Multifocal Lung Cancer

Transcription

1 Multifocal Lung Cancer P. De Leyn, MD, PhD Department of Thoracic Surgery University Hospitals Leuven Belgium

2 LEUVEN LUNG CANCER GROUP Department of Thoracic Surgery Department of Pneumology Department of Radiotherapy Department of Nuclear Medicine Department of Radiology P. De Leyn, W. Coosemans, H. Decaluwé, G. Decker, T. Lerut, Ph. Nafteux, D. Van Raemdonck, H. van Veer J. Vansteenkiste, K. Nackaerts, C. Dooms S. Peeters C. Deroose W. Dewever

3 Multifocal Lung Cancer 1. Introduction - definitions 2. Satellite Nodules 3. Synchronous Primary Lung Cancer Study University Hospitals Leuven Literature overview 4. Multifocal GGO lesions 5. Field cancerization 6. Conclusions

4 1. Introduction Imaging modalities have improved (HRCT; PET-CT) Screening programs Survival has improved Second focus of suspicious nodule in lung

5 Synchronous lesion Squamous cell ca RUL? -Benign lesion -Metastasis -Second primary -

6 Metachronous lesion Separated in time (2 y) ±10% risk of developping second primary lung cancer Martini and Melamed, J Thorac Cardiovasc Surg :

7 Synchronous second malignant lung lesion Is it a metastasis or second primary? Does preoperativehistologyhelp usandhas itanimpact on treatment and outcome? Does current TNM staging helps us? How shouldwe treatit?

8 Synchronous second malignant lung lesion Definitions Type of lesion 6th TNM 7th TNM Some lobe (satellite nodule) Ipsilateral side-other lobe Contalateral side T4 M1 M1 T3 T4 M1a

9 2. Satellite nodules Definition : Same histology -and same lobe as primary cancer -and no systemic metastasis Occurrence : ± 7% (often on specimen diagnosed) Most common type : adenocarcinoma T4 (TNM classification, sixth edition)

10 Satellite nodules IASLC Lung cancer staging project pt4 by same-lobe nodules (R0N0) : 5-Yr survival 45% 7th TNM edition (2009) : Satellite nodule : T4 T3 Rami-Porta et al., J Thorac Oncol 2007,2:

11 Satellite nodules Impact on management Often found only intraoperatively or on pathology When diagnosed pre- or intraoperatively : lobectomy Adjuvant chemotherapy?

12 3. Synchronous multiple primary lung cancer Different histology Same histology, anatomically separated Cancer in different lobes and no N2-N3 involvement and no systemic metastasis M1 (TNM classification, sixth edition) Ipsilateral or contralateral lung Martini and Melamed, J Thorac Cardiovasc Surg :

13 Synchronous same side (other lobe) lesions IASLC Lung cancer staging project n Median survival (mo) 5-yr survival (%) pt4 by other T4 factor pm1 by same-side nodules* M1 distant * Other lobe 7th TNM edition (2009) : Same-side nodules: M1 T4 Rami-Porta et al., J Thorac Oncol 2007,2: Postmus et al., J Thorac Oncol 2007,

14 Synchronous contralateral lung lesions IASLC Lung cancer staging project n Median survival (mo) 1-yr survival (%) 5-yr survival (%) Contralateral lung nodules M1 distant th TNM edition (2009) : Contralateral nodules : M1 distant : M1a M1b Postmus et al., J Thorac Oncol 2007,

15 Synchronous MPLC study UZ Leuven Evaluate results after resection of synchronous bilateral NSCLC Is survival as bad as suggested by TNM staging M1(Stage IV)? De Leyn et al; J Thorac Oncol 2008;34:

16 Material and methods Retrospective analysis Surgical database of bronchial carcinoma UZ (n=3399) Patients with synchronous bilateral lung lesion, proven or suspect for lung cancer Intention to treat with bilateral resection, after extended staging and functional assessment De Leyn et al; J Thorac Oncol 2008;34:

17 Synchronous bilateral lesion 57 patients Bilateral resection N=42 Results Only unilateral resected N=15 -Surgery more extended than expected (3) -Incomplete first resection (4) -Progressive disease at reevaluation (3) -To limited PF at reevaluation (3) -Exploratory thoracotomy contralat side (2) one side benign N=6 Bilateral resection MPLC N=36 Same histology : 18 Different histology : 18 De Leyn et al; J Thorac Oncol 2008;34:

18 Incidence : : 1% : 2.6% Results Extensive search for metastatic disease. Mediastinoscopy : 92%, imaging brain : 89% Staged thoracotomy. Mean interval : 2.2 months Mean follow-up : 41.6 months De Leyn et al; J Thorac Oncol 2008;34:

19 Results Type of resection : One side Other side No Pneumonectomy (Bi)Lobectomy (Bi)lobectomy Limited resection Limited resection (Bi)Lobectomy Limited resection Limited resection Limited resection Limited resection Limited resection : 26 (36,1% of procedures) De Leyn et al; J Thorac Oncol 2008;34:

20 Histology of resected tumors Squamous Small cell neuroendocrin differentiation Large cell Bronchoalveolar Adenosquamous 2 1 Adenocarcinoma FIRST SECOND Identical histology : 50% (reviewed by experienced pathologist)

21 Synchronous bilateral NSCLC N Median Survival (m) 2-yr Survival (%) 5-yr Survival (%) P Bilateral resection % 38% Histology Same Other % 85.7% 31.1% 45.5% 0.31 Limited resection No Yes % 69.5% 40% 36.7% 0.69 De Leyn et al; J Thorac Oncol 2008;34:

22 Synchronous MPLC 5-yr SURVIVAL Study n % bilateral Satellite nodules % BAC All Same or diff histol Ipsilat vs contralat pn0 pn+ Trousse (2007) Chang (2007) Mun (2007) % Yes excluded 34% 92 12% Yes 4% 35% % No 45% 76% NS NS 51% 15% NS NS 52% 15% NA NA NA NA De Leyn (2008) Voltolini (2010) Finley (2010) Fabian (2011) % No 3% 38% 50 70% No excluded 31% % Yes excluded 64% (3Y) 67 66% Yes excluded 53% NS NS NA NA NS NS 57% 0% NS NS NA NA NS NS NA NA Kocaturk (2012) 26 38% Yes NA 50% NS NS NA NA

23 Synchronous MPLC : how to treat? 5-yr survival : 35-50% Nodal disease is important prognostic factor Carefull investigation for distant and mediastinal metastasis (1) If N0 and M0, radical treatment is justified (1) Shen et al. Chest 2007;132:290S-305S

24 Synchronous MPLC : How to treat? Extent of resection : usually segmentectomy for smaller or contralateral lesion Usually staged resections for bilateral lesions Reports of bilateral simultaneous limited resections for AIS lesions (1) (1) Mun et al. Ann Thorac Surg 2007;83:

25 Synchronous MPLC : histology? No difference in survival if tumors have identical or different histology Using mutational and molecular profiles, over 50% of MPLC with same histology have different tumor clonality (1) Comprehensive histological assessment (comparing % histological subtypes and other histological features) is as good as molecular characterization (2). (1) Chang et al. Clin Cancer Res 2007;13:52-58 (2) Girard et al. Am J Surg Pathol 2009;33:

26 5. Multiple GGO lesions Multifocal disease is well known in AIS- MIA (previously BAC) Etiology? Resection? Extent of resection?

27 How to treat?

28 Management of multiple GGO lesions in patients with operable NSCLC Retrospective analysis Patientswithresectionfor NSCLC andother-lobemultiple pure GGO lesions. 8 GGO lesionswereresectedat sametime -4 malignant 32 GGO lesionswerenotexcisedbut followedbyct -Central lesions< 10 mm -Multiple lesions < 10 mm Kim, J Thorac Oncol 2009;4:

29 Management of multiple GGO lesions in patients with operable NSCLC 32 GGO lesionswerefollowedbyct 6 increased : resected (malignant) 6 disappeared 2 decreased 20 stable (median fu of 23,8 mo) Cutoff value8 mm. NPV : 96% Indication for resection Lesion> 8 mm Growing lesion Occurrenceof nodularaspect on CT Kim, J Thorac Oncol 2009;4:

30 Treatment strategy for patients with small periferal lung lesions Prospective study (n=179) Inclusion» Periferal lung lesions 20 mm» No LN on CT Lesions 10 mm of anytype or pure GGO : GGO 11-20mm : Solid lesions mm : Solid lesions mm : Observation If size or density increased resection WWR/segmentectomy + nodal sampling* segmentectomy + nodal dissection* (* if positive: converted to lobectomy) Lobectomy + nodal dissection Kodama et al., Europ J Cardiothorac Surg 2008;34:

31 Treatment strategy for patients with small periferal lung lesions limited resection (n=57%) 5-yr disease-free survival : 98% Kodama et al., Europ J Cardiothorac Surg 2008;34:

32 5. Concept of field cancerization High incidence of synchronous MPLC In clinical series: 1-7% In autopsy series: 3-14% High incidence of metachronous MPLC (10% risk) Multiple sites of histological normal appearing tissue with molecular or genomic abnormalities due to carcinogen exposure (smoking, inflammation, )

33 Field cancerization in lung cancer SCC -Transition from metaplasia, dysplasia, ca in situ -Identical chromosomal deletions in 42% of dysplastic epithelium (1) Peripheral adenocarcinoma - In some types transition from AAH (identical genetic abnormalities) - IdenticalEGFR mutationsare found in normalepithelium adjacenttothe tumor in 24% of EGFR positivetumors (2) (1)Wistuba et al. Oncogene 1999;18: (2)Tang Cancer Res 2005;67:

34 Field cancerization in lung cancer Two compartments with different degree of smoking related genetic damage Kadara et al. Respirology 2012;17:50-65

35 6. Conclusions MPLC is common. After carefull staging radical treatment of MPLC is justified with 5-yr survival 30-40% This is not reflected by the current TNM classification Sublobar resections are used for lesions 2 cm. Further research is needed

36 6. Conclusions (Multiple) pure GGO lesions are a difficult problem. CT follow up is indicated for lesions 1 cm. Sublobar resection (if possible) when lesion is growing or becomes nodular There is convincing evidence of field cancerization theory

37 Thank you! University Hospital Leuven, Belgium Leuven Lung Cancer Group (