Int. J. Radiation Oncology Biol. Phys., Vol. 52, No. 4, pp.

929 –936, 2002

Copyright © 2002 Elsevier Science Inc.
Printed in the USA. All rights reserved
0360-3016/02/$–see front matter

PII S0360-3016(01)02606-2

CLINICAL INVESTIGATION Head and Neck

EFFECT OF TREATMENT DELAY ON OUTCOME OF PATIENTS WITH

EARLY-STAGE HEAD-AND-NECK CARCINOMA RECEIVING
RADICAL RADIOTHERAPY

ANDRÉ FORTIN, M.D., M.SC.,* ISABELLE BAIRATI, M.D., PH.D.,† MICHELE ALBERT, M.D.,*
LYNNE MOORE, M.SC.,† JOSÉE ALLARD, B.A.,* AND CHRISTIAN COUTURE, M.D.‡
Departments of *Radiation Oncology and ‡Pathology, and †Laval University Cancer Research Center, L’Hôtel-Dieu de Québec,
Québec City, Québec, Canada

Purpose: Access to radiotherapy (RT) has been considerably reduced in Quebec since the late 1980s. The aim of
the present study was to analyze the impact of delaying treatment on the outcome of patients with early
head-and-neck squamous cell carcinomas.
Methods and Materials: This retrospective analysis examined the outcome for all 623 patients with early-stage
disease (T1-2, N0-1) who received radical RT between 1988 and 1997 at the Hotel Dieu of Quebec Hospital. Delay
was defined as the time from initial evaluation by a radiation oncologist to the beginning of RT. Delay intervals
were divided as follows: <30 days, 31– 40 days, and >40 days.
Results: A delay of >40 days was significantly associated with an increased risk of local and neck failure and
poorer survival relative to patients treated in <30 days or between 31 and 40 days. The adjusted hazard ratio
and (in parentheses) the 95% confidence interval was 2.6 (1.07– 6.4), 2.73 (1.38 –5.4), and 1.7 (1.1–2.6), respec-
tively, for local failure, neck failure, and survival. In the subgroup of patients with T2N0 disease, delaying RT
for >30 days was associated with a poor outcome, as measured by the same end points.
Conclusion: Delaying RT had a deleterious effect on these patients. RT should be started as soon as possible in
patients with squamous cell carcinoma of the head and neck, preferably within 20 –30 days after evaluation by
a radiation oncologist. © 2002 Elsevier Science Inc.

Radiotherapy, Postoperative radiotherapy, Delay.

INTRODUCTION per month of delay in patients receiving radical RT for carci-

noma of the tonsillar region.
During the past decade, access to radiotherapy (RT) has been
The Committee on Standards of the Canadian Associa-
considerably reduced in Canada, particularly in Québec City.
tion of Radiation Oncologists recommends that the interval
The effect of treatment delay on the ultimate outcome of
between an evaluation by a radiation oncologist and the
patients with head-and-neck cancers is unknown.
initiation of RT be no ⬎2 weeks (10). In a study done by
Several studies have evaluated the risk associated with
Mackillop and Zhou (11), the median waiting times before
delay in starting adjuvant RT, particularly for breast cancer.
the start of RT were 29 days in Canada and 10 days in the
Delaying RT in this setting is usually associated with in-
United States for carcinoma of the larynx. In Canada, an
creased local failure (1, 2).
acceptable delay for beginning RT after referral to the
Few studies have evaluated the risk of delaying RT for
radiation oncologist is considered to be 20 days, compared
head-and-neck carcinomas (3– 8). In the earliest known study,
with 10 days in United States.
Vikram et al. (8) showed that postoperative RT should be
The aim of the present study was to determine the effect
started ⬍6 weeks after surgery for maximal effectiveness.
of delay on the outcome of patients receiving radical RT as
However, they later showed that the risk associated with delay
the sole therapy for head-and-neck carcinoma.
disappeared when a dose of ⱖ60 Gy was delivered (6). Trotti
and Klotch (7) showed in a prospective analysis that to be most
effective, postoperative RT should not be delayed ⬎30 days. It METHODS AND MATERIALS
is unclear how delays affect the outcome of patients receiving
only radical RT for head-and-neck carcinoma (4, 5). The study group for this retrospective analysis comprised all
O’Sullivan et al. (9) observed a decrease in local control of 8% 1095 consecutive patients receiving radical RT for head-and-

Reprint requests to: André Fortin, M.D., Department of Radia- Acknowledgment—We acknowledge Guylaine Daigle for her tech-
tion Oncology de l’université Laval, L’Hôtel-Dieu de Québec, 11 nical assistance.
Côte du Palais, Québec City, Québec, G1R 2J6 Canada. Tel: (418) Received Oct 11, 1999, and in revised form May 14, 2001.
691-5264; Fax: (418) 691-5268; E-mail: afortin@videotron.ca Accepted for publication May 22, 2001.

929
930 I. J. Radiation Oncology ● Biology ● Physics Volume 52, Number 4, 2002

Table 1. Distribution of selected patient, tumor, and treatment characteristics according to delay

Delay (d)

Variable ⱕ30 31–40 ⬎40 p

Gender
Male 336 (81.0) 72 (82.8) 95 (78.5)
Female 79 (19.0) 15 (17.2) 26 (21.5) 0.73
Age (y)
⬍70 297 (71.6) 66 (75.9) 82 (67.8)
ⱖ70 118 (28.4) 21 (24.1) 39 (32.2) 0.44
Year of treatment
1988–1994 285 (68.9) 45 (51.7) 67 (55.4)
1995–1998 130 (31.3) 42 (48.3) 54 (44.6) 0.001*
T stage
T1 256 (61.7) 49 (56.3) 78 (64.5)
T2 159 (38.3) 38 (43.7) 43 (35.5) 0.49
N stage
N0 370 (89.2) 73 (83.9) 113 (93.4)
N1 45 (10.8) 14 (16.1) 8 (6.6) 0.09
Site
Glottis 230 (55.4) 40 (46.0) 55 (45.5)
Supraglottic region 77 (18.6) 22 (25.3) 19 (15.7)
Hypopharynx 9 (2.2) 2 (2.3) 1 (0.8)
Oropharynx 39 (9.4) 10 (11.5) 19 (15.7)
Oral cavity 54 (13.0) 13 (14.9) 27 (22.3)
Nasopharynx 6 (1.4) 0 0 0.06
Brachytherapy
No 402 (96.9) 80 (91.9) 103 (85.1) 0.001*
Yes 13 (3.1) 7 (8.1) 18 (14.9)
Neck dissection
No 410 (98.8) 82 (94.2) 118 (97.5) 0.02*
Yes 5 (1.2) 5 (5.8) 3 (2.5)
Dose rate (Gy/d)
⬍0.12 29 (7.0) 7 (8.1) 21 (17.3)
0.12–0.15 285 (68.7) 59 (67.8) 67 (55.4)
ⱖ0.16 101 (24.3) 21 (24.1) 33 (27.3) 0.007*

* Significant by chi-square or Fisher’s exact test.

Data presented as the number of patients, with the percentage in parentheses.

neck carcinoma between 1988 and 1997 at the Hotel Dieu of
Quebec Hospital. The present analysis focuses on the 623
patients with early-stage (T1-2 and N0-1) disease. No patients
were excluded, even if they received a palliative dose of
radiation, because it was of interest to determine, for instance,
whether the delay may have led to disease progression and
thereafter to the administration of palliative RT.
The following data were compiled: patient age and sex,
tumor stage (T and N), tumor histologic grade, anatomic site
of the tumor, patient smoking status at the time of evalua-
tion, and patient performance status. The treatment data
recorded were the photon energy, radiation dose, treatment
duration, and boost of brachytherapy.
Treatment
In our institution, patients with T1-T2 head-and-neck carci-
nomas are treated by surgery or receive radical RT. For larger
tumors (T3-T4), surgery is usually the first option; radical RT
is used when the morbidity associated with surgery is antici-
pated to be too high (e.g., glossectomy or soft palate resection).
Disease in the neck is managed according to the treatment of
the primary lesion. Patients receiving initial brachytherapy
usually undergo in the same procedure a neck dissection;
otherwise, neck dissection is reserved for salvage if external
beam RT fails. In radical RT, two large fields are used to
deliver 60 –70 Gy. Patients are immobilized using a plastic
mask and, before treatment, undergo dosimetry and simulation
during treatment planning.
Staging is performed at the time of examination by the
radiation oncologist. For our analysis, patients’ charts were
reviewed to verify the tumor stage at the beginning of the RT.
Statistical analysis
Definition of delay. Delay was defined as the time be-
tween first examination by the radiation oncologist and
beginning of external beam RT. We chose 30 days as the
“basic” delay time because it is the median delay in Canada.
Patients were grouped as follows: those treated within 30
days, those treated within 31– 40 days, and those treated
⬎40 days after initial examination by the radiation oncol-
ogist. In the Cox model (12), delay was incorporated suc-
cessively as a dummy variable.
 Effect of radiotherapy delay ● A. FORTIN et al. 931

Fig. 1. Local recurrence-free survival rate according to delay interval.

Statistics
Curves showing the incidence of local and neck tumor
failures were obtained according to the Kaplan–Meier
method (13). Statistical differences between curves were
calculated using the log–rank tests (12). The distribution of
selected characteristics according to delay was compared
using the chi-square test and Fisher’s exact test, when
necessary. The relationship between delay and the three end
points of interest (local tumor recurrence, neck tumor re-
currence, and patient death, regardless of cause) was eval-
uated using Cox proportional hazard models. For each end
point, follow-up was calculated as the time between the date
of diagnosis and the date of the event or the date of last
contact with the patient. Hazard ratios (HRs) and their 95%

Fig. 2. Neck recurrence-free survival rate according to delay interval.

932 I. J. Radiation Oncology ● Biology ● Physics
Fig. 3. Survival rate according to delay interval.
confidence intervals (95% CIs) were adjusted for several
variables (patient age, patient sex, date of treatment, T and
N stages, tumor site, presence/absence of brachytherapy,
presence/absence of neck dissection, and dose rate) to con-
trol for potential confounding. In 1 case, the proportional
hazards assumption of the Cox model was invalid because
the HR of local recurrence changed depending on whether
the data were obtained before or after 600 days of follow-
up. To account for this problem, we introduced an interac-
tion term between delay and follow-up time (before and
after 600 days) in the Cox proportional hazards model (13).
RESULTS
Delay
There are three kinds of treatment delay. First, there is the
delay from biopsy to referral for examination by a radiation
oncologist. In the present study, the median length of this
type of delay was 9 days and remained relatively constant
throughout the study period. Second, there is delay from the
time of referral to the time of the first examination by a
radiation oncologist. That time was also constant in the
present analysis at 8.5 days, except after 1995, when it
increased a little bit to 10 days. Finally, there is the delay
from the time of initial examination by the radiation oncol-
ogist to the initiation of RT. The median length of this delay
was ⬍14 days in 1989, and then slowly increased to a
maximum of 31 days in 1997.
The total median delay from biopsy to RT among our
patients was 28 days in 1989, 46 days in 1995, and 55 days
in 1997.
In the period from 1989 to 1997, 30% of patients were
Volume 52, Number 4, 2002
treated in ⬍10 days from initial examination by a radiation
oncologist, and 20% of patients were treated ⬎40 days after
evaluation. In 1993 and 1997, only 22% of the patients were
treated within 10 days, and up to 33% of them were treated
after 40 days.
Tumor growth between first evaluation by a radiation
oncologist and initiation of RT
Tumor staging was done during the patients’ initial ex-
amination by the radiation oncologist, but the patients’
charts were reviewed to determine whether the tumor had
progressed by the beginning of treatment. If the treating
radiation oncologist stated that disease had progressed or
was stable, that determination was noted. Otherwise, tumor
progression status was recorded as unknown.
We found 42 patients for which tumor progression was
clearly noted by the treating radiation oncologist. Progres-
sion was observed in 14 patients with T1 disease, 14 with
T2 disease, 15 with N0 disease, and 5 with N1 disease. Nine
patients showed progression in both the T and N stage and
one progression that remained in the same stage. For 219
patients, disease stability was noted. It was not possible to
determine whether the disease had progressed in 362 pa-
tients.
The median time from the initial evaluation by a radiation
oncologist to treatment was 33 days for patients with pro-
gressive disease, 20 days for patients with stable disease,
and 20 days for patients of unknown disease status (p ⬍
0.00001, analysis of variance).
The 3-year locoregional control rate was 80%, 75%, and
40%, respectively, for patients with unknown, stable, and
progressive disease ( p ⫽ 0.00001). For N0 patients with-
 Effect of radiotherapy delay ● A. FORTIN et al. 933

Table 2. Hazard ratios and their 95% confidence intervals describing the association between prognostic variables and
local recurrence

Adjusted
Variable Crude HR 95% CI HR* 95% CI

Follow-up ⬍600 d
ⱕ30 d delay 1.00 — 1.00 —
30–40 d delay 1.16 0.67–2.01 1.18 0.67–2.07
⬎40 d delay 1.03 0.62–1.71 1.06 0.61–1.85
Follow-up ⱖ600 d
ⱕ30 d delay 1.00 — 1.00 —
30–40 d delay 0.75 0.17–3.25 0.77 0.18–3.36
⬎40 d delay 2.77 1.19–6.44 2.60 1.07–6.31
Gender
Male 1.00 — 1.00 —
Female 0.65 0.40–1.08 0.64 0.39–1.07
Age (y)
⬍70 1.00 — 1.00 —
ⱖ70 0.84 0.56–1.27 0.91 0.59–1.38
Year of treatment
ⱕ1994 1.00 — 1.00 —
⬎1994 0.54 0.35–0.84 0.60 0.37–0.97
T stage
T1 1.00 — 1.00 —
T2 2.40 1.69–3.40 1.97 1.31–2.96
N stage
N0 1.00 — 1.00 —
N1 2.18 1.39–3.43 1.54 0.92–2.56
Site
Glottis 1.00 — 1.00 —
Supraglottic region 1.56 0.97–2.51 1.09 0.64–1.85
Hypopharynx/nasopharynx 2.89 1.24–6.75 1.98 0.81–4.83
Oropharynx/oral cavity 2.12 1.42–3.16 1.12 0.67–1.89
Brachytherapy
No 1.00 — 1.00 —
Yes 2.74 1.67–4.52 1.26 0.63–2.54
Neck dissection
No 1.00 — 1.00 —
Yes 2.62 1.15–5.94 1.19 0.47–2.99
Dose rate (Gy/d)
⬍0.12 1.00 — 1.00 —
0.12–0.15 0.48 0.30–0.75 0.77 0.44–1.37
ⱖ0.16 0.22 0.11–0.43 0.57 0.25–1.29

* Adjusted models include all variables in Table 2.

Abbreviations: HR ⫽ hazard ratio; CI ⫽ confidence interval.

out disease progression, the 3-year neck disease control rate
was 92%. For patients who had progressed to N1 stage
disease, the neck control rate was only 48% ( p ⬍0.00).
Effect of delay
The following sections relate our findings on the effect of
delay between the time of the initial evaluation by a radia-
tion oncologist and the beginning of external beam RT. The
distribution of selected patient, tumor, and treatment char-
acteristics according to the delay is shown in Table 1. The
median delay was 21 days (lower quartile ⱕ7, upper quar-
tile ⱖ35). The median delay time was 19 days, 22 days, and
22.5 days for patients with T1N0, T2N0, and T1-2N1 dis-
ease, respectively. The median delay for laryngeal cancers
was 18 days; it was 21 days for tumors at other sites.
Univariate analysis. Delay significantly affected the rates
of local control (Fig. 1), neck control (Fig. 2), and survival
(Fig. 3).
Figure 1 shows that delay had no effect on local control
until 600 days of follow-up. However, after 600 days of
follow-up, it becomes apparent that patients treated ⬎40
days after evaluation had a lower local control rate than
patients in the other two delay-time groups.
Figure 2 shows that delay was significantly associated with
neck failure. The 3-year rate for neck-disease control was 91%,
89%, and 79% for patients treated ⱕ30, 31– 40, and ⬎40 days
after initial evaluation, respectively (p ⫽ 0.02).
Absolute survival was also significantly associated with
delay (Fig. 3). The 3-year survival rate decreased by 15%
for patients treated ⬎40 days after evaluation compared
with the other patients.
Cox multivariate analysis. HRs describing the association
934 I. J. Radiation Oncology ● Biology ● Physics Volume 52, Number 4, 2002

Table 3. Hazard ratios and 95% confidence intervals describing the association between prognostic variables and neck recurrence

Variable Crude HR 95% CI Adjusted HR* 95% CI

Delay (d)
ⱕ30 1.00 — 1.00 —
31–40 1.25 0.55–2.87 1.26 0.54–2.95
⬎40 2.38 1.29–4.42 2.73 1.38–5.42
Gender
Male 1.00 — 1.00 —
Female 0.86 0.42–1.78 0.58 0.27–1.21
Age (y)
⬍70 1.00 — 1.00 —
ⱖ70 1.04 0.56–1.92 0.94 0.49–1.79
Year of treatment
ⱕ1994 1.00 — 1.00 —
⬎1994 0.92 0.49–1.72 0.71 0.37–1.38
T stage
T1 1.00 — 1.00 —
T2 3.72 2.06–6.73 2.02 1.04–3.93
N stage
N0 1.00 — 1.00 —
N1 3.46 1.87–6.40 2.10 1.07–4.12
Site
Glottis 1.00 — 1.00 —
Supraglottic region 6.97 2.70–17.97 5.30 1.86–15.14
Hypopharynx/nasopharynx 10.66 2.67–42.66 8.62 1.98–37.44
Oropharynx/oral cavity 9.11 3.76–22.05 7.04 2.58–19.25
Brachytherapy
No 1.00 — 1.00 —
Yes 1.70 0.68–4.27 0.41 0.13–1.29
Neck dissection
No 1.00 — 1.00 —
Yes 0.88 0.12–6.39 0.38 0.05–2.92
Dose rate (Gy/d)
⬍0.12 1.00 — 1.00 —
0.12–0.15 0.43 0.21–0.86 0.69 0.30–1.61
ⱖ0.16 0.35 0.14–0.88 1.27 0.42–3.82

* Adjusted models include all variables in Table 3.

Abbreviations as in Table 2.

between prognostic variables and local control, neck con-
trol, and survival are shown in Tables 2– 4, respectively.
The variables usually associated with outcome were in-
cluded in the Cox model. A variable describing the total
dose of radiation and the treatment duration was introduced
as the dose rate (in grays per day). Because a new radiation
oncologist arrived in 1994, the variable year of treatment
was also introduced in the Cox model (ⱕ1994 or ⬎1994).
Results from the Cox model for local control are shown
in Table 2. Local control was not influenced by delay until
600 days of follow-up. After 600 days, the HR of local
failure was 2.6 for patients treated ⬎40 days after evalua-
tion relative to patients treated within 30 days. Treating
between 31 and 40 days was not associated with more
failure than treatment in ⱕ30 days.
Control of neck disease was also independently associ-
ated with delay (Table 3). The HR of neck failure was 2.7
and 1.26 when patients were treated ⬎40 days and 31– 40
days, respectively, after initial evaluation by a radiation
oncologist, relative to patients treated in ⱕ30 days.
Survival was also independently associated with delay
(Table 4), but only when comparing patients treated ⬎40
days with patients treated ⱕ30 days after consultation.
It should be noted in Tables 2– 4 that the crude and adjusted
HRs associated with delay are very similar, indicating that the
effect of delay is not dependent on confounding factors.
Subgroup analysis. The subgroup of patients that
seemed to be most influenced by delay was the group of
191 patients with Stage T2N0 carcinoma. In this group,
the 3-year locoregional control rate was 70%, 57%, and
44%, respectively, for patients treated within 30 days,
between 31 and 40 days, and ⬎40 days after initial
evaluation by a radiation oncologist ( p ⫽ 0.03) (Fig. 4).
The adjusted HR was 1.95 (95% CI 1.1–3.4) for patients
treated between 31 and 40 days relative to patients
treated within 30 days.
DISCUSSION
In Quebec City, delay to the start of RT began to rise at
the end of the 1980s because of an increase in the number
of patients. When our institution changed its cobalt ma-
 Effect of radiotherapy delay ● A. FORTIN et al. 935

Table 4. Hazard ratios and 95% confidence intervals describing trol rates decreased significantly when treatment was started
the association between prognostic variables and mortality ⬎30 days after evaluation.
Crude Adjusted Disease progression between the first evaluation by a
Variable HR 95% CI HR* 95% CI radiation oncologist and treatment was noted in the charts of
42 patients. We found that progression correlated highly
Delay (d) with waiting time and with poor outcome. It is possible that
ⱕ30 1.00 — 1.00 —
31–40 1.14 0.70–1.88 1.08 0.65–1.79
patients who had disease progression also had aggressive
⬎40 1.72 1.15–2.26 1.70 1.10–2.63 disease, which would have been difficult to cure whatever
Gender the delay. It is also possible that ⬎42 patients had disease
Male 1.00 — 1.00 — progression, because subtle growth would likely not have
Female 0.77 0.50–1.20 0.65 0.41–1.02 been noticed. A mass that enlarges from 2 cm to 2.5 cm in
Age (y)
⬍70 1.00 — 1.00 —
diameter is likely to be considered stable; however, this
ⱖ70 1.40 0.99–1.98 1.46 1.02–2.09 increase of only 25% in diameter translates into a 100%
Year of treatment increase in volume.
ⱕ1994 1.00 — 1.00 — We also analyzed the cohort of 472 patients with more
⬎1994 0.92 0.60–1.39 0.89 0.57–1.40 advanced stage (T3-T4 or N2-N3) disease who received
T stage
T1 1.00 — 1.00 —
radical RT during the same period (1989 –1997). In this
T2 1.69 1.22–2.34 1.16 0.80–1.69 group of patients, delay seems to have had no effect.
N stage However, patients whose tumors are already in an ad-
N0 1.00 — 1.00 — vanced stage have ⬍40% probability of locoregional
N1 2.05 1.35–3.11 1.66 1.04–2.65 control. The rate of survival for a patient with a Stage T4
Site
Glottis 1.00 — 1.00 —
cancer was just a little bit lower than that for a patient
Supraglottic with a Stage T3 lesion (5-year survival rate of 33% for T3
region 2.69 1.77–4.07 2.41 1.51–3.85 disease relative to 29% for T4 lesion). The same was
Hypopharynx/ observed when comparing survival rates of patients with
nasopharynx 2.35 0.93–5.93 2.05 0.79–5.36 N2 and N3 disease. On the contrary, control of neck
Oropharynx/
oral cavity 2.36 1.58–3.51 1.82 1.12–2.97
disease was very much affected if the tumor passed from
Brachytherapy N0 to N1. In our series, the neck failure rate increased
No 1.00 — 1.00 — from 10% for patients with N0 disease to 25% for those
Yes 1.56 0.88–2.76 0.84 0.40–1.76 with N1 disease, an increase of 150%. Moreover, in this
Neck dissection group of patients, the radiation oncologist introduced a
No 1.00 — 1.00 — bias by treating patients with more advanced disease
Yes 1.59 0.65–3.88 1.01 0.39–2.66
Dose rate (Gy/d)
more quickly. We found that patients with T4 and N3
⬍0.12 1.00 — 1.00 — cancer were treated faster than others.
0.12–0.15 0.68 0.42–1.10 0.88 0.49–1.56 This study was not a randomized study, and therefore,
ⱖ0.16 0.41 0.21–0.80 0.70 0.32–1.55 some imbalance occurred between groups for some prog-
nostic factors. However, a retrospective study is the only
* Adjusted models include all variables in Table 4.
Abbreviations as in Table 2. method to evaluate the risk associated with treatment delay.
The Cox model showed that even when correcting for
disease stage and tumor site, longer delay remained a sig-
chines for linear accelerator units in 1992 and 1993, the nificant predictor of failure.
It is not possible from our study to establish a clear-cut
delay increased dramatically during the transition period.
maximal value for the beginning of RT (i.e., a time before
After a short improvement in 1994 and 1995, the delay
which radical RT would not affect outcome). In our series of
increased again, peaking in 1997 and 1998. Increased num-
patients with early-stage carcinoma of the head and neck,
bers of patients (who used staff and equipment for breast
waiting ⬎40 days was associated with a decrease in sur-
and prostate cancer screening), insufficient equipment and vival. In a more homogeneous group of patients with T2N0
staff (doctors, physicists, and technologists), and increased cancer, the cutoff value seemed to be 30 days. For neck
demand for more complex technology all contributed to the recurrence, the HR increased from 1.26 to 2.7 when patients
rise in delay. In this study, we report the consequence of this were treated at 31– 40 and ⬎40 days, respectively, relative
rise in delay on the cohort of patients treated for head-and- to those treated in ⱕ30 days. It is therefore possible that
neck carcinoma during this period. waiting ⬎30 days after the initial evaluation and staging by
In the cohort of patients with early-stage (T1-2, N0-1) a radiation oncologist is harmful to the patient.
disease, control of local and neck cancer was compromised Is it possible to extrapolate these data to the delay between
if treatment was started ⬎40 days after the initial evaluation diagnosis and the initiation of RT? Is a total delay of ⬎30 – 40
by a radiation oncologist. In a more homogeneous group of days deleterious for the patient? We cannot answer this ques-
patients with Stage T2N0 carcinoma, the locoregional con- tion using our data, because the tumor stage at the time of
936 I. J. Radiation Oncology ● Biology ● Physics
Fig. 4. Local recurrence-free survival rate among patients with T2N0 disease according to delay interval.
biopsy was often unknown. However, Allison et al. (13) con-
cluded that professional delays of ⬎1 month increase the
likelihood for late-stage disease at diagnosis. It is therefore
reasonable to assume that a total delay of ⬍40 days would
obtain the optimal results from RT. In our series, the median
delay between biopsy and the initial evaluation by a radiation
oncologist was 19 days; therefore, for the patient to experience
a total delay of ⬍40 days, RT would have to start no more than
20 days after that evaluation.
Few authors have studied the effect of treatment delay.
However, Barton et al. (4) did not find any effects from a
delay in the treatment of early-stage laryngeal carcinomas.
REFERENCES
1. Richards MA, Westcombe AM, Love SB, et al. Influence of
delay on survival in patients with breast cancer: A systematic
review. Lancet 1999;353:1129 –1126.
2. Robinson E, Mohilever J. Factors affecting delay in diagnosis
of breast cancer: Relationship of delay to stage of disease. Isr
J Med Sci 1986;22:333–338.
3. Allison P, Franco E, Black M, et al. The role of professional
diagnostic delays in the prognosis of upper aerodigestive tract
carcinoma. Oral Oncol 1998;34:147–153.
4. Barton MB, Morgan G, Smee R, et al. Does waiting time
affect the outcome of larynx cancer treated by radiotherapy?
Radiother Oncol 1997;44:137–141.
5. Lee AW, Chan DK. T1 nasopharyngeal carcinoma: The effect
of waiting time on tumor control. Int J Radiat Oncol Biol Phys
1994;30:1111–1117.
6. Schiff PB, Harrison LB, Strong EW, et al. Impact of the time
interval between surgery and postoperative radiation therapy
on locoregional control in advanced head and neck cancer.
J Surg Oncol 1990;43:203–208.
Volume 52, Number 4, 2002
However, only 10% of their patients started their treatment
⬎30 days, compared with 32% of the patients in our series.
Lee and Chan (5), who studied patients with nasopharyn-
geal carcinomas, found that the rate of local failure was not
affected by the length of delay, but that the rate of neck
failure increased with the delay time.
In conclusion, our study shows that delaying RT is del-
eterious for patients with early-stage head-and-neck carci-
nomas. It is, however, difficult to determine a cutoff value
for the beginning of RT after initial examination by a
radiation oncologist. Given the evidence, we believe that
this period should not exceed ⬎20 –30 days.
7. Trotti A, Klotch D. Postoperative accelerated radiotherapy in
high-risk squamous cell carcinoma of the head and neck: Long-
term results of a prospective trial. Head Neck 1998;20:119 –130.
8. Vikram B, Strong EW, Shah J, et al. Elective postoperative
radiation therapy in stages III and IV epidermoid carcinoma of
the head and neck. Am J Surg 1980;140:580 –584.
9. O’Sullivan B, Mackillop W, Grice B, et al. The influence of
delay in the initiation of definitive radiotherapy in carcinoma
of the tonsillar region. Int J Radiat Oncol Biol Phys 1998;
42(Suppl):323 (abstract).
10. Mackillop WJ, Fu H, Quirt CF, et al. Waiting for radiotherapy
in Ontario. Int J Radiat Oncol Biol Phys 1994;30:221–228.
11. Mackillop WJ, Zhou Y. A comparison of delays in the treat-
ment of cancer with radiation in Canada and the United States.
Int J Radiat Oncol Biol Phys 1995;32:531–539.
12. Hill C, Com-Nougué C, Kramar A. Analyse statistique des
données de survie. Paris: Flammarion; 1990.
13. Therneau TM, Grambsch PM. Modeling survival data: Ex-
tending the Cox model. New York: Springer-Verlag; 2000.