Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6&7 randomized controlled trialBackground
Although head and
neck cancer can be cured by
radiotherapy, the optimum treatment
time for locoregional control is
unclear. We aimed to find out
whether shortening of treatment time
by use of six instead of five
radiotherapy fractions per week
improves the tumour response in
squamous-cell carcinoma.
Methods
We did a
multicentre, controlled, randomised
trial. Between January, 1992, and
December, 1999, of
1485 patients treated with
primary radiotherapy alone, 1476
eligible patients were randomly
assigned
five (n=726) or six (n=750)
fractions per week at the same total
dose and fraction number (66—68 Gy
in 33—34 fractions to all tumour
sites except well-differentiated T1
glottic tumours, which were
treated with 62 Gy). All patients,
except those with glottic cancers,
also received the hypoxic
radiosensitiser nimorazole. Analysis
was by intention to treat.
Findings
More than 97% of
the patients received the planned
total dose. Median overall treatment
times were 39 days (sixfraction
group) and 46 days (five-fraction
group). Overall
5-year locoregional control rates
were 70% and 60% for the
six-fraction and five-fraction
groups, respectively
(p=0·0005). The whole benefit of
shortening of treatment time was
seen for
primary tumour control (76 vs 64%
for six and five fractions,
p=0·0001), but was non-significant
for neck-node control. Six compared
with five fractions per week
improved preservation of the voice
among patients with laryngeal cancer
(80 vs 68%, p=0·007).
Disease-specific survival improved
(73 vs 66% for six and five
fractions, p=0·01) but not
overall survival. Acute morbidity
was significantly more frequent with
six than with five fractions, but
was transient.
Interpretation
The shortening of
overall treatment time by increase
of the weekly number of fractions is
beneficial in patients with head and
neck cancer. The
six-fractions-weekly regimen has
become the standard treatment in
Denmark.
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Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysisBackground
Several trials
have studied the role of
unconventional fractionated
radiotherapy in head and neck
squamous cell carcinoma, but the
effect of such treatment on survival
is not clear. The aim of this
meta-analysis was to assess whether
this type of radiotherapy could
improve survival.
Methods
Randomised trials
comparing conventional radiotherapy
with hyperfractionated or
accelerated radiotherapy, or both,
in patients with non-metastatic
HNSCC were identified and updated
individual patient data were
obtained. Overall survival was the
main endpoint. Trials were grouped
in three pre-specified categories:
hyperfractionated, accelerated, and
accelerated with total dose
reduction.
Findings
15 trials with 6515 patients
were included. The median follow-up
was 6 years. Tumours sites were
mostly oropharynx and larynx; 5221
(74%) patients had stage III—IV
disease (International Union Against
Cancer, 1987).
There was a significant survival
benefit with altered fractionated
radiotherapy, corresponding to an
absolute benefit of 3·4% at 5 years
(hazard ratio 0·92, 95% CI
0·86—0·97; p=0·003).
The benefit was significantly higher
with hyperfractionated radiotherapy
(8% at 5 years) than with
accelerated radiotherapy (2% with
accelerated fractionation
without total dose reduction and
1·7% with total dose reduction at 5
years, p=0·02). There was a
benefit on locoregional control in
favor of altered fractionation
versus conventional radiotherapy
(6·4% at 5 years; p<0·0001),
which was particularly efficient in
reducing local failure, whereas the
benefit on nodal control was less
pronounced. The
benefit was significantly higher in
the youngest patients (hazard
ratio 0·78 [0·65—0·94] for under 50
year olds, 0·95 [0·83—1·09] for
51—60 year olds, 0·92 [0·81—1·06]
for 61—70 year olds, and 1·08
[0·89—1·30] for over 70 year olds;
test for trends p=0·007).
Interpretation
Altered
fractionated radiotherapy improves
survival in patients with head and
neck squamous cell carcinoma.
Comparison of the different types of
altered radiotherapy suggests that
hyperfractionation has the greatest
benefit.
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