Full text of DOI:10.1053/clon.2001.9254

Clinical Oncology (2001)13:202–203
The Royal College of Radiologists
Clinical Oncology
#
Editorial
Palliative Radiotherapy for Lung Cancer: Is it Enough?
C. Rees and M. E. R. O’Brien
Royal Marsden Hospital NHS Trust, Sutton, UK
Lung cancer is now the leading cause of cancer deaths
in both men and women in the UK. Non-small cell
lung cancer (NSCLC) accounts for approximately
As discussed in the Quddus et al.’s article in this
Journal [2], two Medical Research Council studies
have been carried out in this field. A small survival
advantage (median 2 months, 5% at 1 year and 3% at
2 years) has been shown for more intensive radio-
therapy (39 Gy in 13 fractions, 5 days per week
compared with 17 Gy in two fractions 1 week apart)
for patients with inoperable NSCLC that is too
advanced for potentially curative radiotherapy and
who have good performance status (World Health
Organization (WHO) 0–2). Patients in the more
intensive arm experienced more toxicity and less
rapid palliation of symptoms. Previously, a single
dose of radiotherapy has been shown effectively to
palliate patients with a poor performance status
(WHO 3–4) with no impact on survival.
8
0% of all primary lung cancers and approximately
two-thirds of patients present with inoperable,
advanced disease. The 5-year survival for patients
with Stage IIIb disease is approximately 5%; it is 1%
for Stage IV patients. Survival rates in the UK are
lower than in Europe [1]. This has been attributed to
the inadequate provision of appropriate cancer
treatment and a lack of appropriately trained cancer
specialists.
The article in this issue by Quddus et al. is a
retrospective study of treatment of patients with
NSCLC who received radiotherapy of ten fractions
or fewer and survived for 5 years or more. The
surviving patients (61/4531 i.e. 1.3%) were hetero-
geneous with respect to the initial stage, with 46%
staged as I or II; 29% of the total surviving had no
histological diagnosis but were assumed to have
NSCLC. The survival of 1.3% of the initial cohort at 5
years may have been expected without radiotherapy,
although there was evidence of a maintained
radiological response in 55%. Long-term survival
was more frequent in patients receiving ten-fraction
regimens on univariate analysis, but we do not know
if this was independent of performance status or stage.
Prognostic factors have been identified that affect
the response to radiotherapy and chemotherapy, and
also survival, with stage being the most important
prognostic factor [3]. Other factors affecting response
include performance status, metastatic disease in liver
and bone; and the use of combination chemotherapy
In the last decade there has been increasing interest
in the use of multimodality therapy, although, despite
increasing evidence for the role of chemotherapy in
the palliation of lung cancer, there still remains
resistance to its use. The palliative use of chemo-
therapy is no longer controversial in the United States
(ASCO guidelines 1997 [9]). A meta-analysis of 52
randomized trials of chemotherapy in NSCLC
demonstrated a survival advantage tor cisplatin-
based chemotherapy (hazard ratio 0.73; 27% reduc-
tion in risk of death and 10% improvement in survival
at 1 year) compared with best supportive care in
advanced disease. The addition of chemotherapy to
radical radiotherapy for locally advanced disease gave
a hazard ratio of 0.87 (13% reduction in the risk of
death, absolute benefit of 4% at 2 years) [10,11].
Chemotherapy can palliate symptoms in advanced
disease, with symptomatic relief seen after one or two
courses [12], and a total of three courses of triple
therapy has been shown to be as effective as a
prolonged treatment course [13]. Newer cytotoxic
agents such as navelbine, gemcitabine, docetaxel and
paclitaxel have all been evaluated as single agents
compared with chemotherapy and have been shown to
palliate symptoms, maintain or improve quality of
life, and have a positive effect on survival [14–17].
The current literature would support the role of
cisplatin-based chemotherapy for good performance
[
4,5]. Poor performance status, pretreatment weight
loss, comorbidity and raised serum lactate dehydro-
genase levels have been associated with poor survival
[
6]. Age and histological subtype have not been
shown to correlate with response and survival. Poor
performance status has been associated with an
increased risk of toxicity with chemotherapy and
with early death [7,8].
Correspondence and offprint requests to: M. E. R. O’Brien, Lung
Unit, Royal Marsden Hospital NHS Trust, Downs Road, Sutton,
Surrey SM2 5PT, UK. E-mail; maryo@icr.ac.uk

6
. AIbain KS, Crowley JJ, LeBlanc M, et al. Survival
determinants in extensive-stage non-small-cell lung
cancer: the South West Oncology Group experience. J
Clin Oncol 1991;9:1618–26.
status, informed patients with inoperable lung cancer
some Stage IIIa, Stage IIIb and Stage IV). With this
evidence, it is now necessary to determine the best
multimodality palliation’ with the most effective and
best tolerated combination of cytotoxic drugs, the
optimum dose of radiotherapy, and have to select
those patients with advanced lung cancer who will
benefit. The choice of which palliative option to use
should not be an ‘either/or’; it should be a decision on
appropriateness and a relative order of palliative
options. We still do not know the role of high-dose
palliative radiotherapy with chemotherapy compared
with either option alone.
Future advances in the treatment of advanced lung
cancer may lie in the development of novel
approaches, such as drugs that may suppress tumour
angiogenesis, gene therapy and immunotherapy.
Renewed interest in screening may also enable
patients to be diagnosed at an earlier stage and
continued emphasis should be placed on the dangers
of smoking. It is to be hoped that the future will see
reports on large series of patients treated with
palliative chemotherapy with and without radio-
therapy, so that we can speculate once again on
what contributes to ‘cure’.
(
‘
7. Ruckdeschel JC, Finkelstein DM, Ettinger DS, et al. A
randomized trial of the four most active regimens for
metastatic non-small-cell lung cancer. J Clin Oncol
1
986;4:14–22.
8
9
. Dark G, O’Brien MER. The effective management of lung
cancer. In: Muers M, editor. UK Key Advances Clinical
Series 2001. Aesculapuis Medical Press, UK
. American Society of Clinical Oncology. Clinical practice
guidelines for the treatment of unresectable non-small-cell
lung cancer. J Clin Oncol 1997;15:2996–3018.
10. NSCLC Collaborative Group. Chemotherapy in non-small
cell lung cancer: a meta-analysis using updated data on
individual patients from 52 randomised clinical trials.
Non-small Cell Lung Cancer Collaborative Group. BMJ
1
995;311:899–909.
11. Souquet PJ, Chauvin F, Boissel JP, et al. Polychemother-
apy in advanced non small cell lung cancer: a meta-
analysis. Lancet 1993;3432:19–21.
1
2. Ellis PA, Smith IE, Hardy JR, et al. Symptom relief with
MVP (mitomycin C, vinblastine and cisplatin) chemother-
apy in advanced non-small-cell lung cancer. Br J Cancer
1995;71:366–70.
1
3. Smith IE, O’Brien MER, Norton A, et al. Duration of
chemotherapy for advanced non-small cell lung cancer
(
NSCLC): A Phase III randomised trial of 3 versus 6
courses of mitomycin C, vinblastine, cisplatin (MVP). J
Clin Oncol. In press.
1
1
1
4. Gridelli C, Perrone F, Gallo C, et al. Effects of vinorelbine
on quality of life and survival of elderly patients with
advanced non-small cell lung cancer. The Elderly Lung
Cancer Vinorelbine Italian Study Group. J Natl Cancer
Inst 1999;98:66–72.
5. Anderson H, Hopwood P, Stephens RJ, et al. Gemcitabine
plus best supportive care (BSC) versus BSC in inoperable
non-small cell lung cancer: a randomised trial with quality
of life as the primary outcome. Br J Cancer 2000;83:447–
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