studies.
• Tumor response to anticancer therapies has been
  recognized to be largely based on apoptosis
  induction
• Active p53 has emerged as an important modulator
  of DNA-damage-induced apoptosis.

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EGFR
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Molecular Markers of Prognosis

• p53
• EGFR
• erbB2
• ERCC1
• RRM1
• PTEN
• ErbB-1

- cyclin A - PCNA -p16 -RASS1A -FHIT -k-ras -DNA
methylation
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Molecular Markers of Prognosis

• Volm and colleagues found that diminished
  expression of fas, ERbB-1, cyclin A and PCNA
  coincided with long term survival
• Two multi-institutional trials (ACOSOG 20030 and
  CALGB 9761) indicate that DNA methylation
  profiles are associated with tumor histology and
  stage, as well as response to therapy and overall
  survival in lung cancer patients.

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Excision Repair Cross Complemantation Group 1
(ERCC1)

• Protein component of nucleotide excision repair
  complex
• This complex reognizes and repairs
  cisplatin-induced DNA adducts
• Therefore it is thought to be important for
  resistance to platinum agents.

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Olaussen et. al, NEJM, 2006
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Chen HY, et al. NEJM, 2007
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Survival Based on ERCC1 expression
ERCC1, median 86 months
ERCC1-, median 44 months
p0.01
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Zheng et. al, NEJM
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Pathologically Tailored Surgical Therapy?
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Neadjuvant Therapy Routine or Selective?
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Kandioler-Eckerberger D, et al. J Thorac
Cardiovasc Surg1999
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Molecularly Tailored Surgical Therapy?
Lee et al., Lung Cancer, 2007
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Genotypically Tailored Surgical Therapy?
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Genotypically Tailored Therapy

• Fas-1377 A/G polymorphism was investigated
• There was no relationship between Fas-1377 G-A
  polymorphism and lung cancer, but smoking seemed
  to increase the possibility of inducing lung
  cancer in AG genotypes more than other genotypes.

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Genotypically Tailored Surgical Therapy ?
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Genotypically Tailored Surgical Therapy ?
Relationship between polymorphisims of gene
encoding microsomal epoxide hydrolase and lung
cancer
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NCCN- Guideline-2009
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Survival According to ERCC1 expression in
Neoadjuvant Chemotherapy Administered Patients
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Postoperative Complications and Survival
Song et al., Annals of Thoracic Surgery, 2007
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Future Studies

• Molecular mechanisms associated with ERCC1
• Randomized studies regarding molecularly tailored
  surgical therapies.
• Clinical studies based on genomics and
  proteomics
• Large studies with molecular PET markers.

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Acknowledgements

• Nur Ürer,
• Nur Büyükpinarbasili,
• Ilhan Yaylim,
• Zelal Erkisi,
• Ali Kiliçgün
• Turgay Isbir

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