New Developments in the Management of Lung Cancer

Transcription

1 New Developments in the Management of Lung Cancer Dr Mike Henry Dr Marcus Kennedy Dr Deirdre Fitzgerald - SpR Department of Respiratory Medicine The Rapid Access Lung Cancer Service Regional Cancer Centre at CUH

2 New Developments in the Management of Lung Cancer Local developments CUH RALC and MDT Screening for lung cancer where are we? Cases - Deirdre Fitzgerald Solitary pulmonary nodules and early stage cancers Haemoptysis the critical symptom Worrying symptoms Atypical presentations of lung cancer New treatment options Personalised chemotherapy for lung cancer Interventional bronchoscopy Marcus Kennedy

3 Context Lung Cancer in Ireland Stats Lung cancer is the leading cause of cancer mortality in Ireland representing approximately 20% of all deaths due to cancer. In women % of cancer deaths. In men - Most common cause of cancer death 24.4% of cancer deaths *All-Ireland cancer statistics, second report, , a joint report on incidence and mortality for the island of Ireland, NI Cancer Registry and National Cancer Registry Ireland.^ SEER database, accessed at January 2009.

4 Cancer Deaths by Type 2007 ALL MALE 4226 FEMALE 3691 ALL 7917 LUNG MALE 1014 FEMALE 647 ( ) ALL 1661 BREAST MALE 3 FEMALE 611 ( ) ALL 614 PROSTATE MALE 550 FEMALE 0 ALL 550 COLORECTAL MALE 558 FEMALE 400 ALL 958 Lung cancer kills more Irish people every year than breast and colon cancer combined. Inhale 2 O Connor/ Brennan

5 Lung Cancer Worldwide numbers are worse 1 2 million people die each year Projected to be 10 million by 2030 Full consequences of the tobacco epidemic are yet to come 350 million smokers in China

6 Patient Identification Resectable lung cancer will seldom be diagnosed based on history or physical 50% will have evidence of unresectability at the time of first diagnosis Further testing reveals another 15% 5-10% will be found unresectable at surgery Therefore, only 25-30% are resectable and therefore potentially curable

7 Screening for Lung Cancer Where are we?

8 CXR screening for lung cancer Lung cancer mortality in the three trials Routine chest X rays in smokers bring forward the diagnosis of lung cancer but they do not prevent or delay death No (rate) of lung cancer deaths screened control London 86 (0.3%) 72 (0.3%) Prague 64 (2.0%) 47 (1.5%) Mayo Clinic 80 (1.7%) 72 (1.6%)

9 CT is bound to be a good screening test for lung cancer Why do a randomised controlled trial with mortality endpoints? Let s just start doing it That s what they said about chest Xray screening.

10 Baseline and annual screening of at risk individuals 1.3% detection rate at baseline and 0.3% annual follow up No control group? Justification for annual low dose CT in high risk individuals

11 Should We Screen?

12 Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening The National Lung Screening Trial Research Team N Engl J Med Volume 365(5): August 4, 2011

13 Results of Three Rounds of Screening. The National Lung Screening Trial Research Team. N Engl J Med 2011;365:

14 Cumulative Numbers of Lung Cancers and of Deaths from Lung Cancer. The National Lung Screening Trial Research Team. N Engl J Med 2011;365:

15 Study Overview The National Lung Screening Trial investigators report that persons undergoing three annual screening examinations with low-dose computed tomography had a 20% reduction in lung-cancer mortality as compared with those screened with annual chest radiography.

16 Lung Cancer in Ireland Could we do better? Currently >75% of patients present with locally advanced or disseminated disease. 5-year survival figures for Ireland are only 10% for women. These compare to rates of 16% in France and 18.5% for the United States^.

17 ITS guidelines Who should be referred to Rapid Access Clinic? Patient with haemoptysis, particularly in a smoker. CXR or CT scan suggests lung cancer Guidelines for the diagnosis and treatment of lung cancer. 3 RD edition. Feb

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19 Urgent Referral Rapid Access Lung Cancer Dec 2010 Fax RALC referral form to or FAO Mike Henry / Marcus Kennedy 2 dedicated lung cancer specialists Mike Henry / Marcus Kennedy Secretary Helen dedicated lung cancer nurse specialists Sharon Guiry Pauline O Dea

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21 RALC clinic Monday am Mike Henry or Marcus Kennedy + SpR KPI patients must be seen within 10 working days of referral CT in advance of clinic Lung cancer CNS spirometry and information. Approx 30% referrals have cancer. Follow up patients post radical therapy for 5 years Virtual SPN clinic

22 RALC clinic Monday am We often defer decision on next test until the following days MDT If palpable supraclavicular node cytopath FNA usually same day results Dr Julie McCarthy If pleural effusion ultrasound guided tap cytopath usually same day results. Patient spends some time with CNS information given Smoking cessation advice

23 Cork MDT Cork MDT

24 Total Number of New Primary Lung Cancers 2011 In total there were 254 patients diagnosed with a new primary lung cancer at MDM in 2011 at CUH. 92 of those diagnosed at MDM during 2011 came from the RALC. A further 85 patients came from other referral sources at CUH (e.g. inpatient referrals, incidental radiological findings, A&E referrals etc.) and the other 77 were referred from other hospitals. Referral Source of New Lung Cancers 2011 Other hospital, 77, 30% RALC, 92, 37% Other CUH, 85, 33%

25 KPI Clinic Access 2012 Jan - Jun There has been an increase of 33% in clinic attendances in 2012 in comparison to 2011 and this has affected our Access KPI. RALC New Clinic Attendances 2011 vs Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

26 Surgical resection rates in CUH 42 patients had a surgical resection for primary lung cancer in the first 6 months of This is an increase of 75% in comparison with 2011 when 24 patients had surgery during the same period. Experience of lung cancer care: Timeliness and outcomes of the Cork Thoracic Oncology Group, southern Ireland O brien E et al ERC 2010

27 Case 1 T O R 78 year old male, asymptomatic Ex-smoker > 60years Attended GP for check up Noted to have right basal crackles + sent for CXR Nodule on CXR Referred to RALC

28 CT Thorax

29 Discussed at Lung MDT Spirometry: FEV1 2.83L ECOG: 0 Booked for PET + CT guided biopsy

30 PET

31 Management Stage 1b lung cancer T2N0M0 by PET staging Referred for surgical opinion + reviewed this week For VATS excision, frozen section +/- right lower lobectomy.

32 Indeterminate SPN 4-8 mm* >8 mm Highly suspicious for CA Solid Contrast CT/PET/Bx F/U CT (volumetrics) 6-12/24 mo. + - Biopsy/resect F/U 6/12/24 * nodules < 4 mm = no followup (non-high-risk patient))

33 Lung Nodule Follow Up Fleischner Society Guidelines Prof Felix Fleischner Radiology, 2005 Nov;237(2):

34 Case 2 RE How do you investigate the mediastinum 71 year old male Presented to GP with persistant cough and dyspnoea, retrosternal discomfort Current heavy smoker, 50 pack year hx OGD - Normal

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38 Blind (TBNA) TBNA in NSCLC, meta analysis Yield 39-78% Holty J et al, Thorax meta analysis -

39 CT + MS: Evolving staging strategies CT + PET + E(B)US + (MS): CT/PET + E(B)US + (MS):

40 EBUS

41 Invasive mediastinal staging of lung cancer Patients N0 Sensitivity % FP % FN % Prevalence % Mediastinoscopy % 0% 11% 39% EBUS-NA % 0% 20% 68% EUS-NA % 0.7% 19% 61% Detterbeck et al., Chest 2007;132:202S-220S

42 Provide access to different areas of the mediastinum In combination most mediastinal LNs can be sampled In four series the accuracy of EUS-FNA and EBUS-TBNA in combination for the diagnosis of mediastinal cancer was 95% MESK EUS EBUS Herth et al., AJRCCM, 2005; Rintoul et al., Eur Respir J, 2005; Vilman et al., Endoscopy, 2006; Wallace et al., JAMA 2008

43 Benefits Low risk procedure Day case Comparable sensitivity If not better Cost benefit On site cytology A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thoracic Cardiovasc Surg Dec;142(6): e1. Epub 2011 Oct 2.

44 EBUS AND ROSE EBUS TBNA same day diagnosis and staging 85% success rate in CUH only

45 Case - Atypical Presentation 67 year old male Heavy smoker Admitted for ix of proteinuria Membraneous Glomerulonephritis on renal bx CXR on admission Nephrotic syndrome associated with lung adenocarcinoma: report of an autopsy case. Komori S, Nakazawa E et al. Nihon Jinzo Gakkai Shi. 2009;51(2):

46 CT guided biopsy confirmed squamous cell carcinoma Pleural fluid negative for malignancy

47 PET Confirmed locally invasive disease Stage IIIa on radiology

48 Management Left upper lobectomy Discharged well last week

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50 BTS guidelines Radical surgery for up to Stg IIIa tumours Includes T4, N0-1. Surgery for N2 disease can be considered if non fixed, non bulky, localised nodes. Lung preserving surgery: Wedge resection for small lesions Sleeve lobectomy instead of pneumonectomy

51 Kim E A et al. Radiographics 2002;22:67-86 Sleeve lobectomy

52 Case 4 MO S 64 year old female Never smoker Presented with haemoptysis Locally advanced disease Diagnosed with Stage IIIa adenocarcinoma Non smoking female adenocarcinoma Tested for EGFR status positive

53 Started on erlotinib 150mg bd EGFR TKI Maximal therapy achieved Feb 2012

54 July 2011 Feb 2012

55 Combined chemotherapy with a view to further tumour shrinkage to allow for radiotherapy (cisplatin and pemetrexed) Initial response but progression of disease on follow up CXR Referred for palliative care June 2012

56 P Interaction (comparing HRs 0.48 vs. 2.85): <0.001 N Engl J Med 2009;361:

57 Tailored Chemotherapy Genetic mutations associated with tumour growth and metastases Numerous genes identified Targets at present include: EGFR (Erlotinib) ALK (Crizotinib) KRAS resistance to TKI Cataldo VD et al. N Engl J Med 2011;364:

58 Molecular Classification of Adenocarcinoma Western (Adeno) East Asian Sun Y, et al. J Clin Oncol 2010;28: Pao W, Girard N. Lancet Oncol 2011;12:175-80

59 Comprehensive genetic profiling of 500 each of lung squamous and adeno carcinomas