Kamil Konopka Department of Oncology University Hospital in Cracow Lung cancer epidemiology Most common malignancy worldwide 14 of all new cancers are lung cancers Lung cancer NSCLCampSCLC is the second most common cancer in both men and women excluding skin cancers ID: 1035988
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1. Multidisciplinary approach to lung cancerKamil KonopkaDepartment of Oncology, University Hospital in Cracow
2. Lung cancer epidemiologyMost common malignancy worldwide14% of all new cancers are lung cancersLung cancer (NSCLC&SCLC) is the second most common cancer in both men and women (excluding skin cancers)Lung cancer is the leading cause of cancer deaths in men and women; about 1 out of 4 cancer deaths are from lung cancerEstimations in USA for 2017 are: - about 222 500 new cases - about 155 870 deaths from lung cancer
3. Epidemiology
4. Etiology & risk factorsSmoking – responsible for more than 80% of lung cancer, smoking 20 cigarettes per day increases one’s risk of cancer 20-fold;Second-hand smoke - 30% increased riskAsbestos – especially when combined with smoking (90-fold increased risk)http://oncologypro.esmo.org
5. Lung cancer risk American Cancer Society, 2012
6. Lung cancer survivalAbout 16% people with lung cancer survived 5 years after diagnosis
7. Lung cancerHow to improve survival rates?
8. People with high-risk of developing lung cancerage 55-74 at least 30 packyears former smokers, who stopped smoking within the last 15 yearsn=53454RLow-dose CT1x/yearRadiography1x/yearThe National Lung Screening Trial (NLST)LUNG CANCER SCREENING National Lung Screening Trial Research Team.N Engl J Med 2011; 365: 395-409.
9. LUNG CANCER SCREENINGThe National Lung Screening Trial (NLST)20.0% decrease in mortality from lung cancer was observed in the low-dose CT group as compared with the radiography group. National Lung Screening Trial Research Team.N Engl J Med 2011; 365: 395-409.
10. Lung cancer symptoms Cough – 80% of symptomatic pts,Dyspnea, stridor, haemopytsisReccuring pnaeumonia – bronchi obstructionPleural effusion (exudate)Chest painShoulder and arm painHorner’s syndromeUnilateral diaphargm paresis
11. Lung cancer – diagnostic procedures and stagingHistory and physical examinationChest X-rayCT scan – chest and upper abdomen (liver and adrenal glands), mediastinal lymph nodesPET–CT – distant metastases, mediastinal lymph nodes (+/-)Histology/cytology: - central tumors – bronchoscopy - peripheral tumors – transthoracic needle biopsy, thoracotomy
12. Lung cancer – diagnostic procedures and stagingPET scanTreatment strategy change in up to 40% of patients
13. Lung cancer – diagnostic procedures and stagingMediastinoscopy – mediastinal lymph nodes biopsy (N1 vs N2)EBUS (endobronchial ultrasound) i EUS (endoscopic ultrasound) Thoracoscopy and thoracocentesisEBUSEUS
14. Lung cancer staging UICC TNM 8th edition (January 2017):Chest CT scanPET-scanRecommended brain MRINeedle aspiration under EBUS/EUS:cN2: abnormal mediastinal nodescN1: hilar nodescN0: if central tumor or size >3 cmMediastinoscopy if EBUS/EUS are negative but high suspicion for nodal involvement
15. Lung cancer staging – TNM 8th edition
16. Lung cancer - histopathology
17. Lung cancer – histopathology & smoking
18. Lung cancer StageVery earlyEarlyLate
19. Lung cancer - treatment Stage I – IIIA - surgery
20. NSCLC treatment - surgery
21. NSCLC treatment - surgeryVATS (video-assisted thoracoscopic surgery) - peripheral tumors up to 6 cm - minimally invasive surgery - eligibility - stages I to IIIA - less pain after operation - better quality of life
22. Lung cancerHow could we improve survival?
23. NSCLC treatment – radiation tehrapyAdjuvant Rth - N2 positive ? - R1 resection - narrow margins ?
24. NSCLC treatment – adjuvant chemotherapyPisters KMW i wsp. J Clin Oncol 2007; 25:5506-5518
25. NSCLC treatment – adjuvant chemotherapyLACE meta-analysisPignon J-P i wsp. J Clin Oncol 2008;26:3552-3559Adjuvant chemotherapy improves OS in NSCLC
26. Lung cancer I-IIIAStandard treatmentOperationAdjuvant chemotherapy (>IB)What if cancer is very small?
27. NSCLC treatment – radiation therapyStereotacticRadiosurgery (SBS/SBRT)Precise delivery of high doses of radiation to the limited volume of tissue in hypofractionated schedulehang JY et al. Lancet Oncol 2015;16(6):630-637
28. NSCLC treatment – radiation tehrapy (SBRT)T1-T2 N0 M0Peripheral tumorsPatients medically unfit to undergo surgeryPatients who declined surgery
29. SABR for stage ITumors >5cm and/or moderately central location, radical RT with conventional schedulesNSCLC treatment – radiation tehrapyPatients unfit for surgeryPooled analysis: SABR vs surgeryPostmus et al. Ann Oncol 2017Chang et al. Lancet Oncol 2015
30. Lung cancer stage IIIA-IIIBWhat if cancer is very big?
31. Lung cancer IIIA-IIIBStageNeoCTHCRTH
32. Loco-regional strategyPotentially resectable N2:Single station N2Indcution CT recommandedNo pneumonectomyPostmus et al. Ann Oncol 2017
33. Loco-regional strategyCTRT is SOC for stage IIIA-B60-66 Gy, 30-33 fractions, No PCICisplatin-based CT + etoposide, vinorelbine, pemetrexed (non-sq)Concomitant > sequential2 to 4 cyclesPostmus et al. Ann Oncol 2017
34. Lung cancer treatment stage I-IIIDiagnostic tests includes PET-CT and brain metastasesStage I-II: surgery +/- adjuvant chemotherapy - Rth is an option for unfit patientsStage III: heterogenous - Single station N2 without pneumonectomy – consider surgery - Otherwise the standard is CTRT based on cisplatinAdjuvant chemotherapy: T>4 cm or N+ disease, preferably with cisplatinNo molecular profile needed, no targeted therapies allowed
35. NSCLC treatment – stage IVPalliative chemotherapyTargeted therapiesPalliative radiotherapyBSC
36. NSCLC treatment – palliative chemotherapyRamalingam i wsp. The Oncologist 2008;13(suppl 1):5–13Two drugs schedules based on cisplatinPS 0-1Similar outcomes for different chemotherapy regimens
37. NSCLC treatment – palliative chemotherapyJ Clin Oncol 2008; 26:4617-4625
38. NSCLC treatment – palliative chemotherapy
39. NSCLC treatment – palliative chemotherapyPemetrexed + cisplatin better in non-squamous cell lung carcinoma- Gemcytabine + cisplatin better in squamous cell lung carcinoma
40. NSCLC treatment – palliative chemotherapy I line Gemcitabine 1250 mg/m2 d 1,8 Cisplatin 80 mg/m2 d 1 q3w all histologies Vinorelbine 30 mg/m2 d 1, 8 Cisplatin 80-100 mg/m2 d1 q3w all histologies Pemetrexed 500 mg/m2 d 1 Cisplatin 75 mg/m2 d 1 q3w non squamous NSCLC Docetaxel 75 mg/m2 d 1 Cisplatin 75 mg/m2 d 1 q3w all histologies Paklitaxel 175 mg/m2 (3 h) d 1 Carboplatin AUC 5-6 d 1 q3w all histologiesOptimal regimen for first line therapy is four cycles of platinum-based chemotherapy, in terms of tolerability and survival benefits.
41. NSCLC treatment – stage IV targeted therapyAnti-EGFRALK- positive NSCLCImmunotherapy
42. NSCLC - anti-EGFR treatment
43. NSCLC - anti-EGFR treatmentErlotinib and gefitinib – 1st generation tyrosine kinase inhibitors (TKI)Clinical predictive factors of response: - female - Asian - never-smokers - adenocarcinoma
44. NSCLC - anti-EGFR treatment
45. NSCLC - anti-EGFR treatmentIPASS trial Progression-free survivalMok T. et al. Ann Oncol 2008;19(suppl 8)
46. NSCLC - anti-EGFR treatmentAfatinib – 2nd generation anti-EGFR TKI OS in 1st line treatmentLUX-LUNG3 TRIAL: afatinib vs cisplatin/pemetrexed HR=0,54; p=0,0015LUX-LUNG 6 TRIAL: afatinib vs cisplatin/gemcitabine HR=0,64; p=0,0229
47. NSCLC - anti-EGFR treatmentOsimertinib – 3rd generation, irreversible EGFR TKI designed to both inhibit EGFR sensitizing and EGFR T790M resistance mutationsClinically proven activity against CNS metastases
48. NSCLC - anti-EGFR treatment
49. NSCLC targeted treatmentFusion geneEML4-ALK2-7% NSCLC patientsCrizotinib – oral ALK inhibitor
50. Immunotherapy
51. Immunotherapy NivolumabHumanized IgG4 monoclonal antibodyAnti-PD-1 antibody enhancing autoimmune response of the “host”Proved to be effective in 2nd line treatment of NSCLCBoth squamous and non-squamous NSCLC19% of patients experienced complete or partial tumor shrinkage, effect lasted for an average 17 mo (in docetaxel group response lasted an average 6 mo only!!)
52. Immunotherapy
53. ImmunotherapyImproved OS in nivolumab arm (squamous NSCLC)
54. NSCLC treatment – radiation tehrapy Palliative Rth: - bone metastases - brain metastases - local control of symptoms (cough, haemoptysis)
55. NSCLC treatment – BSCImproved QoL and survival !!!
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58. Small cell lung cancer (SCLC)13% of all lung cancer casesNeuroendocrine differentiation: positive staining for chromogranine, synaptophisineParaneoplastic syndromes due to neuroendocrine activity (Cushing`s syndrome, SIADH)
59. Small cell lung cancer (SCLC)Large mass, hilar and mediastinal lymphadenopathyIn the most cases primary systemic disease (very high metastatic potential)
60. Small cell lung cancer (SCLC) - stagingLimited stage: confined to the chest and regional lymph nodes (1/3 pts)Extensive stage: distant metastases (2/3 pts)
61. Small cell lung cancer (SCLC) – LD (limited disease) treatmentChemoradiotherapy (EP regimen: cisplatin + etoposide) - concurrent: - better outcomes - higher toxicity - sequential: - worse outcomes - lower toxicity
62. Small cell lung cancer (SCLC) – LD (limited disease) treatmentProphylactic Cranial Irradiation (PCI): - after chemoradiation - partial or complete response (PR/CR) in CT - PS 0-1 - 3-5 weeks after the last administration of chemotherapy 3-year OS PCI group: 20,7% no-PCI group: 15,3%
63. Small cell lung cancer (SCLC) – ED (extensive disease) treatment70% of SCLC patientsSoC chemotherapy EP (cisplatin+etoposide)4-6 cyclesIf any response -> PCI - decrease in incidence of symptomatic CNS metastases - prolongs survival
64. Small cell lung cancer (SCLC) – ED (extensive disease) treatment2nd line treatment: - PD within 3 months – refractory disease - PD 3-6 months – topotecan, CAV - PD >6 months – EP re-induction
65. Thank you for your attention !