1. (Sequential rather than) concurrent CTRT is
the doable strategy in routine clinical
practice in NSCLC
Dr Ajeet Kumar Gandhi
MD (AIIMS); DNB; UICCF (MSKCC, USA)
Assistant professor, Radiation oncology
Dr RMLIMS, Lucknow

2. Indication of concurrent CTRT in
NSCLC
 Inoperable IIIA-B NSCLC
 Borderline operable Stage III NSCLC
 Pre-operative CTRT for superior sulcus tumors
 Post-op CTRT

3. Inoperable NSCLC
Inoperable IIIA-B:
•Concurrent CTRT
•Sequential CTRT
•No consolidative CT

4. Definitive management RT
 Sequential CTRT versus RT alone: Showed
improved survival with CTRT [3 RCTs: CALGB,
Intergroup, Le Chevalier et al]
 Concurrent CTRT versus RT alone*: Both
increased OS as well as PFS with CTRT (HR
0.7)
*N Engl J Med 1992;326(8):524–530
*Cochrane Database Syst Rev 2010;(6):CD002140

5.  IPD Analysis of NSCLC Collaborative group
 Six RCTs with 1,205 patients; Median follow up 6 years
 IIIA-B patients (~90% patients); 50% Sq and 30%
Adeno
 >60 years (55%); >65 years (36%); >70 years (15-20%)
 ECOG PS 0 (50%); PS 1 (46%)

6. Trial Accrual
Period
Patients CTRT Seq RT
CALGB 8831 1988-1989 91 60 Gray/30#
Carboplatin
60 Gray/30#
Cis/Vib
WJLCG 1992-1994 314 28 Gray/14# x2
Cis/Vind/Mito
56 Gray/28#
Cis/Vind/Mito
RTOG 9410 1994-1998 407 60 Gray/30#
Cisp/Vinblastine
60 Gray/30#
Cisp/Vinblastine
GMMA Ankara
1995
1995-1996 30 36 Gray/12#
12.5 Gray/5#
Cis Daily
36 Gray/12#
12.5 Gray/5#
Cis/Etoposide
GLOT-GFPC
NPC 95-01
1996-2000 205 66 Gray/33#
Cis/Etoposide
66 Gray/33#
Cis/Vib
EORTC 08972 1999-2003 158 66 Gray/33#
Cis Daily
66 Gray/33#
Cis/Gem

7. “CTRT increased acute oesophageal toxicity (grade 3-4) from 4%
to 18%; P=.001. There was no significant difference regarding
acute pulmonary toxicity”
5.7% (18.1% to
23.8%) at 3 years
4.5% at 5 years

8. Arm 1: Median OS 14.6 Months
Arm 2: Median OS 17 Months
HR=0.812 (CI 0.663-0.996)
P=0.046

10. Concurrent versus Sequential
 Better OS: 5-10% (2-5
years)
 Treatment related
morbidities higher:
Esophagitis
Radiation Pneumonitis
 Other morbidities:
Comparable

11. Concurrent versus Sequential
What is the problem then??
 Suitability of the
patient:
Age
 Performance
status
 Medical co-
morbidities
 Weight loss
 Concerns of
enhanced toxicity:
Esophagitis
Radiation
Pneumonitis
Cardiac toxicities
Others

14. Subjective decisions: Seq vs. Conc. CTRT

15. Toxicities: Con vs. Seq
 Radiotherapy techniques: 2D mostly in
earlier trials
 Dosimetric parameters for Esophagitis and
Pneumonitis less clear at the inception of
these trials
 Doses to these OARs not quality controlled

16. Radiation Techniques: Does it
matter??
Trial Treatment
Regimen
RT Technique Toxicities
Auperin Meta-
Analysis
Varied 3-DCRT in one
and 2DRT in
others
Esophagitis:
18%
Others: NR
RTOG 9410 63 Gray with
Cis/Vinblast
2DRT Esophagitis:
22%
RP: 4%
RTOG 0617 60 Gray with
concurrent
pacli/carbo
Approx 50%
IMRT
RP=7%
Esophagitis=7%

18. OARs Dose constraints
Spine Dmax <50 Gray
Lung-PTV V20<37%
Mean lung dose <20 Gray
Esophagus Dmean <34 Gy (Not absolute)
Heart 1/3rd <60 Gray
2/3rd <45 Gray
3/3rd < 40 Gray

20. Systematic analysis of
toxicity after radical
irradiation: pneumonitis
and esophagitis (STRIPE)

25. Inoperable NSCLC (IIIA-B)
Suitable for Conc. CTRT
Reassess:
Fear & non-doable approach
of physician?
Elderly patient?
Concerns of toxicities?
Technique of RT?
Dosimetric parameters?
No
Yes

26. Thank you