what to do in stage iii non small-cell lung cancer?
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What to do in stage III non small-cell lung cancer?
Miklos Pless
28. November 2013
2
CRT: Concomitant vs. SequentialMeta-Analysis 2010 (HR 0.84, Cochrane 0.74)
Auperin, JCO 2010
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CRT: Chemotherapy type not so important?CALGB 9431 (phase II)
Vokes, JCO 2007
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Vokes, JCO 2007
CRT: Role of induction chemotherapyCALGB 39801
5Yamamoto S. et al., J. Clin. Oncol. 30, 2012, suppl. Abstr.7000
45 trials, 9 phase III, 36 phase II with 51 arms
No difference between the two groups,
med OS: CT 18.5 mo vs no CT 18.1 mo
CRT: role of consolidation CT after CRT?
6
HR 0.925
Curran, JNCI 2011
CRT: role of hyperfractionationRTOG 9410
Arm 3: 70 Gy: 1.2 Gy 2x/d
Arm 2: 63 Gy: 1.8 Gy/d
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CRT: Role of high doses of RTRTOG 0617
Bradley , ASCO 2013
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Operable stage IIIA:Adjuvant Chemotherapy: OS better!
Winton, NEJM 2005
9PORT Cochrane, 2010
Operable Stage IIIADoes adjuvant RT help? NO!
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•Unresectable (?) N2
•With response to Induction
3 x Cis/Carbo + X
•OP vs. RT (60 Gy)
•1. EP: OS
•50% complete resection!
•41% downstaging to ≤ypN1
•Unresectable (?) N2
•With response to Induction
3 x Cis/Carbo + X
•OP vs. RT (60 Gy)
•1. EP: OS
•50% complete resection!
•41% downstaging to ≤ypN1
JNCI, 2007
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Resectable N2 Induction CRT:
3x Cis/Eto + RT 45 Gy
If no PD: RT to 61Gy vs. OP
1. EP: OS
Resectable N2 Induction CRT:
3x Cis/Eto + RT 45 Gy
If no PD: RT to 61Gy vs. OP
1. EP: OS
Lancet 2009
PFSOS
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The activity of the SAKK groupSAKK 16/96 (Phase II)
3 x Cisplatin/Taxotere neoadjuvant (Betticher, JCO 2003)Overall Survival (ITT population, n=90)
0
.2
.4
.6
.8
1
0 10 20 30 40 50 60
Months
Overall survival
complete
resection
incomplete
resectionp<0.0001
all
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Is trimodal better than bimodal?SAKK 16/00
Presented by: Miklos Pless
Stratification factors: Mediastinal bulk (≥5cm vs. <5cm), weight loss (≥5% vs. <5% in past 6 months), center
*
* *
* Staging: (PET-) CT: PD went off study
14
Overall Survival
Treatment Median OS (95% CI)RT 27.1 (18.8, 42.8)
no RT 26.2 (21.0, 52.1)
HR = 1.145 (95% CI: 0.786-1669)
Pless ASCO 2013
Time (months)
Ove
rall
Su
rviv
al
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0 24 48 72 96 120 1440
0.2
0.4
0.6
0.8
1
# at riskRTno RT
98 43 19 7 6 1 097 41 21 10 2 0 0
Chemo/RT/SurgeryChemo/Surgery
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Stage III
• Very heterogeneous disease
• <30% can be cured (70-80% are NOT!)
• Both local and distant relapse are a problem!
• Requires bimodal treatment
• always Chemotherapy: minor effect
• Surgery vs. Radiotherapy?
• Trimodal treatment?
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Summary & Conclusions
Which Chemotherapy? (Cis-)Platinum based, concurrent
type and dose
Which Radiotherapy? >60 Gy, less than 70 Gy
type, dose, fraction
Which combination?
Surgery + Chemotherapy Stage IIIA/N2
Radiotherapy + Chemotherapy Stage IIIB/IIIA?
all three? Probably not
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