Surprise N2 at thoracotomy small peripheral ACA

1
Surprise N2 at thoracotomy(small peripheral
ACA)

• ESMO International Symposium
• On Chest Tumors
• Geneva, March 30 2007
• Eric Vallières MD FRCSC
• Swedish Cancer Institute
• Seattle, WA

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Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

3
Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

4
Surprise N2 at thoracotomy(all comers)

• We should try to minimize the occurrence of
  surprise N2 as best we can with appropriate
  pre-thoracotomy staging
• In 2007, such occurrence should potentially be
  lower now that we have CT-PET staging, EBUS/ EUS
  FNA!!!

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Surprise N2 at thoracotomy(all comers)

• Mediastinoscopy
• still an important player
• in the
• mediastinal staging game

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Surprise N2 at thoracotomy(all comers)

• Despite CT and PET staging as well as mandated
  mediastinoscopy staging for radiological N1 and
  central malignancies, pN2 occurred in 14 of pts
  on S9900 (cT2N0-T1-2N1 diseases)

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Surprise N2 at thoracotomy(all comers)

• Impossible to tell
• how many of truly surprise N2s
• made up the pN2 populations
• on the IALT(26) and ANITA (27 ) trials...

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This is not what this talk is about!!!!
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Surprise N2 at thoracotomy(small peripheral
ACA)
CT-PET cT1N0M0, max SUV 7, mediastino negative
2.2cm Stage IA Adenocarcinoma
10
Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

11
Resect or close and hopefully come back after
induction therapy

• No randomized data to guide us
• Decision analysis model published in 2003
  suggested that closing was superior but weak

Ferguson MK J Thorac CV Disease 2003 126
1935-42
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Resect or close and hopefully come back after
induction therapy

• First, you are going to be very happy if you did
  a med and it was negative.
• Or
• If no med was done,
• YOU ARE GOING TO WISH YOU HAD DONE ONE

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Resect or close and hopefully come back after
induction therapy

• Recommend evaluate
• 1.the extent of the nodal disease and
• 2. the ability to achieve R0 resection.

14
Resect or close and hopefully come back after
induction therapy

• Close if
• R1-2 resection likely
• Cannot get to negative highest nodal station
• Multi level mediastinal nodal station involvement
• Paratracheal involvement with lower and middle
  lobar primary ???

15
Heterogeneity within the Stage IIIA N2
LN-Positive Population

• N 702

André et al J Clin Oncol 18 2981-89, 2000
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Resect or close and hopefully come back after
induction therapy

• With adequate preop evaluation, most of these
  cases are likely to be R0 resected in 2007
• Most surgeons favor R0 resection (with systematic
  nodal dissection) and postop therapy

Goldstraw P et al J Thor CV Surg 107 19-28, 1994
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Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

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IALT Interaction with p stage
Hazard ratio
Stage I
p0.41
Stage II
Stage III
Total effect
0.86
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Overall Survival - Stage III A (pT1-2 N2, pT3
N0-3)
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Results - LACE

• Overall HR (death) 0.89 (CI 0.82-0.96, p lt0.005)
• HR (death) by stage
• IA 1.41 (CI 0.96- 2.09
• IB 0.93 (CI 0.78-1.10)
• II 0.83 (CI 0.73-0.95)
• III 0.83 (CI 0.73-0.95)

Pignon JP et al, J Clin Oncol 2006, 24(18S) 366S
abstract 7008
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Adjuvant platinum chemo -Subset Analysis -
StageJoan Schiller ASCO 2006 Discussion
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Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

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Surprise N2 at thoracotomy(small peripheral
ACA)

Is there a role for adjuvant radiotherapy in
this era of adjuvant chemotherapy? ANITA, non
randomized delivery of sequential adjuvant RTX ,
in a descriptive analysis suggests possible
detriment with pN1 disease but benefit for pN2
disease
Douillard JY et al, Lancet Oncol 2006 7 719-27
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Douillard JY et al, Lancet Oncol 2006 7 719-27
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PORT revisited

• Population-based cohort (SEER) 7465 pts
• i.e. non randomized data
• PORT improved survival
• in patients with resected N2 disease
• (but not N0-1)

Lally BE et al, J Clin Oncol 2006 24 2998-3006
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PORT
PORT
Lally BE et al, J Clin Oncol 2006 24 2998-3006
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Surprise N2 at thoracotomy(small peripheral
ACA)

There may be a role for adjuvant radiotherapy in
this era of adjuvant C
Bonner JA, J Clin Oncol 24(19)2978-9, 2006
Le Pechoux et al, J Clin Oncol 25(7)e10-11, 2007
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Surprise N2 at thoracotomy(small peripheral
ACA)

If PORT, concurrent or sequential ?Concurrent
likely more toxic and may come at cost of
systemic treatment ( ECOG 3590)
Keller SM, NEJM 2000 3431217-22
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Outline

• A few comments
• Resect or close
• Adjuvant chemotherapy
• Adjuvant radiation therapy
• Trials

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SWOG S0623 Resected minimal N2
Phase II Randomized 2 arm design

cN0-1 but pT1-3N2 R0
Cddp/ docetaxel 4
Cddp/ etoposide/ Radiation 2 cycles/ 1.8 Gy daily
28 (50.4)
Radiation 1.8 Gy daily 28 (50.4)
Docetaxel 3
N 120 in 1-2 yrs
PIs Quejada, Mirkovic, Albain, Calhoun
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SWOG Resected minimal N2- FUTURE ?
Phase III

cN0-1 but pT1-3N2 R0
Chemo alone
The winner of S0623
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LUNG ART
Phase III

R0 resected N2 disease Preop or postop chemo
Sequential PORT
No PORT
Intergroup IFrancophoneCT, EORTC, LARSpainG
N 700
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