xerostomia

1. XEROSTOMIA LEVEL AND QUALITY OF LIFE AFTER NASOPHARYNGEAL
CANCER RADIOTHERAPY, INTENSITY MODULATED RADIATION THERAPY VS
CONVENTIONAL
Abstract
Introduction: Radiation in nasopharyngeal cancer in Indonesia is currently the main choice of
therapeutic modality. the use of radiation techniques in most patients in Indonesia is a
conventional type using two-dimensional techniques. This conventional technique causes severe
side effects of advanced toxicity. the most common toxicity caused by radiation is xerostomia.
the use of imrt techniques can limit the radiation dose received by critical organs including the
parotid gland so that it can alleviate xerostomia and improve quality of life
Method: Twenty NPC patients using IMRT technique and 20 patients using 2DCRT technique
were collected consecutively. Whole saliva flow (stimulated and not stimulated) were measured
in every subject. European Organization for Research and Treatment of Cancer (EORTC) core
questionnaire, and EORTC head and neck module (QLQ-H&N35) were also completed. Both
questionnaire and saliva flow were collected at one time ( cross sectional study ), with criteria
that all subject already pass 6 months after last radiation date.
Result: The IMRT group makes higher saliva flow rate than 2DCRT group (p<0.001), and if
categorized into CTCAE criteria the IMRT group achieve better degree of xerostomia than
2DCRT group (p<0.05). in IMRT group, there was moderate correlation between recovery time
and saliva flow rate (p<0.05). from the QLO-C30 questionnaire score, the IMRT group prove to
be better than 2DCRT group in categories : Global health status, physical functioning, Emotional
functioning, pain and insomnia (p<0.05). From the head and neck module questionnaire (QLQ-
H&N35), IMRT group also prove to be better in categories : head and neck pain. Swallowing,
speech problems, trouble with social eating, trouble with social contact, dry mouth (p<0.05), &
sticky saliva (p<0.001).
Conclusion : IMRT was significantly superior to 2DCRT in preserving and sparing the salivary
gland especially parotid, and improve quality of life.
Introduction
the main management of nasopharyngeal cancer is surgery and radiotherapy. however, the
difficulty of surgical procedures is mainly due to the location of the nasopharynx which is
difficult to achieve and the difficulty in obtaining sufficient incisions so that radiotherapy is the
first choice because it is able to produce good results and is able to reach difficult areas.1
At present, nasopharyngeal cancer therapy provides better survival rates and local control due to
technological developments and numerous studies on nasopharyngeal cancer. the use of
chemotherapy combined with radiation has been shown to increase the survival of patients,
especially at advanced stages. besides that the development of diagnostic technology and
improved radiation techniques play a role in increasing the success of nasopharyngeal cancer
therapy. Radiation techniques such as IMRT (intensity modulated radiation therapy) or 3DCRT

2. (three-dimensional conformal) or a combination with brachytherapy can provide larger doses at
the location of nasopharyngeal tumors but reduce toxic side effects on normal tissue
Radiation in nasopharyngeal cancer in Indonesia is currently the main choice of therapeutic
modality. the use of radiation techniques in most patients in Indonesia is a conventional type
using two-dimensional techniques. This conventional technique causes severe side effects of
advanced toxicity. the most common toxicity caused by radiation is xerostomia.
The use of IMRT techniques that have been running since 2009 provides new hope in improving
the quality of therapy. the IMRT technique can limit the radiation dose received by critical
organs including the parotid gland so that this technique can improve xerostomia specifically and
the quality of life of patients in general. This study aims to compare the further side effects
caused by the IMRT and 3DCRT techniques, especially xerostomia degrees and quality of life
scores
Method
This study was a cross-sectional analysis to compare the degree of xerostomia and quality of life
scores of nasopharyngeal cancer patients treated using conventional 2D techniques with those
using the IMRT technique at Department of Radiotherapy, Cipto Mangunkusumo Hospital,
Indonesia from August 2012 until December 2012.
the target population was all nasopharyngeal carcinoma patients who had been treated for
curative purposes using conventional 2D or IMRT techniques in the RSCM radiotherapy
department. accessible population is the target population in the last three years (2009-2012) and
lives in the Jakarta and surrounding areas, which can be contacted, or come to RSCM for control.
The research subject approval form was included before carrying out this research.
the selection of samples from accessible populations was carried out using non-probability
sampling. the method used is consecutive sampling. from the conventional 2D group, all subjects
who came to control the ENT polyclinic and fulfilled the selection criteria will be included until
the required number of subjects is fulfilled. whereas in the IMRT group, the selection of subjects
was carried out in consecutive sampling based on the sequence of medical record data which was
earlier
Twenty NPC patients using IMRT technique and 20 patients using 2DCRT technique were
collected consecutively. Whole saliva flow (stimulated and not stimulated) were measured in
every subject. European Organization for Research and Treatment of Cancer (EORTC) core
questionnaire, and EORTC head and neck module (QLQ-H&N35) were also completed. Both
questionnaire and saliva flow were collected at one time ( cross sectional study ), with criteria
that all subject already pass 6 months after last radiation date.
Result
From this study, a total of 40 research subjects were divided into two groups. ages ranged from
17 to 60 years with a mean age of 43.7 years in the conventional 2D group, and 18 to 68 years
with an average age of 48.3 years in the IMRT group. measurement of the flow of saliva is
divided into stimulated and not stimulated. at the unstimulated salivary flow rate using an
independent sample T-test where 2D techniques have a mean of 0.196 (SD 0.156) (IK95% 0.12;
0.61) ml / minute with a median value of 0.20 ml / minute while the IMRT technique has a mean

3. 0.5 (SD 0.254) (IK95% 0.38; 0.61) ml / minute with a median value of 0.50 ml / minute. at
stimulated salivary flow rate, 2D technique has a mean of 0.188 (SD 0.219) (IK95% 0.08; 0.29)
ml / minute with a mean value of 0.10 ml / minute while the IMRT technique has an average
value of 1.085 (SD 0.409) ( IK95% 0.89; 1.27) ml / minute with a median value of 1.00 ml /
minute.
The comparison of salivary flow rates not stimulated between radiation techniques if
converted to the degree of the Common Terminology Criteria for Adverse Events (CTCAE
version 3).
the results of the calculation of salivary flow rate statistics based on the CTCAE category, the
degree of xerostomia using 2D radiation techniques there are 7 cases of grade 1, 6 cases of grade
2 and 7 cases of grade 3 while those using the IMRT technique have 16 cases of grade 1, 3 cases
of grade 2 and 1 case of grade 3.
Correlation between recovery time and saliva flow rate
the relationship between recovery time and salivary flow rate is divided into two groups, namely
conventional 2D and IMRT techniques. in conventional 2D techniques, the correlation of
recovery time with salivary flow rate not stimulated using Pearson correlation test with r = 0.108
and p = 0.652. on the correlation of recovery time with stimulated saliva flow rate using the
spearman correlation test with r = 0.272 and p = 0.246. in the IMRT technique, the correlation of
recovery time with the salivary flow rate was not stimulated using the Spearman correlation test
obtained r = 0.555 and p = 0.011. the correlation of recovery time with stimulated saliva flow
rate using the spearman correlation test with r = 0.517 and p = 0.02.
Correlation between salivary flow rate and average dose received by the parotid gland
(IMRT)
the results of the correlation test between the average dose of the parotid gland (Gy) and the
salivary flow rate. the correlation test was divided into two, stimulated saliva flow rates and not
stimulated in subjects who received therapy with the IMRT technique. at parotid average doses
with not stimulated salivary flow rate using Pearson bivariate correlation test obtained r = -0.521
and p = 0.018. At parotid average doses with stimulated saliva flow rate using Pearson bivariate
correlation test, r = -0.458 and p = 0.042
The results of the EORTC questionnaire data
the results of the EORTC questionnaire data were divided into 2 groups, namely the quality of
life questionnaire in general with the QLQ-C30 and a more specific questionnaire asking about
the area of the neck head with the QLQ-H & N35.
In processing QLQ-C30 questionnaire data using the Mann Whitney test there were significant
differences in the Global Health Status (QoL) where the mean 2D was 70.8 with SD (16.1)
(CI95% 63.3; 78.3) median (66.6 ) while IMRT, mean 82.9 SD (21.19) (CI95% 72.9; 92.8)
median (87.5). at physical functioning (PF2) obtained in 2D mean 79.3 SD (18.08) (CI95% 70.8;
87.7) median (80) whereas at IMRT mean 93 SD (9.04) (CI95% 88, 7; 97.2) median 96.6.
emotional functioning (EF) is obtained in 2D mean 71.2 SD (18.82) (CI95% 62.4; 80) median
(75) whereas in IMRT it is obtained mean 88.3 SD (18.21) (CI95% 79 , 8; 96.8) median (95.8).
results on pain (PA) for 2D mean 21.6 SD (27.62) (CI95% 8.7; 34.5) median (16.6) and at IMRT
mean 6.6 SD (11.34) (CI95 1.3%, 11.9) median 0. Insomnia (SL) is obtained in 2D mean 20 with
SD (22.68) (CI95% 9.3; 30.6) median (16.6) and in IMRT mean 6.6 SD (13.67) (CI95% 0.2;
13.0) median (0)
The results of the QLH-H & N35 questionnaire data

4. In processing the QLQ-H & N35 questionnaire data using the Mann Whitney test there were
significant differences in Pain (HNPA) where the mean 2D was 20.4 with SD (29.05) (CI95%
6.8; 34.0) median (8.3) while IMRT, mean 4.5 SD (10.28) (CI95% -0.2; 9.3) median (0). on
swallowing (HNSW) was obtained in 2D mean 29.5 SD (24.84) (CI95% 17.9; 41.2) median (25)
whereas in IMRT mean 14.5 SD (14.01) (CI95% 8 , 0; 21.1) median (12.5). Speech problems
(HNSP) were obtained in 2D mean 22.7 SD (20.85) (CI95% 13.0; 32.5) median (22.2) whereas
in IMRT the mean was 11.1 SD (16.51) (CI95% 3.3; 18.8) median (0). results of trouble with
social eating (HNSO) for 2D mean 37.9 SD (29.55) (CI95% 24.0; 51.7) median (33.3) and at
IMRT mean 16.2 SD (18.43 ) (CI95% 7.6; 24.8) median 8.3. in Dry mouth (HNDR) it was found
in 2D mean 70 with SD (30.39) (CI95% 55.7; 84.2) median (66.6) and at IMRT mean 45 SD
(29.16) (CI95% 31 , 3; 58.6) median (50)
Discussion
Based on previous research by Lee et al., in the management of nasopharyngeal cancer, the
IMRT technique has severe mucositis side effects. this happens because the accumulation of
doses is quite high in the oral mucosa.2 Xerostomia is the main symptom of late side effects in
nasopharyngeal cancer. the salivary flow rate decreased after the salivary gland received a dose
of 10-15 Gy. Saliva production continues to decline to doses of 20-40 Gy, and above 40 Gy
decreases to more than 75% of production.3
The IMRT group made the higher saliva flow rate than 2DCRT group (p <0.001) both at the
stimulated saliva flow rate and not stimulated. this indicates that the salivary gland still has better
function after radiation with the IMRT technique than 2D techniques. in the comparison of
stimulated and unstimulated salivary flow rates in the 2D group, there was no significant
difference (p = 0.23) whereas in the IMRT group there were significant differences (p <0.001)
where when the parotid gland was stimulated by food, more saliva would be produced than the
saliva flow rate is not stimulated
if categorized into CTCAE criteria the IMRT group achieve better degree of xerostomia than
2DCRT group (p<0.05). the use of the IMRT technique is more experienced in lower degrees of
xerostomia (degree 1), while the use of conventional 2D has a higher degree of xerostomia
(second and third degree). this means that the IMRT technique did not damage the salivary gland
too much and the salivary gland can still work better than conventional 2D techniques
in 2D group, there was a weak correlation between recovery time and saliva flow rate. the longer
the recovery time, the higher the saliva flow rate. but this statistic does not have a significant
relationship. based on this study, it was found that the salivary flow rate cannot recover over
time. too large doses received by the salivary gland cause this to happen. in conventional 2D
techniques opposing laterally, the parotid gland can be exposed to a dose of 60-70 Gy. whereas
in the literature it is said that the maximum dose of the parotid gland to irreversible is 60 Gy.
(13) (4). whereas in IMRT group, there was a moderate correlation between recovery time and
saliva flow rate (p <0.05) where the longer the recovery time, the higher the salivary flow rate
both at the stimulated salivary flow rate and not stimulated. this proves that IMRT patients after
salivary gland radiation therapy can recover over time.

5. From the QLO-C30 questionnaire score, the IMRT group prove to be better than 2DCRT group
in categories : Global health status, physical functioning, Emotional functioning, pain and
insomnia (p<0.05). From the head and neck module questionnaire (QLQ-H&N35), IMRT group
also prove to be better in categories : head and neck pain. Swallowing, speech problems, trouble
with social eating, trouble with social contact, dry mouth (p<0.05), & sticky saliva (p<0.001).
Overall the use of the IMRT technique has been shown to reduce the side effects of xerostomia
and provide a better quality of life. xerostomia in the IMRT group can also improve over time.
however, there is a lack in the EORTC questionnaire in the form of no measurement criteria for
hearing function. reduced hearing function is one of the most side effects besides xerostomia and
soft tissue fibrosis. (39). so far, xerostomia is believed to be the main factor causing the decline
in the quality of life of patients, but the direct causal relationship between these two things
cannot be ascertained. The use of the IMRT technique in nasopharyngeal cancer not only reduces
xerostomia complaints but also in other organs in the head and neck region which ultimately
improves overall quality of life (12)
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