Place de la chirurgie pulmonaire dans les Cancers primitifs et Chirurgie de Métastasectomie Pulmonaire

(1)

Place de la chirurgie pulmonaire dans les Cancers primitifs et Chirurgie de

Métastasectomie Pulmonaire

A.J. PONCELET, Ph. NOIRHOMME.

Department of Cardio-Thoracic Surgery, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium.

ECU-UCL 24 Mars 2007

(2)

Chirurgie pour tumeurs primitives

• Plan

– Introduction – Multimodalite

– ‘Guidelines’ et Interdisciplinarite

• Staging

• Operabilite

• Resequabilite

– Evolution a court terme

– Evolution a long terme

(3)

• Cancer Bronchique non à petites cellules – NSCLC (75%)

• Cancer Bronchique à petites cellules – SCLC (25%)

• Mesothéliome malin INTRODUCTION

(4)

T1 T2 T3 T4

N0 Ia Ib IIb IIIb

N1 IIa IIb IIIa IIIb

N2 IIIa IIIa IIIa IIIb

N3 IIIb IIIb IIIb IIIb

M+ IV IV IV IV

TNM staging system and Surgery for NSCLC (Moutain 1997)

MULTIMODAL

(5)

Stades (Ib), IIa and IIb

Chimiothérapie Adjuvante (à base de Cisplatine)

IALCT, N Engl J Med 2004, 350:351-60 JBR, NEJM 2005, 352;25 :2589-97

Stade IIIa

Chimiothérapie Néo-adjuvante (ou d’ induction) - à base de Cisplatine

Re-stadification complète et sélection des

‘répondeurs’ (partiel/complet)

Maladie stable (single N2 station) Multimodality

J Clin Oncol 2005, 23:3257-3269

(6)

Belgian Society Pneumology:

Bosquee Leon Duplaquet Fabrice Galdermans Danny Germonpre Paul Lecomte Jacques Ninane Vincent van Meerbeeck Jan Vansteenkiste Johan

Belgian Society Radiation Oncology:

Lievens Yolande Van Houtte Paul Chaltin Marie Bral Samuel Rosier JF

Belgian Society of CardioThoracic Surgery:

Bosschaerts Thierry Capello Matteo De Leyn Paul

De Roover Dominique Poncelet Alain

Proot Luc Van Schil Paul Vermassen Frank

Belgian Society Medical Oncology:

Humblet Yves

Vansteenkiste Johan

Pathologist Weynand Brigit

Members of the Guideline Development Committee Respiratory Oncology (2005-2006)

(7)

Bronchoscopie

(sensibilité de détection faible si tumeur periphérique < 2cm)

Chest CT scan (IV contrast)

Etage thoracique et abdominal supérieur Informations sur T, N et M

FDG-PET

Pour patients Stade I-III avec attitude curative, indispensable car améliore la sélection des patients

Cytoponction echoguidée par voie endoscopique (transoesophagienne , transbronchique) Examen peu invasif, à recommander en première ligne afin de prouver l’ atteinte ganglionnaire médiastinale. ( ! learning curve)

Mediastinoscopie (cervicale)

Biopsies d’ au moins 4 des 6 stations ganglionnaires accessibles. (2 ipsilatérales, 1 contralaterale et station 7).

Epanchement Pleural

Evaluation cytologique indispensable (si (+), T4 irrésequable )

CT cérébral (IV contrast) ou IRM

« Guidelines » & Stadification des NSCLC

(8)

« Guidelines » & Opérabilité = Evaluation Fonctionnelle Cardio-respiratoire essentiellement

Criteria

1 ECOG score 0,1 ou 2

2 Absence de co-morbidité majeure rendant le risque de

‘morbidité-mortalité’ opératoire prohibitif (cardiac cause) 3 Fonction pulmonaire autorisant la resection

parenchymateuse proposée

(Valeur de VEMS prédite post-op > 30% des valeurs prédites (ou > 0.8L)

pred poFEV1 = pre FEV1 (n segm. resséqués/ n total segm.)

(9)

Poumon Dt n segm

LSD 3

LMD 2

LID 5

Poumon G n segm.

LSG 4

LIG 5

1 segm =¹/¹⁹or 0.0526 (VEMS préop)

(10)

« Guidelines » per-opératoire = Evaluation de la Réséquabilité

Résection Complète = Seule attitude acceptable pour chirurgie de résection parenchymateuse

3 Critères doivent être respectés pour un label de “Resection Complete”:

a) Marges de résection saines microscopiquement

b) Curage ganglionnaire systématique

Le curage devrait inclure au moins six ganglions dont 3 #10 et/ou #11

3 # N2 et au moins 1 ggl #7

c) Pas de rupture capsulaire dans les ganglions prélevés séparément.

(11)

Résultats à court terme : Morbidity-Mortality

Direct Relationship to Preoperative

Direct Relationship to Preoperative PFT PFT ’ ’ s s

Lobectomy

Lobectomy # # Pneumonectomy Pneumonectomy

Surgical Volume & Outcomes

(12)

Iizasa T & al. Ann Thorac Surg 2004;77:1896-1902

1/ Preoperative pulmonary function as a prognostic factor for NSCLC

Cancer Unrelated Death

N = 402 patients All Stage I NSCLC

(13)

Respiratory disease 13 4

Cardiac disease 4 3

Brain vascular disease

1 5

Second malignancy 10 7

Other 7 4

Total

Cause of Death FEV1% < 70%

(n = 100)

FEV₁% 70%

(n = 302)

FEV₁% = percent forced expiratory volume in 1 second.

a Values are number of patients.

b p value < 0.0001 with ²test.

35 23^b

Iizasa T & al. Ann Thorac Surg 2004;77:1896-1902

Preoperative pulmonary function as a prognostic factor for NSCLC

(14)

Type of resection

Lobectomy 77 62

Bilobectomy 17 14

Pneumonectomy 23 18

Wedge resection 8 6

No. of Patients (n = 125)

%

Birim O. & al. Ann Thorac Surg 2003;76:1796-1801

Lung resection for non–small-cell lung cancer in patients older than 70 y.oy.o..

76 %

2/ Operative risk for Lobectomy ≠ Pneumonectomy

(15)

Minor complications 71 57

Supraventricular arrhythmia 38 30

Air leak > 5 d 26 21

Transfusion 19 15

Atelectasis 9 7

Infection 6 5

Paresis of recurrent nerve 3 2

Major complications 16 13

Empyema 6 5

Pneumonia 5 4

Myocardial infarction 2 2

Bronchopleural fistula 2 2

ARDS 2 2

Ventricular arrhythmia 1 1

Ventilatory support > 72 h 1 1

Pulmonary edema 1 1

Cardiac failure 1 1

Renal failure 1 1

Birim O. & al. Ann Thorac Surg 2003;76:1796-1801

Overall 30-d Mortality

= 3.2%

(%) n =

(16)

Variables Rate, %

30-d mortality rate

HUG 10.3

CVP 6.3

Cardiovascular complications

Arrhythmias 24.9

Heart failure 0.5

Myocardial infarction 0.5

Stroke 1

Pulmonary emboli 2.6

Pulmonary complications

Bronchopneumonia 7.8

Atelectasis 2.6

Bronchopleural fistula 4.7

Re-intubation 2.1

Prolonged chest drainage ( > 7 days) 2.6

Reperfusion edema 2.1

Renal dysfunction

Elevation of plasma creatinine ( > 20%) 2.6

Licker M and al. Chest. 2002;121:1890-1897

Mortality and Complications Following Pneumonectomy

Major complic. = 27%

Minor complic. = 31%

(17)

Mortality

Bach. PB. and al. N Engl J Med 2001 345:181-188

Low Surgical Volume

Low Surgical Volume # # High Surgical Volume High Surgical Volume

(18)

Morbidity

Bach. PB. and al. N Engl J Med 2001 345:181-188

(19)

Birkmeyer JD,and al. N Engl J Med 2002; 346:1128-1137

Similar trends for every major surgical procedures Similar trends for every major surgical procedures

(20)

(21)

van Rens, M. Th. M. et al. Chest 2000;117:374-379

1970-1992

Ia 60-65%

Ib 50%

IIa 45%

IIb 35%

Résultats à long terme : Survie et Récidive(s)

1/ Early Stage

(22)

IALT, NEJM 2004, 350;4 : 351-360 JBR, NEJM 2005, 352;25 :2589-97

Ia 85%

Ib 70%

IIa 55-60%

IIb 45%

National Cancer Institute of Canada Clinical Trials Group - JBR10

1997-2001 Ib

II

(23)

The International Early Lung Cancer Action Program Investigators (IELCAPI). N Engl J Med 2006;355:1763-1771

2/ Very Early Stage (CT scan screening)

1993-2005

n= 484/31,567 pa Incidence : 1.5%

Mean ∅ = 13mm Stage I = 85% pa

(24)

Betticher DC, J Clin Oncol. 2003 May 1;21(9):1752-9.

Rosell R, Lung Cancer. 1999 Oct;26(1):7-14

3/ Advanced Stage

1989-1997

1997-2000

(25)

Small Cell Lung Cancer (SCLC)

Most aggressive lung cancer

Responsive to chemotherapy and radiation but recurrence rate is high even in early stage

WHO revised classification

Small cell carcinoma Oat Cell

Intermediate

Mixed small cell/large cell carcinoma

Combined small cell carcinomas

(26)

SCLC: Staging and place for surgery

• Very Limited Stage

Defined as solitary tumor, less than 3cm diameter, without mediastinal nodal or extranodal metastatic site.

• Limited Stage

Defined as tumor involvement of one lung, the mediastinum and ipsilateral and/or contralateral supraclavicular lymph nodes.

• Extensive Stage

Defined as tumor that has spread beyond one lung, mediastinum, and supraclavicular lymph nodes.

Common distant sites of metastases are the adrenals, bone, liver, bone marrow, and brain.

(27)

Stages Ia through IIb

Chimiothérapie Adjuvante/Neo-adjuvante Prophylactic Cranial Irradiation

N0 and N1 subgroups

Badzio A and al. Eur J Cardiothorac Surg. 2004;26(1):183-8 N 134 patients

Retrospective, case control

Surg + adj. chemo vs chemo/XRT 67 pa / arm

Multimodality

(28)

Malignant Mesothelioma

80% intrathoracic

20% primary site = peritoneum

Age : 50-70 M/F 3.6 to 1

(29)

Cugell, D. W. et al. Chest 2004;125:1103-1117

Period of latency Epidemiology and perspectives

(30)

Diagnostic

• CXR : 80-95% Pleural effusion

• CT-scan : Sensitivity >>> CXR

• PET-FDG scan for Nodal and M stating

• Histologic diagnosis is mandatory

– Pleural cytology 25-33%

– Closed-chest needle biopsy 21-77%

– Thoracoscope biospy 90%

– VATS >90% and staging

XRT post-biopsy for local control

(31)

• Three histologic types of mesothelioma;

– epithelioid, 50%;

– sarcomatous or mesenchymal, 16%;

– mixed, 34%.

The epithelioid subtype has the best prognosis

(32)

T1a T1b T2 T3 T4

N0 Ia Ib II III IV

N1 III III III III IV

N2 III III III III IV

N3 IV IV IV IV IV

M+ IV IV IV IV IV

Surgery as a part of multi-modal treatment : Selection of patients

(33)

Pleuro-pneumonectomy Stage Ia, Ib and Stage II

Pleurectomy – Decortication

Stage Ia, Ib and Stage II unfit for EPPn + XRT and chemo-sensitizing molecules

Paclitaxel Carboplatin

(34)

Stage I Epithelial

Stage I

NON Epithelial

Stage II/III All Types

Evaluate for EPP EPP

Aduvant Chemotherapy platin-based

pemetrexed or gemcitabin Adjuvant XRT

NeoAduvant Chemotherapy platin-based

pemetrexed or gemcitabin

Re-Staging

Downstaging to N0/1 Evaluate for EPP EPP

Ajuvant XRT

Treatment Algorythm for Mesothelioma

(35)

EPP

Exclusions Criteria

• ECOG > 1 (KI < 70%)

• ppoFEV₁< 1L/s

• Room air pCO₂> 45 mmHg

• Room air pO₂< 65 mm Hg

• EF < 45%

Borderline

FEV₁< 2L/s radionuclide ventilation-perfusion pulmonary scanning

D. Sugarbaker, J Thor Cardiovasc Surg, 1999: 117: 54-65

(36)

Authors Year Nu Pa Stage IMIG

Epithelial Operative Mortality

2-year surv 5-yr Surv

Worn 1974 62 N/a N/a N/a 37 10

Butchart 1976 29 N/a 11 31 10 3

DeLaria 1978 11 N/a 9 0 27 N/a

Da Valle 1986 33 N/a 20 9 24 6

Ruffie 1989 23 I-III 12 13 17 N/a

Allen 1994 40 N/a 26 7.5 22.5 10

Rusch 1996 50(131) N/a (76%) 6 ~ 40 [Med 9.9mo]

Sugarbaker 1999 183 I-III 103 3.8 37 14

Weder 2004 19 I-III 14 0 37 [Med 23mo]

Stahel

(SAKK17/00)

2005 45(61) I-III N/a 2 67 (1-yr) [Med 26.3mo]

(18.4 mo)

Flores 2005 9 III/IV N/a 0 N/a N/a

Edwards 2006 92 I-IV 71 7.6 34 15

Summary 612

NeoAdj Chemo XRT

Adj Chemo XRT

Adj Chemo or adj. XRT

(37)

Place de la chirurgie pulmonaire dans les Cancers primitifs et dans la

Chirurgie de Métastasectomie

Pulmonaire

(38)

Métastasectomies pulmonaires

1/ Introduction

2/ Revue Générale (Registre international)

3/ UCL Experience

(39)

Historical aspect of surgery

in Pulmonary Metasastic Disease : Survival

1884 (Kronlein, Berl Klin Wschschr) 7 yrs*

1930 (Torek, Arch Surg) n/a*

1939 (Barney and Churchill, J Urol) 23 yrs*

1947 (Alexander and Haight, Surg Gynecol Obstet)

n= 24 patients (8 sarcoma, 16 carcinoma)

12/24 tumor recurrence-free, (f-up 1-12yrs) 50%

1965 (Thomford, J Thorac Cardiovasc Surg)

n= 205 patients (20% sarcoma, 80% carcinoma)

77% 1-yr survival and at 5-yr f-up 30 %

(40)

Métastasectomies pulmonaires

Physio-pathologie

• Poumon = premier lit capillaire de drainage de la plupart des tumeurs primitives

• Le plus souvent, fixation en périphérie

• 10 à 20 % des patients avec métastases

pulmonaires ont une maladie confinée au

poumon

(41)

Diagnostic

• Asymptomatique

• Découverte lors d’un contrôle systématique

• Ct Scan :

sensible (peu de faux [-]) non-spécifique (bcp faux [+])

sous-estime le nombre de lésions

• Ponction trans-thoracique

• Nodule solitaire fréquent pour sarcome et

mélanome

(42)

Indication de résection chirurgicales

• Si Contrôle local de la tumeur primitive

• Si Résection complète possible

• Si Réserve fonctionnelle suffisante

• Si Absence d’autres localisations métastatiques?

(43)

Technique opératoire

• « Wedge » resection (épargne parenchymateuse)

• Exploration manuelle ⇔ Thoracoscopie (single)

• Si bilat : Sternotomie ⇔ Thoracotomie bilat.

séquentielle.

(44)

Métastasectomies pulmonaires

Analyse de Survie

(Toutes origines primitives confondues)

• Survie à 5ans 36%

• Survie à 10 ans 26%

• Survie à 15 ans 22%

(médiane de survie : 35 mois)

(45)

Patients' features

Resection Complete Incomplete Total

Age:Mean (range) 44 (2-93) 43 (2-79) 44 (2-93) Sex Male 2587 345 2932

Female 1984 289 2273 Type

Epithelial 1984 276 2260 Sarcoma 1917 256 2173 Germ cell 318 45 363 Melanoma 282 46 328

Other 70 11 81

II/ Overview: Métastasectomies pulmonaires

(International Registry : 5206 pts)

Pastorino et al. J Thorac Cardiovasc Surg 113 (1997) :37-49

(46)

Patients' features

Resection Complete Incomplete Total

Approach

Monolateral thoracotomy 2770 341 3111 Bilateral thoracotomy 534 42 576

Sternotomy 1179 236 1415

Thoracoscopy 84 9 93 Resection

Wedge 3012 461 3473 Segment. 409 40 449 Lobectomy 1014 95 1109 Pneumonectomy 112 21 133 Other resections 344 102 446

(47)

Overall Survival : Prognostic Factors

Complete Resection

(48)

Intervalle libre Overall Survival

(49)

Nombre de métastases Overall Survival : Prognostic Factors

(50)

Histologie Overall Survival : Prognostic Factors

(51)

Overall Survival : Prognostic Factors combined

(CR, FI, Nu mets and Histo)

(52)

Métastasectomies pulmonaires

1/ Introduction

2/ Revue Générale (Registre international)

3/ UCL Experience

(53)

• Study period : 1990-2002

• 93 patients / 134 procedures

• Retrospective analysis of consecutive patients

• All thoracic explorations included

• Patients data collection

– Hospital charts, PCP and/or oncologist

– Follow-up completed from 02/06 and 06/06

– Mean follow-up time : 43 months (range 1-169 mo)

AJ Poncelet et al., Eur J Cardiothor Surg 31 (2007) :171-180

“Prognostic factors for long-term survival in patients with thoracic metastatic disease: a 10- year experience”

(54)

Patients characteristics

• Sex ratio (m:f ) 1.2 :1

• Mean age 52.2 y.o. (range 3-84)

• Number of metastasis : 233 (2.5/pa)

• Number of procedure

– One : 80 patients (including 9 sequential bilateral) – More than one : 18 patients

• Adjuvant chemotherapy (pre or post): 76/93 patients

(55)

Operative Strategies

Wedge 48

Segmentectomy 4 Lobectomy 17 Pneumonectomy 7 Other resections 17

Mediastinal LN dissection 49/93 patients

nLN/pa 4.5/pa (1-33)

R status

R0 70 pa

R1/R2 23 pa (14/9 pa) 70/93 pR0

(75.2%)

(56)

Pathology (n=93)

Epithelial 47

(Colo-rectal, renal and breast)

Sarcoma 21

(all histological subtypes)

Teratoma 6

Melanoma 4

Other tumors 15

Major Morbidity (5%)

7/139 procedures,

requiring reoperations 3/139

pulm infarc 1

empyema 1

diaphr. hernia 1

90-day Mortality (2.2%)

3/139 procedures (sequential lobectomies/Bilob)

LOS mean 8.4 days (3-57d)

RESULTS

(57)

Survival at

1-yr

82%

3-yr

55%

5-yr

44%

(58)

(59)

3-yr and 5-yr Survival

Pathology (n=) 3-yr 5-yr

Epithelial (47) 59% 42 %

Sarcoma (21) 47 % 47 %

Teratoma (6) 50% 50%

Melanoma (4) 50% 50%

Others (15) 78% 78%

(60)

Epithelial Tumors

Pathology (n=) 3-yr 5-yr

Colo-rectal (26) 69 % 37 %

Renal (11) 28 % 19 %

Breast (9) 31% 16 %

(61)

Statistics (1)

β p H.R. 95% CI

Age 0.27 .38 1.3 0.7-2.4

Sex 0.55 .08 1.7 0.9-3.2

Primary pN 1.02 .09 2.7 0.8-9.2

DFI 0.02 .95 1 0.5-1.9

Nu mets 1.38 .0000 3.97 2.1-7.4

‘Other’ mets 0.1 .74 1.1 0.6-2.1

(62)

Statistics (2)

β p H.R. 95% CI

Type

Resection

0.33 .34 1.4 0.7-2.8

Uni vs Bilateral

0.4 .23 1.5 0.8-2.9

Size Mets 0.52 .11 1.7 0.9-3.2

pR Status 1.16 .0006 3.2 1.6-6.2

pN Status 0.19 .69 1.2 0.5-3.2

Redo-Mets -0.58 .14 0.6 0.3-1.2

(63)

Analysis of Colo-rectal and Sarcoma subgroups

β p H.R. 95% CI

Uni vs Bilat 1.3 .04 3.7 1-12.7

Nu mets 3.2 .003 23.7 2.8-198

pR status - - - -

pN status* 1.4 .24 4.2 0.4-47

Prior Hep. Mets* 0.3 .7 1.3 0.4-4.6

Colo-Rectal Metastatic group (n= 26)

(64)

Analysis of Colo-rectal and Sarcoma subgroups

β p H.R. 95% CI

Uni vs Bilat 0.7 .24 2.1 0.6-7.4

Nu mets 1.8 .01 6.1 1.5-24.6

pR status 2 .003 7.6 2-29.4

pN status* - - - -

Nu redo-mets -1.9 .08 0.15 0.2-1.2

Sarcoma Metastatic group (n= 21)

(65)

• In those selected patients, understanding that a complete resection can be anticipated, surgery for metastatic disease results in 3-yr and 5-yr overall survival of 60% and 43%, respectively.

• Both in univariate and multivariate analysis, the number of

metastasis and complete pathological resection are significant variables that influences outcome.

• In this series of patients, variables such as DFI, other site than pulmonary, N status of the primary tumor, type of resection did not had influence on survival .

Conclusions (1)

(66)

• Patients in whom repeated metastasectomies are performed do at least as well as the others.

• In the colo-rectal subgroup, in addition to number of metastasis and the completeness of surgery, bilateral disease appears to convey a negative outcome.