Non-small cell lung cancer Lancet 2011;378: Peter Goldstraw, David Ball, James R Jett, Thierry Le Chevalier, Eric Lim, Andrew G Nicholson, Frances A Shepherd

Advances in pathology Advances in early diagnosis Prognostic factors Advances in surgical treatment Advances in chemotherapy in adjuvant, induction, and multimodal settings Advances in systemic therapy for advanced disease Advances in radiotherapy

Advances in pathology previous classification : for pathologists by pathologists recent update multidisciplinary and international composition rapid development of genetic data mainly therapy-driven immunohistochemistry importance of multidisciplinary review whether molecular data should be sought need for further sampling whether clinical features might assist in planning of future management The pathologist should now be part of these discussions, not least to ensure judicious use of tissue

Advances in pathology “bronchioloalveolar carcinoma” the absence of standardised criteria across disciplines pathologists : adenocarcinomain-situ oncologists : include advanced disease  adenocarcinoma with BAC portion

increased need for IHC and genetic data to inform treatment response and prognosis

Advances in early diagnosis CT screening

Advances in early diagnosis susceptibility gene for lung cancer 15q24-25 three genes that encode nicotinic acetylcholine receptor subunits simply be associated with nicotine dependence

Prognostic factors The variables that are associated with prognosis tumour-related : primary site, cell type, extent of disease patient-related : performance status, comorbidity, sex environmental factors : nutrition and the choice, quality of treatment  useful individually or combined to form a composite prognostic index.

Prognostic factors anatomical extent of disease (TNM classification) one of the most important prognostic factors The seventh edition of the TNM classification published late in 2009, came into effect from Jan 1, 2010 significant changes in some T and M descriptors based on proposals by the International Staging Project of the International Association for the Study of Lung Cancer (IASLC)

novel aspects of the seventh edition definition of visceral pleural invasion clarification of the distinction between lung metastases and multiple synchronous primary tumors new nodal chart

J Thorac Oncol. 2008;3: 457–466

Advances in surgical treatment improve our understanding of the role of surgery in staging, selection, and surgical management of patients with lung cancer mediastinoscopy and mediastinal lymph-node biopsy use of PET and PET/CT endobronchial and endoscopic ultrasound and to stage the mediastinum (sensitivity (88%) and specifi city (100%)) be used to confirm negative results of ultrasound aspiration biopsy

Advances in surgical treatment  VATS lung resection conflicting results lower systemic recurrences and improved 5-year survival with VATS? ↔ 1.6-times increase in complications with VATS  intraoperative lymph-node management importance of surgical lymph-node staging by recommending at least six nodes or stations to be sampled  management of patients with poor lung function bronchoplastic and angioplastic sleeve resections sublobar (wedge resection or segmentectomy)

Bnsh Joumal of Cancer (1998) 78(5)

Advances in chemotherapy in adjuvant, induction, and multimodal settings despite optimum surgical management the 5-year survival rate of resected NSCLC : 25%~73%

Advances in chemotherapy in adjuvant, induction, and multimodal settings ERCC1, RRM1, MSH2, β-tubulin, BRCA1 predictive value for selection of patients who will benefit from adjuvant platin-based chemotherapy targeted agents and vaccine therapy preoperative treatment with chemotherapy down staging(about 50% of cases) sometimes allowing a complete resection front-line attack of micrometastases. the compliance with preoperative chemotherapy -- 90% (60–70% for postoperative chemotherapy)

CCRT in locally advanced inoperable NSCLC Annals of Oncology 17: 473–483, 2006

Advances in systemic therapy for advanced disease  Chemotherapy the mainstay of treatment for advanced stage IIIB and IV NSCLC platinum-based doublet single agents : in elderly patients or poor performance subsets multitargeted anti-folate agent pemetrexed - be less active in patients with squamous cancers

The Oncologist 2009;14:253–263

Advances in systemic therapy for advanced disease  platinum-based doublets + molecularly targeted agents angiogenesis inhibitor bevacizumab monoclonal antibody targeting vascular endothelial growth factor carboplatin paclitaxel, cisplatin gemcitabine, carboplatin pemetrexed the potential for toxic effects and added cost cetuximab monoclonal antibody directed against the epidermal growth factor receptor (EGFR) increased response rates no significant or clinically meaningful survival benefit

Advances in systemic therapy for advanced disease  EGFR normally found on surface of epithelial cells often overexpressed in human malignancies EGFR-activating mutation  critical biological determinant for proper Tx exon 18 deletion, exon 21 mutation, exon 18  response to TKI adenoca, Asian, non-smoker, women, non-mucinous cancer EGFR TKI, gefitinib

Gefitinib is superior to carboplatin–paclitaxel as an initial treatment for adenocarcinoma among nonsmokers or former light smokers in East Asia N Engl J Med 2009;361:

Advances in systemic therapy for advanced disease  EML4-ALK EML4-ALK fusion oncogene : inversion on the short arm of ch 2 similar patients chracteristics of EGFR mutation oral TKI that targets MET and EML4–ALK, Crizotinib

Advances in radiotherapy important roles in both curative and palliative treatment of NSCLC curative radiotherapy good performance status, inoperable disease, localized to the primary site, with or without regional lymph-node involvement (stages I–III) precise definition of the cancer’s anatomical extent crucial for accurate placement and shaping of the radiotherapy beams because of ventilatory and cardiac motion amount of intrafraction motion - recorded by four-dimensional CT