Josep Belda. Cirujano Torácico€¦ · Kim TCS 2014 PET/CT Dooms (ASTER 2). Chest 2015 PET/CT +...

Cirugía tras tratamiento neoadyuvante

Josep Belda. Cirujano Torácico

No tengo ningún conflictode interésrelacionadocon el temade esta presentación.

1. Selección de pacientes para cirugía.

2. Cirugía en pacientes con ycN2 residual

3. Resultados tratamiento trimodal tras una VAMLA

4. Complicaciones quirúrgicas tras inducción. Factores de riesgo.

5. Neumonectomía tras inducción

Resecable. R0

Paciente operable

Riesgo quirúrgico / beneficio terapéutico

Complete resection in LC. Rami-Porta R. IASLC Staging Committee. LC. 2005

Infiltrative and discreteN2/N3 involvement. Ramnath. ACCP guidelines. Chest 2013

ERS/ESTS guidelines on fitness for radical therapy in LC patients (surgery and CT/RT). BrunelliERJ 2009

Median

(mo)

5-Year

estimate OS

CT/RT/Surgery 23.6 27.2%

CT/RT 22.2 20.3%

p=0.10p=0.24HR 0.87

(95%CI 0.70-1.10)

Overall survival of

intention-to-treat .

T1-3pN2M0

Radiotherapy plus chemotherapy with or without surgical resection for stage

III NSCLC: a phase III RCT. Albain K. Lancet 2019. Intergroup Trial 0139

CT/RT CT/RT Log Rank

Mediana sv 34 m 22 m p=0,002

OS 5 a. 36% 18%

Lobectomía

CT/RT CT/RT Log rank

Mediana sv 19 m 29 m p=ns

OS 5 a. 22% 24%

Neumonectomía

OS matching analysis (any ypT/ypN)

Albain. Lancet 2019. Intergroup trial 0139

Any T Median sv 5yr OS

pN0 34,4 m 41%

pN1-3

pN unknown26,4 m 24%

No surgery 7,9 m 8%

ypT0N0 (RPC) 39,8 m 42%

Albain. Lancet 2019. Intergroup trial 0139

Repeat mediastinoscopy in all its indications: experience with 96patients and 101 procedures. Call S. EJCTS. 2011.

P<0.0001

cN2 confirmados, inducción (CRT/CT) más cirugía

Repeat mediastinoscopy:

S 0.74, NPV 0.79, A 0.87

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 NSCLC: a multi-institutional study. Oncologic Group

for the Study of Lung Cancer (SEOR). Couñago F, et al. Clin Trans Oncol 2019

Thomas et al. Lancet Oncol 2008Carreta et al. World J Surg 2008Albain et al. Lancet 2009Li et al. Clin Lung Cancer 2009Decaluwé et al. EJCTS 2009Higgins et al. Int J Rad Oncol Biol Phys 2009Krasna et al. Ann Thorac Surg 2010Call et al. EJCTS 2011;Paul et al. J Thorac Cardiovasc Surg 2011Pataer et al. JTO 2012Steger et al. ICVTS 2012;Loccoco et al. EJCTS 2013;Yang et al. EJCTS 2016. Couñago et al. Clin Transl Oncol 2019

Strauss et al. J Clin Oncol 1992Albain et al. J Clin Oncol 1995Rice et al. Ann Thorac Surg 1998Stamatis et al. Ann Thorac Surg 1999Okada et al. Chest 2000Bueno et al. Ann Thorac Surg 2000Voltolini et al. EJCTS 2001Cyjon et al. ATS 2002Betticher et al. J Clin Oncol 2003Rusch et al. Lung Cancer 2005Van Meerbeeck et al. Lung Cancer 2005Van Meerbeeck et al. J Natl Cancer Inst 2007Garrido et al. J Clin Oncol 2007

Initial results of pulmonary resection after neoadjuvant nivolumab in patients

with resectable NSCLC. Bott MJ. JTCVS 2019

Major pathologic response/CPR

– 24% LCMC3

– 24% NEOSTAR

– 45% Bott (MSKCC & JH)

– 80% NADIM

sin mas complicaciones ni mortalidad perioperatorias…

Probablemente… NO deben

hacerse resecciones mayores

que una lobectomía

o Rice et al. Ann Thorac Surg 1998o Stamatis et al. Ann Thorac Surg 1999o Okada et al. Chest 2000o Bueno et al. Ann Thorac Surg 2000o Betticher et al. J Clin Oncol 2003o Albain et al. J Clin Oncol 2005o Van Meerbeeck et al. J Natl Cancer Inst 2007o Uy KL, et al J Thorac Cardiovasc Surg 2007o Decaluwe H, et al. Eur J Cardiothorac Surg 2009o Yang ChF, et al. Eur J Cardiothorac Surg 2016. o Couñago F, eat al. Clin Transl Oncol 2019

Probablemente… SOLO

deberían operarse ycN0-1

…el problema de la

reestadificación

The accuracy of clinical staging of stage I-IIIa NSCLC: An analysis based

on individual participant data. Navani. Chest 2019.

A systematic review of restaging after induction therapy for

stage IIIa LC: Prediction of p-stage. de Cabanyes C. JTO 2010

Postinduction PET assessment of N2 nodes is not associated with ypN2

or overall survival in stage IIIA NSCLC. Ripley RT. JTCVS 2016 MSKCC

43% PET N2 negative

39% PET N2-avid disease.

N=100 IIIA-N2 confirmado patol.

CT + Cirugia

62% ypN2

S E PD

Postinduction

PET for ypN2

59% 55% 57%

P =0.251

SUVmax decrease on PET/TC after neoadjuvant CT is a prognostic

classifier for long-term outcome after multimodality treatment: Secondary analysis of

a randomized trial for resectable stage IIIA/B NSCLC. Pöttgen Ch, et al. JCO 2016

ESPATUE trial

Phase III. Surgery vs

definitive concurrent CRT

boost in patients with

resectable stage IIIA-N2

and selected IIIB NSCLC

after induction CT and

concurrent CRT

Kaplan–Meier estimated OS according to the LNR for pN2

Porque hay “pocos” ganglios afectos

Mediastinal downstaging after induction is not a significant prognostic factor to select patients who would benefit from surgery: the clinical value of the lymph node ratio. Renaud, et al. ICVTS 2015

• SV pN2 con LNR bajo = pN1 con LNR alto

• Downstaging mediastínico NO seria un

factor pronóstico suficiente para

contraindicar la cirugia tras la inducción

“Poco N2” porque es “solo” microscópico

Surgery for patients with persistent pathological N2 IIIA NSCLC after induction

RCT: the microscopic seed of doubt. Meacci E. EJCTS 2011

• 161 IIIA-N2

• Induction CRT

• 40 pN2 (26%)

Microscopic (---) and macroscopic ( ) LN involvement survival functions.

The impact of residual multi-level N2 disease after induction therapy

for NSCLC. Sawabata, et al. LC 2003

“Poco N2” porque hay pocos niveles afectos

Resultados tratamiento trimodal tras una VAMLA

CentralN1 > 3cm

• Vilmann. ERJ 2015. ESGE/ERS/ESTS

• Majem. Clin Transl Oncol 2019. GECP,

SECT, SEPAR, SEOM, SERAM, SEOR, SEMNIM

• Eberhartdt. AO 2015. ESMO

• De Leyn. EJCTS 2014. ESTS/ERS

• Darling. Curr Oncol 2011. Ontario Guidelines

• Silvestri. Chest 2013. ACCP.

• Ramnath. Chest 2013. ACCP

Mediastino normal en PET/TC: recomendaciones EBUS

y/o mediastinoscopia

VideoAssisted Mediastinoscopic Lymphadenectomy for staging NSCLC. Call S. Ann Thorac Surg 2016.

n= 32

uN2= 13 (40.7%)

cN1

T >3cm

cN0

n= 63

uN2= 14 (22.2%) n= 31

uN2= 2 (6.4%)

cN0

T ≤ 3cm

cN1 based on:

Watanabe. ATS 2005 CT

Hishida. Thorax 2007 CT

Cerfolio. ATS 2015 PET/CT

Al.Sarraf. EJCTS 2008 PET/CT

Kim TCS 2014 PET/CT

Dooms (ASTER 2). Chest 2015

PET/CT + EBUS + Mediastinoscopy + surgery if all negative

Call. ATS 2016 PET/CT+ VAMLA + surgery if neg.

c/pN2

44%

28%

26%

24% RL8% LL

19%

16%

41%

Nuestra experiencia con pacientes cN2 diagnosticados con VAMLA

2010-17

250 cN0-1

35 N2(14.5%)

QT+ RT(>60Gy)

7 casos no candidatos

tratamiento trimodal

ReestadificaciónPET-CT

✓ Tumor estable✓Ausencia enf.

extratorácica

28 cN2Reestadificar quirúrgicamente el

mediastino después de una VAMLA no es posible


Progresion8 cases

Estabilidad / Respuesta20 cases

Inoperable7 casos

Resección13 casos (46%)

7% RPC.1 neumonect.


3-y Sv 5-y Sv

CT + RT + C 85% 74%

C+ RT 25% 0%

Unfit for C+RT 14.3% 0%

p=0.0001

CT+RT+C

CT + RT

Unfit for C+RT

Survival – all N2 cases (n=35)

1. Edad2. Lado derecho3. DLCO pre post inducción4. Dosis (altas) de radioterapia5. Albúmina6. Pérdida de sangre

Factores de riesgo

Is pulmonary function damaged by neoadjuvant lung cancer therapy?

A comprehensive serial time-trend analysis of pulmonary function after

induction radiochemotherapy plus surgery. Margaritora S, et al. JTCVS 2010

23% caída 4 semanas tras inducción

Mortalidad de la neumonectomía tras inducción

Trat. 30/90 (%) D(%) I (%)

Doddoli JTCVS 05 11/21 16/25 7/15

Alan JSO 06 QT 9 12,5 10

Daly ATS 06 QT/RT (59,4 Gy) 13

Cerfolio ATS 05 QT/RT (<60 vs. ≥60 Gy) 2 vs. 3,7

Van Schil ERJ 05 EORTC 08941 QT 7 6 9

Mansour EJCTS 07 QT 7/12

Albain Lancet 2009 INT 0139 09 QT/RT 26

D’Amato ATS 09 QT 9/12 11 7

Weder JTCVS 10 QT±RT /3

Broderick JTCVS 16 QT/RT 8

Cashiragi CLC 18 2,6/8,6

Yamaguchi ST 19 QT/RT 0/3

An analysis, systematic review, and meta-analysis of the perioperative

mortality after neoadjuvant therapy and pneumonectomy for NSCLC

Kim AW, et al JTCVS 2012

Postoperative complications after induction CRT in patients

with NSCLC. Fujita S. EJCTS 2006

• 124 patients with NSCLC

• Induction CRT + surgery

• Only RT> 45 Gy predicted postop.

complications (p<0.021)

1. DLCO pre y postinducción!

2. Cirugía entre 6-8 semanas tras la inducción.

3. La mortalidad a los 90 días, es el doble que a los 30!

4. La neumonectomía, es un procedimiento de alto riesgo.

5. Hay que cubrir el muñón bronquial con cualquier plastia.

Tanto como puedan…

1. formen un buen equipo (MDT)

2. eviten operar pacientes cyN2

3. eviten la neumonectomía

4. miren la mortalidad a 90 días

Josep Belda. Cirujano Torácico€¦ · Kim TCS 2014 PET/CT Dooms (ASTER 2). Chest 2015 PET/CT +...

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