Transcript DIAMOND BILIARY STENTING

Discussion Panel on
Primary Radiochemotherapy
Volker Budach, MD, PhD
Head Department
for Radiation Oncology
Charité Campus-Mitte
Berlin
Interdisciplinary Workshop on
Modern Treatment Options
Statements on Head and Neck Caner
Frankfurt, 27-28 of January 2006
V. Budach – Statements on H&N Cancer - 1
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Update of the MACH-NC database
focusing on concomitant chemo-radiotherapy.
J Bourhis, C Amand, JP Pignon
on behalf of the
Meta-Analysis of Chemotherapy in Head and Neck Cancer
(MACH-NC) Collaborative Group
V. Budach – Statements on H&N Cancer - 7
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Purposes
• Confirm the magnitude of the benefit of CT on survival
• Validate the effect in concomitant RT-CT because of
uncertainties in the MACH-NC-1* due to heterogeneity
between trials
• Increase the statistical power to allow subgroup and
subset analyses
Bourhis et al., JCO 2005, Abstract
V. Budach – Statements on H&N Cancer - 8
MACH-NC
Material & Methods
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Eligibility criteria
Trials properly randomized
performed between 1965 and 2000
R
Loco-regional + chemotherapy
Loco-regional treatment
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 9
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Material and Methods
Data collection and checking
Updated individual
data collected for all
randomized patients
from published and
unpublished trials
Extensive checking
& validation to ensure
integrity of rando-mization
and follow-up in
collaboration with
investigators
V. Budach – Statements on H&N Cancer - 10
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Material and Methods
Statistical methods
Absolute benefit
calculated from
baseline survival
and RR
Intent
to treat
analysis
Logrank test
stratified by
trial
Survival times
used to calculate
relative risk
(RR)
V. Budach – Statements on H&N Cancer - 11
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
New randomized trials
Included 1994-2000
24 trials & 5 699 patients
 10% in adjuvant
 5% in neoadjuvant
 85% in concomitant
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 12
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Data analyzed
87 randomized trials and 16 640
patients
3-arm trials
2 x 2 trials
 105 comparisons and 17 858 pts
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 13
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Chemotherapy timing
(n= 17 858)
Adjuvant
14%
Concomitant
54%
Neoadjuvant
32%
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 14
Site of the primary (n= 17 858)
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
PERCENT
19
Bourhis et al., JCO 2005, Abstr.
15
10
5
0
Oral cav.
Treatment:
Oroph.
Larynx
Hypoph. Others
Chemotherapy
No Chemotherapy
V. Budach – Statements on H&N Cancer - 15
Stage (UICC 1997) (n= 17 858)
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
PERCENT
40
30
20
10
Bourhis et al., JCO 2005, Abstr.
0
Stage I-II
Treatment:
Stage III
Chemotherapy
Stage IV
No Chemotherapy
V. Budach – Statements on H&N Cancer - 16
Overall Survival
All trials (N=17858 patients)
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
1.00
p<0.0001
0.80
Chemotherapy
Control
Difference : 5 %
0.60
36 %
0.40
31 %
0.20
Median follow-up = 5.7 years
0.00
0
1
2
3
4
5
6
Years
7
8
9
899
794
623
572
469
431
10
Bourhis et al., JCO 2005, Abstr.
At risk
8988
8870
6158 4334 3342 2536 1837 1288
5855 3967 2917 2166 1570 1104
332
307
V. Budach – Statements on H&N Cancer - 17
MACH-NC
Overall survival : Concomitant trials
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
19% + 3%
19% + 3%
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 22
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
1.00
Overall Survival
Concomitant Trials (N=9615 patients)
p < 0.0001
0.80
Difference : 8 %
Chemotherapy
Control
0.60
0.40
35 %
27 %
0.20
0.00
0
At risk
4824
4791
1
2
3
4
5
6
7
8
9
10
Years
3180
2952
2231 1715 1312
1908 1359 1016
940
746
677
531
481
394
362
304
284 233
246 186
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 23
MACH-NC
Meta-Analysis of Chemotherapy
in Head & Neck Cancer
Overall survival : Concomitant trials (n = 9 615)
Inclusion
Hazard ratio
(95% CI)
Chemotherapy Heterogeneity
effect (p)
(p)
Difference
survival rate
At 2
At 5
years years
7,1 % 6,4 %
1965-1993 0,82 (0,76 ; 0,88)
<0,0001
<0,0001
1994-2000 0,81 (0,76 ; 0,87)
<0,0001
0,27
6,6 %
6,6 %
0,81 (0,77 ; 0,86)
<0,0001
0,0001
6,8 %
6,5 %
Total
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 24
MACH-NC
Concomitant trials survival by type of local treatment
Met a-Analy sis of Chemot herapy
in Head & Neck Cancer
21% + 7
17% + 3
27% + 5
1% + 13
Bourhis et al., JCO 2005, Abstr.
V. Budach
– Statements
ononH&N
V. Budach,
Statements
H&NCancer
Cancer -2930
MACH-NC
Concomitant trials : effect by type of CT
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
23% + 5
26% + 5
19% + 5
10% + 4
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 31
MACH-NC
Concomitant trials: with or without platin
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
23% + 5
20% + 6
26% + 5
11% + 4
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 33
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Conclusion
Small benefit of chemotherapy on
survival = confirmed (5%)
Evidence of a higher survival benefit with
concurrent = confirmed
Absolute benefit in concomitant = 8% at
5 years (11% with Cisplatin alone)
Benefit of chemotherapy observed in post-op,
and with definitive RT (conventional or
hyperfractionated)
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 34
MACH-NC
Met a-Analysis of Chemot herapy
in Head & Neck Cancer
Acknowledgments
• Trialists and patients
• Association pour la Recherche sur le
Cancer
• Aventis, Sanofi Synthelabo
• Institut Gustave-Roussy
• Programme Hospitalier de Recherche
Clinique
Bourhis et al., JCO 2005, Abstr.
V. Budach – Statements on H&N Cancer - 35
Standard Fractionated Radiotherapy ±
Concurrent Chemotherapy
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 36
Standard Fractionated Radiotherapy ±
Concurrent Chemotherapy
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 37
Altered Fractionated Radiotherapy ±
Concurrent Chemotherapy (same OTT)
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 38
Altered Fractionated Radiotherapy ±
Concurrent Chemotherapy (same OTT)
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 39
Altered Fractionated Radiotherapy ±
Concurrent Chemotherapy (prolonged OTT)
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 40
Altered Fractionated Radiotherapy ±
Concurrent Chemotherapy (prolonged OTT)
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 41
Median Survival Impact of Cytostatic Drugs
with Concurrent Chemoradiation
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 42
Chemoradiation vs. Radiotherapy
Only studies published after 1992
Reduction of odds ratios
hyperfract. XRT vs. convent. XRT
accelerat. XRT vs. convent. XRT
concurr. CXRT vs. convent. XRT
HFX-AF-XRT vs. HFX-AF-XRT +
concurr. CHX
Local control
0.50
0.83
0.33
0.53
Survival
0.60
0.90*
0.43
0.54
*= not significant
W. Budach et al., BMC Cancer 2006, in press
V. Budach – Statements on H&N Cancer - 45
Locally Advanced Squamous Cell Carcinomas
of the Oro- und Hypopharynx
Conclusions
Concurrent chemoradiation is the standard of
care for inoperable H&N-Cancer !
For patients not amenable for concurrent CXRT,
hyperfractionated XRT is the standard of care!
V. Budach – Statements on H&N Cancer - 46
Perspectives in Head and Neck Cancer
Potential improvement of the Therapeutic Index
by means of:
Optimized Radiotherapy Techniques

“IMRT” = Intensity-Modulated RadioTherapy for dose escalation
and organs at risk/tissue protection
Small molecules
 EGFR-MoAb (Cetuximab, Erbitux, Gefinitib)
 Cox-II Inhibitors
 Bevacuzimab
Cytostatic drugs:
 Taxanes (Paclitaxel, Doxetaxel), Gemcitabine, Irinotecan
V. Budach – Statements on H&N Cancer - 47
Open Questions in the Definitive Treatment of
Locally Advanced Head and Neck Cancer
 Optimal combination of chemoradiation with
standard or altered fractionation?
 Do late effects of chemoradiation compromize
the therapeutic benefit (therapeutic ratio )?
 Can the addition of „small molecules“
additionally improve chemoradiation results?
 Is there a definitive role of surgery (for salvage)
after chemoradiation?
V. Budach – Statements on H&N Cancer - 48