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IS SEVERE CONFLUENT MUCOSITIS PRECISELY
QUANTIFIED AS A DOSE-LIMITING FACTOR IN ALTERED
RADIOTHERAPY FOR HEAD NECK CANCER?
Boguslaw Maciejewski, MD, PhD, Andrzej Wygoda,
MD, PhD, Krzysztof Skladowski, MD, PhD
Cancer Center M. Sklodowska-Curie Memorial
Institute Gliwice, Poland
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The use of various
scoring systems, different interpretation of the
term confluent mucositis and therefore, center
to center and observer to observer differences in
scoring of morphological and functional effects
make quantification and comparision of
acute toxicity of various fractionated regimens
difficult and uncertain. The aim of this study
is to evaluate acute mucosal reactions (AMR)
caused by conventional and accelerated
irradiation using modified Dische scoring system
and to analyse differences in the
incidence and severity of the AMR depending on
frequency and regularity of scoring.
OBJECTIVES
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MATERIAL METHODS
Material 66 cases of sq. c.c. of oral cavity,
oro- or hypopharynx and supraglottic larynx,
being a part of the CAIR-1 and CAIR-2 trials.
Average age of 57 yrs (39-73 yrs). PFS-ZUBROD
0-1. Radiotherapy used as a primary treatment
two groups CF (conventional) and AF
(accelerated) each group consists of 33 cases
randomly enrolled. CF 70-72 Gy in 1,8-2,0 Gy
fractions in 50-55 days (5 fx/7 days) Acc.
Dose/week ? AD 9-10 Gy AF 70-72 Gy in 1,8 Gy
fractions in 40 days (7 fx/7 days) AMR scoring
DISCHE system which places emphasis on both
morphological and functional items. Each item
was scored between 0 and 3 or 4 by 2 independent
observers. Average scores were added up and the
sum was taken as a measure of both objective and
functional acute effects. The maximum score was
24. Scoring always started one day prior RT (as a
reference score) and continued regularly
everyday, always at the same hour, till complete
healing of the AMR. Everyday regular scores (a)
were used to simulate (b) trice-a-week regular
scoring (Mon-Wed-Fri) (c) once-a-week regular
scoring (Fri) (d) once-a-week irregular scoring
(any day) Supportive treatment 56 of 66 cases
26 in the CF (79) and 30 in the AF (91)
received steroid and non steroid
anti-inflammatory drugs, analgetics, antibiotics,
parenteral nutrition. None required narcotics or
tube feeding.
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RESULTS
Confluent mucositis (CM) was noted on average in
78 (26 pts) in the CF and in 85 (28 pts) in
the AF. However, the course of acute radiation
mucositis is characterized even by an average
severity-time curves for CF and AF regimens (Fig.
1) by wave-like pattern rather than by continuous
tri-phasic pattern (onset-lasting-healing). Figur
e 2 shows individual patterns of CM in the
analyzed groups. Classic tri-phasic pattern of
the CM (onset-duration-healing)was noted in 18
cases (55) in the CF and in 22 cases (67) in
the AF, however in 67 of the CF cases (12/18)
and in 27 of the AF (6/22) duration of CM was
unexpectedly short (few days) and occured in
various periods of the course of irradiation. In
some cases the CM decreased to spotted mucositis
to reach the level of CM once again after few
days break, and so on. This wave-like pattern
of the AMR was observed in 8 cases (24) in the
CF and in 6 cases (18) in the group.
Individual example is shown in Figure 3. It is
interesting that in 7 cases (22) in the CF and
in 5 cases (15) in the AF acute mucosal
reactions never transgressed the level of spotted
mucositis.
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Figure 1. Average severity-time curves for CF and
AF group.
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CONVENTIONAL RT
ACCELERATED RT
- the end of RT
Figure 2. Individual patterns of confluent
mucositis in CF and AF groups.
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Fig. 3. Individual severity-time curve
These are examples of individual severity-time
curve drawn using regular everyday scores and it
illustrates wave-like pattern. Using irregular
once-a-week scores confluent mucositis (CM) is
missed giving false negative result.
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INCIDENCE OF CM
WEEKS
- once a week irregular
- 3 times a week
- once a week regular
- everyday
Figure 4. Incidence of confluent mucositis (CM)
depending on frequency and regularity of scoring.
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Histograms on Figure 4 illustrate the rates of CM
in consecutive weeks of
irradiation depending on frequency
and regularity of scoring. There is clear
underestimation of the exact rate
of CM for once-a-week regular or irregular
scoring compared with everyday or trice-a-week
scoring. Table 1 shows significant average
underestimation of the CM in both
CF and AF group when instead of
everyday or at least trice-a-day scoring was used
once-a-day regularly or irregularly about
10-40 of the CM events can easily
be missed.
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Table 1.
SCORING FREQUENCY
HIGHEST INCIDENCE OF CM DURING THE COURSE OF
IRRADIATION CF AF
(a) EVERYDAY (b) TRICE-A-WEEK (c) ONCE-A-WEEK
REGULAR (d) ONCE-A-WEEK IRREGULAR
78 69 39 36
85 80 74 72
(d) vs. (a) ? -42
-13 p0,001
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PERACCHIA
HARARI
NGUYEN
100 50 0
CAIR 2.0
TROG
UNTOLERABLE HIGH RISK CLE
SCH-I
DELANEY
KAANDERS
LAMB
AF
CHA-CHA
VERY SEVERE BUT TOLERABLE
M
EORTC 22851
CF ev.d
CHART
CB
WANG
SCH-II
OH-7
EORTC 22791
SEVERE
SCH-III
O
PMH
RTOG 9003
INCIDENCE of CONFLUENT MUCOSITIS (grade 4)
O
1/wk
CONV.
0 1.0
2.0 3.0
4.0
Relative ACCUMULATED NORMALISED DOSE/week r AND
max
Figure 5.
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Comparison of the present results with the
published data (Figure 5) suggest that the
incidence of the CM has been underestimated in
many previous studies probably due to irregular
and infrequent scoring (own data points for
once-a-week irregular scoring are close to an
average CM curve estimated for published data).
Dotted line represents everyday regular scoring
for the present data sets. It suggests that in
general quantitation of acute radiation mucositis
till now remains uncertain.
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CONCLUSIONS

• Acute mucosal radiation effect (AMR)
• is a complex of morphological and functional
• disorders with different severity and duration
• in individual patients.
• AMR (CM) has usually tri-phasic
• (CM onsetlastinghealing)but in some patients
• it represents wavelike pattern
• Precise quantitation of acute radiation
  mucositis
• need frequent and regular scoring (at least
  trice
• a week).