EDITORIAL
ELECTIVE NODAL IRRADIATION (ENI) DOESN’T APPEAR TO PROVIDE
A CLEAR BENEFIT FOR PATIENTS WITH UNRESECTABLE
NON–SMALL-CELL LUNG CANCER (NSCLC)
S
TEVEN
E. S
CHILD
, M.D.
Department of Radiation Oncology, Mayo Clinic Arizona, Scottsdale, AZ
Elective nodal irradiation (ENI) is the irradiation of clinically
uninvolved lymph node to account for microscopic tumor in-
vasion of these lymph nodes. Dr. Belderbos et al., under the
auspices of the International Atomic Energy Agency, have
compiled a very thorough summary of the literature regard-
ing ENI for non–small-cell lung cancer (NSCLC). Their ma-
jor conclusion was, ‘‘The clinical value of ENI is uncertain.’’
However, it is my opinion that the evidence suggests that pur-
poseful elective nodal irradiation is unlikely to improve pa-
tient outcomes and can increase toxicity. Thus suggesting
that ENI is not beneficial. Additionally, the purposeful inclu-
sion of ENI may hinder progress in treating NSCLC because
it is likely to make the safe escalation of RT dose more chal-
lenging. This discussion will focus primarily on Stage III
NSCLC because that is situation with which radiation oncol-
ogists are most often faced.
The argument against the use of ENI may be summarized
as follows. First, failure is uncommon in nodal regions that
are neither clinically involved nor specifically targeted. Bel-
derbos et al. published the result of a trial that is an excel-
lent example. This study included both positron emission
tomography and computed tomography scanning, which is
consistent with modern state-of-the-art, noninvasive staging.
This radiation therapy (RT) dose-escalation trial prospec-
tively evaluated the incidence of isolated nodal failure
with omission of the ENI (1). Only the metabolic active
lymph nodes were included in the gross target volume. Pos-
itron emission tomography scans were obtained shortly be-
fore the RT in treatment position. Two (3%) of the 67
positron emission tomography–staged patients developed
isolated nodal failures. These results are quite similar to
other published reports (2, 3).
Second, it appears that a dose greater than the conventional
60–70 Gy is required to cure a larger fraction of NSCLC pa-
tients. Le Chevalier et al. reported the results of a randomized
study that compared RT alone to combined RT plus chemo-
therapy (vindesine, cyclophosphamide, cisplatin, and lomus-
tine) in 353 patients with unresectable NSCLC. RT included
the delivery of 65 Gy to both groups (4). The 2-year survival
rate was 14% for patients receiving RT vs. 21% for patients
receiving the combined treatment (p = 0.02). Rebiopsy deter-
mined local control at 1 year was poor in both groups (17%
and 15%, respectively). These local control numbers appear
low compared with those reported in studies that used radio-
graphically determined local control (5–7). However, the
data from Le Chevalier et al. were based on pathologic fac-
tors and may be more accurate than x-ray studies.
Several years ago, in a classic article regarding RT dose
response, Fletcher and Shukovsky wrote that it would re-
quire 80–90 Gy, conventionally fractionated, to locally con-
trol 56% of adenocarcinomas of the breast greater than 5 cm
in diameter (8). There is no reason to believe NSCLCs
would respond differently as they are often at least this large
and most commonly adenocarcinomas. Mehta et al. per-
formed a more recent analysis of dose–response data and
came up with a similar conclusion, ‘‘Standard approaches
to dose escalation using 2 Gy per fraction, five fractions
per week, require doses in excess of 85 Gy to achieve
50% long-term control rate’’ (9). Patient survival appears
to depend on both the dose of RT and the use of systemic
chemotherapy. Multiple Phase III trials have shown that
the addition of chemotherapy to RT significantly enhances
survival especially when administered concurrently (5, 6).
It appears that both a combination of systemic therapy and
greater than standard doses of RT will likely be needed to
further enhance patient survival. However, even standard
dose RT with ENI plus concurrent platinum-based chemo-
therapy is relatively toxic therapy associated with severe
(Grade 3 or greater) adverse events in most patients and fatal
complications in about 2% (7). Thus one might hesitate to
Reprint requests to: Steven E. Schild, M.D., Department of Radi-
ation Oncology, Mayo Clinic Arizona, 13400 E. Shea Blvd., Scotts-
dale, AZ 85259. Tel: (480) 301-8000; Fax: (480) 301-7687; E-mail:
sschild@mayo.edu
Conflict of Interest: None.
Received April 7, 2008. Accepted for publication June 6, 2008.
311
Int. J. Radiation Oncology Biol. Phys., Vol. 72, No. 2, pp. 311–312, 2008
Copyright Ó 2008 Elsevier Inc.
Printed in the USA. All rights reserved
0360-3016/08/$–see front matter
doi:10.1016/j.ijrobp.2008.06.1485