NSCLC management basics

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NSCLC management basics

  1. 1. NON-SMALL CELL LUNG CANCER ALEXANDER DRILON MD Fellow, Thoracic Oncology Service Memorial Sloan Kettering Cancer CenterThe following material is intended for MSKCC internal medicine housestaff teaching purposes only.The slides are courtesy of Dr. Alexander Drillon and were updated for the LibGuide in 2011-2012.
  2. 2. Leading cause of cancerdeath• 85% of patients will die of disease• 2x lung CA vs. breast CA deaths (more than breast + colon)• 70% late stage at diagnosis• early stage: high recurrence rates
  3. 3. history
  4. 4. “Of all the cancers, tobacco-associated lung cancers are the ones which most unequivocally reflect a conflict between biological evolution and the social ratchet of pleasurable behavior and commercial gain.” Mel Greaves Cancer, The Evolutionary Legacy
  5. 5. 20th Century Epidemic• 20 year latency period • Cigarettes manufactured 1910 • Increased incidence in men in 1930s • Incidence in women increased only in 1960s after WW2
  6. 6. Doll and Hill: British Doctors Studycausal relationship established in the 1950s  1964 Surgeon General’s Warning
  7. 7. etiology
  8. 8. Smoking accounts for 90% of all lung cancers • ten years to reduce risk by 75%
  9. 9. Relative Risk of Developing Lung Cancer35302520151050 Smoking + Smoking Passive Smoke Asbestos Radon Asbestos
  10. 10. lung CAscreening
  11. 11. 31K patients484 patients diagnosed with CA85% with Stage I lung CAStage I survival was 88% at 10 years vs. Historical standard of 70% at 5 years
  12. 12. lead time length time
  13. 13. overdiagnosis bias
  14. 14. • POPULATION: • age 55 to 74 • heavy smoker or former smoker (quit within last 15 years) • no prior cancer within past 5 years• 53K patients randomized to CXR vs. low dose helical CT scan  annual imaging x 3
  15. 15. 20% reduction in lung cancer mortality7%reductionin all causemortality
  16. 16. • 3% of scans led to diagnosis of lung CA, NNS 288• high false-positive screening rate in both arms (96% with CT and 95% with CXR)
  17. 17. NSCLC histology
  18. 18. Adenocarcinoma Most common histology (40%) • Least associated with smoking, but majority who get it have been exposed to cigarette smoke (70%) • More common in women Location • peripheral, scar tissue Presentation • frequently metastatic disease • hypertrophic osteoarthropathy, Trosseau’s • BAC: multiple pulmonary nodules
  19. 19. Squamous Cell • Second most common(30%) • most common histology until 1987 • 90% associated with cigarette smoking • P63 characteristic IHC marker • Presentation • centrally located mass • PTHrP: hypercalcemia
  20. 20. Large Cell• Least common subtype (11%) • associated with gynecomastia • advances in histopathologic technique: reclassification of undifferentiated large cell tumors to adenoCA or SCC
  21. 21. staging NSCLC
  22. 22. Stage I Stage II 1-5 cm 5-7 cm 1-7 cm
  23. 23. Stage IIIa Stage IIIb
  24. 24. Stage IV
  25. 25. International System for Staging Percent Surviving at 5 Years Stage Clinical Stage Pathologic Stage IA 50 73 IB 43 58 IIA 36 46 IIB 25 36 IIIA 19 24 IIIB 7 9 IV 2 13
  26. 26. workup
  27. 27. Clinical Staging • PET/CT chest and upper abdomen, bone scan • MRI Brain: brain metastases incidence 10-15%
  28. 28. MediastinalEvaluationnodes larger than 1 cmon CT regardless ofFDG uptake
  29. 29. Mediastinoscopy
  30. 30. Endoscopic Biopsy
  31. 31. Transbronchial Biopsy
  32. 32. NSCLCmanagement surgery
  33. 33. NSCLC Management: Stage I and IIStage Ia SURGERY Ib SURGERY CHEMOStage IIa IIb
  34. 34. Surgical Approach Wedge Resection FVC < 1.5 L
  35. 35. Surgical Approach Lobectomy FVC at least 1.5 L
  36. 36. Surgical Approach Pneumonectomy FVC at least 2L
  37. 37. Preoperative Evaluation Stereotactic Body RT>60 Gy (Timmerman JCO ‘07)
  38. 38. NSCLCmanagement adjuvant chemo surgery
  39. 39. NSCLC Management: Stage I and IIStage Ia SURGERY Ib SURGERY CHEMOStage IIa IIb
  40. 40. RCTs: Adjuvant Chemo IALT • Cisplatin + Etop/Vinor/Vinblas/Vindes Le Chevalier • PORT allowed 2003 • Increased DFS, median OS, OS at 5yr by 4% NCIC • Cisplatin + Vinorelbine Winston • Median OS from 73  94 months (21 mos) NEJM 2005 • Increased OS at 5yr by 15% France • Cisplatin + Vinorelbine Douilliard • Median OS from 43  65 months (12 mos)Lancet Onc 2006
  41. 41. Meta-Analyses: Adjuvant Chemo Hotta • Cisplatin-based chemo, Uracil-Tegafur JCO • N= 5,716 2004 • Increased OS, HR 0.87 • Cisplatin-based chemo • N=4,500 LACE • Stage IB HR 0.92, Stage II HR 0.83, Stage III HR 0.83 Pignon JCO 2008
  42. 42. Adjuvant Chemotherapy 4 Cycles of Therapy • Cisplatin + VinorelbineSURGERY CHEMO • Cisplatin + Docetaxel • Cisplatin + Gemcitabine • Cisplatin + Pemetrexed
  43. 43. NSCLCmanagement multi modality therapy
  44. 44. NSCLC Management sequence of treatments is variableStage IIIa CHEMO SURGERY RT IIIb CHEMORADIATION
  45. 45. Stage IIIb inoperable
  46. 46. NSCLC Management Stage Ia SURGERY Ib SURGERY CHEMO Stage IIa IIbStage IIIa* CHEMO SURGERY RT IIIb CHEMORADIATION Stage IV CHEMO
  47. 47. NSCLCmanagement chemo therapy
  48. 48. Median Overall Survival in Months14121086420
  49. 49. Systemic Therapy: Cisplatin Doublet • Lilenbaum Semin Onc 99 2 drugs > • Lilenbaum ASCO 02 1 drug • Sederholm Semin Onc 02 • Crimo JCO 99 2 drugs < • Soguet Ann Onc 02 3 drugs • Greco Cancer 02 • Belani Semin Onc 01 Cisplatin > • Rosell Ann Onc 02 • Ardizonni Meta JNCI 07 Carboplatin • Hotta Meta JCO 04
  50. 50. Systemic Therapy: Histology Matters • PEMETREXED: non-squamous histology • GEMCITABINE: squamous histology • PACLITAXEL, VINORELBINE: any histology
  51. 51. Systemic Therapy: Maintenance platinum- based therapy Pemetrexed • Increased PFS, Median OS 10.6  13.4 mos (2.8 mo) Ciuleneau Lancet 2009 platinum- based therapy Erlotinib • Increased PFS, Median OS 11  12 mos (2 mo) Cappuzzo Saturn Trial
  52. 52. NSCLCmanagement targeted therapy
  53. 53. Antiangiogenic Therapy
  54. 54. • BEVACIZUMAB till progression of disease• Median OS 10.3  12.3 mos
  55. 55. Epidermal Growth Factor Receptor
  56. 56. Increased OS by 13%HR 0.871Cetuximab 400mg
  57. 57. erlotinib gefitinibtyrosine kinase inhibitors
  58. 58. http://www.egfr-mutation.com/EGFR-lung-cancer/
  59. 59. POPULATION: IIIB or IV adenoCA, never or light smokers, Asian, untreated RESPONSE RATE (Clinical): gefitinib (43%) vs. chemo (32%) RESPONSE RATE (EGFR Mutant): gefitinib (71%) vs. chemo (47%)
  60. 60. QUALITY OF LIFE: better in gefitinib arm NO DIFF MED OS (about 17 mos)
  61. 61. RR 73% vs. 33% PFS 10.8 vs. 5.4 mos p < 0.001
  62. 62. PFS 14.6 months conserved LREA motif small in-frame deletions residues 747-750 point missensemutation mutation PFS 9.7 months
  63. 63. TKI Sensitivity
  64. 64. TKI Resistance
  65. 65. EML4-ALK Inhibition
  66. 66. crizotinib
  67. 67. Lung cancer is NOT one disease. TISSUE IS THE ISSUE
  68. 68. MOLECULAR TREATMENT DELAY TESTING and oncology oncology result treatment referral clinic visit received started Diagnosis Adenocarcinoma oncology oncology MOLECULAR result treatmentbiopsy Adenosquamous referral clinic visit TESTING received started carcinoma NSCLC-NOS WEEK 0 1 2 3 4 5
  69. 69. LUNG CANCERS Carcinoid Large CellLarge Cell Neuroendocrine 5%
  70. 70. thank you

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