1) Concurrent chemotherapy and radiation therapy (CTRT) improves survival rates compared to sequential CTRT or radiation therapy alone for inoperable stage III non-small cell lung cancer (NSCLC) based on evidence from randomized clinical trials. 2) However, concurrent CTRT is also associated with higher treatment-related toxicities like esophagitis and radiation pneumonitis. 3) Whether a patient receives concurrent or sequential CTRT depends on an assessment of their suitability in terms of age, performance status, medical comorbidities, and concerns about enhanced toxicity risks from the concurrent approach. Radiation technique and dosimetric parameters also impact toxicity risks.

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