7. Conclusions and French
guidelines
• This trial showed the strength
of the combination of
radiotherapy, chemotherapy
and the surgery for operable
patients with a resectable
sulcus superior tumor.
• This is included in the 2021
French recommendations
(publication soon!)
7
9. Patients and treatments
• Eligible patients
– Pathologically proven, locally advanced T1–3N2M0, stage IIIA/N2
– Staging by PET-CT and brain MRI
– N2 be proven by mediastinoscopy or endobronchial ultrasonography,
endoscopic ultra sonography, or bronchoscopy with transbronchial fine-
needle aspiration
• Chemotherapy
– 3 cycles of cisplatin and docetaxel every 3 weeks
• Sequential Radiotherapy
– 44 Gy in 15 fractions over a 3 weeks period (2.9 Gy / fraction)
9
Cisplatin 100mg/m² J1
Docetaxel 75mg/m² J1
x 3 cycles
arm RTCT
117 patients
arm CT
113 patients
SURGERY
SURGERY
Cisplatin 100mg/m² J1
Docetaxel 75mg/m² J1
x 3 cycles
Sequential
Radiotherapy
44Gy en 15 x 2.9 Gy
11. Results
11
9% 19%
RTC :12.8 months (95% CI 9.7–22.9)
CT: 11.6 months (8.4–15.2)
HR 1.1, 95% CI 0.8–1.4, p=0.67
Median overall survival
- RTCT: 37.1 months
(95% CI 22.6–50.0)
- CT: 26.2 months
(95% CI 19.9–52.1)
HR 1.0, 95% CI 0.7–1.4
12. Conclusion
• Despite good local and regional control, RT-
CT failed to demonstrate a role in neo-
adjuvant treatment
– Dose ?
– No concurrent chemo-RT?
– Number of patients per arm? Time for
inclusion – number of centers -
heterogeneity
12
17. Conclusions
• In this metaanalysis combinaison of the three
therapies seems unuseful:
– RT can be avoided in RT-CT + S
– But :
• old studies
• Small number of patients per trials
17
19. Littérature:Issue of N2 patients
• 2 meta-analysis 1998/2016
• One cohort analysis 2006
• One randomized analysis 2020
19
20. Post Operative Radiation
Therapy
Post-Operative RadioTherapy Overview (Lancet
1998)
• 2128 pts : 808 pts stage III included in 9
randomized trials
Surgery alone (1072 pts)
2-yr OS: 55%
surgery + PORT(1056 pts)
2-yr OS: 48%
PORT, Lancet 1998
21. Analyse par sous-groupe
Hazard Ratio
RT better No RT better
0.0 0.5 1.0 1.5 2.0
0
1
2
Nodal Status
Stage 1
2
3
Test for trend
c2
(1)=13.194, p=0.0003
Test for trend
c2
(1)=5.780, p=0.016
PORT, Lancet 1998
Deletere effect
22. Cohort of 7465 pts operated-on Stages II, III
NSCLC SEER Data base
N0 pts N2 pts
N1 pts
All pts
Port Port
Port
Port
Surgery + PORT: improvement of overall survival for N2 patients (p<.004)
5 yr OS
S 41%,
Port 31%
5 yr OS
S 20%,
Port 27%
5 yr OS
S 34%,
Port 30%
3 yr OS
S 47%,
Port 41%
Lally and al, JCO 2006
23. Retrospective study of PORT after complete surgery
• Large number of patient
• Similar conclusions than the 1998 metaanalysis
for N0 and N1
• Improvement for N2? But numerous factors
were not studied in the analysis
25. Method
• Period of inclusion 1965-2016
• Individual data of 11 trial with individual data
• 2343 participants (1511 deaths)
25
26. Main results
26
(HR) of 1.18 (95% CI 1.07 to 1.31)
An 18% relative increase in risk of death
An absolute detriment of 5% at two years (95%CI: 2% to 9%)
Reducing overall survival from 58% to 53%.
38. Incomplete resection
• 1 cohort analysis
– Result of the treatment
• 1 randomised trial
– Management before « incomplete »
resection
38
39. Patients
• National Cancer Data Base
• Lobectomy or pneumectomy
• App. 1900 patients R1 or R2 resection
• 3395 included patients
– 1207 (35.6%) received PORT
– dose 50-74 Gy
39
42. Randomisation
• 579 pts, "unresectable" N2
NSCLC received 3 cycles of
induction Pt-based chemo
• Nonprogressors after
chemotherapy
– RT or surgery
42
43. Results
• Surgery increase Local
Control but no difference in 5yr-
OS (~15%) or Median Survival
(16.5 mo)
• Surgery increase Toxicity-
related mortality (9% vs. <1%)
43
Progression-free survival
44. Conclusions
• Surgery did not improve OS or PFS
• Given low morbidity and mortality, RT
should be preferred modality
• RT arm used older techniques of 3DCRT and included
elective nodes
• Surgery arm included 47% pneumectomies
• only 50% had R0 resection
44
45. « NON OPERABLE » – « NON
RESECTABLE » PATIENTS
CONCURRENT OR SEQUENTIAL
RT-CT ?
45
46. Metaanalysis 1
• 19 randomised trials (2728 patients)
– Concurrent chemoradiotherapy versus
radiotherapy alone
• 6 randomised trials (1024 patients)
– concurrent versus sequential chemoradiation
O’Rourke N et al. Cochrane Database of Systematic
Reviews 2010
46
47. Results
• RT-CT vs RT
– Reduced overall risk of death (HR 0.71, 95% CI 0.64 to
0.80)
– Reduced overall progression‐free survival at any site (HR
0.69, 95% CI 0.58 to 0.81)
• Concurrent vs sequential RT-CT
– Improvement of overall survival (HR 0.74, 95% CI 0.62 to
0.89) 10% absolute survival benefit at 2 years.
– More treatment‐related deaths (4% vs 2%) no statistical
significance (RR 2.02, 95% CI 0.90 to 4.52).
– increased severe oesophagitis with concurrent treatment
(RR 4.96, 95%CI 2.17 to 11.37)
47
56. Conclusion
• In inoperable patients, unresectable tumor,
with IIIA-B tumor adding Durvalumab lead to
improve progression-free and overall
survival
56
58. Conclusion of the conclusions
• There is not opposition between surgery and
radiotherapy – we are not in the same fields
• Surgery can cure operable patients with resectable
tumor IIIA tumors
– We can cure together (RT + Surgery) advanced
superior sulcus tumor
• Radiotherapy (with chemo) try to cure inoperable or
unresectable IIIA tumors (and IIIB)
• Consolidation treatments can not replace bad
selection of patients and an non-optimal treatment
(non adapted radiotherapy)
58